Many studies have shown that the development of allergic asthma is associated with intestinal microbiota dysbiosis.Based on the gut-lung axis theory,probiotic intervention may be a potential strategy for respiratory d...Many studies have shown that the development of allergic asthma is associated with intestinal microbiota dysbiosis.Based on the gut-lung axis theory,probiotic intervention may be a potential strategy for respiratory diseases.Lacticaseibacillus paracasei K56 was reported to regulate gut microbiota in mice.However,its effect on allergic asthma has not been reported.In this study,we investigated the effect of the K56 on ovalbumininduced asthma and its possible mechanisms.Our results showed that K56 reduced asthma symptoms and inflammatory cell infiltration in the lung of asthmatic mice.And K56 regulated the differentiation of helper T cells in the lung and intestine.Results from 16S r RNA gene sequencing showed that K56 prophylaxis significantly elevated the richness of Akkermansia and Burkholderia.Meanwhile,K56 abrogated the decrease in the levels of short-chain fatty acids(SCFAs)in the feces.In addition,a rebound in the m RNA expression of the SCFA receptors was observed after K56 prophylaxis.Notably,the regulatory T cell(Treg)frequencies and the FFAR3 levels were positively correlated.These results suggest that K56 could attenuate asthma,possibly by modulating the intestinal microbiota and regulating Treg differentiation through SCFA metabolized.Our study showed that K56 may be used as a probiotic to prevent pulmonary inflammation and dysbiosis of the intestinal microbiota in allergic asthma.展开更多
Cancer immunotherapy using immune-checkpoint inhibitors(ICIs)has revolutionized the field of cancer treatment;however,ICI efficacy is constrained by progressive dysfunction of CD8+tumor-infiltrating lymphocytes(TILs),...Cancer immunotherapy using immune-checkpoint inhibitors(ICIs)has revolutionized the field of cancer treatment;however,ICI efficacy is constrained by progressive dysfunction of CD8+tumor-infiltrating lymphocytes(TILs),which is termed T cell exhaustion.This process is driven by diverse extrinsic factors across heterogeneous tumor immune microenvironment(TIME).Simultaneously,tumorigenesis entails robust reshaping of the epigenetic landscape,potentially instigating T cell exhaustion.In this review,we summarize the epigenetic mechanisms governing tumor microenvironmental cues leading to T cell exhaustion,and discuss therapeutic potential of targeting epigenetic regulators for immunotherapies.Finally,we outline conceptual and technical advances in developing potential treatment paradigms involving immunostimulatory agents and epigenetic therapies.展开更多
The accurate equilibrium structures of S_3 and S_3^- are determined by the coupled-cluster method with single, double excitation and perturbative triple excitation(CCSD(T)) with basis sets of aug-cc-pV(n+d)Z(n = T, Q,...The accurate equilibrium structures of S_3 and S_3^- are determined by the coupled-cluster method with single, double excitation and perturbative triple excitation(CCSD(T)) with basis sets of aug-cc-pV(n+d)Z(n = T, Q, 5, or 6), complete basis set extrapolation functions with two-parameters and three-parameters, together with considering the contributions due to the core-valence electron correlation, scalar relativistic effects, spin–orbit coupling, and zero-point vibrational corrections. Our calculations show that both the neutral S_3 and anion S_3^- have open forms with C_(2r) vsymmetry. On the basis of the stable geometries, the adiabatic electron affinity of S_3 is determined to be 19041(11) cm^(-1), which is in excellent agreement with the experimental data(19059(7) cm^(-1)). The dependence of geometries and electron affinity on the computation level and physical corrections is discussed. The present computational results are helpful to the experimental molecular spectroscopy and bonding of S_3.展开更多
Integral experiments on tungsten slab samples were carried out on the D-T neutron source facility at China Institute of Atomic Energy. Leakage neutron spectra from the irradiated tungsten target were measured by the t...Integral experiments on tungsten slab samples were carried out on the D-T neutron source facility at China Institute of Atomic Energy. Leakage neutron spectra from the irradiated tungsten target were measured by the time-of-flight technique. Accuracy of the nuclear data for tungsten was examined by comparing the measured neutron spectra with the leakage neutron spectra simulated using the MCNP-4C code with evaluated nuclear data of the JEFF-3.2, FENDL-3.0 and TENDL-2014 libraries. The results show that the calculations with JEFF-3.2 agree well with the measurements in the whole energy range and all angles, whereas the spectra calculated with FENDL-3.0 and TENDL-2014 have some discrepancies with the experimental data.展开更多
Type 1 diabetes mellitus(T1DM) lacks insulin secretion due to autoimmune deficiency of pancreaticβ-cells.Protecting pancreatic islets and enhancing insulin secretion has been therapeutic approaches.Mannogalactoglucan...Type 1 diabetes mellitus(T1DM) lacks insulin secretion due to autoimmune deficiency of pancreaticβ-cells.Protecting pancreatic islets and enhancing insulin secretion has been therapeutic approaches.Mannogalactoglucan is the main type of polysaccharide from natural mushroom,which has potential medicinal prospects.Nevertheless,the antidiabetic property of mannogalactoglucan in T1DM has not been fully elucidated.In this study,we obtained the neutral fraction of alkali-soluble Armillaria mellea polysaccharide(AAMP-N) with the structure of mannogalactoglucan from the fruiting body of A.mellea and investigated the potential therapeutic value of AAMP-N in T1DM.We demonstrated that AAMP-N lowered blood glucose and improved diabetes symptoms in T1DM mice.AAMP-N activated unfolded protein response(UPR) signaling pathway to maintain ER protein folding homeostasis and promote insulin secretion in vivo.Besides that,AAMP-N promoted insulin synthesis via upregulating the expression of transcription factors,increased Ca^(2+) signals to stimulate intracellular insulin secretory vesicle transport via activating calcium/calmodulin-dependent kinase Ⅱ(CamkⅡ) and cAMP/PKA signals,and enhanced insulin secretory vesicle fusion with the plasma membrane via vesicle-associated membrane protein 2(VAMP2).Collectively,these studies demonstrated that the therapeutic potential of AAMP-N on pancreatic islets function,indicating that mannogalactoglucan could be natural nutraceutical used for the treatment of T1DM.展开更多
Milk fat globule membrane(MFGM),which contains abundant glycoproteins and phospholipids,exerts beneficial effects on intestinal health and immunomodulation.The aim of this study was to evaluate the protective effects ...Milk fat globule membrane(MFGM),which contains abundant glycoproteins and phospholipids,exerts beneficial effects on intestinal health and immunomodulation.The aim of this study was to evaluate the protective effects and possible underlying mechanisms of MFGM on cow’s milk allergy(CMA)in aβ-lactoglobulin(BLG)-induced allergic mice model.MFGM was supplemented to allergic mice induced by BLG at a dose of 400 mg/kg body weight.Results demonstrated that MFGM alleviated food allergy symptoms,decreased serum levels of lipopolysaccharide,pro-inflammatory cytokines,immunoglobulin(Ig)E,Ig G1,and Th2 cytokines including interleukin(IL)-4,while increased serum levels of Th1 cytokines including interferon-γand regulatory T cells(Tregs)cytokines including IL-10 and transforming growth factor-β.MFGM modulated gut microbiota and enhanced intestinal barrier of BLG-allergic mice,as evidenced by decreased relative abundance of Desulfobacterota,Rikenellaceae,Lachnospiraceae,and Desulfovibrionaceae,while increased relative abundance of Bacteroidetes,Lactobacillaceae and Muribaculaceae,and enhanced expressions of tight junction proteins including Occludin,Claudin-1 and zonula occludens-1.Furthermore,MFGM increased fecal short-chain fatty acids(SCFAs)levels,which elevated G protein-coupled receptor(GPR)43 and GPR109A expressions.The increased expressions of GPR43 and GPR109A induced CD103+dendritic cells accumulation and promoted Tregs differentiation in mesenteric lymph node to a certain extent.In summary,MFGM alleviated CMA in a BLG-induced allergic mice model through enhancing intestinal barrier and promoting Tregs differentiation,which may be correlated with SCFAs-mediated activation of GPRs.These findings suggest that MFGM may be useful as a promising functional ingredient against CMA.展开更多
基金supported by grants from the National Natural Science Foundation of China(82174113,81473656)National Center of Technology Innovation for Dairy(No.2023-JSGG-15)。
文摘Many studies have shown that the development of allergic asthma is associated with intestinal microbiota dysbiosis.Based on the gut-lung axis theory,probiotic intervention may be a potential strategy for respiratory diseases.Lacticaseibacillus paracasei K56 was reported to regulate gut microbiota in mice.However,its effect on allergic asthma has not been reported.In this study,we investigated the effect of the K56 on ovalbumininduced asthma and its possible mechanisms.Our results showed that K56 reduced asthma symptoms and inflammatory cell infiltration in the lung of asthmatic mice.And K56 regulated the differentiation of helper T cells in the lung and intestine.Results from 16S r RNA gene sequencing showed that K56 prophylaxis significantly elevated the richness of Akkermansia and Burkholderia.Meanwhile,K56 abrogated the decrease in the levels of short-chain fatty acids(SCFAs)in the feces.In addition,a rebound in the m RNA expression of the SCFA receptors was observed after K56 prophylaxis.Notably,the regulatory T cell(Treg)frequencies and the FFAR3 levels were positively correlated.These results suggest that K56 could attenuate asthma,possibly by modulating the intestinal microbiota and regulating Treg differentiation through SCFA metabolized.Our study showed that K56 may be used as a probiotic to prevent pulmonary inflammation and dysbiosis of the intestinal microbiota in allergic asthma.
基金supported by the National Natural Science Foundation of China(82273202,82370948,82072996,82170941)the Fundamental Research Funds for the Central Universities(2042022dx0003)+1 种基金the Hubei Province International Science and Technology Cooperation Project(2021EHB027)the National Key Research and Development Program(2022YFC2504200).
文摘Cancer immunotherapy using immune-checkpoint inhibitors(ICIs)has revolutionized the field of cancer treatment;however,ICI efficacy is constrained by progressive dysfunction of CD8+tumor-infiltrating lymphocytes(TILs),which is termed T cell exhaustion.This process is driven by diverse extrinsic factors across heterogeneous tumor immune microenvironment(TIME).Simultaneously,tumorigenesis entails robust reshaping of the epigenetic landscape,potentially instigating T cell exhaustion.In this review,we summarize the epigenetic mechanisms governing tumor microenvironmental cues leading to T cell exhaustion,and discuss therapeutic potential of targeting epigenetic regulators for immunotherapies.Finally,we outline conceptual and technical advances in developing potential treatment paradigms involving immunostimulatory agents and epigenetic therapies.
基金Project supported by the National Natural Science Foundation of China(Grant Nos.11874179,11447194,11574114,and 11874177)the Natural Science Foundation of Jilin Province,China(Grant No.20180101289JC)
文摘The accurate equilibrium structures of S_3 and S_3^- are determined by the coupled-cluster method with single, double excitation and perturbative triple excitation(CCSD(T)) with basis sets of aug-cc-pV(n+d)Z(n = T, Q, 5, or 6), complete basis set extrapolation functions with two-parameters and three-parameters, together with considering the contributions due to the core-valence electron correlation, scalar relativistic effects, spin–orbit coupling, and zero-point vibrational corrections. Our calculations show that both the neutral S_3 and anion S_3^- have open forms with C_(2r) vsymmetry. On the basis of the stable geometries, the adiabatic electron affinity of S_3 is determined to be 19041(11) cm^(-1), which is in excellent agreement with the experimental data(19059(7) cm^(-1)). The dependence of geometries and electron affinity on the computation level and physical corrections is discussed. The present computational results are helpful to the experimental molecular spectroscopy and bonding of S_3.
基金supported by the National Natural Science Foundation of China(No.11605097,91426301,and 11605257)Doctoral Scientific Research Foundation of Inner Mongolia University for the Nationalities(No.BS365)the‘‘ADS project 302’’of the Chinese Academy of Sciences(No.XDA03030200)
文摘Integral experiments on tungsten slab samples were carried out on the D-T neutron source facility at China Institute of Atomic Energy. Leakage neutron spectra from the irradiated tungsten target were measured by the time-of-flight technique. Accuracy of the nuclear data for tungsten was examined by comparing the measured neutron spectra with the leakage neutron spectra simulated using the MCNP-4C code with evaluated nuclear data of the JEFF-3.2, FENDL-3.0 and TENDL-2014 libraries. The results show that the calculations with JEFF-3.2 agree well with the measurements in the whole energy range and all angles, whereas the spectra calculated with FENDL-3.0 and TENDL-2014 have some discrepancies with the experimental data.
基金funded by the National Natural Science Foundation of China (32371341,31872674)the Scientific and Technologic Foundation of Jilin Province (20230202050NC)the Fundamental Research Funds for the Central Universities (CGZH202206)。
文摘Type 1 diabetes mellitus(T1DM) lacks insulin secretion due to autoimmune deficiency of pancreaticβ-cells.Protecting pancreatic islets and enhancing insulin secretion has been therapeutic approaches.Mannogalactoglucan is the main type of polysaccharide from natural mushroom,which has potential medicinal prospects.Nevertheless,the antidiabetic property of mannogalactoglucan in T1DM has not been fully elucidated.In this study,we obtained the neutral fraction of alkali-soluble Armillaria mellea polysaccharide(AAMP-N) with the structure of mannogalactoglucan from the fruiting body of A.mellea and investigated the potential therapeutic value of AAMP-N in T1DM.We demonstrated that AAMP-N lowered blood glucose and improved diabetes symptoms in T1DM mice.AAMP-N activated unfolded protein response(UPR) signaling pathway to maintain ER protein folding homeostasis and promote insulin secretion in vivo.Besides that,AAMP-N promoted insulin synthesis via upregulating the expression of transcription factors,increased Ca^(2+) signals to stimulate intracellular insulin secretory vesicle transport via activating calcium/calmodulin-dependent kinase Ⅱ(CamkⅡ) and cAMP/PKA signals,and enhanced insulin secretory vesicle fusion with the plasma membrane via vesicle-associated membrane protein 2(VAMP2).Collectively,these studies demonstrated that the therapeutic potential of AAMP-N on pancreatic islets function,indicating that mannogalactoglucan could be natural nutraceutical used for the treatment of T1DM.
文摘小细胞肺癌(small-cell lung cancer,SCLC)约占肺癌的15%,恶性程度高,尽管对治疗敏感,但患者缓解持续时间短,预后极差。在化疗时代,广泛期SCLC(extensive stage SCLC,ES-SCLC)患者5年总生存率约为5%,到了免疫治疗时代,靶向程序性死亡受体1/程序性死亡配体1(programmed death 1/programmed death ligand 1,PD-1/PD-L1)的免疫检查点抑制剂联合化疗成为ES-SCLC一线治疗的新标准,疗效有所提升,但仍只有少数患者可以获得长期生存,5年生存率仅约10%左右。一个重要的原因是,ES-SCLC患者的后线治疗仍未取得实质性进展,需要开发ES-SCLC的新疗法。
基金supported by the National Key Research and Development Program of China(Grant No.2019YFC1605000)National Natural Science Foundation of China(Grant No.31871806)the Beijing Livestock Industry Innovation Team(BAIC05-2023)。
文摘Milk fat globule membrane(MFGM),which contains abundant glycoproteins and phospholipids,exerts beneficial effects on intestinal health and immunomodulation.The aim of this study was to evaluate the protective effects and possible underlying mechanisms of MFGM on cow’s milk allergy(CMA)in aβ-lactoglobulin(BLG)-induced allergic mice model.MFGM was supplemented to allergic mice induced by BLG at a dose of 400 mg/kg body weight.Results demonstrated that MFGM alleviated food allergy symptoms,decreased serum levels of lipopolysaccharide,pro-inflammatory cytokines,immunoglobulin(Ig)E,Ig G1,and Th2 cytokines including interleukin(IL)-4,while increased serum levels of Th1 cytokines including interferon-γand regulatory T cells(Tregs)cytokines including IL-10 and transforming growth factor-β.MFGM modulated gut microbiota and enhanced intestinal barrier of BLG-allergic mice,as evidenced by decreased relative abundance of Desulfobacterota,Rikenellaceae,Lachnospiraceae,and Desulfovibrionaceae,while increased relative abundance of Bacteroidetes,Lactobacillaceae and Muribaculaceae,and enhanced expressions of tight junction proteins including Occludin,Claudin-1 and zonula occludens-1.Furthermore,MFGM increased fecal short-chain fatty acids(SCFAs)levels,which elevated G protein-coupled receptor(GPR)43 and GPR109A expressions.The increased expressions of GPR43 and GPR109A induced CD103+dendritic cells accumulation and promoted Tregs differentiation in mesenteric lymph node to a certain extent.In summary,MFGM alleviated CMA in a BLG-induced allergic mice model through enhancing intestinal barrier and promoting Tregs differentiation,which may be correlated with SCFAs-mediated activation of GPRs.These findings suggest that MFGM may be useful as a promising functional ingredient against CMA.
