A novel and reactive oxygen species(ROS)responsive astaxanthin phenylboronic acid derivative(AstaDPBA)was constructed by grafting phenylboronic acid(PBA)onto astaxanthin succinate diester(AstaD),and its chemical struc...A novel and reactive oxygen species(ROS)responsive astaxanthin phenylboronic acid derivative(AstaDPBA)was constructed by grafting phenylboronic acid(PBA)onto astaxanthin succinate diester(AstaD),and its chemical structure and physicochemical property were identified.AstaD-PBA could effectively improve the ROS quenching ability in the lipopolysaccharide(LPS)-induced RAW264.7 cell inflammation model.Then,the bioactivity of AstaD-PBA was studied by 4 zebrafish ROS-responsive infl ammatory models induced by LPS,copper(Cu^(2+)),high-fat diet,and dextran sodium sulfate(DSS).The results suggest that AstaD-PBA might have high biosafety and the best effect on ulcerative colitis(UC)induced by DSS.Furtherly,AstaDPBA significantly alleviated and treated weight loss and colonic shrinkage,inhibited infl ammatory cytokines,and maintained microbiota homeostasis to improve UC in C57BL/6J mice.Alistipes and Oscillibacter were expected to be considered UC marker fl ora according to the Metastats analysis and Pearson correlation Mantel test(P<0.01)of 16S rRNA gene sequencing data.In conclusion,AstaD-PBA has been promised to be a functional compound to improve UC and maintain intestinal microbiota homeostasis.展开更多
The current single-atom catalysts(SACs)for medicine still suffer from the limited active site density.Here,we develop a synthetic method capable of increasing both the metal loading and mass-specific activity of SACs ...The current single-atom catalysts(SACs)for medicine still suffer from the limited active site density.Here,we develop a synthetic method capable of increasing both the metal loading and mass-specific activity of SACs by exchanging zinc with iron.The constructed iron SACs(h^(3)-FNC)with a high metal loading of 6.27 wt%and an optimized adjacent Fe distance of~4 A exhibit excellent oxidase-like catalytic performance without significant activity decay after being stored for six months and promising antibacterial effects.Attractively,a“density effect”has been found at a high-enough metal doping amount,at which individual active sites become close enough to interact with each other and alter the electronic structure,resulting in significantly boosted intrinsic activity of single-atomic iron sites in h^(3)-FNCs by 2.3 times compared to low-and medium-loading SACs.Consequently,the overall catalytic activity of h^(3)-FNC is highly improved,with mass activity and metal mass-specific activity that are,respectively,66 and 315 times higher than those of commercial Pt/C.In addition,h^(3)-FNCs demonstrate efficiently enhanced capability in catalyzing oxygen reduction into superoxide anion(O_(2)·^(−))and glutathione(GSH)depletion.Both in vitro and in vivo assays demonstrate the superior antibacterial efficacy of h^(3)-FNCs in promoting wound healing.This work presents an intriguing activity-enhancement effect in catalysts and exhibits impressive therapeutic efficacy in combating bacterial infections.展开更多
Flexible surface micro-discharge plasma is a non-thermal plasma technique used for treating wounds in a painless way, with significant efficacy for chronic or hard-to-heal wounds. In this study, a confined space was d...Flexible surface micro-discharge plasma is a non-thermal plasma technique used for treating wounds in a painless way, with significant efficacy for chronic or hard-to-heal wounds. In this study, a confined space was designed to simulate wound conditions, with gelatin used to simulate wound tissue. The distinction between open and confined spaces was explored, and the effects of temperature, humidity, discharge power and the gap size within the confined space on the plasma characteristics were analyzed. It was found that temperature, humidity and discharge power are important factors that affect the concentration distribution of active components and the mode transition between ozone and nitrogen oxides. Compared to open space, the concentration of ozone in confined space was relatively lower, which facilitated the formation of nitrogen oxides. In open space, the discharge was dominated by ozone initially. As the temperature,humidity and discharge power increased, nitrogen oxides in the gas-phase products were gradually detected. In confined space, nitrogen oxides can be detected at an early stage and at much higher concentrations than ozone concentration. Furthermore, as the gap of the confined space decreased, the concentration of ozone was observed to decrease while that of nitrate increased, and the rate of this concentration change was further accelerated at higher temperature and higher power. It was shown that ozone concentration decreased from 0.11 to 0.03 μmol and the nitrate concentration increased from 20.5 to 24.5 μmol when the spacing in the confined space was reduced from 5 to 1 mm, the temperature of the external discharge was controlled at 40 ℃, and the discharge power was 12 W. In summary, this study reveals the formation and transformation mechanisms of active substances in air surface micro-discharge plasma within confined space, providing foundational data for its medical applications.展开更多
The great promise of photodynamic therapy(PDT) has thrusted the rapid progress of developing highly effective photosensitizers(PS) in killing cancerous cells and bacteria. To mitigate the intrinsic limitations of the ...The great promise of photodynamic therapy(PDT) has thrusted the rapid progress of developing highly effective photosensitizers(PS) in killing cancerous cells and bacteria. To mitigate the intrinsic limitations of the classical molecular photosensitizers, researchers have been looking into designing new generation of nanomaterial-based photosensitizers(nano-photosensitizers) with better photostability and higher singlet oxygen generation(SOG) efficiency, and ways of enhancing the performance of existing photosensitizers. In this paper, we review the recent development of nano-photosensitizers and nanoplasmonic strategies to enhance the SOG efficiency for better PDT performance. Firstly, we explain the mechanism of reactive oxygen species generation by classical photosensitizers, followed by a brief discussion on the commercially available photosensitizers and their limitations in PDT. We then introduce three types of new generation nanophotosensitizers that can effectively produce singlet oxygen molecules under visible light illumination, i.e., aggregation-induced emission nanodots, metal nanoclusters (< 2 nm), and carbon dots. Different design approaches to synthesize these nano-photosensitizers were also discussed. To further enhance the SOG rate of nano-photosensitizers, plasmonic strategies on using different types of metal nanoparticles in both colloidal and planar metal-PS systems are reviewed. The key parameters that determine the metal-enhanced SOG(ME-SOG) efficiency and their underlined enhancement mechanism are discussed. Lastly, we highlight the future prospects of these nanoengineering strategies, and discuss how the future development in nanobiotechnology and theoretical simulation could accelerate the design of new photosensitizers and ME-SOG systems for highly effective image-guided photodynamic therapy.展开更多
BACKGROUND:Individuals who survive a cardiac arrest often sustain cognitive impairments due to ischemia-reperfusion injury.Mesenchymal stem cell(MSC)transplantation is used to reduce tissue damage,but exosomes are mor...BACKGROUND:Individuals who survive a cardiac arrest often sustain cognitive impairments due to ischemia-reperfusion injury.Mesenchymal stem cell(MSC)transplantation is used to reduce tissue damage,but exosomes are more stable and highly conserved than MSCs.This study was conducted to investigate the therapeutic effects of MSC-derived exosomes(MSC-Exo)on cerebral ischemia-reperfusion injury in an in vitro model of oxygen-glucose deprivation/reperfusion(OGD/R),and to explore the underlying mechanisms.METHODS:Primary hippocampal neurons obtained from 18-day Sprague-Dawley rat embryos were subjected to OGD/R treatment,with or without MSC-Exo treatment.Exosomal integration,cell viability,mitochondrial membrane potential,and generation of reactive oxygen species(ROS)were examined.Terminal deoxynucleotidyl transferase-mediated 2’-deoxyuridine 5’-triphosphate nickend labeling(TUNEL)staining was performed to detect neuronal apoptosis.Moreover,mitochondrial function-associated gene expression,Nrf2 translocation,and expression of downstream antioxidant proteins were determined.RESULTS:MSC-Exo attenuated OGD/R-induced neuronal apoptosis and decreased ROS generation(P<0.05).The exosomes reduced OGD/R-induced Nrf2 translocation into the nucleus(2.14±0.65 vs.5.48±1.09,P<0.01)and increased the intracellular expression of antioxidative proteins,including superoxide dismutase and glutathione peroxidase(17.18±0.97 vs.14.40±0.62,and 20.65±2.23 vs.16.44±2.05,respectively;P<0.05 for both).OGD/R significantly impaired the mitochondrial membrane potential and modulated the expression of mitochondrial functionassociated genes,such as PINK,DJ1,LRRK2,Mfn-1,Mfn-2,and OPA1.The abovementioned changes were partially reversed by exosomal treatment of the hippocampal neurons.CONCLUSIONS:MSC-Exo treatment can alleviate OGD/R-induced oxidative stress and dysregulation of mitochondrial function-associated genes in hippocampal neurons.Therefore,MSCExo might be a potential therapeutic strategy to prevent OGD/R-induced neuronal injury.展开更多
In this paper, we report on the contrastive analysis of inactivation efficiency of E. coli cells in solution with different disinfection methods. Compared with the hydrogen peroxide solution and the ozone gas, the atm...In this paper, we report on the contrastive analysis of inactivation efficiency of E. coli cells in solution with different disinfection methods. Compared with the hydrogen peroxide solution and the ozone gas, the atmospheric-pressure He plasma can completely kill the E. coli cells in the shortest time. The inactivation efficiency of E. coli cells in solution can be well described by using the chemical reaction rate model. X-ray photoelectron spectroscopy(XPS) analysis shows that the C–O or C=O content of the inactivated E. coli cell surface by plasma is predominantly increased, indicating the quantity of oxygen-containing species in plasma is more than those of two other methods, and then the C–C or C–H bonds can be broken, leading to the etching of organic compounds. Analysis also indicates that plasma-generated species can play a crucial role in the inactivation process by their direct reactions or the decompositions of reactive species, such as ozone into OH radicals in water, then reacting with E. coli cells.展开更多
Recently, we found some errors in Fig. 3 of the article Chin. Phys. B 24 085201 (2015). Upon a thorough examination of the raw data materials, we confirm that the image error did not impact any of the findings and con...Recently, we found some errors in Fig. 3 of the article Chin. Phys. B 24 085201 (2015). Upon a thorough examination of the raw data materials, we confirm that the image error did not impact any of the findings and conclusions of the paper. Based on this, we have made corrections to the original article.展开更多
Post-traumatic peritendinous adhesion presents a significant challenge in clinical medicine.This study proposes the use of diamond-like carbon(DLC)deposited on polylactic acid(PLA)membranes as a biophysical mechanism ...Post-traumatic peritendinous adhesion presents a significant challenge in clinical medicine.This study proposes the use of diamond-like carbon(DLC)deposited on polylactic acid(PLA)membranes as a biophysical mechanism for anti-adhesion barrier to encase ruptured tendons in tendon-injured rats.The results indicate that PLA/DLC composite membrane exhibits more efficient anti-adhesion effect than PLA membrane,with histological score decreasing from 3.12±0.27 to 2.20±0.22 and anti-adhesion effectiveness increasing from 21.61%to 44.72%.Mechanistically,the abundant C=O bond functional groups on the surface of DLC can reduce reactive oxygen species level effectively;thus,the phosphorylation of NF-κB and M1 polarization of macrophages are inhibited.Consequently,excessive inflammatory response augmented by M1 macrophage-originated cytokines including interleukin-6(IL-6),interleukin-1β(IL-1β),and tumor necrosis factor-α(TNF-α)is largely reduced.For biocompatibility evaluation,PLA/DLC membrane is slowly absorbed within tissue and displays prolonged barrier effects compared to traditional PLA membranes.Further studies show the DLC depositing decelerates the release of degradation product lactic acid and its induction of macrophage M2 polarization by interfering esterase and PLA ester bonds,which further delays the fibrosis process.It was found that the PLA/DLC membrane possess an efficient biophysical mechanism for treatment of peritendinous adhesion.展开更多
Reactive oxygen species(ROS)plays important roles in living organisms.While ROS is a double-edged sword,which can eliminate drug-resistant bacteria,but excessive levels can cause oxidative damage to cells.A core–shel...Reactive oxygen species(ROS)plays important roles in living organisms.While ROS is a double-edged sword,which can eliminate drug-resistant bacteria,but excessive levels can cause oxidative damage to cells.A core–shell nanozyme,Ce O_(2)@ZIF-8/Au,has been crafted,spontaneously activating both ROS generating and scavenging functions,achieving the multifaceted functions of eliminating bacteria,reducing inflammation,and promoting wound healing.The Au Nanoparticles(NPs)on the shell exhibit high-efficiency peroxidase-like activity,producing ROS to kill bacteria.Meanwhile,the encapsulation of Ce O_(2) core within ZIF-8 provides a seal for temporarily limiting the superoxide dismutase and catalase-like activities of Ce O_(2) nanoparticles.Subsequently,as the ZIF-8 structure decomposes in the acidic microenvironment,the Ce O_(2) core is gradually released,exerting its ROS scavenging activity to eliminate excess ROS produced by the Au NPs.These two functions automatically and continuously regulate the balance of ROS levels,ultimately achieving the function of killing bacteria,reducing inflammation,and promoting wound healing.Such innovative ROS spontaneous regulators hold immense potential for revolutionizing the field of antibacterial agents and therapies.展开更多
As a new form of regulated cell death,ferroptosis has unraveled the unsolicited theory of intrinsic apoptosis resistance by cancer cells.The molecular mechanism of ferroptosis depends on the induction of oxidative str...As a new form of regulated cell death,ferroptosis has unraveled the unsolicited theory of intrinsic apoptosis resistance by cancer cells.The molecular mechanism of ferroptosis depends on the induction of oxidative stress through excessive reactive oxygen species accumulation and glutathione depletion to damage the structural integrity of cells.Due to their high loading and structural tunability,nanocarriers can escort the delivery of ferro-therapeutics to the desired site through enhanced permeation or retention effect or by active targeting.This review shed light on the necessity of iron in cancer cell growth and the fascinating features of ferroptosis in regulating the cell cycle and metastasis.Additionally,we discussed the effect of ferroptosis-mediated therapy using nanoplatforms and their chemical basis in overcoming the barriers to cancer therapy.展开更多
Background:Kirsten rat sarcoma(KRAS)and mutant KRAS^(G12D)have been implicated in human cancers,but it remains unclear whether their activation requires ubiquitination.This study aimed to investigate whether and how F...Background:Kirsten rat sarcoma(KRAS)and mutant KRAS^(G12D)have been implicated in human cancers,but it remains unclear whether their activation requires ubiquitination.This study aimed to investigate whether and how F-box and leucine-rich repeat 6(FBXL6)regulates KRAS and KRAS^(G12D)activity in hepatocellular carcinoma(HCC).Methods:We constructed transgenic mouse strains LC(LSL-Fbxl6^(KI/+);Alb-Cre,n=13),KC(LSL-Kras^(G12D/+);Alb-Cre,n=10)and KLC(LSL-Kras^(G12D/+);LSL-Fbxl6^(KI/+);Alb-Cre,n=12)mice,and then monitored HCC for 320 d.Multiomics approaches and pharmacological inhibitors were used to determine oncogenic signaling in the context of elevated FBXL6 and KRAS activation.Co-immunoprecipitation(Co-IP),Western blotting,ubiquitination assay,and RAS activity detection assay were employed to investigate the underlying molecular mechanism by which FBXL6 activates KRAS.The pathological relevance of the FBXL6/KRAS/extracellular signal-regulated kinase(ERK)/mammalian target of rapamycin(mTOR)/proteins of relevant evolutionary and lymphoid interest domain 2(PRELID2)axis was evaluated in 129 paired samples from HCC patients.Results:FBXL6 is highly expressed in HCC as well as other human cancers(P<0.001).Interestingly,FBXL6 drives HCC in transgenic mice.Mechanistically,elevated FBXL6 promotes the polyubiquitination of both wild-type KRAS and KRAS^(G12D)at lysine 128,leading to the activation of both KRAS and KRAS^(G12D)and promoting their binding to the serine/threonine-protein kinase RAF,which is followed by the activation of mitogen-activated protein kinase kinase(MEK)/ERK/mTOR signaling.The oncogenic activity of the MEK/ERK/mTOR axis relies on PRELID2,which induces reactive oxygen species(ROS)generation.Furthermore,hepatic FBXL6 upregulation facilitates KRAS^(G12D)to induce more severe hepatocarcinogenesis and lung metastasis via the MEK/ERK/mTOR/PRELID2/ROS axis.Dual inhibition of MEK and mTOR effectively suppresses tumor growth and metastasis in this subtype of cancer in vivo.In clinical samples,FBXL6 expression positively correlates with p-ERK(χ^(2)=85.067,P<0.001),p-mTOR(χ^(2)=66.919,P<0.001)and PRELID2(χ^(2)=20.891,P<0.001).The Kaplan-Meier survival analyses suggested that HCC patients with high FBXL6/p-ERK levels predicted worse overall survival(log-rank P<0.001).Conclusions:FBXL6 activates KRAS or KRAS^(G12D)via ubiquitination at the site K128,leading to activation of the ERK/mTOR/PRELID2/ROS axis and tumorigenesis.Dual inhibition of MEK and mTOR effectively protects against FBXL6-and KRAS^(G12D)-induced tumorigenesis,providing a potential therapeutic strategy to treat this aggressive subtype of liver cancer.展开更多
The changes of hydrogen peroxide （H2O2） metabolism and antioxidant enzyme activities in a hybrid poplar （Populus simonii xp. pyramidalis ＇Opera 8277＇） in response to rnechanical damage （MD） and herbivore wound...The changes of hydrogen peroxide （H2O2） metabolism and antioxidant enzyme activities in a hybrid poplar （Populus simonii xp. pyramidalis ＇Opera 8277＇） in response to rnechanical damage （MD） and herbivore wounding （HW） were investigated to determine whether H2O2 could function as the secondary messenger in the signaling of systemic resistance. Results show that H2O2 was generated in wounded leaves through MD and HW treatments and systemically in unwounded leaves around the wounded leaves. The activities of antioxidant enzymes such as superoxide dismutase （SOD）, catalase （CAT） and ascorbate peroxidase （APX） were also enhanced. However, the H2O2 accumulation and antioxidant enzyme activities were inhibited in MD leaves through the pretreatment with DPI （which is a specific inhibitor of NADPH oxidase）. The results of this study suggest that H2O2 could be systemically induced by MD and HW treatments, and H2O2 metabolism was closely related to the change in SOD, APX and CAT activities. A high level of antioxidant enzymes could decrease membrane lipid peroxidation levels and effectively induce plant defense responses.展开更多
For dispersed ceria-zirconia-based solid solutions prepared via the polymerized complex method and annealed at 700 ℃, effects of bulk doping by Ca, Mn, Co, Bi or Nb cations and surface modification by Mn and Pt on th...For dispersed ceria-zirconia-based solid solutions prepared via the polymerized complex method and annealed at 700 ℃, effects of bulk doping by Ca, Mn, Co, Bi or Nb cations and surface modification by Mn and Pt on their structural features, surface/bulk oxygen reactivity and catalytic activity in methane combustion are considered. With up to 20 mol% doping, a structural type of homogeneous solid solutions of anion-deficient fluorite with disordered anion vacancies is formed. Doping by transition metal cations or Pt increases the mobility and reactivity of the surface/bulk oxygen. A broad variation in specific rates of methane combustion for the studied systems was observed, suggesting structural sensitivity of this reaction. In general, there is no universal relationship between the oxygen mobility, the reactivity and the catalytic activity in methane combustion, which is explained by the factor of specific methane activation on surface active sites. For the Pt-promoted samples, Pt efficiency in methane activation depends on the Pt-support interaction, and the most favorable ones being mixed Pt/MnOx and Pt/NbOx clusters on the surface of the supports that exhibit high lattice oxygen mobilities.展开更多
Antibacterial activity of zinc oxide nanoparticles(Zn O-NPs) has received significant interest worldwide particularly by the implementation of nanotechnology to synthesize particles in the nanometer region. Many micro...Antibacterial activity of zinc oxide nanoparticles(Zn O-NPs) has received significant interest worldwide particularly by the implementation of nanotechnology to synthesize particles in the nanometer region. Many microorganisms exist in the range from hundreds of nanometers to tens of micrometers. Zn O-NPs exhibit attractive antibacterial properties due to increased specific surface area as the reduced particle size leading to enhanced particle surface reactivity. Zn O is a bio-safe material that possesses photo-oxidizing and photocatalysis impacts on chemical and biological species. This review covered Zn O-NPs antibacterial activity including testing methods, impact of UV illumination, Zn O particle properties(size, concentration, morphology, and defects), particle surface modification, and minimum inhibitory concentration. Particular emphasize was given to bactericidal and bacteriostatic mechanisms with focus on generation of reactive oxygen species(ROS) including hydrogen peroxide(H2O2), OH-(hydroxyl radicals), and O2-2(peroxide). ROS has been a major factor for several mechanisms including cell wall damage due to Zn O-localized interaction, enhanced membrane permeability, internalization of NPs due to loss of proton motive force and uptake of toxic dissolved zinc ions.These have led to mitochondria weakness, intracellular outflow, and release in gene expression of oxidative stress which caused eventual cell growth inhibition and cell death. In some cases, enhanced antibacterial activity can be attributed to surface defects on Zn O abrasive surface texture. One functional application of the Zn O antibacterial bioactivity was discussed in food packaging industry where Zn O-NPs are used as an antibacterial agent toward foodborne diseases. Proper incorporation of Zn O-NPs into packaging materials can cause interaction with foodborne pathogens, thereby releasing NPs onto food surface where they come in contact with bad bacteria and cause the bacterial death and/or inhibition.展开更多
Background: Cerebral ischemia-reperfusion injury(CIRI) refers to a secondary brain injury that can occur when the blood supply to the ischemic brain tissue is restored. However, the mechanism underlying such injury re...Background: Cerebral ischemia-reperfusion injury(CIRI) refers to a secondary brain injury that can occur when the blood supply to the ischemic brain tissue is restored. However, the mechanism underlying such injury remains elusive.Methods: The 150 male C57 mice underwent middle cerebral artery occlusion(MCAO) for 1 h and reperfusion for 24 h,Among them, 50 MCAO mice were further treated with Mitochondrial division inhibitor 1(Mdivi-1) and 50 MCAO mice were further treated with N-acetylcysteine(NAC). SH-SY5Y cells were cultured in a low-glucose culture medium for 4 h under hypoxic conditions and then transferred to normal conditions for 12 h. Then, cerebral blood flow, mitochondrial structure, mitochondrial DNA(mtDNA) copy number, intracellular and mitochondrial reactive oxygen species(ROS),autophagic flux, aggresome and exosome expression profiles, cardiac tissue structure, mitochondrial length and cristae density, mtDNA and ROS content, as well as the expression of Drp1-Ser616/Drp1, RIP1/RIP3, LC3 II/I, TNF-α,IL-1β, etc., were detected under normal or Drp1 interference conditions.Results: The mtDNA content, ROS levels, and Drp1-Ser616/Drp1 were elevated by 2.2, 1.7 and 2.7 times after CIRI(P<0.05). However, the high cytoplasmic LC3 II/I ratio and increased aggregation of p62 could be reversed by 44%and 88% by Drp1 short hairpin RNA(shRNA)(P<0.05). The low fluorescence intensity of autophagic flux and the increased phosphorylation of RIP3 induced by CIRI could be attenuated by ROS scavenger, NAC(P<0.05). RIP1/RIP3inhibitor Necrostatin-1(Nec-1) restored 75% to a low LC3 II/I ratio and enhanced 2 times to a high RFP-LC3 after Drp1 activation(P<0.05). In addition, although CIRI-induced ROS production caused no considerable accumulation of autophagosomes(P>0.05), it increased the packaging and extracellular secretion of exosomes containing p62 by 4–5 times, which could be decreased by Mdivi-1, Drp1 shRNA, and Nec-1(P<0.05). Furthermore, TNF-α and IL-1βincreased in CIRI-derived exosomes could increase RIP3 phosphorylation in normal or oxygen–glucose deprivation/reoxygenation(OGD/R) conditions(P<0.05).Conclusions: CIRI activated Drp1 and accelerated the p62-mediated formation of autophagosomes while inhibiting the transition of autophagosomes to autolysosomes via the RIP1/RIP3 pathway activation. Undegraded autophagosomes were secreted extracellularly in the form of exosomes, leading to inflammatory cascades that further damaged mitochondria, resulting in excessive ROS generation and the blockage of autophagosome degradation,triggering a vicious cycle.展开更多
Rapid evolution and propagation of multidrug resistance among bacterial pathogens are outpacing the development of new antibiotics,but antimicrobial photodynamic therapy(aPDT)provides an excellent alternative.This tre...Rapid evolution and propagation of multidrug resistance among bacterial pathogens are outpacing the development of new antibiotics,but antimicrobial photodynamic therapy(aPDT)provides an excellent alternative.This treatment depends on the interaction between light and photoactivated sensitizer to generate reactive oxygen species(ROS),which are highly cytotoxic to induce apoptosis in virtually all microorganisms without resistance concern.When replacing light with low-frequency ultrasonic wave to activate sensitizer,a novel ultrasounddriven treatment emerges as antimicrobial sonodynamic therapy(aSDT).Recent advances in aPDT and aSDT reveal golden opportunities for the management of multidrug resistant bacterial infections,especially in the theranostic application where imaging diagnosis can be accomplished facilely with the inherent optical characteristics of sensitizers,and the generated ROS by aPDT/SDT cause broad-spectrum oxidative damage for sterilization.In this review,we systemically outline the mechanisms,targets,and current progress of aPDT/SDT for bacterial theranostic application.Furthermore,potential limitations and future perspectives are also highlighted.展开更多
The structural change-mediated catalytic activity regulation plays a significant role in the biological functions of natural enzymes.However,there is virtually no artificial nanozyme reported that can achieve natural ...The structural change-mediated catalytic activity regulation plays a significant role in the biological functions of natural enzymes.However,there is virtually no artificial nanozyme reported that can achieve natural enzyme-like stringent spatiotemporal structure-based catalytic activity regulation.Here,we report a subnanostructural transformable gold@ceria(STGC-PEG)nanozyme that performs tunable catalytic activities via near-infrared(NIR)light-mediated sub-nanostructural transformation.The gold core in STGC-PEG can generate energetic hot electrons upon NIR irradiation,wherein an internal sub-nanostructural transformation is initiated by the conversion between CeO;and electron-rich state of CeO;-x,and active oxygen vacancies generation via the hot-electron injection.Interestingly,the sub-nanostructural transformation of STGC-PEG enhances peroxidase-like activity and unprecedentedly activates plasmon-promoted oxidase-like activity,allowing highly efficient low-power NIR light(50 m W cm;)-activated photocatalytic therapy of tumors.Our atomic-level design and fabrication provide a platform to precisely regulate the catalytic activities of nanozymes via a light-mediated sub-nanostructural transformation,approaching natural enzyme-like activity control in complex living systems.展开更多
The average human life span has markedly increased in modem society largely attributed to advances in medical and therapeutic sciences that have successfully reduced important health risks. However, advanced age resul...The average human life span has markedly increased in modem society largely attributed to advances in medical and therapeutic sciences that have successfully reduced important health risks. However, advanced age results in numerous alterations to cellular and subcellular components that can impact the overall health and function of an individual. Not surprisingly, advanced age is a major risk factor for the development of heart disease in which elderly populations observe increased morbidity and mortality. Even healthy individuals that appear to have normal heart function under resting conditions, actually have an increased susceptibility and vulnerability to stress. This is confounded by the impact that stress and disease can have over time to both the heart and vessels. Although, there is a rapidly growing body of literature investigating the effects of aging on the heart and how age-related alterations affect cardiac function, the biology of aging and underlying mechanisms remain unclear. In this review, we summarize effects of aging on the heart and discuss potential theories of cellular aging with special emphasis on mitoehondrial dysfunction.展开更多
Background The mitochondrial Na^＋/Ca^2＋ exchanger, NCLX, plays an important role in the balance between Ca2. influx and efflux across the mitochondrial inner membrane in endothelial ceils. Mitochondrial metabolism i...Background The mitochondrial Na^＋/Ca^2＋ exchanger, NCLX, plays an important role in the balance between Ca2. influx and efflux across the mitochondrial inner membrane in endothelial ceils. Mitochondrial metabolism is likely to be affected by the activity of NCLX because Ca^2＋ activates several enzymes of the Krebs cycle. It is currently believed that mitochondria are not only centers of energy produc- tion but are also important sites of reactive oxygen species （ROS） generation and nucleotide-binding oligomerization domain receptor 3 （NLRP3） inflammasome activation. Methods ＆ Results This study focused on NCLX function, in rat aortic endothelial cells （RAECs）, induced by glucose. First, we detected an increase in NCLX expression in the endothelia of rats with diabetes mellitus, which was induced by an injection of streptozotocin. Next, colocalization of NCLX expression and mitochondria was detected using confocal analysis. Suppression of NCLX expression, using an siRNA construct （siNCLX）, enhanced mitochondrial Ca^2＋ influx and blocked efflux induced by glucose. Unexpectedly, silencing of NCLX expression induced increased ROS generation and NLRP3 inflammasome activation. Conclusions These findings suggest that NCLX affects glucose-dependent mitochondrial Ca^2＋ signaling, thereby regulating ROS generation and NLRP3 in- flammasome activation in high glucose conditions. In the early stages of high glucose stimulation, NCLX expression increases to compensate in order to self-protect mitochondrial maintenance, stability, and function in endothelial cells.展开更多
基金provided by the National Key R&D Program of China(2018YFC0311206)the Fundamental Research Funds for the Central Universities of China(202012018).
文摘A novel and reactive oxygen species(ROS)responsive astaxanthin phenylboronic acid derivative(AstaDPBA)was constructed by grafting phenylboronic acid(PBA)onto astaxanthin succinate diester(AstaD),and its chemical structure and physicochemical property were identified.AstaD-PBA could effectively improve the ROS quenching ability in the lipopolysaccharide(LPS)-induced RAW264.7 cell inflammation model.Then,the bioactivity of AstaD-PBA was studied by 4 zebrafish ROS-responsive infl ammatory models induced by LPS,copper(Cu^(2+)),high-fat diet,and dextran sodium sulfate(DSS).The results suggest that AstaD-PBA might have high biosafety and the best effect on ulcerative colitis(UC)induced by DSS.Furtherly,AstaDPBA significantly alleviated and treated weight loss and colonic shrinkage,inhibited infl ammatory cytokines,and maintained microbiota homeostasis to improve UC in C57BL/6J mice.Alistipes and Oscillibacter were expected to be considered UC marker fl ora according to the Metastats analysis and Pearson correlation Mantel test(P<0.01)of 16S rRNA gene sequencing data.In conclusion,AstaD-PBA has been promised to be a functional compound to improve UC and maintain intestinal microbiota homeostasis.
基金supported by the National Key Research and Development Program of China(Grant No.2022YFB3804500)the National Natural Science Foundation of China(Grant No.52202352,22335006)+4 种基金the Shanghai Municipal Health Commission(Grant No.20224Y0010)the CAMS Innovation Fund for Medical Sciences(Grant No.2021-I2M-5-012)the Basic Research Program of Shanghai Municipal Government(Grant No.21JC1406000)the Fundamental Research Funds for the Central Universities(Grant No.22120230237,2023-3-YB-11,22120220618)the Basic Research Program of Shanghai Municipal Government(23DX1900200).
文摘The current single-atom catalysts(SACs)for medicine still suffer from the limited active site density.Here,we develop a synthetic method capable of increasing both the metal loading and mass-specific activity of SACs by exchanging zinc with iron.The constructed iron SACs(h^(3)-FNC)with a high metal loading of 6.27 wt%and an optimized adjacent Fe distance of~4 A exhibit excellent oxidase-like catalytic performance without significant activity decay after being stored for six months and promising antibacterial effects.Attractively,a“density effect”has been found at a high-enough metal doping amount,at which individual active sites become close enough to interact with each other and alter the electronic structure,resulting in significantly boosted intrinsic activity of single-atomic iron sites in h^(3)-FNCs by 2.3 times compared to low-and medium-loading SACs.Consequently,the overall catalytic activity of h^(3)-FNC is highly improved,with mass activity and metal mass-specific activity that are,respectively,66 and 315 times higher than those of commercial Pt/C.In addition,h^(3)-FNCs demonstrate efficiently enhanced capability in catalyzing oxygen reduction into superoxide anion(O_(2)·^(−))and glutathione(GSH)depletion.Both in vitro and in vivo assays demonstrate the superior antibacterial efficacy of h^(3)-FNCs in promoting wound healing.This work presents an intriguing activity-enhancement effect in catalysts and exhibits impressive therapeutic efficacy in combating bacterial infections.
基金supported by Postgraduate Research&Practice Innovation Program of Jiangsu Province (No. 1003016001)。
文摘Flexible surface micro-discharge plasma is a non-thermal plasma technique used for treating wounds in a painless way, with significant efficacy for chronic or hard-to-heal wounds. In this study, a confined space was designed to simulate wound conditions, with gelatin used to simulate wound tissue. The distinction between open and confined spaces was explored, and the effects of temperature, humidity, discharge power and the gap size within the confined space on the plasma characteristics were analyzed. It was found that temperature, humidity and discharge power are important factors that affect the concentration distribution of active components and the mode transition between ozone and nitrogen oxides. Compared to open space, the concentration of ozone in confined space was relatively lower, which facilitated the formation of nitrogen oxides. In open space, the discharge was dominated by ozone initially. As the temperature,humidity and discharge power increased, nitrogen oxides in the gas-phase products were gradually detected. In confined space, nitrogen oxides can be detected at an early stage and at much higher concentrations than ozone concentration. Furthermore, as the gap of the confined space decreased, the concentration of ozone was observed to decrease while that of nitrate increased, and the rate of this concentration change was further accelerated at higher temperature and higher power. It was shown that ozone concentration decreased from 0.11 to 0.03 μmol and the nitrate concentration increased from 20.5 to 24.5 μmol when the spacing in the confined space was reduced from 5 to 1 mm, the temperature of the external discharge was controlled at 40 ℃, and the discharge power was 12 W. In summary, this study reveals the formation and transformation mechanisms of active substances in air surface micro-discharge plasma within confined space, providing foundational data for its medical applications.
基金Agency for Science,Technology,and Research(A*STAR)for providing financial support via SINGA scholarshipthe research support funding from the Newcastle University(RSA/CCEAMD5010)。
文摘The great promise of photodynamic therapy(PDT) has thrusted the rapid progress of developing highly effective photosensitizers(PS) in killing cancerous cells and bacteria. To mitigate the intrinsic limitations of the classical molecular photosensitizers, researchers have been looking into designing new generation of nanomaterial-based photosensitizers(nano-photosensitizers) with better photostability and higher singlet oxygen generation(SOG) efficiency, and ways of enhancing the performance of existing photosensitizers. In this paper, we review the recent development of nano-photosensitizers and nanoplasmonic strategies to enhance the SOG efficiency for better PDT performance. Firstly, we explain the mechanism of reactive oxygen species generation by classical photosensitizers, followed by a brief discussion on the commercially available photosensitizers and their limitations in PDT. We then introduce three types of new generation nanophotosensitizers that can effectively produce singlet oxygen molecules under visible light illumination, i.e., aggregation-induced emission nanodots, metal nanoclusters (< 2 nm), and carbon dots. Different design approaches to synthesize these nano-photosensitizers were also discussed. To further enhance the SOG rate of nano-photosensitizers, plasmonic strategies on using different types of metal nanoparticles in both colloidal and planar metal-PS systems are reviewed. The key parameters that determine the metal-enhanced SOG(ME-SOG) efficiency and their underlined enhancement mechanism are discussed. Lastly, we highlight the future prospects of these nanoengineering strategies, and discuss how the future development in nanobiotechnology and theoretical simulation could accelerate the design of new photosensitizers and ME-SOG systems for highly effective image-guided photodynamic therapy.
基金supported by a grant from the National Natural Science Foundation of China(81701872)。
文摘BACKGROUND:Individuals who survive a cardiac arrest often sustain cognitive impairments due to ischemia-reperfusion injury.Mesenchymal stem cell(MSC)transplantation is used to reduce tissue damage,but exosomes are more stable and highly conserved than MSCs.This study was conducted to investigate the therapeutic effects of MSC-derived exosomes(MSC-Exo)on cerebral ischemia-reperfusion injury in an in vitro model of oxygen-glucose deprivation/reperfusion(OGD/R),and to explore the underlying mechanisms.METHODS:Primary hippocampal neurons obtained from 18-day Sprague-Dawley rat embryos were subjected to OGD/R treatment,with or without MSC-Exo treatment.Exosomal integration,cell viability,mitochondrial membrane potential,and generation of reactive oxygen species(ROS)were examined.Terminal deoxynucleotidyl transferase-mediated 2’-deoxyuridine 5’-triphosphate nickend labeling(TUNEL)staining was performed to detect neuronal apoptosis.Moreover,mitochondrial function-associated gene expression,Nrf2 translocation,and expression of downstream antioxidant proteins were determined.RESULTS:MSC-Exo attenuated OGD/R-induced neuronal apoptosis and decreased ROS generation(P<0.05).The exosomes reduced OGD/R-induced Nrf2 translocation into the nucleus(2.14±0.65 vs.5.48±1.09,P<0.01)and increased the intracellular expression of antioxidative proteins,including superoxide dismutase and glutathione peroxidase(17.18±0.97 vs.14.40±0.62,and 20.65±2.23 vs.16.44±2.05,respectively;P<0.05 for both).OGD/R significantly impaired the mitochondrial membrane potential and modulated the expression of mitochondrial functionassociated genes,such as PINK,DJ1,LRRK2,Mfn-1,Mfn-2,and OPA1.The abovementioned changes were partially reversed by exosomal treatment of the hippocampal neurons.CONCLUSIONS:MSC-Exo treatment can alleviate OGD/R-induced oxidative stress and dysregulation of mitochondrial function-associated genes in hippocampal neurons.Therefore,MSCExo might be a potential therapeutic strategy to prevent OGD/R-induced neuronal injury.
基金Part of this paper was presented at the 8th Congress of Toxicology in Developing Countries(8CTDC)under the auspices of International Union of Toxicology(IUTOX)September 10-13,2012:at Centara Grand at Central Ladprao,Bangkok,Thailand.
基金supported by the Natural Science Foundation of Fujian Province,China(Grant No.2014J01025)the National Natural Science Foundation of China(Grant No.11275261)the Funds from the Fujian Provincial Key Laboratory for Plasma and Magnetic Resonance,China
文摘In this paper, we report on the contrastive analysis of inactivation efficiency of E. coli cells in solution with different disinfection methods. Compared with the hydrogen peroxide solution and the ozone gas, the atmospheric-pressure He plasma can completely kill the E. coli cells in the shortest time. The inactivation efficiency of E. coli cells in solution can be well described by using the chemical reaction rate model. X-ray photoelectron spectroscopy(XPS) analysis shows that the C–O or C=O content of the inactivated E. coli cell surface by plasma is predominantly increased, indicating the quantity of oxygen-containing species in plasma is more than those of two other methods, and then the C–C or C–H bonds can be broken, leading to the etching of organic compounds. Analysis also indicates that plasma-generated species can play a crucial role in the inactivation process by their direct reactions or the decompositions of reactive species, such as ozone into OH radicals in water, then reacting with E. coli cells.
文摘Recently, we found some errors in Fig. 3 of the article Chin. Phys. B 24 085201 (2015). Upon a thorough examination of the raw data materials, we confirm that the image error did not impact any of the findings and conclusions of the paper. Based on this, we have made corrections to the original article.
基金supported by the National Natural Science Foundation of China(No.82172408,81772314,and 81922045)the Original Exploration project(22ZR1480300)+5 种基金Outstanding Academic Leaders(Youth)project(21XD1422900)of Shanghai Science and Technology Innovation Action PlanPrinciple Investigator Innovation Team of Both Shanghai Sixth People’s Hospital and Shanghai Institute of Nutrition and Health,Shanghai Jiao Tong University Medical College“Two-hundred Talent”Program(No.20191829)The Second Three-Year Action Plan for Promoting Clinical Skills and Clinical Innovation in Municipal Hospitals of Shanghai Shenkang(No.SHDC2020CR4032)Shanghai Excellent Academic Leader ProgramShanghai Engineering Research Center for Orthopaedic Material Innovation and Tissue Regeneration(No.20DZ2254100)China Postdoctoral Science Foundation(2023M742347).
文摘Post-traumatic peritendinous adhesion presents a significant challenge in clinical medicine.This study proposes the use of diamond-like carbon(DLC)deposited on polylactic acid(PLA)membranes as a biophysical mechanism for anti-adhesion barrier to encase ruptured tendons in tendon-injured rats.The results indicate that PLA/DLC composite membrane exhibits more efficient anti-adhesion effect than PLA membrane,with histological score decreasing from 3.12±0.27 to 2.20±0.22 and anti-adhesion effectiveness increasing from 21.61%to 44.72%.Mechanistically,the abundant C=O bond functional groups on the surface of DLC can reduce reactive oxygen species level effectively;thus,the phosphorylation of NF-κB and M1 polarization of macrophages are inhibited.Consequently,excessive inflammatory response augmented by M1 macrophage-originated cytokines including interleukin-6(IL-6),interleukin-1β(IL-1β),and tumor necrosis factor-α(TNF-α)is largely reduced.For biocompatibility evaluation,PLA/DLC membrane is slowly absorbed within tissue and displays prolonged barrier effects compared to traditional PLA membranes.Further studies show the DLC depositing decelerates the release of degradation product lactic acid and its induction of macrophage M2 polarization by interfering esterase and PLA ester bonds,which further delays the fibrosis process.It was found that the PLA/DLC membrane possess an efficient biophysical mechanism for treatment of peritendinous adhesion.
基金supported by the Natural Science Foundation of Fujian Province of China(No.2022J01043)China Scholarship Council(201806315005 and 201703170071).
文摘Reactive oxygen species(ROS)plays important roles in living organisms.While ROS is a double-edged sword,which can eliminate drug-resistant bacteria,but excessive levels can cause oxidative damage to cells.A core–shell nanozyme,Ce O_(2)@ZIF-8/Au,has been crafted,spontaneously activating both ROS generating and scavenging functions,achieving the multifaceted functions of eliminating bacteria,reducing inflammation,and promoting wound healing.The Au Nanoparticles(NPs)on the shell exhibit high-efficiency peroxidase-like activity,producing ROS to kill bacteria.Meanwhile,the encapsulation of Ce O_(2) core within ZIF-8 provides a seal for temporarily limiting the superoxide dismutase and catalase-like activities of Ce O_(2) nanoparticles.Subsequently,as the ZIF-8 structure decomposes in the acidic microenvironment,the Ce O_(2) core is gradually released,exerting its ROS scavenging activity to eliminate excess ROS produced by the Au NPs.These two functions automatically and continuously regulate the balance of ROS levels,ultimately achieving the function of killing bacteria,reducing inflammation,and promoting wound healing.Such innovative ROS spontaneous regulators hold immense potential for revolutionizing the field of antibacterial agents and therapies.
基金National Natural Science Foundation of China[82274366]The National Multidisciplinary Innovation Team Project of Traditional Chinese Medicine:Multi-dimensional Evaluation and Multidisciplinary Innovation Team of Southwest Traditional Chinese Medicine Resources[ZYYCXTD-D-202209]+2 种基金The Youth Talent Promotion Project of China Association of Chinese Medicine[2021-QNRC2-A09]The Major Project of Sichuan Provincial Administration of Traditional Chinese Medicine(2023ZD01)the financial support from the Indian Council of Medical Research(ICMR),New Delhi,India,through Extramural Research Grants.
文摘As a new form of regulated cell death,ferroptosis has unraveled the unsolicited theory of intrinsic apoptosis resistance by cancer cells.The molecular mechanism of ferroptosis depends on the induction of oxidative stress through excessive reactive oxygen species accumulation and glutathione depletion to damage the structural integrity of cells.Due to their high loading and structural tunability,nanocarriers can escort the delivery of ferro-therapeutics to the desired site through enhanced permeation or retention effect or by active targeting.This review shed light on the necessity of iron in cancer cell growth and the fascinating features of ferroptosis in regulating the cell cycle and metastasis.Additionally,we discussed the effect of ferroptosis-mediated therapy using nanoplatforms and their chemical basis in overcoming the barriers to cancer therapy.
基金supported by the National Natural Science Foundation of China(82370631)the Talent Foundations from Army Medical University(4174C6),the Chongqing Government(CQYC20220303727)to Xie CMthe National Natural Science Foundation of China(31900449)to Xiong HJ.
文摘Background:Kirsten rat sarcoma(KRAS)and mutant KRAS^(G12D)have been implicated in human cancers,but it remains unclear whether their activation requires ubiquitination.This study aimed to investigate whether and how F-box and leucine-rich repeat 6(FBXL6)regulates KRAS and KRAS^(G12D)activity in hepatocellular carcinoma(HCC).Methods:We constructed transgenic mouse strains LC(LSL-Fbxl6^(KI/+);Alb-Cre,n=13),KC(LSL-Kras^(G12D/+);Alb-Cre,n=10)and KLC(LSL-Kras^(G12D/+);LSL-Fbxl6^(KI/+);Alb-Cre,n=12)mice,and then monitored HCC for 320 d.Multiomics approaches and pharmacological inhibitors were used to determine oncogenic signaling in the context of elevated FBXL6 and KRAS activation.Co-immunoprecipitation(Co-IP),Western blotting,ubiquitination assay,and RAS activity detection assay were employed to investigate the underlying molecular mechanism by which FBXL6 activates KRAS.The pathological relevance of the FBXL6/KRAS/extracellular signal-regulated kinase(ERK)/mammalian target of rapamycin(mTOR)/proteins of relevant evolutionary and lymphoid interest domain 2(PRELID2)axis was evaluated in 129 paired samples from HCC patients.Results:FBXL6 is highly expressed in HCC as well as other human cancers(P<0.001).Interestingly,FBXL6 drives HCC in transgenic mice.Mechanistically,elevated FBXL6 promotes the polyubiquitination of both wild-type KRAS and KRAS^(G12D)at lysine 128,leading to the activation of both KRAS and KRAS^(G12D)and promoting their binding to the serine/threonine-protein kinase RAF,which is followed by the activation of mitogen-activated protein kinase kinase(MEK)/ERK/mTOR signaling.The oncogenic activity of the MEK/ERK/mTOR axis relies on PRELID2,which induces reactive oxygen species(ROS)generation.Furthermore,hepatic FBXL6 upregulation facilitates KRAS^(G12D)to induce more severe hepatocarcinogenesis and lung metastasis via the MEK/ERK/mTOR/PRELID2/ROS axis.Dual inhibition of MEK and mTOR effectively suppresses tumor growth and metastasis in this subtype of cancer in vivo.In clinical samples,FBXL6 expression positively correlates with p-ERK(χ^(2)=85.067,P<0.001),p-mTOR(χ^(2)=66.919,P<0.001)and PRELID2(χ^(2)=20.891,P<0.001).The Kaplan-Meier survival analyses suggested that HCC patients with high FBXL6/p-ERK levels predicted worse overall survival(log-rank P<0.001).Conclusions:FBXL6 activates KRAS or KRAS^(G12D)via ubiquitination at the site K128,leading to activation of the ERK/mTOR/PRELID2/ROS axis and tumorigenesis.Dual inhibition of MEK and mTOR effectively protects against FBXL6-and KRAS^(G12D)-induced tumorigenesis,providing a potential therapeutic strategy to treat this aggressive subtype of liver cancer.
文摘The changes of hydrogen peroxide （H2O2） metabolism and antioxidant enzyme activities in a hybrid poplar （Populus simonii xp. pyramidalis ＇Opera 8277＇） in response to rnechanical damage （MD） and herbivore wounding （HW） were investigated to determine whether H2O2 could function as the secondary messenger in the signaling of systemic resistance. Results show that H2O2 was generated in wounded leaves through MD and HW treatments and systemically in unwounded leaves around the wounded leaves. The activities of antioxidant enzymes such as superoxide dismutase （SOD）, catalase （CAT） and ascorbate peroxidase （APX） were also enhanced. However, the H2O2 accumulation and antioxidant enzyme activities were inhibited in MD leaves through the pretreatment with DPI （which is a specific inhibitor of NADPH oxidase）. The results of this study suggest that H2O2 could be systemically induced by MD and HW treatments, and H2O2 metabolism was closely related to the change in SOD, APX and CAT activities. A high level of antioxidant enzymes could decrease membrane lipid peroxidation levels and effectively induce plant defense responses.
文摘For dispersed ceria-zirconia-based solid solutions prepared via the polymerized complex method and annealed at 700 ℃, effects of bulk doping by Ca, Mn, Co, Bi or Nb cations and surface modification by Mn and Pt on their structural features, surface/bulk oxygen reactivity and catalytic activity in methane combustion are considered. With up to 20 mol% doping, a structural type of homogeneous solid solutions of anion-deficient fluorite with disordered anion vacancies is formed. Doping by transition metal cations or Pt increases the mobility and reactivity of the surface/bulk oxygen. A broad variation in specific rates of methane combustion for the studied systems was observed, suggesting structural sensitivity of this reaction. In general, there is no universal relationship between the oxygen mobility, the reactivity and the catalytic activity in methane combustion, which is explained by the factor of specific methane activation on surface active sites. For the Pt-promoted samples, Pt efficiency in methane activation depends on the Pt-support interaction, and the most favorable ones being mixed Pt/MnOx and Pt/NbOx clusters on the surface of the supports that exhibit high lattice oxygen mobilities.
基金support from a research university Grant number 1001/PFIZIK/814174 of Universiti Sains Malaysia(USM)
文摘Antibacterial activity of zinc oxide nanoparticles(Zn O-NPs) has received significant interest worldwide particularly by the implementation of nanotechnology to synthesize particles in the nanometer region. Many microorganisms exist in the range from hundreds of nanometers to tens of micrometers. Zn O-NPs exhibit attractive antibacterial properties due to increased specific surface area as the reduced particle size leading to enhanced particle surface reactivity. Zn O is a bio-safe material that possesses photo-oxidizing and photocatalysis impacts on chemical and biological species. This review covered Zn O-NPs antibacterial activity including testing methods, impact of UV illumination, Zn O particle properties(size, concentration, morphology, and defects), particle surface modification, and minimum inhibitory concentration. Particular emphasize was given to bactericidal and bacteriostatic mechanisms with focus on generation of reactive oxygen species(ROS) including hydrogen peroxide(H2O2), OH-(hydroxyl radicals), and O2-2(peroxide). ROS has been a major factor for several mechanisms including cell wall damage due to Zn O-localized interaction, enhanced membrane permeability, internalization of NPs due to loss of proton motive force and uptake of toxic dissolved zinc ions.These have led to mitochondria weakness, intracellular outflow, and release in gene expression of oxidative stress which caused eventual cell growth inhibition and cell death. In some cases, enhanced antibacterial activity can be attributed to surface defects on Zn O abrasive surface texture. One functional application of the Zn O antibacterial bioactivity was discussed in food packaging industry where Zn O-NPs are used as an antibacterial agent toward foodborne diseases. Proper incorporation of Zn O-NPs into packaging materials can cause interaction with foodborne pathogens, thereby releasing NPs onto food surface where they come in contact with bad bacteria and cause the bacterial death and/or inhibition.
基金supported by the National Natural Science Foundation of China (81700429)the China Postdoctoral Science Foundation (2021MD703924)+1 种基金the Chongqing Postdoctoral Innovative Talents Support Program (CQBX2021018)the Kuanren Talents Program of the second affiliated hospital of Chongqing Medical University。
文摘Background: Cerebral ischemia-reperfusion injury(CIRI) refers to a secondary brain injury that can occur when the blood supply to the ischemic brain tissue is restored. However, the mechanism underlying such injury remains elusive.Methods: The 150 male C57 mice underwent middle cerebral artery occlusion(MCAO) for 1 h and reperfusion for 24 h,Among them, 50 MCAO mice were further treated with Mitochondrial division inhibitor 1(Mdivi-1) and 50 MCAO mice were further treated with N-acetylcysteine(NAC). SH-SY5Y cells were cultured in a low-glucose culture medium for 4 h under hypoxic conditions and then transferred to normal conditions for 12 h. Then, cerebral blood flow, mitochondrial structure, mitochondrial DNA(mtDNA) copy number, intracellular and mitochondrial reactive oxygen species(ROS),autophagic flux, aggresome and exosome expression profiles, cardiac tissue structure, mitochondrial length and cristae density, mtDNA and ROS content, as well as the expression of Drp1-Ser616/Drp1, RIP1/RIP3, LC3 II/I, TNF-α,IL-1β, etc., were detected under normal or Drp1 interference conditions.Results: The mtDNA content, ROS levels, and Drp1-Ser616/Drp1 were elevated by 2.2, 1.7 and 2.7 times after CIRI(P<0.05). However, the high cytoplasmic LC3 II/I ratio and increased aggregation of p62 could be reversed by 44%and 88% by Drp1 short hairpin RNA(shRNA)(P<0.05). The low fluorescence intensity of autophagic flux and the increased phosphorylation of RIP3 induced by CIRI could be attenuated by ROS scavenger, NAC(P<0.05). RIP1/RIP3inhibitor Necrostatin-1(Nec-1) restored 75% to a low LC3 II/I ratio and enhanced 2 times to a high RFP-LC3 after Drp1 activation(P<0.05). In addition, although CIRI-induced ROS production caused no considerable accumulation of autophagosomes(P>0.05), it increased the packaging and extracellular secretion of exosomes containing p62 by 4–5 times, which could be decreased by Mdivi-1, Drp1 shRNA, and Nec-1(P<0.05). Furthermore, TNF-α and IL-1βincreased in CIRI-derived exosomes could increase RIP3 phosphorylation in normal or oxygen–glucose deprivation/reoxygenation(OGD/R) conditions(P<0.05).Conclusions: CIRI activated Drp1 and accelerated the p62-mediated formation of autophagosomes while inhibiting the transition of autophagosomes to autolysosomes via the RIP1/RIP3 pathway activation. Undegraded autophagosomes were secreted extracellularly in the form of exosomes, leading to inflammatory cascades that further damaged mitochondria, resulting in excessive ROS generation and the blockage of autophagosome degradation,triggering a vicious cycle.
基金supported by the National Key Research and Development Program of China(2017YFA0205201 and 2016YFC0106900)the National Natural Science Foundation of China(81925019,81422023,81701752,81901808,and U1705281)+2 种基金the Fundamental Research Funds for the Central Universities(20720200019 and 20720190088)the Program for New Century Excellent Talents in University,China(No.NCET-13-0502)the China Postdoctoral Science Foundation(2019M662545)。
文摘Rapid evolution and propagation of multidrug resistance among bacterial pathogens are outpacing the development of new antibiotics,but antimicrobial photodynamic therapy(aPDT)provides an excellent alternative.This treatment depends on the interaction between light and photoactivated sensitizer to generate reactive oxygen species(ROS),which are highly cytotoxic to induce apoptosis in virtually all microorganisms without resistance concern.When replacing light with low-frequency ultrasonic wave to activate sensitizer,a novel ultrasounddriven treatment emerges as antimicrobial sonodynamic therapy(aSDT).Recent advances in aPDT and aSDT reveal golden opportunities for the management of multidrug resistant bacterial infections,especially in the theranostic application where imaging diagnosis can be accomplished facilely with the inherent optical characteristics of sensitizers,and the generated ROS by aPDT/SDT cause broad-spectrum oxidative damage for sterilization.In this review,we systemically outline the mechanisms,targets,and current progress of aPDT/SDT for bacterial theranostic application.Furthermore,potential limitations and future perspectives are also highlighted.
基金We acknowledge financial support by the National Natural Science Foundation of China(32071374,32000985,81761148029,81620108028)Program of Shanghai Academic Research Leader under the Science and Technology Innovation Action Plan(21XD1422100)+3 种基金Leading Talent of“Ten Thousand Plan”-National High-Level Talents Special Support Plan,One Belt and One Road International Cooperation Project from Key Research and Development Program of Zhejiang Province(2019C04024)the Zhejiang Provincial Natural Science Foundation of China(LR22C100001,LGF19C100002,LQ21H300003)Zhejiang Province Medical and Health Science Research Project(2021KY666),and Zhejiang Pharmaceutical Association(2019ZYY12)Open access funding provided by Shanghai Jiao Tong University
文摘The structural change-mediated catalytic activity regulation plays a significant role in the biological functions of natural enzymes.However,there is virtually no artificial nanozyme reported that can achieve natural enzyme-like stringent spatiotemporal structure-based catalytic activity regulation.Here,we report a subnanostructural transformable gold@ceria(STGC-PEG)nanozyme that performs tunable catalytic activities via near-infrared(NIR)light-mediated sub-nanostructural transformation.The gold core in STGC-PEG can generate energetic hot electrons upon NIR irradiation,wherein an internal sub-nanostructural transformation is initiated by the conversion between CeO;and electron-rich state of CeO;-x,and active oxygen vacancies generation via the hot-electron injection.Interestingly,the sub-nanostructural transformation of STGC-PEG enhances peroxidase-like activity and unprecedentedly activates plasmon-promoted oxidase-like activity,allowing highly efficient low-power NIR light(50 m W cm;)-activated photocatalytic therapy of tumors.Our atomic-level design and fabrication provide a platform to precisely regulate the catalytic activities of nanozymes via a light-mediated sub-nanostructural transformation,approaching natural enzyme-like activity control in complex living systems.
文摘The average human life span has markedly increased in modem society largely attributed to advances in medical and therapeutic sciences that have successfully reduced important health risks. However, advanced age results in numerous alterations to cellular and subcellular components that can impact the overall health and function of an individual. Not surprisingly, advanced age is a major risk factor for the development of heart disease in which elderly populations observe increased morbidity and mortality. Even healthy individuals that appear to have normal heart function under resting conditions, actually have an increased susceptibility and vulnerability to stress. This is confounded by the impact that stress and disease can have over time to both the heart and vessels. Although, there is a rapidly growing body of literature investigating the effects of aging on the heart and how age-related alterations affect cardiac function, the biology of aging and underlying mechanisms remain unclear. In this review, we summarize effects of aging on the heart and discuss potential theories of cellular aging with special emphasis on mitoehondrial dysfunction.
基金This work was supported by the National Natural Science Foundation of China （Grant No. 81173625, 81373458） Thanks for the kind help of Dr. Wang （Pulmonary Division, Boston Children＇s Hospital, MA, USA）, who was extremely helpful in the revision of the language.
文摘Background The mitochondrial Na^＋/Ca^2＋ exchanger, NCLX, plays an important role in the balance between Ca2. influx and efflux across the mitochondrial inner membrane in endothelial ceils. Mitochondrial metabolism is likely to be affected by the activity of NCLX because Ca^2＋ activates several enzymes of the Krebs cycle. It is currently believed that mitochondria are not only centers of energy produc- tion but are also important sites of reactive oxygen species （ROS） generation and nucleotide-binding oligomerization domain receptor 3 （NLRP3） inflammasome activation. Methods ＆ Results This study focused on NCLX function, in rat aortic endothelial cells （RAECs）, induced by glucose. First, we detected an increase in NCLX expression in the endothelia of rats with diabetes mellitus, which was induced by an injection of streptozotocin. Next, colocalization of NCLX expression and mitochondria was detected using confocal analysis. Suppression of NCLX expression, using an siRNA construct （siNCLX）, enhanced mitochondrial Ca^2＋ influx and blocked efflux induced by glucose. Unexpectedly, silencing of NCLX expression induced increased ROS generation and NLRP3 inflammasome activation. Conclusions These findings suggest that NCLX affects glucose-dependent mitochondrial Ca^2＋ signaling, thereby regulating ROS generation and NLRP3 in- flammasome activation in high glucose conditions. In the early stages of high glucose stimulation, NCLX expression increases to compensate in order to self-protect mitochondrial maintenance, stability, and function in endothelial cells.
