Autoimmune hepatitis is an inflammatory liver disease primarily mediated by T cell.It has not been fully elucidated about the pathogenesis,and it is presently thought to be related to genetic susceptibility,infection ...Autoimmune hepatitis is an inflammatory liver disease primarily mediated by T cell.It has not been fully elucidated about the pathogenesis,and it is presently thought to be related to genetic susceptibility,infection and environmental triggers,and abnormal autoimmune regulation.Recent studies have found that traditional Chinese medicine can improve the biochemical indicators and clinical symptoms of patients with autoimmune hepatitis.This article reviews the specific mechanism of traditional Chinese medicine on treating autoimmune hepatitis in order to propose new ideas for its clinical diagnosis and treatment.展开更多
Student evaluation,which involves assessing students using specific standards,techniques,and methods,encompasses self-evaluation by students,evaluation by educators,and so on.It has long been a focal point and challen...Student evaluation,which involves assessing students using specific standards,techniques,and methods,encompasses self-evaluation by students,evaluation by educators,and so on.It has long been a focal point and challenge in China’s educational system reform.This paper aims to broaden the approach to developing and reforming student evaluation within the context of China’s new era by summarizing its evolving characteristics,analyzing its pain points,and comparing the concepts and standards of student evaluation in developed countries with those in China.展开更多
To tackle energy crisis and achieve sustainable development, aqueous rechargeable zinc ion batteries have gained widespread attention in large-scale energy storage for their low cost, high safety, high theoretical cap...To tackle energy crisis and achieve sustainable development, aqueous rechargeable zinc ion batteries have gained widespread attention in large-scale energy storage for their low cost, high safety, high theoretical capacity, and environmental compatibility in recent years. However, zinc anode in aqueous zinc ion batteries is still facing several challenges such as dendrite growth and side reactions(e.g., hydrogen evolution), which cause poor reversibility and the failure of batteries. To address these issues, interfacial modification of Zn anodes has received great attention by tuning the interaction between the anode and the electrolyte. Herein, we present recent advances in the interfacial modification of zinc anode in this review. Besides, the challenges of reported approaches of interfacial modification are also discussed.Finally, we provide an outlook for the exploration of novel zinc anode for aqueous zinc ion batteries.We hope that this review will be helpful in designing and fabricating dendrite-free and hydrogenevolution-free Zn anodes and promoting the practical application of aqueous rechargeable zinc ion batteries.展开更多
High-nickel single-crystal layered oxide material has become the most promising cathode material for electric vehicle power battery due to its high energy density.However,this material still suffers from structural de...High-nickel single-crystal layered oxide material has become the most promising cathode material for electric vehicle power battery due to its high energy density.However,this material still suffers from structural degradation during cycling and especially the severe interfacial reactions at elevated temperatures that exacerbate irreversible capacity loss.Here,a simple strategy was used to construct a dualfunction Li_(1.5)Al_(0.5)Ge_(1.5)P_(3)O_(12)(LAGP)protective layer on the surface of the high-nickel single-crystal(SC)cathode material,leading to SC@LAGP material.The strong Al-O bonding effectively inhibits the release of lattice oxygen(O)at elevated temperatures,which is supported by the positive formation energy of O vacancy from first-principal calculations.Besides,theoretical calculations demonstrate that the appropriate amount of Al doping accelerates the electron and Li^(+)transport,and thus reduces the kinetic barriers.In addition,the LAGP protective layer alleviates the stress accumulation during cycling and effectively reduces the erosion of materials from the electrolyte decomposition at elevated temperatures.The obtained SC@LAGP cathode material demonstrates much enhanced cycling stability even at high voltage(4.6 V)and elevated temperature(55℃),with a high capacity retention of 91.3%after 100 cycles.This work reports a simple dual-function coating strategy that simultaneously stabilizes the structure and interface of the single-crystal cathode material,which can be applied to design other cathode materials.展开更多
Zinc metal anodes face several challenges,including the uncontrolled formation of dendrites,hydrogen evolution,and corrosion,which seriously hinder their application in practice.To address the above problems such as d...Zinc metal anodes face several challenges,including the uncontrolled formation of dendrites,hydrogen evolution,and corrosion,which seriously hinder their application in practice.To address the above problems such as dendrite formation and corrosion,we present a simple and applicable immersion method that enables in situ formation of a zinc phytate(PAZ)coating on the surface of commercial Zn flakes via a substitution reaction.This protective coating mitigates corrosion of zinc flakes by the electrolyte,reduces the interfacial impedance,and accelerates the migration kinetics of zinc ions.Besides,this method can preferentially expose the(002)crystal plane with strong atomic bonding,which not only improves the corrosion resistance of the zinc flake,but can also guide the parallel deposition of zinc ions along the(002)crystal plane and reduce the formation of dendrites.Benefiting from the above advantages,the PAZ@Zn‖Cu half-cell has shown over 900 cycles with average coulombic efficiency(CE)of99.81%at 4 mA cm^(-2).Besides,the PAZ@Zn‖PAZ@Zn symmetric cell operate stably for>1000 h at5 mA cm^(-2)and>340 h at 10 mA cm^(-2).Furthermore,we demonstrated that this in situ chemical treatment enables the formation of a robust,well-bound protective coating.This method provides insights for advancing the commercialization of zinc anodes and other metal anodes.展开更多
Mitochondria-targeted sonodynamic therapy(SDT)is a promising strategy to inhibit tumor growth and activate the anti-tumor immune responses.Identifying the mechanisms underlying mitochondria-targeted SDT,further optimi...Mitochondria-targeted sonodynamic therapy(SDT)is a promising strategy to inhibit tumor growth and activate the anti-tumor immune responses.Identifying the mechanisms underlying mitochondria-targeted SDT,further optimizing its efficacy,developing novel sonosensitizer carriers with good biocompatibility pose major challenges to the clinical practice of SDT.In this study,we investigated the mechanisms of mitochondria-targeted SDT and demonstrated that it suppressed the mitochondrial electron transport chain(ETC)in pancreatic cancer cells through RNA-sequencing analysis.Based on these findings,we constructed the functional lipid droplets(LDs)(CPI-613/IR780@LDs),which combined mitochondria-targeted SDT with the tricarboxylic acid(TCA)cycle inhibitor CPI-613.CPI-613/IR780@LDs synergistically inhibited the TCA cycle and the ETC of mitochondrial aerobic respiration to reduce oxygen consumption and increase reactive oxygen species(ROS)generation at the tumor site,thus enhancing the efficacy of SDT in hypoxic pancreatic cancer.Moreover,the combination of mitochondria-targeted SDT and anti-PD-1 antibody exhibited excellent tumor inhibition and activated anti-tumor immune responses by increasing tumorinfiltrating CD8+T cells and reducing regulatory T cells,synergistically arresting the growth of both primary and metastatic pancreatic tumors.Meanwhile,lipid droplets are cell-derived biological carriers with natural mitochondrial targeting ability and can achieve efficient hydrophobic drug loading through active phagocytosis.Therefore,the functional lipid droplet-based SDT combined with anti-PD-1 antibody holds great potential in the clinical treatment of hypoxic pancreatic cancer.展开更多
Methyl tert-butyl ether (MTBE),as a widely used gasoline additive,is suspected of being environmentally toxic.MTBE accumulates mainly in adipose tissue,but its effect on obesity or obesity-related metabolic disorders ...Methyl tert-butyl ether (MTBE),as a widely used gasoline additive,is suspected of being environmentally toxic.MTBE accumulates mainly in adipose tissue,but its effect on obesity or obesity-related metabolic disorders has not been well understood yet.Therefore,we examined the effect of MTBE on the adipose function and the related metabolic processes with both 3T3-L1 cell line and C57BL/6J mice model.We found that exposure to MTBE at the environmental relevant concentration (100 μmol/L) could significantly induce differentiation of preadipocyte and disturb insulin-stimulated glucose uptake of mature adipocyte.The in vivo observation in male mice showed a positive correlation of visceral white adipose tissue (vWAT) expansion and cell size increase with MTBE treatment in 14 weeks.Glucose tolerance and insulin sensitivity tests demonstrated that MTBE at 1000 μg/(kg·day) disturbed the systemic glucose metabolism in a gender-specific manner,which might be partly attributed to the alterations of gut microbiota community at genus level with respect to Akkermansia,Clostridium XIVb,and Megamonas.In summary,our study characterized the effect of MTBE on adipose tissue function and glucose homeostasis in vitro and in vivo,and revealed that systemic disorders of the glucose metabolism might be modulated by the related gut microbiota.展开更多
A sequential anode-cathode double-chamber microbial fuel cell (MFC), in which the effluent of anode chamber was used as a continuous feed for an aerated cathode chamber, was constructed in this experiment to investi...A sequential anode-cathode double-chamber microbial fuel cell (MFC), in which the effluent of anode chamber was used as a continuous feed for an aerated cathode chamber, was constructed in this experiment to investigate the performance of brewery wastewater treatment in conjugation with electricity generation. Carbon fiber was used as anode and plain carbon felt with biofilm as cathode. When hydraulic retention time (HRT) was 14.7 h, a relatively high chemical oxygen demand (COD) removal efficiency of 91.7%-95.7% was achieved under long-term stable operation. The MFC displayed an open circuit voltage of 0.434 V and a maximum power density of 830 mW/m^3 at an external resistance of 300 0. To estimate the electrochemical performance of the MFC, electrochemical measurements were carried out and showed that polarization resistance of anode was the major limiting factor in the MFC. Since a high COD removal efficiency was achieved, we conclude that the sequential anode-cathode MFC constructed with bio-cathode in this experiment could provide a new approach for brewery wastewater treatment.展开更多
Osteosarcoma is a kind of bone tumor with highly proliferative and invasive properties,a high incidence of pulmonary metastasis and a poor prognosis.Chemotherapy is the mainstay of treatment for osteosarcoma.Currently...Osteosarcoma is a kind of bone tumor with highly proliferative and invasive properties,a high incidence of pulmonary metastasis and a poor prognosis.Chemotherapy is the mainstay of treatment for osteosarcoma.Currently,there are no molecular targeted drugs approved for osteosarcoma treatment,particularly effective drugs for osteosarcoma with pulmonary metastases.It has been reported that fibroblast activation protein alpha(FAPa)is upregulated in osteosarcoma and critically associated with osteosarcoma progression and metastasis,demonstrating that FAPa-targeted agents might be a promising therapeutic strategy for osteosarcoma.In the present study,we reported that the FAPa-activated vinblastine prodrug Z-GP-DAVLBH exhibited potent antitumor activities against FAPa-positive osteosarcoma cells in vitro and in vivo.Z-GP-DAVLBH inhibited the growth and induced the apoptosis of osteosarcoma cells.Importantly,it also decreased the migration and invasion capacities and reversed epithelial-mesenchymal transition(EMT)of osteosarcoma cells in vitro and suppressed pulmonary metastasis of osteosarcoma xenografts in vivo.Mechanistically,Z-GP-DAVLBH suppressed the AXL/AKT/GSK-3β/β-catenin pathway,leading to inhibition of the growth and metastatic spread of osteosarcoma cells.These findings demonstrate that Z-GP-DAVLBH is a promising agent for the treatment of FAPa-positive osteosarcoma,particularly osteosarcoma with pulmonary metastases.展开更多
Proximity labeling catalyzed by promiscuous enzymes,such as APEX2,has emerged as a powerful approach to characterize multiprotein complexes and protein-protein interactions.However,current methods depend on the expres...Proximity labeling catalyzed by promiscuous enzymes,such as APEX2,has emerged as a powerful approach to characterize multiprotein complexes and protein-protein interactions.However,current methods depend on the expression of exogenous fusion proteins and cannot be applied to identify proteins surrounding post-translationally modified proteins.To address this limitation,we developed a new method to label proximal proteins of interest by antibody-mediated protein A-ascorbate peroxidase 2(pA-APEX2) labeling(AMAPEX).In this method,a modified protein is bound in situ by a specific antibody,which then tethers a pA-APEX2 fusion protein.Activation of APEX2 labels the nearby proteins with biotin;the biotinylated proteins are then purified using streptavidin beads and identified by mass spectrometry.We demonstrated the utility of this approach by profiling the proximal proteins of histone modifications including H3 K27 me3,H3 K9 me3,H3 K4 me3,H4 K5 ac,and H4 K12 ac,as well as verifying the co-localization of these identified proteins with bait proteins by published ChIP-seq analysis and nucleosome immunoprecipitation.Overall,AMAPEX is an efficient method to identify proteins that are proximal to modified histones.展开更多
Alcohol consumption causes significant liver damage,including hepatitis,fibrosis,cirrhosis,and even primary liver carcinoma.Metadoxine(MTDX)is considered to be a beneficial treatment for alcoholic liver disease(ALD)be...Alcohol consumption causes significant liver damage,including hepatitis,fibrosis,cirrhosis,and even primary liver carcinoma.Metadoxine(MTDX)is considered to be a beneficial treatment for alcoholic liver disease(ALD)because it accelerates the metabolism and elimination of ethanol.However,the underlying mechanism is not well understood.Here,the rat model of ALD was developed by feeding with 50%ethanol at the dose of 5 g/kg,and samples of serum and liver tissue were collected to test the levels of liver injury and inflammation and evaluate the hepatoprotective function of MTDX in alcohol-induced liver injury.Further investigation on the infiltration of immune cells was performed to understand the potential hepatoprotective mechanism of MTDX in the ALD model.The results showed that MTDX attenuated liver injury,evidenced by decreased levels of alanine transaminase(ALT),aspartate aminotransferase(AST),and alkaline phosphatase(ALP).Meanwhile,the liver proinflammatory environment was improved after MTDX treatment,evidenced by decreased levels of TNF-α,IL-6,and NLRP3 in the liver tissue.Furthermore,inhibited infiltrations of macrophages and neutrophils were observed in MTDX-treated ALD rats compared with the untreated ALD rats.Our results indicated that MTDX played an important role in preventing the progression of ALD,and the underlying mechanisms might be related to its function of attenuating liver inflammation by inhibiting immune cell infiltration.展开更多
Interfacial electron transfer between electroactive biofilm and the electrode was crucial step for microbial fuel cells(MFCs).A three-dimensional multilayer porous sponge coating with nitrogen-doped carbon nanotube/po...Interfacial electron transfer between electroactive biofilm and the electrode was crucial step for microbial fuel cells(MFCs).A three-dimensional multilayer porous sponge coating with nitrogen-doped carbon nanotube/polyaniline/manganese dioxide(S/N-CNT/PANI/MnO2)electrode has been developed for MFC anode.Here,the S/N-CNT/PANI/MnO2 anode can function as a biocapacitor,able to store electrons generated from the degradation of organic substrate under the open circuit state and release the accumulated electrons upon requirement.Thus,the mismatching of the production and demand of the electricity can be overcome.Comparing with the sponge/nitrogen-doped carbon nanotube(S/N-CNT)bioanode,S/N-CNT/PANI/MnO2 capacitive bioanode displays a strong interaction with the microbial biofilm,advancing the electron transfer from exoelectrogens to the bioanode.The maximum power density of MFC with S/N-CNT/PANI/MnO2 capacitive bioanode is 1019.5 mW/m^2,which is 2.2 and5.8 times as much as that of S/N-CNT/MnO2 bioanode and S/N-CNT bioanode(470.7 mW/m^2 and176.6 mW/m^2),respectively.During the chronoamperometric experiment with 60 min of charging and 20 min of discharging,the S/N-CNT/PANI/MnO2 capacitive bioanode was able to store 10743.9 C/m^2,whereas the S/N-CNT anode was only able to store 3323.4 C/m^2.With a capacitive bioanode,it is possible to use the MFC simultaneously for production and storage of electricity.展开更多
Prostate cancer is one of the most common cancers in men worldwide, and the number of diagnosed patients has dramatically increased in recent years. Currently, the clinical parameters used to diagnose prostate cancer,...Prostate cancer is one of the most common cancers in men worldwide, and the number of diagnosed patients has dramatically increased in recent years. Currently, the clinical parameters used to diagnose prostate cancer, such as Gleason score, pathological tumor staging, and prostate-specific antigen(PSA) expression level, are considered insufficient to inform recommendation to guide clinical practice. Thus, identification of a novel biomarker is necessary. TWIST is one of the well-studied targets and is correlated with cancer invasion and metastasis in several human cancers. We have investigated two largest prostate cancer patient cohorts available in GEO database and found that TWIST expression is positive correlated with Gleason score and associated with poorer survival. By using a prostate cancer cohort and a prostate cancer cell line dataset, we have identified three potential downstream targets of TWIST, PPM1 A, SRP72 and TBCB. TWIST's prognostic capacity is lost when the gene is mutated. Further investigation in the prostate cancer cohort revealed that gene expression of SERPINA, STX7, PDIA2, FMP5, GP1 BB, VGLL4,KCNMA1, SHMT2, SAA4 and DIDO1 influence the prognostic significance of TWIST and vice versa. Importantly, eight out of these ten genes are prognostic indicator by itself. In conclusion, our study has further confirmed that TWIST is a prognostic marker in prostate cancer, identified its potential downstream targets and genes that could possibly give additional prognostic value to predict TWIST-mediated prostate cancer progression.展开更多
The prevalence of SARS-CoV-2 variants of concern(VOCs) is still escalating throughout the world. However, the level of neutralization of the inactivated viral vaccine recipients’ sera and convalescent sera against al...The prevalence of SARS-CoV-2 variants of concern(VOCs) is still escalating throughout the world. However, the level of neutralization of the inactivated viral vaccine recipients’ sera and convalescent sera against all VOCs,including B.1.1.7(Alpha), B.1.351(Beta), P.1(Gamma), B.1.617.2(Delta), and B.1.1.529(Omicron) remains to be lack of comparative analysis. Therefore, we constructed pseudoviruses of five VOCs using a lentiviral-based system and analyzed their viral infectivity and neutralization resistance to convalescent and BBIBP-CorV vaccinee serum at different times. Our results show that, compared with the wild-type strain(WT), five VOC pseudoviruses showed higher infection, of which B.1.617.2 and B.1.1.529 variant pseudoviruses exhibited higher infection rates than wild-type or other VOC strains, respectively. Sera from 10 vaccinated individuals at the 1, 3and 5-month post second dose or from 10 convalescent at 14 and 200 days after discharge retained neutralizing activity against all strains but exhibited decreased neutralization activity significantly against the five VOC variant pseudoviruses over time compared to WT. Notably, 100%(30/30) of the vaccinee serum samples showed more than a 2.5-fold reduction in neutralizing activity against B.1.1.529, and 90%(18/20) of the convalescent serum samples showed more than 2.5-fold reduction in neutralization against B.1.1.529. These findings demonstrate the reduced protection against the VOCs in vaccinated and convalescent individuals over time, indicating that it is necessary to have a booster shot and develop new vaccines capable of eliciting broad neutralization antibodies.展开更多
Leydig cell(LC)is one of the most important somatic cell types in testis,which localized in the interstitium between seminiferous tubules.The major function of Leydig cells is to produce steroid hormone,androgens.LC d...Leydig cell(LC)is one of the most important somatic cell types in testis,which localized in the interstitium between seminiferous tubules.The major function of Leydig cells is to produce steroid hormone,androgens.LC differentiation exhibits a biphasic pattern in rodent testes,which are divided into two different temporal mature populations,fetal Leydig cells(FLCs)and adult Leydig cells(ALCs).FLCs are transiently present in fetal testes and undergo involution or degeneration after birth.FLCs are completely devoid and replaced by ALCs in adult testes.Comparing to ALCs,FLCs display unique morphology,ultrastructure and functions.The origin of FLCs has been debated for many years,but it is still a mystery.Many factors have been reported regulating the specification,proliferation and differentiation of FLCs.FLCs degenerate in a few weeks postnatally,however,the underlying mechanism is still unknown.In this review,we will focus on the fate determination of FLCs,and summarize the resent progress on the morphology,ultrastructure,function,origin and involution of FLCs.展开更多
文摘Autoimmune hepatitis is an inflammatory liver disease primarily mediated by T cell.It has not been fully elucidated about the pathogenesis,and it is presently thought to be related to genetic susceptibility,infection and environmental triggers,and abnormal autoimmune regulation.Recent studies have found that traditional Chinese medicine can improve the biochemical indicators and clinical symptoms of patients with autoimmune hepatitis.This article reviews the specific mechanism of traditional Chinese medicine on treating autoimmune hepatitis in order to propose new ideas for its clinical diagnosis and treatment.
文摘Student evaluation,which involves assessing students using specific standards,techniques,and methods,encompasses self-evaluation by students,evaluation by educators,and so on.It has long been a focal point and challenge in China’s educational system reform.This paper aims to broaden the approach to developing and reforming student evaluation within the context of China’s new era by summarizing its evolving characteristics,analyzing its pain points,and comparing the concepts and standards of student evaluation in developed countries with those in China.
基金financial support from the National Natural Science Foundation of China (52272261 and 52104300)。
文摘To tackle energy crisis and achieve sustainable development, aqueous rechargeable zinc ion batteries have gained widespread attention in large-scale energy storage for their low cost, high safety, high theoretical capacity, and environmental compatibility in recent years. However, zinc anode in aqueous zinc ion batteries is still facing several challenges such as dendrite growth and side reactions(e.g., hydrogen evolution), which cause poor reversibility and the failure of batteries. To address these issues, interfacial modification of Zn anodes has received great attention by tuning the interaction between the anode and the electrolyte. Herein, we present recent advances in the interfacial modification of zinc anode in this review. Besides, the challenges of reported approaches of interfacial modification are also discussed.Finally, we provide an outlook for the exploration of novel zinc anode for aqueous zinc ion batteries.We hope that this review will be helpful in designing and fabricating dendrite-free and hydrogenevolution-free Zn anodes and promoting the practical application of aqueous rechargeable zinc ion batteries.
基金financially supported by the National Natural Science Foundation of China(51974368,51774333)the Hunan Provincial Natural Science Foundation of China(2020JJ2048)。
文摘High-nickel single-crystal layered oxide material has become the most promising cathode material for electric vehicle power battery due to its high energy density.However,this material still suffers from structural degradation during cycling and especially the severe interfacial reactions at elevated temperatures that exacerbate irreversible capacity loss.Here,a simple strategy was used to construct a dualfunction Li_(1.5)Al_(0.5)Ge_(1.5)P_(3)O_(12)(LAGP)protective layer on the surface of the high-nickel single-crystal(SC)cathode material,leading to SC@LAGP material.The strong Al-O bonding effectively inhibits the release of lattice oxygen(O)at elevated temperatures,which is supported by the positive formation energy of O vacancy from first-principal calculations.Besides,theoretical calculations demonstrate that the appropriate amount of Al doping accelerates the electron and Li^(+)transport,and thus reduces the kinetic barriers.In addition,the LAGP protective layer alleviates the stress accumulation during cycling and effectively reduces the erosion of materials from the electrolyte decomposition at elevated temperatures.The obtained SC@LAGP cathode material demonstrates much enhanced cycling stability even at high voltage(4.6 V)and elevated temperature(55℃),with a high capacity retention of 91.3%after 100 cycles.This work reports a simple dual-function coating strategy that simultaneously stabilizes the structure and interface of the single-crystal cathode material,which can be applied to design other cathode materials.
基金supported by the National Natural Science Foundation of China(51974368)the Hunan Provincial Natural Science Foundation of China(2020JJ2048)the Natural Science Foundation of Hunan Province China(2021JJ30823)。
文摘Zinc metal anodes face several challenges,including the uncontrolled formation of dendrites,hydrogen evolution,and corrosion,which seriously hinder their application in practice.To address the above problems such as dendrite formation and corrosion,we present a simple and applicable immersion method that enables in situ formation of a zinc phytate(PAZ)coating on the surface of commercial Zn flakes via a substitution reaction.This protective coating mitigates corrosion of zinc flakes by the electrolyte,reduces the interfacial impedance,and accelerates the migration kinetics of zinc ions.Besides,this method can preferentially expose the(002)crystal plane with strong atomic bonding,which not only improves the corrosion resistance of the zinc flake,but can also guide the parallel deposition of zinc ions along the(002)crystal plane and reduce the formation of dendrites.Benefiting from the above advantages,the PAZ@Zn‖Cu half-cell has shown over 900 cycles with average coulombic efficiency(CE)of99.81%at 4 mA cm^(-2).Besides,the PAZ@Zn‖PAZ@Zn symmetric cell operate stably for>1000 h at5 mA cm^(-2)and>340 h at 10 mA cm^(-2).Furthermore,we demonstrated that this in situ chemical treatment enables the formation of a robust,well-bound protective coating.This method provides insights for advancing the commercialization of zinc anodes and other metal anodes.
基金the financial support from the National Natural Science Foundation of China(Nos.32201138,82030048,and 82230069)the Key Research and Development Program of Zhejiang Province(No.2019C03077).
文摘Mitochondria-targeted sonodynamic therapy(SDT)is a promising strategy to inhibit tumor growth and activate the anti-tumor immune responses.Identifying the mechanisms underlying mitochondria-targeted SDT,further optimizing its efficacy,developing novel sonosensitizer carriers with good biocompatibility pose major challenges to the clinical practice of SDT.In this study,we investigated the mechanisms of mitochondria-targeted SDT and demonstrated that it suppressed the mitochondrial electron transport chain(ETC)in pancreatic cancer cells through RNA-sequencing analysis.Based on these findings,we constructed the functional lipid droplets(LDs)(CPI-613/IR780@LDs),which combined mitochondria-targeted SDT with the tricarboxylic acid(TCA)cycle inhibitor CPI-613.CPI-613/IR780@LDs synergistically inhibited the TCA cycle and the ETC of mitochondrial aerobic respiration to reduce oxygen consumption and increase reactive oxygen species(ROS)generation at the tumor site,thus enhancing the efficacy of SDT in hypoxic pancreatic cancer.Moreover,the combination of mitochondria-targeted SDT and anti-PD-1 antibody exhibited excellent tumor inhibition and activated anti-tumor immune responses by increasing tumorinfiltrating CD8+T cells and reducing regulatory T cells,synergistically arresting the growth of both primary and metastatic pancreatic tumors.Meanwhile,lipid droplets are cell-derived biological carriers with natural mitochondrial targeting ability and can achieve efficient hydrophobic drug loading through active phagocytosis.Therefore,the functional lipid droplet-based SDT combined with anti-PD-1 antibody holds great potential in the clinical treatment of hypoxic pancreatic cancer.
基金supported by the Strategic Priority Research Program of CAS(No.XDB14040201)National Natural Science Foundation of China(Nos.21806179,21621064 and21672255)
文摘Methyl tert-butyl ether (MTBE),as a widely used gasoline additive,is suspected of being environmentally toxic.MTBE accumulates mainly in adipose tissue,but its effect on obesity or obesity-related metabolic disorders has not been well understood yet.Therefore,we examined the effect of MTBE on the adipose function and the related metabolic processes with both 3T3-L1 cell line and C57BL/6J mice model.We found that exposure to MTBE at the environmental relevant concentration (100 μmol/L) could significantly induce differentiation of preadipocyte and disturb insulin-stimulated glucose uptake of mature adipocyte.The in vivo observation in male mice showed a positive correlation of visceral white adipose tissue (vWAT) expansion and cell size increase with MTBE treatment in 14 weeks.Glucose tolerance and insulin sensitivity tests demonstrated that MTBE at 1000 μg/(kg·day) disturbed the systemic glucose metabolism in a gender-specific manner,which might be partly attributed to the alterations of gut microbiota community at genus level with respect to Akkermansia,Clostridium XIVb,and Megamonas.In summary,our study characterized the effect of MTBE on adipose tissue function and glucose homeostasis in vitro and in vivo,and revealed that systemic disorders of the glucose metabolism might be modulated by the related gut microbiota.
基金Project supported by the Heilongjiang Science and Technology Key Projects (No. GC07A305)the Fund of Harbin Engineering University (No. HEUFT08008)the Daqing Science and Technology Key Projects (No. SGG2008-029), Heilongjiang, China
文摘A sequential anode-cathode double-chamber microbial fuel cell (MFC), in which the effluent of anode chamber was used as a continuous feed for an aerated cathode chamber, was constructed in this experiment to investigate the performance of brewery wastewater treatment in conjugation with electricity generation. Carbon fiber was used as anode and plain carbon felt with biofilm as cathode. When hydraulic retention time (HRT) was 14.7 h, a relatively high chemical oxygen demand (COD) removal efficiency of 91.7%-95.7% was achieved under long-term stable operation. The MFC displayed an open circuit voltage of 0.434 V and a maximum power density of 830 mW/m^3 at an external resistance of 300 0. To estimate the electrochemical performance of the MFC, electrochemical measurements were carried out and showed that polarization resistance of anode was the major limiting factor in the MFC. Since a high COD removal efficiency was achieved, we conclude that the sequential anode-cathode MFC constructed with bio-cathode in this experiment could provide a new approach for brewery wastewater treatment.
基金supported by National Natural Science Foundation of China(grant numbers:82003796,81803566,81973340 and 81630095)Local Innovative and Research Teams Project of the Guangdong Pearl River Talents Program(grant number:2017BT01Y036,China)+5 种基金National High-level Personnel of the Special Support Program(DM Zhang,China)National Science and Technology Major Project(grant number:2018ZX09711001008-008,China)Key-Area Research and Development Program of Guangdong Province(grant number:2020B1111110004,China)Natural Science Foundation of Guangdong Province(grant number:2019A1515010144,China)Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research,College of Pharmacy(grant number:2020B1212060076,China)Special Funds for the Cultivation of Guangdong College Students’Scientific and Technological Innovation(grant number:pdjh2021a0052,China)。
文摘Osteosarcoma is a kind of bone tumor with highly proliferative and invasive properties,a high incidence of pulmonary metastasis and a poor prognosis.Chemotherapy is the mainstay of treatment for osteosarcoma.Currently,there are no molecular targeted drugs approved for osteosarcoma treatment,particularly effective drugs for osteosarcoma with pulmonary metastases.It has been reported that fibroblast activation protein alpha(FAPa)is upregulated in osteosarcoma and critically associated with osteosarcoma progression and metastasis,demonstrating that FAPa-targeted agents might be a promising therapeutic strategy for osteosarcoma.In the present study,we reported that the FAPa-activated vinblastine prodrug Z-GP-DAVLBH exhibited potent antitumor activities against FAPa-positive osteosarcoma cells in vitro and in vivo.Z-GP-DAVLBH inhibited the growth and induced the apoptosis of osteosarcoma cells.Importantly,it also decreased the migration and invasion capacities and reversed epithelial-mesenchymal transition(EMT)of osteosarcoma cells in vitro and suppressed pulmonary metastasis of osteosarcoma xenografts in vivo.Mechanistically,Z-GP-DAVLBH suppressed the AXL/AKT/GSK-3β/β-catenin pathway,leading to inhibition of the growth and metastatic spread of osteosarcoma cells.These findings demonstrate that Z-GP-DAVLBH is a promising agent for the treatment of FAPa-positive osteosarcoma,particularly osteosarcoma with pulmonary metastases.
基金supported by the National Key R&D Program of China(Grant No.2019YFA0903803)the Major Program of National Natural Science Foundation of China(Grant No.32090031)+10 种基金the General Program of National Natural Science Foundation of China(Grant Nos.31971354 and 32070610)the National Natural Science Foundation of China for Young Scholars(Grant No.32000580)the Guangdong Province Fund for Distinguished Young Scholars,China(Grant No.2021B1515020109)the Key Project from Natural Science Foundation of Guangdong Province,China(Grant No.2020B1515120034)the Guangdong Provincial Key Laboratory of Synthetic Genomics,China(Grant No.2019B030301006)the Shenzhen Key Laboratory of Synthetic Genomics,China(Grant No.ZDSYS201802061806209)the Project from Shenzhen Science and Technology Innovation Committee,China(Grant No.JCYJ20170818164014753)the Mayo Clinic Cancer Center Eagles Cancer Fund awarded to ZWthe Mayo Clinic Cancer Center Hematologic Malignancies Program awarded to ZWthe Mayo Clinic division of Hematology awarded to ZWthe Mayo Clinic Center for Biomedical Discovery awarded to SMO,United States。
文摘Proximity labeling catalyzed by promiscuous enzymes,such as APEX2,has emerged as a powerful approach to characterize multiprotein complexes and protein-protein interactions.However,current methods depend on the expression of exogenous fusion proteins and cannot be applied to identify proteins surrounding post-translationally modified proteins.To address this limitation,we developed a new method to label proximal proteins of interest by antibody-mediated protein A-ascorbate peroxidase 2(pA-APEX2) labeling(AMAPEX).In this method,a modified protein is bound in situ by a specific antibody,which then tethers a pA-APEX2 fusion protein.Activation of APEX2 labels the nearby proteins with biotin;the biotinylated proteins are then purified using streptavidin beads and identified by mass spectrometry.We demonstrated the utility of this approach by profiling the proximal proteins of histone modifications including H3 K27 me3,H3 K9 me3,H3 K4 me3,H4 K5 ac,and H4 K12 ac,as well as verifying the co-localization of these identified proteins with bait proteins by published ChIP-seq analysis and nucleosome immunoprecipitation.Overall,AMAPEX is an efficient method to identify proteins that are proximal to modified histones.
基金Jinan Technology Development Program(Grant No.201907035)。
文摘Alcohol consumption causes significant liver damage,including hepatitis,fibrosis,cirrhosis,and even primary liver carcinoma.Metadoxine(MTDX)is considered to be a beneficial treatment for alcoholic liver disease(ALD)because it accelerates the metabolism and elimination of ethanol.However,the underlying mechanism is not well understood.Here,the rat model of ALD was developed by feeding with 50%ethanol at the dose of 5 g/kg,and samples of serum and liver tissue were collected to test the levels of liver injury and inflammation and evaluate the hepatoprotective function of MTDX in alcohol-induced liver injury.Further investigation on the infiltration of immune cells was performed to understand the potential hepatoprotective mechanism of MTDX in the ALD model.The results showed that MTDX attenuated liver injury,evidenced by decreased levels of alanine transaminase(ALT),aspartate aminotransferase(AST),and alkaline phosphatase(ALP).Meanwhile,the liver proinflammatory environment was improved after MTDX treatment,evidenced by decreased levels of TNF-α,IL-6,and NLRP3 in the liver tissue.Furthermore,inhibited infiltrations of macrophages and neutrophils were observed in MTDX-treated ALD rats compared with the untreated ALD rats.Our results indicated that MTDX played an important role in preventing the progression of ALD,and the underlying mechanisms might be related to its function of attenuating liver inflammation by inhibiting immune cell infiltration.
基金supported by the National Natural Science Foundation of China (Nos.21878060 and 21476053)China Scholarship Council (No.201806685019)
文摘Interfacial electron transfer between electroactive biofilm and the electrode was crucial step for microbial fuel cells(MFCs).A three-dimensional multilayer porous sponge coating with nitrogen-doped carbon nanotube/polyaniline/manganese dioxide(S/N-CNT/PANI/MnO2)electrode has been developed for MFC anode.Here,the S/N-CNT/PANI/MnO2 anode can function as a biocapacitor,able to store electrons generated from the degradation of organic substrate under the open circuit state and release the accumulated electrons upon requirement.Thus,the mismatching of the production and demand of the electricity can be overcome.Comparing with the sponge/nitrogen-doped carbon nanotube(S/N-CNT)bioanode,S/N-CNT/PANI/MnO2 capacitive bioanode displays a strong interaction with the microbial biofilm,advancing the electron transfer from exoelectrogens to the bioanode.The maximum power density of MFC with S/N-CNT/PANI/MnO2 capacitive bioanode is 1019.5 mW/m^2,which is 2.2 and5.8 times as much as that of S/N-CNT/MnO2 bioanode and S/N-CNT bioanode(470.7 mW/m^2 and176.6 mW/m^2),respectively.During the chronoamperometric experiment with 60 min of charging and 20 min of discharging,the S/N-CNT/PANI/MnO2 capacitive bioanode was able to store 10743.9 C/m^2,whereas the S/N-CNT anode was only able to store 3323.4 C/m^2.With a capacitive bioanode,it is possible to use the MFC simultaneously for production and storage of electricity.
基金supported by the University of Macao Multi-Year Research Grants (MYRG2015-00065FHS)the Macao Science and Technology Development Fund (FDCT 018-2015-A1) to Dr. Hang Fai Kwok research group
文摘Prostate cancer is one of the most common cancers in men worldwide, and the number of diagnosed patients has dramatically increased in recent years. Currently, the clinical parameters used to diagnose prostate cancer, such as Gleason score, pathological tumor staging, and prostate-specific antigen(PSA) expression level, are considered insufficient to inform recommendation to guide clinical practice. Thus, identification of a novel biomarker is necessary. TWIST is one of the well-studied targets and is correlated with cancer invasion and metastasis in several human cancers. We have investigated two largest prostate cancer patient cohorts available in GEO database and found that TWIST expression is positive correlated with Gleason score and associated with poorer survival. By using a prostate cancer cohort and a prostate cancer cell line dataset, we have identified three potential downstream targets of TWIST, PPM1 A, SRP72 and TBCB. TWIST's prognostic capacity is lost when the gene is mutated. Further investigation in the prostate cancer cohort revealed that gene expression of SERPINA, STX7, PDIA2, FMP5, GP1 BB, VGLL4,KCNMA1, SHMT2, SAA4 and DIDO1 influence the prognostic significance of TWIST and vice versa. Importantly, eight out of these ten genes are prognostic indicator by itself. In conclusion, our study has further confirmed that TWIST is a prognostic marker in prostate cancer, identified its potential downstream targets and genes that could possibly give additional prognostic value to predict TWIST-mediated prostate cancer progression.
基金supported by the National Natural Science Foundation of China (82041001, 81761128020)
文摘The prevalence of SARS-CoV-2 variants of concern(VOCs) is still escalating throughout the world. However, the level of neutralization of the inactivated viral vaccine recipients’ sera and convalescent sera against all VOCs,including B.1.1.7(Alpha), B.1.351(Beta), P.1(Gamma), B.1.617.2(Delta), and B.1.1.529(Omicron) remains to be lack of comparative analysis. Therefore, we constructed pseudoviruses of five VOCs using a lentiviral-based system and analyzed their viral infectivity and neutralization resistance to convalescent and BBIBP-CorV vaccinee serum at different times. Our results show that, compared with the wild-type strain(WT), five VOC pseudoviruses showed higher infection, of which B.1.617.2 and B.1.1.529 variant pseudoviruses exhibited higher infection rates than wild-type or other VOC strains, respectively. Sera from 10 vaccinated individuals at the 1, 3and 5-month post second dose or from 10 convalescent at 14 and 200 days after discharge retained neutralizing activity against all strains but exhibited decreased neutralization activity significantly against the five VOC variant pseudoviruses over time compared to WT. Notably, 100%(30/30) of the vaccinee serum samples showed more than a 2.5-fold reduction in neutralizing activity against B.1.1.529, and 90%(18/20) of the convalescent serum samples showed more than 2.5-fold reduction in neutralization against B.1.1.529. These findings demonstrate the reduced protection against the VOCs in vaccinated and convalescent individuals over time, indicating that it is necessary to have a booster shot and develop new vaccines capable of eliciting broad neutralization antibodies.
基金the National Basic Research Program of China(“973”project)(No.2007CB947502)the CAS Innovation Project(No.KSCX2-YW-R-081)the National Nature Science Foundation of China(Grant No.31071271).
文摘Leydig cell(LC)is one of the most important somatic cell types in testis,which localized in the interstitium between seminiferous tubules.The major function of Leydig cells is to produce steroid hormone,androgens.LC differentiation exhibits a biphasic pattern in rodent testes,which are divided into two different temporal mature populations,fetal Leydig cells(FLCs)and adult Leydig cells(ALCs).FLCs are transiently present in fetal testes and undergo involution or degeneration after birth.FLCs are completely devoid and replaced by ALCs in adult testes.Comparing to ALCs,FLCs display unique morphology,ultrastructure and functions.The origin of FLCs has been debated for many years,but it is still a mystery.Many factors have been reported regulating the specification,proliferation and differentiation of FLCs.FLCs degenerate in a few weeks postnatally,however,the underlying mechanism is still unknown.In this review,we will focus on the fate determination of FLCs,and summarize the resent progress on the morphology,ultrastructure,function,origin and involution of FLCs.