Uric acid(UA)is a naturally antioxidant that is strongly associated with the development and progression of Parkinson's disease(PD).The purine diet is an important exogenous pathway that modulates blood UA levels....Uric acid(UA)is a naturally antioxidant that is strongly associated with the development and progression of Parkinson's disease(PD).The purine diet is an important exogenous pathway that modulates blood UA levels.Deep brain stimulation(DBS)is an important tool for PD treatment.This study aimed to explore the effects of preoperative purine diet on the prognosis of patients with PD after DBS.Sixty-four patients with PD who underwent DBS were included in this study,and their clinical data,blood UA levels,and daily purine intake.Patients were followed up for improvement 1 year after surgery.We found that patient higher purine intake was strongly associated with the rate of improvement after DBS and was a protective factor for patient prognosis.Daily purine intake from meat and seafood was significantly higher in the responsive patients than in the lessresponsive patients.Mediation analysis showed that UA mediated 78%of the effect of purine intake on motor symptom improvement after DBS.In summary,we observed that purine intake is strongly associated with the rate of improvement in motor symptoms after subthalamic nucleus-DBS in patients with PD.This study provides a reference for preoperative diet planning in patients with PD undergoing DBS.展开更多
BACKGROUND:Rapid and accurate identification of high-risk patients in the emergency departments(EDs)is crucial for optimizing resource allocation and improving patient outcomes.This study aimed to develop an early pre...BACKGROUND:Rapid and accurate identification of high-risk patients in the emergency departments(EDs)is crucial for optimizing resource allocation and improving patient outcomes.This study aimed to develop an early prediction model for identifying high-risk patients in EDs using initial vital sign measurements.METHODS:This retrospective cohort study analyzed initial vital signs from the Chinese Emergency Triage,Assessment,and Treatment(CETAT)database,which was collected between January 1^(st),2020,and June 25^(th),2023.The primary outcome was the identification of high-risk patients needing immediate treatment.Various machine learning methods,including a deep-learningbased multilayer perceptron(MLP)classifier were evaluated.Model performance was assessed using the area under the receiver operating characteristic curve(AUC-ROC).AUC-ROC values were reported for three scenarios:a default case,a scenario requiring sensitivity greater than 0.8(Scenario I),and a scenario requiring specificity greater than 0.8(Scenario II).SHAP values were calculated to determine the importance of each predictor within the MLP model.RESULTS:A total of 38,797 patients were analyzed,of whom 18.2%were identified as high-risk.Comparative analysis of the predictive models for high-risk patients showed AUC-ROC values ranging from 0.717 to 0.738,with the MLP model outperforming logistic regression(LR),Gaussian Naive Bayes(GNB),and the National Early Warning Score(NEWS).SHAP value analysis identified coma state,peripheral capillary oxygen saturation(SpO_(2)),and systolic blood pressure as the top three predictive factors in the MLP model,with coma state exerting the most contribution.CONCLUSION:Compared with other methods,the MLP model with initial vital signs demonstrated optimal prediction accuracy,highlighting its potential to enhance clinical decision-making in triage in the EDs.展开更多
Cryopreservation of red blood cells(RBCs)provides great potential benefits for providing transfusion timely in emergencies.High concentrations of glycerol(20%or 40%)are used for RBC cryopreservation in current clinica...Cryopreservation of red blood cells(RBCs)provides great potential benefits for providing transfusion timely in emergencies.High concentrations of glycerol(20%or 40%)are used for RBC cryopreservation in current clinical practice,which results in cytotoxicity and osmotic injuries that must be carefully controlled.However,existing studies on the low-glycerol cryopreservation of RBCs still suffer from the bottleneck of low hematocrit levels,which require relatively large storage space and an extra concentration process before transfusion,making it inconvenient(time-consuming,and also may cause injury and sample lose)for clinical applications.To this end,we develop a novel method for the glycerol-free cryopreservation of human RBCs with a high final hematocrit by using trehalose as the sole cryoprotectant to dehydrate RBCs and using core–shell alginate hydrogel microfibers to enhance heat transfer during cryopreservation.Different from previous studies,we achieve the cryopreservation of human RBCs at high hematocrit(>40%)with high recovery(up to 95%).Additionally,the washed RBCs post-cryopreserved are proved to maintain their morphology,mechanics,and functional properties.This may provide a nontoxic,high-efficiency,and glycerol-free approach for RBC cryopreservation,along with potential clinical transfusion benefits.展开更多
Parkinson's disease(PD)is one of the most common neurodegenerative diseases.The loss of dopaminergic(DAergic)neurons in the substantia nigra and the decrease of dopamine(DA)levels accelerate the process of PD.L-Er...Parkinson's disease(PD)is one of the most common neurodegenerative diseases.The loss of dopaminergic(DAergic)neurons in the substantia nigra and the decrease of dopamine(DA)levels accelerate the process of PD.L-Ergothioneine(EGT)is a natural antioxidant derived from microorganisms,especially in edible mushrooms.EGT can penetrate blood-brain barrier and its levels are significantly decreased in the plasma of PD patients.Therefore,we speculated that EGT could ameliorate PD,and determined its effect on PD development by using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced PD mouse models and neurotoxin 1-methyl-4-phenylpyridinium(MPP^(+))-induced cell models.Our results show that EGT alleviated MPTP-induced behavioral dysfunction in mice.Mechanistically,we innovatively revealed that EGT was a key regulator of DJ-1.EGT restored DA levels by activating the DJ-1-nuclear receptor-related factor 1(Nurr1)axis.Furthermore,it reduced reactive oxygen species(ROS)levels by regulating the DJ-1-nuclear factor erythroid 2-related factor 2(Nrf2)pathway,which inhibited oxidative stress-induced DAergic neuronal apoptosis.Combined treatment with DJ-1-si RNA transfection revealed that blocking DJ-1 reversed EGT upregulated Nurr1 and Nrf2 expression in the nucleus,which significantly decreased the benefits of EGT.Taken together,our study suggests that EGT can ameliorate PD and be considered as a strategy for PD treatment.展开更多
This study aims to uncover the hormetic process of luteolin,a common dietary flavone,in neuronal cells through its role in inducing mitochondrial stress.In rat pheochromocytoma PC12 cells,luteolin at low concentration...This study aims to uncover the hormetic process of luteolin,a common dietary flavone,in neuronal cells through its role in inducing mitochondrial stress.In rat pheochromocytoma PC12 cells,luteolin at low concentrations caused a mild and reversible loss of mitochondrial membrane potential(MMP),while high concentrations of luteolin triggered intense and sustained depolarization of MMP.The MMP disturbance was shown to have a close association with the trophic and/or toxic effects triggered by luteolin;because the common mitochondrial uncouplers shared similar bi-phase dose-response on cell viability,as that of luteolin.Along with the induced MMP pertubation,luteolin triggered the development of autophagy and mitophagy,as determined by m Cherry-GFP-LC3B tandem protein,and by the co-localization of mitochondrial/lysosomal staining.Subsequent application of autophagy inhibitors in the cultures blocked the luteolin-induced neurotrophic activities and sensitized the cells to be less resistant to luteolin-mediated cytotoxicity.Other flavonoids also displayed similar properties in the cultures,indicating that these compounds act as hormetic pharmacological inducers that stimulate cells to become more resilient and adapt to threats.This study provides a unifying mechanistic explanation for the neuro-beneficial effects of luteolin and other flavonoids.展开更多
Proton nuclear(^(1)H)is the observed nucleus on which most magnetic resonance imaging(MRI)applications depend.Most traditional^(1)H MRI can provide structural and functional information about organisms,while various n...Proton nuclear(^(1)H)is the observed nucleus on which most magnetic resonance imaging(MRI)applications depend.Most traditional^(1)H MRI can provide structural and functional information about organisms,while various non-proton nuclei(X-nuclei)MRI can provide more metabolic information.However,due to the relatively poor signal-to-noise ratio(SNR)of X-nuclei MRI,their applications are quite rare compared to^(1)H.Benefit from the rapid developments of MRI hardware and software technologies,X-nuclei MRI has recently attracted increasing interests in biomedical research.This review firstly introduces some current methods to improve the SNR of X-nuclei MRI.Secondly,this review describes biomedical applications of X-nuclei MRI,especially focusing on the current use of X-nuclei(^(13)C,^(17)O,^(19)F,^(23)Na and^(31)P)MRI to study related diseases in different organs,including the brain,liver,kidney,heart and bone.Finally,perspectives studies on X-nuclei imaging and its potential applications are described in biomedical research.展开更多
Background The high rate of long-term relapse is a major cause of smoking cessation failure.Recently,neurofeedback training has been widely used in the treatment of nicotine addiction;however,approximately 30%of subje...Background The high rate of long-term relapse is a major cause of smoking cessation failure.Recently,neurofeedback training has been widely used in the treatment of nicotine addiction;however,approximately 30%of subjects fail to benefit from this intervention.Our previous randomised clinical trial(RCT)examined cognition-guided neurofeedback and demonstrated a significant decrease in daily cigarette consumption at the 4-month follow-up.However,significant individual differences were observed in the 4-month follow-up effects of decreased cigarette consumption.Therefore,it is critical to identify who will benefit from pre-neurofeedback.Aims We examined whether the resting-state electroencephalography(EEG)characteristics from pre-neurofeedback predicted the 4-month follow-up effects and explored the possible mechanisms.Methods This was a double-blind RCT.A total of 60 participants with nicotine dependence were randomly assigned to either the real-feedback or yoked-feedback group.They underwent 6 min closed-eye resting EEG recordings both before and after two neurofeedback sessions.A follow-up assessment was conducted after 4 months.Results The frontal resting-state theta power spectral density(PSD)was significantly altered in the real-feedback group after two neurofeedback visits.Higher theta PSD in the real-feedback group before neurofeedback was the only predictor of decreased cigarette consumption at the 4-month follow-up.Further reliability analysis revealed a significant positive correlation between theta PSD pre-neurofeedback and post-neurofeedback.A leave-one-out cross-validated linear regression of the theta PSD pre-neurofeedback demonstrated a significant correlation between the predicted and observed reductions in cigarette consumption at the 4-month follow-up.Finally,source analysis revealed that the brain mechanisms of the theta PSD predictor were located in the orbital frontal cortex.Conclusions Our study demonstrated changes in the resting-state theta PSD following neurofeedback training.Moreover,the resting-state theta PSD may serve as a prognostic marker of neurofeedback effects.A higher resting-state theta PSD predicts a better long-term response to neurofeedback treatment,which may facilitate the selection of individualised interventions.展开更多
Cardiac arrest(CA)is one of the most common causes of death.[1-3]Despite extensive studies on the management of CA,the global survival rate in adults is only approximately 7%,and 30-day survival is even less than 2%in...Cardiac arrest(CA)is one of the most common causes of death.[1-3]Despite extensive studies on the management of CA,the global survival rate in adults is only approximately 7%,and 30-day survival is even less than 2%in China.[4]Some studies have shown that CA patients of cardiac and non-cardiac origin may differ in underlying diseases,clinical manifestations,and prognosis,which leads to diff erences in terms of the pathophysiological mechanism and treatment measure.[5,6]However,little is known about the risk factors in relation to the prognosis of CA across arrest etiologies.展开更多
The high incidence of catheter-associated urinary tract infections,which are dominated by drugresistant bacteria,has attracted an increasing number of researchers interested in solving this public health problem.The p...The high incidence of catheter-associated urinary tract infections,which are dominated by drugresistant bacteria,has attracted an increasing number of researchers interested in solving this public health problem.The purpose of this study was to explore the killing effect of lowtemperature air plasma(LTAP)on extended-spectrum beta-lactamase-producing Escherichia coli and high level gentamycin resistance enterococci under two simulated environments in vitro.The results showed that the survival rate of these two kinds of bacteria decreased to less than20%after being treated by LTAP in different environments for 5 min.A comparison of the LTAP treatments showed that the killing efficacy of the two kinds of bacteria in the early stage(0-1 min)was up to 50%.Moreover,the results of transmission electron microscopy,reactive nitrogen species measurement,and a temperature test indicated that the bactericidal effect of the LTAP treatment on the two kinds of bacteria worked through the destruction of the ribosome and other organelles inside the bacteria,rather than the thermal effect,to achieve sterilization.展开更多
Background Internet gaming disorder(IGD)is a mental health issue that affects individuals worldwide.However,the lack of knowledge about the biomarkers associated with the development of IGD has restricted the diagnosi...Background Internet gaming disorder(IGD)is a mental health issue that affects individuals worldwide.However,the lack of knowledge about the biomarkers associated with the development of IGD has restricted the diagnosis and treatment of this disorder.Aims We aimed to reveal the biomarkers associated with the development of IGD through resting-state brain network analysis and provide clues for the diagnosis and treatment of IGD.Methods Twenty-six patients with IGD,23 excessive internet game users(EIUs)who recurrently played internet games but were not diagnosed with IGD and 29 healthy controls(HCs)performed delay discounting task(DDT)and Iowa gambling task(IGT).Resting-state functional magnetic resonance imaging(fMRI)data were also collected.Results Patients with IGD exhibited significantly lower hubness in the right medial orbital part of the superior frontal gyrus(ORBsupmed)than both the EIU and the HC groups.Additionally,the hubness of the right ORBsupmed was found to be positively correlated with the highest excessive internet gaming degree during the past year in the EIU group but not the IGD group;this might be the protective mechanism that prevents EIUs from becoming addicted to internet games.Moreover,the hubness of the right ORBsupmed was found to be related to the treatment outcome of patients with IGD,with higher hubness of this region indicating better recovery when undergoing forced abstinence.Further modelling analysis of the DDT and IGT showed that patients with IGD displayed higher impulsivity during the decision-making process,and impulsivity-related parameters were negatively correlated with the hubness of right ORBsupmed.Conclusions Our findings revealed that the impulsivity-related right ORBsupmed hubness could serve as a potential biomarker of IGD and provide clues for the diagnosis and treatment of IGD.展开更多
This review details Eilema group in the subfamily the Korean species of the Arctiinae of Erebidae： 19 species in five genera （Manulea, Collita, Katha, Dolgoma, and Wittia）, a new species （Collita hwacheonensis Bay...This review details Eilema group in the subfamily the Korean species of the Arctiinae of Erebidae： 19 species in five genera （Manulea, Collita, Katha, Dolgoma, and Wittia）, a new species （Collita hwacheonensis Bayar- saikhan ＆ Bae, sp. nov.）, and an unrecorded species [C. vetusta aegrota （Butler 1877）]. All species are diagnosed, and figures of the adults and genitalia and a key to species based on male genital structure of Eilema group in South Korea are included.展开更多
In this study, we report Monopis crocicapitella （Clemens, 1859） （Tineidae）, which was collected from bat guano in a cave in the southern region of Korea, for the first time from East Asia. We briefly redescribe an...In this study, we report Monopis crocicapitella （Clemens, 1859） （Tineidae）, which was collected from bat guano in a cave in the southern region of Korea, for the first time from East Asia. We briefly redescribe and illustrate the external morphology and genital structures of both sexes. Also, we discuss the local habitat characteristics and some of the ecological information that was observed during our field investi-gation.展开更多
The abnormal expansion of G-rich hexanucleotide repeat,GGGGCC(G4C2),in chromosome 9 open reading frame 72(C9orf72)is known to be the prevailing genetic cause of two fatal degenerative neurological diseases,amyotrophic...The abnormal expansion of G-rich hexanucleotide repeat,GGGGCC(G4C2),in chromosome 9 open reading frame 72(C9orf72)is known to be the prevailing genetic cause of two fatal degenerative neurological diseases,amyotrophic lateral sclerosis(ALS)and frontotemporal dementia(FTD).It is well known that the DNA G4C2 repeat expansion with different lengths can form G-quadruplexes which affect gene transcription related to ALS/FTD,therefore it is crucial to understand DNA G4C2 G-quadruplex structures.Herein,by utilizing nuclear magnetic resonance(NMR)spectroscopy,we examined DNA G-quadruplex structure adopted by two G4C2 hexanucleotide repeats with an inosine substitution at position 4,d(G4C2)2-I4.We show that d(G4C2)2-I4 folds into an eight-layer parallel tetrameric G-quadruplex containing two parallel dimeric G-quadruplexes stacking together through p-p interaction via 50-to-50 mode in solution.Each dimeric G-quadruplex unit involves two propeller loops composed of two cytosine bases.This result is consistent with the observation in the crystal structure of d(G4C2)2.Our work not only sheds light on the structural diversity of G-quadruplexes adopted by d(G4C2)n but also provides a structural basis for drug design in treatment of ALS and FTD.展开更多
Conventional microscopes designed for submicron resolution in biological research are hindered by a limited field of view,typically around 1 mm.This restriction poses a challenge when attempting to simultaneously anal...Conventional microscopes designed for submicron resolution in biological research are hindered by a limited field of view,typically around 1 mm.This restriction poses a challenge when attempting to simultaneously analyze various parts of a sample,such as different brain areas.In addition,conventional objective lenses struggle to perform consistently across the required range of wavelengths for brain imaging in vivo.Here we present a novel mesoscopic objective lens with an impressive field of view of 8 mm,a numerical aperture of 0.5,and a working wavelength range from 400 to 1000 nm.We achieved a resolution of 0.74μm in fluorescent beads imaging.The versatility of this lens was further demonstrated through high-quality images of mouse brain and kidney sections in a wide-field imaging system,a confocal laser scanning system,and a two-photon imaging system.This mesoscopic objective lens holds immense promise for advancing multi-wavelength imaging of large fields of view at high resolution.展开更多
Recently,a study on a 0.05 T,low-cost,low-power,and computing-driven shielding-free ultra-low-field(ULF)magnetic resonance imaging(MRI)scannerwas published.This work enhances the image quality of MRI and reduces the s...Recently,a study on a 0.05 T,low-cost,low-power,and computing-driven shielding-free ultra-low-field(ULF)magnetic resonance imaging(MRI)scannerwas published.This work enhances the image quality of MRI and reduces the scanning time based on deep learning methods,which is of great significance to enhancing the popularization and availability of MRI[1](https://www.science.org/doi/abs/10.1126/science.adm7168).展开更多
Bacterial small laccases(SLAC) are promising industrial biocatalysts due to their ability to oxidize a broad range of substrates with exceptional thermostability and tolerance for alkaline p H. Electron transfer betwe...Bacterial small laccases(SLAC) are promising industrial biocatalysts due to their ability to oxidize a broad range of substrates with exceptional thermostability and tolerance for alkaline p H. Electron transfer between substrate, copper centers, and O2is one of the key steps in the catalytic turnover of SLAC. However, limited research has been conducted on the electron transfer pathway of SLAC and SLAC-catalyzed reactions, hindering further engineering of SLAC to produce tunable biocatalysts for novel applications. Herein, the combinational use of electron paramagnetic resonance(EPR) and ultraviolet-visible(UV-vis) spectroscopic methods coupled with redox titration were employed to monitor the electron transfer processes and obtain further insights into the electron transfer pathway in SLAC. The reduction potentials for type 1 copper(T1Cu), type 2 copper(T2Cu) and type 3copper(T3Cu) were determined to be 367 ± 2 mV, 378 ± 5 m V and 403 ± 2 mV,respectively. Moreover, the reduction potential of a selected substrate of SLAC, hydroquinone(HQ), was determined to be 288 mV using cyclic voltammetry(CV). In this way, an electron transfer pathway was identified based on the reduction potentials. Specifically,electrons are transferred from HQ to T1Cu, then to T2Cu and T3Cu, and finally to O2.Furthermore, superhyperfine splitting observed via EPR during redox titration indicated a modification in the covalency of T2Cu upon electron uptake, suggesting a conformational alteration in the protein environment surrounding the copper sites, which could potentially influence the reduction potential of the copper sites during catalytic processes. The results presented here not only provide a comprehensive method for analyzing the electron transfer pathway in metalloenzymes through reduction potential measurements, but also offer valuable insights for further engineering and directed evolution studies of SLAC in the aim for biotechnological and industrial applications.展开更多
As the key component of wireless data transmission and powering,stretchable antennas play an indispensable role in flexible/stretchable electronics.However,they often suffer from frequency detuning upon mechanical def...As the key component of wireless data transmission and powering,stretchable antennas play an indispensable role in flexible/stretchable electronics.However,they often suffer from frequency detuning upon mechanical deformations;thus,their applications are limited to wireless sensing with wireless transmission capabilities remaining elusive.Here,a hierarchically structured stretchable microstrip antenna with meshed patterns arranged in an arched shape showcases tunable resonance frequency upon deformations with improved overall stretchability.The almost unchanged resonance frequency during deformations enables robust on-body wireless communication and RF energy harvesting,whereas the rapid changing resonance frequency with deformations allows for wireless sensing.The proposed stretchable microstrip antenna was demonstrated to communicate wirelessly with a transmitter(input power of−3 dBm)efficiently(i.e.,the receiving power higher than−100 dBm over a distance of 100 m)on human bodies even upon 25%stretching.The flexibility in structural engineering combined with the coupled mechanical-electromagnetic simulations,provides a versatile engineering toolkit to design stretchable microstrip antennas and other potential wireless devices for stretchable electronics.展开更多
Atomic magnetometers operated in the spin-exchange relaxation-free(SERF)regime are the promising sensor to replace superconducting quantum interference devices(SQUIDs)in the biomagnetism field.The SERF magnetometer wi...Atomic magnetometers operated in the spin-exchange relaxation-free(SERF)regime are the promising sensor to replace superconducting quantum interference devices(SQUIDs)in the biomagnetism field.The SERF magnetometer with compact size and good performance is crucial to the new generation of wearable magnetoencephalography(MEG)system.In this paper,we developed a compact and closed-loop SERF magnetometer with the dimensions of 15.0×22.0×30.0 mm^(3)based on a single-beam configuration.The bandwidth of the magnetometer was extended to 675 Hz while the sensitivity was maintained at 22 f T/Hz^(1/2).A nearly 3-fold enhancement of the bandwidth was obtained in comparison with the open-loop control.The implementation of the closed-loop control also greatly improved the dynamic range,enabling the magnetometer to be robust against the disturbance of the ambient field.Moreover,the magnetometer was successfully applied for the detection of humanα-rhythm and auditory evoked fields(AEFs),which demonstrated the potential to be extended to multi-channel MEG measurements for future neuroscience studies.展开更多
BACKGROUND:Patients with sepsis often exhibit an acute inflammatory response,followed by an immunosuppressive phase with a poor immune response.However,the underlying mechanisms have not been fully elucidated.METHODS:...BACKGROUND:Patients with sepsis often exhibit an acute inflammatory response,followed by an immunosuppressive phase with a poor immune response.However,the underlying mechanisms have not been fully elucidated.METHODS:We sought to comprehensively characterize the transcriptional changes in neutrophils of patients with sepsis by transcriptome sequencing.Additionally,we conducted a series of experiments,including real-time quantitative polymerase chain reaction(RT-qPCR)and flow cytometry to investigate the role of arginase-1 signaling in sepsis.RESULTS:Through the analysis of gene expression profiles,we identified that the negative regulation of T cell activation signaling was enriched,and the expression of arginase-1 was high in neutrophils from patients with sepsis.Furthermore,we conducted flow cytometry and found that the function of CD8^(+)T cells in septic patients was impaired.Moreover,neutrophils from septic patients inhibited the percentage of polyfunctional effector CD8^(+)T cells through arginase-1.Additionally,the proportions of granzyme B^(+)IFN^(-)γ^(+)CD8^(+)T and TNF^(-)α^(+)IFN^(-)γ^(+)CD8^(+)T cells increased after inhibition of arginase-1 signaling.CONCLUSION:The impaired effector function of CD8^(+)T cells could be restored by blocking arginase-1 signaling in patients with sepsis.展开更多
Free fatty acids(FFAs)play important roles in cardiovascular disease.Studies have shown that it is an important way for FAs to exert biological effects through their own receptors besides directly participating bioche...Free fatty acids(FFAs)play important roles in cardiovascular disease.Studies have shown that it is an important way for FAs to exert biological effects through their own receptors besides directly participating biochemical reaction in body.Free fatty acid receptor 2(FFA2)can be activated by short-chain FAs and is involved in inflammatory reactions and lipid accumulation.Since the known pathological changes caused by FFA2 are also implicated in cardiac hypertrophy,we hypothesized that FFA2 might be pathogenic in cardiac hypertrophy.This paper showed that FFA2 expression significantly increased in cardiac hypertrophy in vivo and in vitro.FFA2 agonist 4-CMTB or TUG-1375 promoted the expression of the hypertrophy markers ANF and BNP and increased cell surface area in vitro,which was further strengthened by FFA2 overexpression,suggesting that FFA2 might contribute to cardiomyocyte hypertrophy.Furthermore,4-CMTB treatment or FFA2 overexpression combined with 4-CMTB treatment elevated the phosphorylation and transcriptional activity of GATA4 and STAT3,which were inhibited by an ERK1/2 inhibitor,and GATA4 and STAT3 knockdown inhibited the elevation of hypertrophy biomarkers in cardiomyocytes treated with 4-CMTB.Taken together,these data indicate that FFA2 can enhance cardiomyocyte hypertrophy by activating STAT3 and GATA4 via ERK1/2,providing a potential new target for therapy.展开更多
文摘Uric acid(UA)is a naturally antioxidant that is strongly associated with the development and progression of Parkinson's disease(PD).The purine diet is an important exogenous pathway that modulates blood UA levels.Deep brain stimulation(DBS)is an important tool for PD treatment.This study aimed to explore the effects of preoperative purine diet on the prognosis of patients with PD after DBS.Sixty-four patients with PD who underwent DBS were included in this study,and their clinical data,blood UA levels,and daily purine intake.Patients were followed up for improvement 1 year after surgery.We found that patient higher purine intake was strongly associated with the rate of improvement after DBS and was a protective factor for patient prognosis.Daily purine intake from meat and seafood was significantly higher in the responsive patients than in the lessresponsive patients.Mediation analysis showed that UA mediated 78%of the effect of purine intake on motor symptom improvement after DBS.In summary,we observed that purine intake is strongly associated with the rate of improvement in motor symptoms after subthalamic nucleus-DBS in patients with PD.This study provides a reference for preoperative diet planning in patients with PD undergoing DBS.
基金Applicable Funding Source University of Science and Technology of China(to YLL)National Natural Science Foundation of China(12126604)(to MPZ)+1 种基金R&D project of Pazhou Lab(Huangpu)(2023K0609)(to MPZ)Anhui Provincial Natural Science(grant number 2208085MH235)(to KJ)。
文摘BACKGROUND:Rapid and accurate identification of high-risk patients in the emergency departments(EDs)is crucial for optimizing resource allocation and improving patient outcomes.This study aimed to develop an early prediction model for identifying high-risk patients in EDs using initial vital sign measurements.METHODS:This retrospective cohort study analyzed initial vital signs from the Chinese Emergency Triage,Assessment,and Treatment(CETAT)database,which was collected between January 1^(st),2020,and June 25^(th),2023.The primary outcome was the identification of high-risk patients needing immediate treatment.Various machine learning methods,including a deep-learningbased multilayer perceptron(MLP)classifier were evaluated.Model performance was assessed using the area under the receiver operating characteristic curve(AUC-ROC).AUC-ROC values were reported for three scenarios:a default case,a scenario requiring sensitivity greater than 0.8(Scenario I),and a scenario requiring specificity greater than 0.8(Scenario II).SHAP values were calculated to determine the importance of each predictor within the MLP model.RESULTS:A total of 38,797 patients were analyzed,of whom 18.2%were identified as high-risk.Comparative analysis of the predictive models for high-risk patients showed AUC-ROC values ranging from 0.717 to 0.738,with the MLP model outperforming logistic regression(LR),Gaussian Naive Bayes(GNB),and the National Early Warning Score(NEWS).SHAP value analysis identified coma state,peripheral capillary oxygen saturation(SpO_(2)),and systolic blood pressure as the top three predictive factors in the MLP model,with coma state exerting the most contribution.CONCLUSION:Compared with other methods,the MLP model with initial vital signs demonstrated optimal prediction accuracy,highlighting its potential to enhance clinical decision-making in triage in the EDs.
基金the National Natural Science Foundation of China(No.82172114)the Anhui Provincial Natural Science Foundation for Distinguished Young Scholars(No.2108085J37).
文摘Cryopreservation of red blood cells(RBCs)provides great potential benefits for providing transfusion timely in emergencies.High concentrations of glycerol(20%or 40%)are used for RBC cryopreservation in current clinical practice,which results in cytotoxicity and osmotic injuries that must be carefully controlled.However,existing studies on the low-glycerol cryopreservation of RBCs still suffer from the bottleneck of low hematocrit levels,which require relatively large storage space and an extra concentration process before transfusion,making it inconvenient(time-consuming,and also may cause injury and sample lose)for clinical applications.To this end,we develop a novel method for the glycerol-free cryopreservation of human RBCs with a high final hematocrit by using trehalose as the sole cryoprotectant to dehydrate RBCs and using core–shell alginate hydrogel microfibers to enhance heat transfer during cryopreservation.Different from previous studies,we achieve the cryopreservation of human RBCs at high hematocrit(>40%)with high recovery(up to 95%).Additionally,the washed RBCs post-cryopreserved are proved to maintain their morphology,mechanics,and functional properties.This may provide a nontoxic,high-efficiency,and glycerol-free approach for RBC cryopreservation,along with potential clinical transfusion benefits.
基金supported by the National Natural Science Foundation of China(U22A20272,82173807,82170497)。
文摘Parkinson's disease(PD)is one of the most common neurodegenerative diseases.The loss of dopaminergic(DAergic)neurons in the substantia nigra and the decrease of dopamine(DA)levels accelerate the process of PD.L-Ergothioneine(EGT)is a natural antioxidant derived from microorganisms,especially in edible mushrooms.EGT can penetrate blood-brain barrier and its levels are significantly decreased in the plasma of PD patients.Therefore,we speculated that EGT could ameliorate PD,and determined its effect on PD development by using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced PD mouse models and neurotoxin 1-methyl-4-phenylpyridinium(MPP^(+))-induced cell models.Our results show that EGT alleviated MPTP-induced behavioral dysfunction in mice.Mechanistically,we innovatively revealed that EGT was a key regulator of DJ-1.EGT restored DA levels by activating the DJ-1-nuclear receptor-related factor 1(Nurr1)axis.Furthermore,it reduced reactive oxygen species(ROS)levels by regulating the DJ-1-nuclear factor erythroid 2-related factor 2(Nrf2)pathway,which inhibited oxidative stress-induced DAergic neuronal apoptosis.Combined treatment with DJ-1-si RNA transfection revealed that blocking DJ-1 reversed EGT upregulated Nurr1 and Nrf2 expression in the nucleus,which significantly decreased the benefits of EGT.Taken together,our study suggests that EGT can ameliorate PD and be considered as a strategy for PD treatment.
基金supported by Hong Kong RGC-GFC 16100921Hong Kong RGC Theme-based Research Scheme(T13-605/18-W)+3 种基金Hong Kong Innovation Technology Fund(PRP/076/20FXITCPD/17-9,MHP/004/21)PD18SC01 and HMRF18SC06HMRF20SC07,AFD20SC01Shenzhen Science and Technology Innovation Committee(ZDSYS201707281432317)。
文摘This study aims to uncover the hormetic process of luteolin,a common dietary flavone,in neuronal cells through its role in inducing mitochondrial stress.In rat pheochromocytoma PC12 cells,luteolin at low concentrations caused a mild and reversible loss of mitochondrial membrane potential(MMP),while high concentrations of luteolin triggered intense and sustained depolarization of MMP.The MMP disturbance was shown to have a close association with the trophic and/or toxic effects triggered by luteolin;because the common mitochondrial uncouplers shared similar bi-phase dose-response on cell viability,as that of luteolin.Along with the induced MMP pertubation,luteolin triggered the development of autophagy and mitophagy,as determined by m Cherry-GFP-LC3B tandem protein,and by the co-localization of mitochondrial/lysosomal staining.Subsequent application of autophagy inhibitors in the cultures blocked the luteolin-induced neurotrophic activities and sensitized the cells to be less resistant to luteolin-mediated cytotoxicity.Other flavonoids also displayed similar properties in the cultures,indicating that these compounds act as hormetic pharmacological inducers that stimulate cells to become more resilient and adapt to threats.This study provides a unifying mechanistic explanation for the neuro-beneficial effects of luteolin and other flavonoids.
基金supported by Chinese Academy of Sciences MRI Technology Alliance under Grant 2020GZ1003.
文摘Proton nuclear(^(1)H)is the observed nucleus on which most magnetic resonance imaging(MRI)applications depend.Most traditional^(1)H MRI can provide structural and functional information about organisms,while various non-proton nuclei(X-nuclei)MRI can provide more metabolic information.However,due to the relatively poor signal-to-noise ratio(SNR)of X-nuclei MRI,their applications are quite rare compared to^(1)H.Benefit from the rapid developments of MRI hardware and software technologies,X-nuclei MRI has recently attracted increasing interests in biomedical research.This review firstly introduces some current methods to improve the SNR of X-nuclei MRI.Secondly,this review describes biomedical applications of X-nuclei MRI,especially focusing on the current use of X-nuclei(^(13)C,^(17)O,^(19)F,^(23)Na and^(31)P)MRI to study related diseases in different organs,including the brain,liver,kidney,heart and bone.Finally,perspectives studies on X-nuclei imaging and its potential applications are described in biomedical research.
基金This work was supported by the National Natural Science Foundation of China(32000750,32171080,71942003,and 32161143022)Grants for Scientific Research of BSKY(XJ201907)from Anhui Medical University+4 种基金Scientific Research Improvement Project of Anhui Medical University(2021xkjT018)Research Fund of Anhui Institute of Translational Medicine(2022zhyx-C02)Basic and Clinical Collaborative Research Improvement Project of Anhui Medical University(2020xkjT020)The Chinese National Programs for Brain Science and Brain-like Intelligence Technology(2021ZD0202101)CAS-VPST Silk Road Science Fund 2021(GLHZ202128).The numerical calculations in this paper have been done on the Medical Big Data Supercomputing Center System of Anhui Medical University and Bioinformatics Center of the University of Science and Technology of China.
文摘Background The high rate of long-term relapse is a major cause of smoking cessation failure.Recently,neurofeedback training has been widely used in the treatment of nicotine addiction;however,approximately 30%of subjects fail to benefit from this intervention.Our previous randomised clinical trial(RCT)examined cognition-guided neurofeedback and demonstrated a significant decrease in daily cigarette consumption at the 4-month follow-up.However,significant individual differences were observed in the 4-month follow-up effects of decreased cigarette consumption.Therefore,it is critical to identify who will benefit from pre-neurofeedback.Aims We examined whether the resting-state electroencephalography(EEG)characteristics from pre-neurofeedback predicted the 4-month follow-up effects and explored the possible mechanisms.Methods This was a double-blind RCT.A total of 60 participants with nicotine dependence were randomly assigned to either the real-feedback or yoked-feedback group.They underwent 6 min closed-eye resting EEG recordings both before and after two neurofeedback sessions.A follow-up assessment was conducted after 4 months.Results The frontal resting-state theta power spectral density(PSD)was significantly altered in the real-feedback group after two neurofeedback visits.Higher theta PSD in the real-feedback group before neurofeedback was the only predictor of decreased cigarette consumption at the 4-month follow-up.Further reliability analysis revealed a significant positive correlation between theta PSD pre-neurofeedback and post-neurofeedback.A leave-one-out cross-validated linear regression of the theta PSD pre-neurofeedback demonstrated a significant correlation between the predicted and observed reductions in cigarette consumption at the 4-month follow-up.Finally,source analysis revealed that the brain mechanisms of the theta PSD predictor were located in the orbital frontal cortex.Conclusions Our study demonstrated changes in the resting-state theta PSD following neurofeedback training.Moreover,the resting-state theta PSD may serve as a prognostic marker of neurofeedback effects.A higher resting-state theta PSD predicts a better long-term response to neurofeedback treatment,which may facilitate the selection of individualised interventions.
基金supported by the Doctoral Scientific Research Foundation of the First Affiliated Hospital of USTC(RC2021023)Key Research and Development Plan of Anhui Province(S2022e07020194).
文摘Cardiac arrest(CA)is one of the most common causes of death.[1-3]Despite extensive studies on the management of CA,the global survival rate in adults is only approximately 7%,and 30-day survival is even less than 2%in China.[4]Some studies have shown that CA patients of cardiac and non-cardiac origin may differ in underlying diseases,clinical manifestations,and prognosis,which leads to diff erences in terms of the pathophysiological mechanism and treatment measure.[5,6]However,little is known about the risk factors in relation to the prognosis of CA across arrest etiologies.
文摘The high incidence of catheter-associated urinary tract infections,which are dominated by drugresistant bacteria,has attracted an increasing number of researchers interested in solving this public health problem.The purpose of this study was to explore the killing effect of lowtemperature air plasma(LTAP)on extended-spectrum beta-lactamase-producing Escherichia coli and high level gentamycin resistance enterococci under two simulated environments in vitro.The results showed that the survival rate of these two kinds of bacteria decreased to less than20%after being treated by LTAP in different environments for 5 min.A comparison of the LTAP treatments showed that the killing efficacy of the two kinds of bacteria in the early stage(0-1 min)was up to 50%.Moreover,the results of transmission electron microscopy,reactive nitrogen species measurement,and a temperature test indicated that the bactericidal effect of the LTAP treatment on the two kinds of bacteria worked through the destruction of the ribosome and other organelles inside the bacteria,rather than the thermal effect,to achieve sterilization.
基金This work was supported by grants from The Chinese National Programs for Brain Science and Brain-like Intelligence Technology(2021ZD0202101)The National Natural Science Foundation of China(32171080,32161143022,71942003,31900766 and 71874170)+3 种基金the Major Project of Philosophy and Social Science Research,Ministry of Education of China(19JZD010)the CAS-VPST Silk Road Science Fund 2021(GLHZ202128)the Collaborative Innovation Program of Hefei Science Center,CAS(2020HSC-CIP001)the Anhui Provincial Key Research and Development Project(202004b11020013).
文摘Background Internet gaming disorder(IGD)is a mental health issue that affects individuals worldwide.However,the lack of knowledge about the biomarkers associated with the development of IGD has restricted the diagnosis and treatment of this disorder.Aims We aimed to reveal the biomarkers associated with the development of IGD through resting-state brain network analysis and provide clues for the diagnosis and treatment of IGD.Methods Twenty-six patients with IGD,23 excessive internet game users(EIUs)who recurrently played internet games but were not diagnosed with IGD and 29 healthy controls(HCs)performed delay discounting task(DDT)and Iowa gambling task(IGT).Resting-state functional magnetic resonance imaging(fMRI)data were also collected.Results Patients with IGD exhibited significantly lower hubness in the right medial orbital part of the superior frontal gyrus(ORBsupmed)than both the EIU and the HC groups.Additionally,the hubness of the right ORBsupmed was found to be positively correlated with the highest excessive internet gaming degree during the past year in the EIU group but not the IGD group;this might be the protective mechanism that prevents EIUs from becoming addicted to internet games.Moreover,the hubness of the right ORBsupmed was found to be related to the treatment outcome of patients with IGD,with higher hubness of this region indicating better recovery when undergoing forced abstinence.Further modelling analysis of the DDT and IGT showed that patients with IGD displayed higher impulsivity during the decision-making process,and impulsivity-related parameters were negatively correlated with the hubness of right ORBsupmed.Conclusions Our findings revealed that the impulsivity-related right ORBsupmed hubness could serve as a potential biomarker of IGD and provide clues for the diagnosis and treatment of IGD.
基金supported by the Incheon National University Research Grant in 2012
文摘This review details Eilema group in the subfamily the Korean species of the Arctiinae of Erebidae： 19 species in five genera （Manulea, Collita, Katha, Dolgoma, and Wittia）, a new species （Collita hwacheonensis Bayar- saikhan ＆ Bae, sp. nov.）, and an unrecorded species [C. vetusta aegrota （Butler 1877）]. All species are diagnosed, and figures of the adults and genitalia and a key to species based on male genital structure of Eilema group in South Korea are included.
基金supported by National Research Institute of Cultural Heritage and Korea Forest Service(Forest Science&Technology Projects,Project No.S121213L110110)
文摘In this study, we report Monopis crocicapitella （Clemens, 1859） （Tineidae）, which was collected from bat guano in a cave in the southern region of Korea, for the first time from East Asia. We briefly redescribe and illustrate the external morphology and genital structures of both sexes. Also, we discuss the local habitat characteristics and some of the ecological information that was observed during our field investi-gation.
基金the National Natural Science Foundation of China to C.L.(No.32071188)Guangdong Basic and Applied Basic Research Foundation to C.L.(No.2020A1515010034)+1 种基金the Research Grants Council of the Hong Kong Special Administrative Region,China to G.Z.(Project No.16103719,16101120,and 161011121,AoE/M-403-16,AOE/M-401/20)Hong Kong Branch of Southern Marine Science and Engineering Guangdong Laboratory(Guangzhou)to G.Z.(Project No.SMSEGL20SC01eH)and VPRDO19RD03-6.
文摘The abnormal expansion of G-rich hexanucleotide repeat,GGGGCC(G4C2),in chromosome 9 open reading frame 72(C9orf72)is known to be the prevailing genetic cause of two fatal degenerative neurological diseases,amyotrophic lateral sclerosis(ALS)and frontotemporal dementia(FTD).It is well known that the DNA G4C2 repeat expansion with different lengths can form G-quadruplexes which affect gene transcription related to ALS/FTD,therefore it is crucial to understand DNA G4C2 G-quadruplex structures.Herein,by utilizing nuclear magnetic resonance(NMR)spectroscopy,we examined DNA G-quadruplex structure adopted by two G4C2 hexanucleotide repeats with an inosine substitution at position 4,d(G4C2)2-I4.We show that d(G4C2)2-I4 folds into an eight-layer parallel tetrameric G-quadruplex containing two parallel dimeric G-quadruplexes stacking together through p-p interaction via 50-to-50 mode in solution.Each dimeric G-quadruplex unit involves two propeller loops composed of two cytosine bases.This result is consistent with the observation in the crystal structure of d(G4C2)2.Our work not only sheds light on the structural diversity of G-quadruplexes adopted by d(G4C2)n but also provides a structural basis for drug design in treatment of ALS and FTD.
基金supported by National Key R&D Program of China(grant no.2022YFC2404201)the Chinese Academy of Sciences Project for Young Scientists in Basic Research(grant no.YSBR067).
文摘Conventional microscopes designed for submicron resolution in biological research are hindered by a limited field of view,typically around 1 mm.This restriction poses a challenge when attempting to simultaneously analyze various parts of a sample,such as different brain areas.In addition,conventional objective lenses struggle to perform consistently across the required range of wavelengths for brain imaging in vivo.Here we present a novel mesoscopic objective lens with an impressive field of view of 8 mm,a numerical aperture of 0.5,and a working wavelength range from 400 to 1000 nm.We achieved a resolution of 0.74μm in fluorescent beads imaging.The versatility of this lens was further demonstrated through high-quality images of mouse brain and kidney sections in a wide-field imaging system,a confocal laser scanning system,and a two-photon imaging system.This mesoscopic objective lens holds immense promise for advancing multi-wavelength imaging of large fields of view at high resolution.
文摘Recently,a study on a 0.05 T,low-cost,low-power,and computing-driven shielding-free ultra-low-field(ULF)magnetic resonance imaging(MRI)scannerwas published.This work enhances the image quality of MRI and reduces the scanning time based on deep learning methods,which is of great significance to enhancing the popularization and availability of MRI[1](https://www.science.org/doi/abs/10.1126/science.adm7168).
基金supported by the National Natural Science Foundation of China (21825703, 21927814)the National Key R&D Program of China (2019YFA0405600, 2019YFA0706900, 2021YFA1200104, 2022YFC3400500)+3 种基金the Strategic Priority Research Program of Chinese Academy of Sciences (XDB0540200, XDB37040201)Plans for Major Provincial Science&Technology Projects (202303a07020004)Basic Research Program Based on Major Scientific Infrastructures,CAS (JZHKYPT-2021-05)the Youth Innovation Promotion Association,CAS (2022455)
文摘Bacterial small laccases(SLAC) are promising industrial biocatalysts due to their ability to oxidize a broad range of substrates with exceptional thermostability and tolerance for alkaline p H. Electron transfer between substrate, copper centers, and O2is one of the key steps in the catalytic turnover of SLAC. However, limited research has been conducted on the electron transfer pathway of SLAC and SLAC-catalyzed reactions, hindering further engineering of SLAC to produce tunable biocatalysts for novel applications. Herein, the combinational use of electron paramagnetic resonance(EPR) and ultraviolet-visible(UV-vis) spectroscopic methods coupled with redox titration were employed to monitor the electron transfer processes and obtain further insights into the electron transfer pathway in SLAC. The reduction potentials for type 1 copper(T1Cu), type 2 copper(T2Cu) and type 3copper(T3Cu) were determined to be 367 ± 2 mV, 378 ± 5 m V and 403 ± 2 mV,respectively. Moreover, the reduction potential of a selected substrate of SLAC, hydroquinone(HQ), was determined to be 288 mV using cyclic voltammetry(CV). In this way, an electron transfer pathway was identified based on the reduction potentials. Specifically,electrons are transferred from HQ to T1Cu, then to T2Cu and T3Cu, and finally to O2.Furthermore, superhyperfine splitting observed via EPR during redox titration indicated a modification in the covalency of T2Cu upon electron uptake, suggesting a conformational alteration in the protein environment surrounding the copper sites, which could potentially influence the reduction potential of the copper sites during catalytic processes. The results presented here not only provide a comprehensive method for analyzing the electron transfer pathway in metalloenzymes through reduction potential measurements, but also offer valuable insights for further engineering and directed evolution studies of SLAC in the aim for biotechnological and industrial applications.
基金This work was in part supported by the International Partnership Program of Chinese Academy of Science(Grant No.154232KYSB20200016)the Suzhou Science and Technology Support Project(Grant No.SYG201905)+2 种基金the National Key Research and Development Program of China(Grant No.2020YFC2007400)H.C.acknowledges the supports provided by the National Science Foundation(NSF)(Grant No.ECCS-1933072)the National Heart,Lung,And Blood Institute of the National Institutes of Health under Award Number R61HL154215,and Penn State University.The partial support from the Center for Biodevices,the College of Engineering,and the Center for Security Research and Education at Penn State is also acknowledged.
文摘As the key component of wireless data transmission and powering,stretchable antennas play an indispensable role in flexible/stretchable electronics.However,they often suffer from frequency detuning upon mechanical deformations;thus,their applications are limited to wireless sensing with wireless transmission capabilities remaining elusive.Here,a hierarchically structured stretchable microstrip antenna with meshed patterns arranged in an arched shape showcases tunable resonance frequency upon deformations with improved overall stretchability.The almost unchanged resonance frequency during deformations enables robust on-body wireless communication and RF energy harvesting,whereas the rapid changing resonance frequency with deformations allows for wireless sensing.The proposed stretchable microstrip antenna was demonstrated to communicate wirelessly with a transmitter(input power of−3 dBm)efficiently(i.e.,the receiving power higher than−100 dBm over a distance of 100 m)on human bodies even upon 25%stretching.The flexibility in structural engineering combined with the coupled mechanical-electromagnetic simulations,provides a versatile engineering toolkit to design stretchable microstrip antennas and other potential wireless devices for stretchable electronics.
基金Project supported by Ji Hua Laboratory(Grant No.X190131TD190)the Research and Development Project for Equipment of Chinese Academy of Sciences(Grant No.YJKYYQ20210051)+1 种基金the Suzhou pilot project of basic research(Grant No.SJC2021024)the Natural Science Foundation of Jiangsu Province,China(Grant No.BK20200215)。
文摘Atomic magnetometers operated in the spin-exchange relaxation-free(SERF)regime are the promising sensor to replace superconducting quantum interference devices(SQUIDs)in the biomagnetism field.The SERF magnetometer with compact size and good performance is crucial to the new generation of wearable magnetoencephalography(MEG)system.In this paper,we developed a compact and closed-loop SERF magnetometer with the dimensions of 15.0×22.0×30.0 mm^(3)based on a single-beam configuration.The bandwidth of the magnetometer was extended to 675 Hz while the sensitivity was maintained at 22 f T/Hz^(1/2).A nearly 3-fold enhancement of the bandwidth was obtained in comparison with the open-loop control.The implementation of the closed-loop control also greatly improved the dynamic range,enabling the magnetometer to be robust against the disturbance of the ambient field.Moreover,the magnetometer was successfully applied for the detection of humanα-rhythm and auditory evoked fields(AEFs),which demonstrated the potential to be extended to multi-channel MEG measurements for future neuroscience studies.
基金This work was supported by the Research Fund for the Key Laboratory of Anhui Province(KLICD-2022-Z2)the Scientific Research Fund of Anhui Medical University(2011×kj083)the Scientific Research Fund of the First People's Hospital of Hefei(201642).
文摘BACKGROUND:Patients with sepsis often exhibit an acute inflammatory response,followed by an immunosuppressive phase with a poor immune response.However,the underlying mechanisms have not been fully elucidated.METHODS:We sought to comprehensively characterize the transcriptional changes in neutrophils of patients with sepsis by transcriptome sequencing.Additionally,we conducted a series of experiments,including real-time quantitative polymerase chain reaction(RT-qPCR)and flow cytometry to investigate the role of arginase-1 signaling in sepsis.RESULTS:Through the analysis of gene expression profiles,we identified that the negative regulation of T cell activation signaling was enriched,and the expression of arginase-1 was high in neutrophils from patients with sepsis.Furthermore,we conducted flow cytometry and found that the function of CD8^(+)T cells in septic patients was impaired.Moreover,neutrophils from septic patients inhibited the percentage of polyfunctional effector CD8^(+)T cells through arginase-1.Additionally,the proportions of granzyme B^(+)IFN^(-)γ^(+)CD8^(+)T and TNF^(-)α^(+)IFN^(-)γ^(+)CD8^(+)T cells increased after inhibition of arginase-1 signaling.CONCLUSION:The impaired effector function of CD8^(+)T cells could be restored by blocking arginase-1 signaling in patients with sepsis.
基金supported by the National Natural Science Foundation of China(No.81760058,81560059,81660042,31800891)the Scientific Research Project of Health and Family Planning Commission of Hunan Province(No.C2017025)+1 种基金the Project of Medical and Health Science and Technology of Shaoxing City(No.2020A13063)the Startup Fund for Research of Shaoxing University(No.20205021)。
文摘Free fatty acids(FFAs)play important roles in cardiovascular disease.Studies have shown that it is an important way for FAs to exert biological effects through their own receptors besides directly participating biochemical reaction in body.Free fatty acid receptor 2(FFA2)can be activated by short-chain FAs and is involved in inflammatory reactions and lipid accumulation.Since the known pathological changes caused by FFA2 are also implicated in cardiac hypertrophy,we hypothesized that FFA2 might be pathogenic in cardiac hypertrophy.This paper showed that FFA2 expression significantly increased in cardiac hypertrophy in vivo and in vitro.FFA2 agonist 4-CMTB or TUG-1375 promoted the expression of the hypertrophy markers ANF and BNP and increased cell surface area in vitro,which was further strengthened by FFA2 overexpression,suggesting that FFA2 might contribute to cardiomyocyte hypertrophy.Furthermore,4-CMTB treatment or FFA2 overexpression combined with 4-CMTB treatment elevated the phosphorylation and transcriptional activity of GATA4 and STAT3,which were inhibited by an ERK1/2 inhibitor,and GATA4 and STAT3 knockdown inhibited the elevation of hypertrophy biomarkers in cardiomyocytes treated with 4-CMTB.Taken together,these data indicate that FFA2 can enhance cardiomyocyte hypertrophy by activating STAT3 and GATA4 via ERK1/2,providing a potential new target for therapy.
