One-third of patients with autoimmune hepatitis(AIH)have cirrhosis at the time of diagnosis.The relevance of these variables,although unknown,is believed to be critical in AIH because of suspected interactions between...One-third of patients with autoimmune hepatitis(AIH)have cirrhosis at the time of diagnosis.The relevance of these variables,although unknown,is believed to be critical in AIH because of suspected interactions between the gut microbiome and genetic factors.Dysbiosis of the gut flora and elevated polymeric immunoglobulin receptor(pIgR)levels have been observed in both patients and mouse models.Moreover,there is a direct relationship between pIgR expression and transaminase levels in patients with AIH.In this study,we aimed to explore how pIgR influences the secretion of regenerating islet-derived 3 beta(Reg3b)and the flora composition in AIH using in vivo experiments involving patients with AIH and a concanavalin A-induced mouse model of AIH.Reg3b expression was reduced in pIgR gene(Pigr)-knockout mice compared to that in wild-type mice,leading to increased microbiota disruption.Conversely,exogenous pIgR supplementation increased Reg3b expression and maintained microbiota homeostasis.RNA sequencing revealed the participation of the interleukin(IL)-17 signaling pathway in the regulation of Reg3b through pIgR.Furthermore,the introduction of external pIgR could not restore the imbalance in gut microbiota in AIH,and the decrease in Reg3b expression was not apparent following the inhibition of signal transducer and activator of transcription 3(STAT3).In this study,pIgR facilitated the upregulation of Reg3b via the STAT3 pathway,which plays a crucial role in preserving the balance of the intestinal microbiota in AIH.Through this research,we discovered new molecular targets that can be used for the diagnosis and treatment of AIH.展开更多
Proteolytic cleavage of tau by asparagine endopeptidase(AEP)creates tau-N368 fragments,which may drive the pathophysiology associated with synaptic dysfunction and memory deterioration in the brain of Alzheimer’s dis...Proteolytic cleavage of tau by asparagine endopeptidase(AEP)creates tau-N368 fragments,which may drive the pathophysiology associated with synaptic dysfunction and memory deterioration in the brain of Alzheimer’s disease patients.Nonetheless,the molecular mechanisms of truncated tau-induced cognitive deficits remain unclear.Evidence suggests that signal transduction and activator of transcription-3(STAT3)is associated with modulating synaptic plasticity,cell apoptosis,and cognitive function.Using luciferase reporter assays,electrophoretic mobility shift assays,western blotting,and immunofluorescence,we found that human tau-N368 accumulation inhibited STAT3 activity by suppressing STAT3 translocation into the nucleus.Overexpression of STAT3 improved tau-N368-induced synaptic deficits and reduced neuronal loss,thereby improving the cognitive deficits in tau-N368 mice.Moreover,in tau-N368 mice,activation of STAT3 increased N-methyl-D-aspartic acid receptor levels,decreased Bcl-2 levels,reversed synaptic damage and neuronal loss,and thereby alleviated cognitive deficits caused by tau-N368.Taken together,STAT3 plays a critical role in truncated tau-related neuropathological changes.This indicates a new mechanism behind the effect of tau-N368 on synapses and memory deficits.STAT3 can be used as a new molecular target to treat tau-N368-induced protein pathology.展开更多
Rice is one of the three most important food crops in the world.Increasing rice yield is an effective way to ensure food security.Grain size is a key factor affecting rice yield;however,the genetic and molecular mecha...Rice is one of the three most important food crops in the world.Increasing rice yield is an effective way to ensure food security.Grain size is a key factor affecting rice yield;however,the genetic and molecular mechanisms regulating grain size have not been fully investigated.In this study,we identified a rice mutant,wide grain 4-D(wg4-D),that exhibited a significant increase in grain width and a decrease in grain length.Histological analysis demonstrated that WG4 affects cell expansion thereby regulating grain size.MutMap-based gene mapping and complementary transgenic experiments revealed that WG4 encodes an alpha-tubulin,OsTubA1.A SNP mutation in WG4 affected the arrangement of cortical microtubules and caused a wide-grain phenotype.WG4 is located in nuclei and cytoplasm and expressed in various tissues.Our results provide insights into the function of tubulin in rice and identifies novel targets the regulation of grain size in crop breeding.展开更多
Interferon regulatory factor 7 plays a crucial role in the innate immune response.However,whether interferon regulatory factor 7-mediated signaling contributes to Parkinson's disease remains unknown.Here we report...Interferon regulatory factor 7 plays a crucial role in the innate immune response.However,whether interferon regulatory factor 7-mediated signaling contributes to Parkinson's disease remains unknown.Here we report that interferon regulatory factor 7 is markedly up-regulated in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of Parkinson's disease and co-localizes with microglial cells.Both the selective cyclic guanosine monophosphate adenosine monophosphate synthase inhibitor RU.521 and the stimulator of interferon genes inhibitor H151 effectively suppressed interferon regulatory factor 7 activation in BV2 microglia exposed to 1-methyl-4-phenylpyridinium and inhibited transformation of mouse BV2 microglia into the neurotoxic M1 phenotype.In addition,si RNA-mediated knockdown of interferon regulatory factor 7 expression in BV2 microglia reduced the expression of inducible nitric oxide synthase,tumor necrosis factorα,CD16,CD32,and CD86 and increased the expression of the anti-inflammatory markers ARG1 and YM1.Taken together,our findings indicate that the cyclic guanosine monophosphate adenosine monophosphate synthase-stimulator of interferon genes-interferon regulatory factor 7 pathway plays a crucial role in the pathogenesis of Parkinson's disease.展开更多
To achieve high energy density in lithium batteries,the construction of lithium-ion/metal hybrid anodes is a promising strategy.In particular,because of the anisotropy of graphite,hybrid anode formed by graphite/Li me...To achieve high energy density in lithium batteries,the construction of lithium-ion/metal hybrid anodes is a promising strategy.In particular,because of the anisotropy of graphite,hybrid anode formed by graphite/Li metal has low transport kinetics and is easy to causes the growth of lithium dendrites and accumulation of dead Li,which seriously affects the cycle life of batteries and even causes safety problems.Here,by comparing graphite with two types of hard carbon,it was found that hybrid anode formed by hard carbon and lithium metal,possessing more disordered mesoporous structure and lithophilic groups,presents better performance.Results indicate that the mesoporous structure provides abundant active site and storage space for dead lithium.With the synergistic effect of this structure and lithophilic functional groups(–COOH),the reversibility of hard carbon/lithium metal hybrid anode is maintained,promoting uniform deposition of lithium metal and alleviating formation of lithium dendrites.The hybrid anode maintains a 99.5%Coulombic efficiency(CE)after 260 cycles at a specific capacity of 500 m Ah/g.This work provides new insights into the hybrid anodes formed by carbon-based materials and lithium metal with high specific energy and fast charging ability.展开更多
The anti-freezing strategy of hydrogels and their self-healing structure are often contradictory,it is vital to break through the molecular structure to design and construct hydrogels with intrinsic anti-freezing/self...The anti-freezing strategy of hydrogels and their self-healing structure are often contradictory,it is vital to break through the molecular structure to design and construct hydrogels with intrinsic anti-freezing/self-healing for meeting the rapid development of flexible and wearable devices in diverse service conditions.Herein,we design a new hydrogel electrolyte(AF/SH-Hydrogel)with intrinsic anti-freezing/self-healing capabilities by introducing ethylene glycol molecules,dynamic chemical bonding(disulfide bond),and supramolecular interaction(multi-hydrogen bond)into the polyacrylamide molecular chain.Thanks to the exceptional freeze resistance(84%capacity retention at-20℃)and intrinsic self-healing capabilities(95%capacity retention after 5 cutting/self-healing cycles),the obtained AF/SH-Hydrogel makes the zinc||manganese dioxide cell an economically feasible battery for the state-of-the-art applications.The Zn||AF/SH-Hydrogel||MnO_(2)device offers a near-theoretical specific capacity of 285 m A h g^(-1)at 0.1 A g^(-1)(Coulombic efficiency≈100%),as well as good self-healing capability and mechanical flexibility in an ice bath.This work provides insight that can be utilized to develop multifunctional hydrogel electrolytes for application in next generation of self-healable and freeze-resistance smart aqueous energy storage devices.展开更多
Objective:To explore which pattern recognition receptors(PRRs)play a key role in the development of hand,foot,and mouth disease(HFMD)by analyzing PRR-associated genes.Methods:We conducted a comparative analysis of PRR...Objective:To explore which pattern recognition receptors(PRRs)play a key role in the development of hand,foot,and mouth disease(HFMD)by analyzing PRR-associated genes.Methods:We conducted a comparative analysis of PRR-associated gene expression in human peripheral blood mononuclear cells(PBMCs)infected with enterovirus 71(EV-A71)which were derived from patients with HFMD of different severities and at different stages.A total of 30 PRR-associated genes were identified as significantly upregulated both over time and across different EV-A71 isolates.Subsequently,ELISA was employed to quantify the expression of the six most prominent genes among these 30 identified genes,specifically,BST2,IRF7,IFI16,TRIM21,MX1,and DDX58.Results:Compared with those at the recovery stage,the expression levels of BST2(P=0.027),IFI16(P=0.016),MX1(P=0.046)and DDX58(P=0.008)in the acute stage of infection were significantly upregulated,while no significant difference in the expression levels of IRF7(P=0.495)and TRIM21(P=0.071)was found between different stages of the disease.The expression levels of BST2,IRF7,IFI16 and MX1 were significantly higher in children infected with single pathogen than those infected with mixed pathogens,and BST2,IRF7,IFI16 and MX1 expression levels were significantly lower in coxsackie B virus(COXB)positive patients than the negative patients.Expression levels of one or more of BST2,IRF7,IFI16,TRIM21,MX1 and DDX58 genes were correlated with PCT levels,various white blood cell counts,and serum antibody levels that reflect disease course of HFMD.Aspartate aminotransferase was correlated with BST2,MX1 and DDX58 expression levels.Conclusions:PRR-associated genes likely initiate the immune response in patients at the acute stage of HFMD.展开更多
BACKGROUND Primary light chain amyloidosis is a rare and complex disease with complex clinical features and is highly susceptible to misdiagnosis and underdiagnosis in the early stages.CASE SUMMARY We report a case of...BACKGROUND Primary light chain amyloidosis is a rare and complex disease with complex clinical features and is highly susceptible to misdiagnosis and underdiagnosis in the early stages.CASE SUMMARY We report a case of a 47-year-old female patient whose only initial symptom was periorbital purpura,which was not taken seriously enough.As the disease progressed,pleural effusion gradually appeared,and after systematic diagnosis and treatment,she was diagnosed with“primary light chain amyloidosis”.She achieved rapid hematological remission after treatment with a daratumumab+bortezomib+cyclophosphamide+dexamethasone regimen.CONCLUSION Periorbital purpura can be the only initial symptom of primary light chain amyloidosis;we should pay attention to the cases where the initial clinical symptoms are only periorbital purpura.展开更多
Objective:To investigate the clinicopathological characteristics and prognostic factors of early-stage breast cancer patients with indications for breast cancer susceptibility genes 1/2(BRCA1/2)genetic testing in Chin...Objective:To investigate the clinicopathological characteristics and prognostic factors of early-stage breast cancer patients with indications for breast cancer susceptibility genes 1/2(BRCA1/2)genetic testing in China.Methods:Based on the indication criteria for BRCA genetic testing specified in the National Comprehensive Cancer Network(NCCN)clinical practice guidelines in oncology,genetic/familial high-risk assessment:Breast and ovarian(Version 2.2019),a retrospective analysis was performed on patients with early-stage invasive breast cancer treated at Breast Disease Center,Peking University First Hospital between January 2008 and December 2016.Clinicopathological characteristics of all patients were analyzed,and prognoses were calculated using the KaplanMeier method and a Cox proportionate hazards model.Results:A total of 906 early-stage breast cancer patients who had indications for BRCA genetic testing and had complete clinicopathological data and follow-up information were included in the study group,accounting for34.7%of all breast cancer patients treated in Breast Disease Center,Peking University First Hospital during the study period.Compared with breast cancer patients without indications for BRCA genetic testing,the overall survival(OS)and disease-free survival(DFS)of patients with indications were not significantly different.In the study group,patients with premenopausal status,high T stage,lymph node positive,estrogen receptor(ER)negative,Ki-67>20%and presence of a vascular tumor thrombus had worse prognosis.There were more family histories of gastrointestinal cancer in patients with related indications than in patients without such indications.Conclusions:Single-center data showed that more than 30%of patients with early-stage breast cancer had indications for BRCA genetic testing.There was no prognostic difference in patients with or without indications for BRCA genetic testing.Premenopausal status,high T stage,lymph node positive,ER negative,Ki-67>20%,and presence of a vascular tumor thrombus were associated with poor prognosis.展开更多
BACKGROUND Butylphthalide(NBP)and edaravone(EDV)injection are common acute ischemic stroke medications in China,but there is a lack of large real-world safety studies on them.This study aimed to determine the incidenc...BACKGROUND Butylphthalide(NBP)and edaravone(EDV)injection are common acute ischemic stroke medications in China,but there is a lack of large real-world safety studies on them.This study aimed to determine the incidence of adverse events,detect relevant safety signals,and assess the risk factors associated with these medications in real-world populations.METHODS In this study,data of acute ischemic stroke patients were extracted from the electronic medical record database of six tertiary hospitals between January 2019 and August 2021.Baseline confounders were eliminated using propensity score matching.The drugs’safety was estimated by comparing the results of 24 laboratory tests standards on liver function,kidney function,lipid level,and coagulation function.The drugs’relative risk was estimated by logistic regression.A third group with patients who did not receive NBP or EDV was constructed as a reference.Prescription sequence symmetry analysis was used to evaluate the associations between adverse events and NBP and EDV,respectively.RESULTS 81,292 patients were included in this study.After propensity score matching,the NBP,EDV,and third groups with 727patients in each group.Among the 15 test items,the incidence of adverse events was lower in the NBP group than in the EDV group,and the differences were statistically significant.The multivariate logistic regression equation revealed that NBP injection was not a promoting factor for abnormal laboratory test results,whereas EDV had statistically significant effects on aspartate transaminase,low-density lipoprotein cholesterol and total cholesterol.Prescription sequence symmetry analysis showed that NBP had a weak correlation with abnormal platelet count.EDV had a positive signal associated with abnormal results in gamma-glutamyl transferase,alanine aminotransferase,aspartate aminotransferase,prothrombin time,and platelet count.CONCLUSIONS In a large real-world population,NBP has a lower incidence of adverse events and a better safety profile than EDV or other usual medications.展开更多
This study aimed to investigate the protective effects of fleshes from two Actinidia chinensis(ACF), pericarps from two A. chinensis(ACP), and fleshes with pericarps from two A. chinensis(ACFP)on high fructose(HF)-ins...This study aimed to investigate the protective effects of fleshes from two Actinidia chinensis(ACF), pericarps from two A. chinensis(ACP), and fleshes with pericarps from two A. chinensis(ACFP)on high fructose(HF)-instigated dyslipidemia, hepatic steatosis, oxidative stress, insulin resistance, and fatty acid metabolism disorders in rats. In general, the above abnormalities were improved after 10 weeks intervention of ACF, ACP, and ACFP. Especially, ACFP considerably ameliorated HF-induced abnormal changes in body weight gain, serum TC, TG, LDL-C and HDL-C levels, as well as serum and hepatic SFAs, MUFAs and PUFAs contents. ACFP also alleviated HF-induced hyperglycemia and hyperinsulinemia, stabilized HF-caused increase in hepatic MDA and serum ALT, AST levels, and restored HF-declined hepatic T-SOD and GSH-Px activities. Besides, histopathology of the liver further endorsed the protective effects of ACFP on hepatocellular injury. Moreover, ACFP increased HF-dropped acetic, propionic and butyric acid levels. Overall, ACFP employs more efficacious protective effects against HF-induced metabolic disorders and liver damage than ACF and ACP. This study delivers a scientific foundation for developing kiwifruit(counting peel)-based dietary supplements for those with glucolipid-metabolic disorders and liver damage.展开更多
The emergence of Event-based Social Network(EBSN) data that contain both social and event information has cleared the way to study the social interactive relationship between the virtual interactions and physical inte...The emergence of Event-based Social Network(EBSN) data that contain both social and event information has cleared the way to study the social interactive relationship between the virtual interactions and physical interactions. In existing studies, it is not really clear which factors affect event similarity between online friends and the influence degree of each factor. In this study, a multi-layer network based on the Plancast service data is constructed. The the user’s events belongingness is shuffled by constructing two null models to detect offline event similarity between online friends. The results indicate that there is a strong correlation between online social proximity and offline event similarity. The micro-scale structures at multi-levels of the Plancast online social network are also maintained by constructing 0 k–3 k null models to study how the micro-scale characteristics of online networks affect the similarity of offline events. It is found that the assortativity pattern is a significant micro-scale characteristic to maintain offline event similarity. Finally, we study how structural diversity of online friends affects the offline event similarity. We find that the subgraph structure of common friends has no positive impact on event similarity while the number of common friends plays a key role, which is different from other studies. In addition, we discuss the randomness of different null models, which can measure the degree of information availability in privacy protection. Our study not only uncovers the factors that affect offline event similarity between friends but also presents a framework for understanding the pattern of human mobility.展开更多
To the Editor:Hepatocellular carcinoma(HCC)is a prevalent form of gastrointestinal malignancies.The current combination of immunotherapy and other treatments improves overall survival compared to conventional therapie...To the Editor:Hepatocellular carcinoma(HCC)is a prevalent form of gastrointestinal malignancies.The current combination of immunotherapy and other treatments improves overall survival compared to conventional therapies,but the immunosuppressive microenvironment of HCC is a significant barrier to the efficacy of immunothera-peutic drugs[1].Tumor immune escape is promoted by interactions among immunosuppressive cells,including tumor-associated macrophages,marrow-derived suppressor cells,tumor-associated neutrophils,cancer-associated fibroblasts,and tumor-infiltrating Tregs[2].展开更多
Rechargeable Mg batteries(RMBs)are a promising large-scale energy-storage technology with low cost and high safety,but the performance is limited by the inferior kinetics of Mg-intercalation cathodes.In the present st...Rechargeable Mg batteries(RMBs)are a promising large-scale energy-storage technology with low cost and high safety,but the performance is limited by the inferior kinetics of Mg-intercalation cathodes.In the present study,an octylamine-supporting interlayer expanded molybdenum diselenide(e-MoSe_(2))is synthesized and used as cathode for RMBs,in comparison with ordinary crystalline MoSe_(2).The octylamine molecules introduced show a strong interaction with the MoSe_(2)layers and increase the layer spacing significantly from 6.46 to 11.5Å.e-MoSe_(2)shows a high Mg-storage capacity of 238 mAh g^(-1)at 50 mA g^(-1)and a superior rate performance of 39 mAh g^(-1)at 10 A g1,far advantageous over crystalline MoSe_(2).e-MoSe_(2)also shows a considerably high structure stability during repeated magnesiation/demagnesiation,providing an outstanding cycling stability for 1000 cycles.Further electrochemical tests demonstrate the high Mg^(2+)diffusion coefficients in e-MoSe_(2).Theoretical computation indicates the interlayer expansion changes the Mg^(2+)diffusion paths from"hollow site→hollow site"to"hollow site→Se atom site→hollow site",largely decreasing the energy barrier and improving the Mg^(2+)diffusion kinetics.The present work highlights an efficient strategy for the improvement of Mg-storage performance for RMB cathodes.展开更多
BACKGROUND Pancreatic cavernous hemangioma(pCH)is a rare type of benign vascular tumor.Making the right diagnosis is challenging due to low clinical suspicion and the lack of existing cross-sectional imaging tools to ...BACKGROUND Pancreatic cavernous hemangioma(pCH)is a rare type of benign vascular tumor.Making the right diagnosis is challenging due to low clinical suspicion and the lack of existing cross-sectional imaging tools to distinguish it from other pancreatic lesions.CASE SUMMARY We describe a male patient,age 18,who presented with a pCH.Computed tomography,magnetic resonance imaging,and ultrasound showed cystic space in the tail of the pancreas.A dark spot sign on the T2 weighted image sequence was observed.Clinically,a mucinous cystic neoplasm with hemorrhage was suspected preoperatively by combining imaging,and the operative indication was clear.The patient underwent a distal pancreatic tumor resection under laparoscopic control.Immunohistochemical staining for CD31 and CD34 was positive;D2-40 was positive in interstitial lymphatic vessels and negative in vascular epithelial cells;and calcium-binding protein was negative.The results support the diagnosis of pCH combined with chronic intracapsular spontaneous hemorrhage.No complications or recurrences were observed during the follow-up period.CONCLUSION Chronic spontaneous hemorrhage may occur in pCH,which may greatly influence the accuracy of diagnosis using imaging modalities.Surgical resection for uncertain pCH seems reasonable with a good outcome.展开更多
背景乙型肝炎病毒(hepatitis B virus,HBV)相关慢性肝病患者外周血T细胞及细胞因子水平与患者免疫功能状态密切相关,不同疾病程度的HBV相关肝病患者的T细胞、细胞因子水平及与肝病阶段的相关性值得进一步探究.目的探究不同阶段HBV相关...背景乙型肝炎病毒(hepatitis B virus,HBV)相关慢性肝病患者外周血T细胞及细胞因子水平与患者免疫功能状态密切相关,不同疾病程度的HBV相关肝病患者的T细胞、细胞因子水平及与肝病阶段的相关性值得进一步探究.目的探究不同阶段HBV相关慢性肝病患者外周血T细胞亚群计数、细胞因子变化特点及关联性.方法本研究为一项观察性研究,共纳入慢性乙型肝炎(chronic hepatitis B,CHB)患者65例,肝硬化失代偿期(decompensated cirrhosis,DCC)患者122例,肝细胞癌(hepatocellular carcinoma,HCC)患者109例,收集患者一般信息、病史、治疗情况及实验室检查结果、Child-Paugh分级及HCC患者肿瘤巴塞罗那分期,分析各项指标,尤其是T细胞亚群计数及细胞因子的组间差异及特征.结果HBV相关肝硬化、HCC患者外周血CD8^(+)T细胞水平与Child分级A到C呈负相关.HCC患者CD8^(+)T细胞绝对计数显著低于DCC[240(150-379)cells/μLvs 277(154-435)cells/μL,P<0.05]及CHB[240(150-379)cells/μL vs 452(269-706)cells/μL,P<0.001]患者.白细胞介素(interleukin,IL)-6、IL-8、肿瘤坏死因子(tumor necrosis factor,TNF)-α在HCC组均最高.DCC、HCC患者Child-Paugh分级越差,CD3^(+)、CD8^(+)T细胞水平越低,IL-6水平越高.HCC患者CD3^(+)、CD8^(+)T细胞水平随着肿瘤巴塞罗那分期由A到D呈下降趋势,IL-6呈上升趋势.且肝硬化、HCC患者CD3^(+)(r=-0.340,P<0.001)、CD8^(+)(r=-0.353,P<0.001)T细胞水平与IL-6升高水平呈显著负相关.结论HBV相关肝硬化、HCC患者外周血CD8^(+)T细胞计数与Child分级(由A到C)呈负相关,且IL-6水平与CD8^(+)T细胞计数存在负相关关系.展开更多
Glucagon-like peptide-1 receptor agonists(GLP-1 RAs)protect against diabetic cardiovascular diseases and nephropathy.However,their activity in diabetic retinopathy(DR)remains unclear.Our retrospective cohort study inv...Glucagon-like peptide-1 receptor agonists(GLP-1 RAs)protect against diabetic cardiovascular diseases and nephropathy.However,their activity in diabetic retinopathy(DR)remains unclear.Our retrospective cohort study involving 1626 T2DM patients revealed superior efficacy of GLP-1 RAs in controlling DR compared to other glucose-lowering medications,suggesting their advantage in DR treatment.By single-cell RNA-sequencing analysis and immunostaining,we observed a high expression of GLP-1R in retinal endothelial cells,which was down-regulated under diabetic conditions.Treatment of GLP-1 RAs significantly restored the receptor expression,resulting in an improvement in retinal degeneration,vascular tortuosity,avascular vessels,and vascular integrity in diabetic mice.GO and GSEA analyses further implicated enhanced mitochondrial gene translation and mitochondrial functions by GLP-1 RAs.Additionally,the treatment attenuated STING signaling activation in retinal endothelial cells,which is typically activated by leaked mitochondrial DNA.Expression of STING mRNA was positively correlated to the levels of angiogenic and inflammatory factors in the endothelial cells of human fibrovascular membranes.Further investigation revealed that the cAMP-responsive element binding protein played a role in the GLP-1R signaling pathway on suppression of STING signaling.This study demonstrates a novel role of GLP-1 RAs in the protection of diabetic retinal vasculature by inhibiting STING-elicited inflammatory signals.展开更多
Objective Obesity is a global health concern with management strategies encompassing bariatric surgery and anti-obesity drugs;however,concerns regarding complexities and side effects persist,driving research for more ...Objective Obesity is a global health concern with management strategies encompassing bariatric surgery and anti-obesity drugs;however,concerns regarding complexities and side effects persist,driving research for more effective,low-risk strategies.The promotion of white adipose tissue(WAT)browning has emerged as a promising approach.Moreover,alisol B 23-acetate(AB23A)has demonstrated efficacy in addressing metabolic disorders,suggesting its potential as a therapeutic agent in obesity management.Therefore,in this study,we aimed to investigate the therapeutic potential of AB23A for mitigating obesity by regulating metabolic phenotypes and lipid distribution in mice fed a high-fat diet(HFD).Methods An obesity mouse model was established by administration of an HFD.Glucose and insulin metabolism were assessed via glucose and insulin tolerance tests.Adipocyte size was determined using hematoxylin and eosin staining.The expression of browning markers in WAT was evaluated using Western blotting and quantitative real-time polymerase chain reaction.Metabolic cage monitoring involved the assessment of various parameters,including food and water intake,energy metabolism,respiratory exchange rates,and physical activity.Moreover,oil red O staining was used to evaluate intracellular lipid accumulation.A bioinformatic analysis tool for identifying the molecular mechanisms of traditional Chinese medicine was used to examine AB23A targets and associated signaling pathways.Results AB23A administration significantly reduced the weight of obese mice,decreased the mass of inguinal WAT,epididymal WAT,and perirenal adipose tissue,improved glucose and insulin metabolism,and reduced adipocyte size.Moreover,treatment with AB23A promoted the expression of browning markers in WAT,enhanced overall energy metabolism in mice,and had no discernible effect on food intake,water consumption,or physical activity.In 3T3-L1 cells,AB23A inhibited lipid accumulation,and both AB23A and rapamycin inhibited the mammalian target of rapamycin-sterol regulatory element-binding protein-1(mTOR-SREBP1)signaling pathway.Furthermore,3-isobutyl-1-methylxanthine,dexamethasone and insulin,at concentrations of 0.25 mmol/L,0.25μmol/L and 1μg/mL,respectively,induced activation of the mTOR-SREBP1 signaling pathway,which was further strengthened by an mTOR activator MHY1485.Notably,MHY1485 reversed the beneficial effects of AB23A in 3T3-L1 cells.Conclusion AB23A promoted WAT browning by inhibiting the mTOR-SREBP1 signaling pathway,offering a potential strategy to prevent obesity.展开更多
基金supported by the National Natural Science Foundation of China(82070593)the Zhejiang Provincial Natural Science Foundation(LD21H030002)+1 种基金the Department of Science and Technology of Zhejiang Province(ZY2019008)the Youth Program of the National Natural Science Foundation of China(82200632).
文摘One-third of patients with autoimmune hepatitis(AIH)have cirrhosis at the time of diagnosis.The relevance of these variables,although unknown,is believed to be critical in AIH because of suspected interactions between the gut microbiome and genetic factors.Dysbiosis of the gut flora and elevated polymeric immunoglobulin receptor(pIgR)levels have been observed in both patients and mouse models.Moreover,there is a direct relationship between pIgR expression and transaminase levels in patients with AIH.In this study,we aimed to explore how pIgR influences the secretion of regenerating islet-derived 3 beta(Reg3b)and the flora composition in AIH using in vivo experiments involving patients with AIH and a concanavalin A-induced mouse model of AIH.Reg3b expression was reduced in pIgR gene(Pigr)-knockout mice compared to that in wild-type mice,leading to increased microbiota disruption.Conversely,exogenous pIgR supplementation increased Reg3b expression and maintained microbiota homeostasis.RNA sequencing revealed the participation of the interleukin(IL)-17 signaling pathway in the regulation of Reg3b through pIgR.Furthermore,the introduction of external pIgR could not restore the imbalance in gut microbiota in AIH,and the decrease in Reg3b expression was not apparent following the inhibition of signal transducer and activator of transcription 3(STAT3).In this study,pIgR facilitated the upregulation of Reg3b via the STAT3 pathway,which plays a crucial role in preserving the balance of the intestinal microbiota in AIH.Through this research,we discovered new molecular targets that can be used for the diagnosis and treatment of AIH.
基金supported in parts by the National Natural Science Foundation of China,Nos.82101501(to QF),and 82201589(to XH)。
文摘Proteolytic cleavage of tau by asparagine endopeptidase(AEP)creates tau-N368 fragments,which may drive the pathophysiology associated with synaptic dysfunction and memory deterioration in the brain of Alzheimer’s disease patients.Nonetheless,the molecular mechanisms of truncated tau-induced cognitive deficits remain unclear.Evidence suggests that signal transduction and activator of transcription-3(STAT3)is associated with modulating synaptic plasticity,cell apoptosis,and cognitive function.Using luciferase reporter assays,electrophoretic mobility shift assays,western blotting,and immunofluorescence,we found that human tau-N368 accumulation inhibited STAT3 activity by suppressing STAT3 translocation into the nucleus.Overexpression of STAT3 improved tau-N368-induced synaptic deficits and reduced neuronal loss,thereby improving the cognitive deficits in tau-N368 mice.Moreover,in tau-N368 mice,activation of STAT3 increased N-methyl-D-aspartic acid receptor levels,decreased Bcl-2 levels,reversed synaptic damage and neuronal loss,and thereby alleviated cognitive deficits caused by tau-N368.Taken together,STAT3 plays a critical role in truncated tau-related neuropathological changes.This indicates a new mechanism behind the effect of tau-N368 on synapses and memory deficits.STAT3 can be used as a new molecular target to treat tau-N368-induced protein pathology.
基金the National Natural Science Foundation of China(32121003),the Sichuan Science and Technology Program(2022ZDZX0012,2022YFQ0026)the Natural Science Foundation of Sichuan province(2022NSFSC1667).
文摘Rice is one of the three most important food crops in the world.Increasing rice yield is an effective way to ensure food security.Grain size is a key factor affecting rice yield;however,the genetic and molecular mechanisms regulating grain size have not been fully investigated.In this study,we identified a rice mutant,wide grain 4-D(wg4-D),that exhibited a significant increase in grain width and a decrease in grain length.Histological analysis demonstrated that WG4 affects cell expansion thereby regulating grain size.MutMap-based gene mapping and complementary transgenic experiments revealed that WG4 encodes an alpha-tubulin,OsTubA1.A SNP mutation in WG4 affected the arrangement of cortical microtubules and caused a wide-grain phenotype.WG4 is located in nuclei and cytoplasm and expressed in various tissues.Our results provide insights into the function of tubulin in rice and identifies novel targets the regulation of grain size in crop breeding.
基金supported by the National Natural Science Foundation of China,Nos.82171429,81771384a grant from Wuxi Municipal Health Commission,No.1286010241190480(all to YS)。
文摘Interferon regulatory factor 7 plays a crucial role in the innate immune response.However,whether interferon regulatory factor 7-mediated signaling contributes to Parkinson's disease remains unknown.Here we report that interferon regulatory factor 7 is markedly up-regulated in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of Parkinson's disease and co-localizes with microglial cells.Both the selective cyclic guanosine monophosphate adenosine monophosphate synthase inhibitor RU.521 and the stimulator of interferon genes inhibitor H151 effectively suppressed interferon regulatory factor 7 activation in BV2 microglia exposed to 1-methyl-4-phenylpyridinium and inhibited transformation of mouse BV2 microglia into the neurotoxic M1 phenotype.In addition,si RNA-mediated knockdown of interferon regulatory factor 7 expression in BV2 microglia reduced the expression of inducible nitric oxide synthase,tumor necrosis factorα,CD16,CD32,and CD86 and increased the expression of the anti-inflammatory markers ARG1 and YM1.Taken together,our findings indicate that the cyclic guanosine monophosphate adenosine monophosphate synthase-stimulator of interferon genes-interferon regulatory factor 7 pathway plays a crucial role in the pathogenesis of Parkinson's disease.
基金Financial support from the National Natural Science Foundation of China (22075320)。
文摘To achieve high energy density in lithium batteries,the construction of lithium-ion/metal hybrid anodes is a promising strategy.In particular,because of the anisotropy of graphite,hybrid anode formed by graphite/Li metal has low transport kinetics and is easy to causes the growth of lithium dendrites and accumulation of dead Li,which seriously affects the cycle life of batteries and even causes safety problems.Here,by comparing graphite with two types of hard carbon,it was found that hybrid anode formed by hard carbon and lithium metal,possessing more disordered mesoporous structure and lithophilic groups,presents better performance.Results indicate that the mesoporous structure provides abundant active site and storage space for dead lithium.With the synergistic effect of this structure and lithophilic functional groups(–COOH),the reversibility of hard carbon/lithium metal hybrid anode is maintained,promoting uniform deposition of lithium metal and alleviating formation of lithium dendrites.The hybrid anode maintains a 99.5%Coulombic efficiency(CE)after 260 cycles at a specific capacity of 500 m Ah/g.This work provides new insights into the hybrid anodes formed by carbon-based materials and lithium metal with high specific energy and fast charging ability.
基金supported by the link project of the National Natural Science Foundation of China(52002052 and 22209020)the Key Research and Development Project of Science and Technology Department of Sichuan Province(2022YFSY0004)+2 种基金the Opening project of the State Key Laboratory of New Textile Materials and Advanced Processing Technology(FZ2021009)the Natural Science Foundation of Sichuan Province(2023NSFSC0995)the Natural Science Foundation of Hunan Province(2022JJ30227)。
文摘The anti-freezing strategy of hydrogels and their self-healing structure are often contradictory,it is vital to break through the molecular structure to design and construct hydrogels with intrinsic anti-freezing/self-healing for meeting the rapid development of flexible and wearable devices in diverse service conditions.Herein,we design a new hydrogel electrolyte(AF/SH-Hydrogel)with intrinsic anti-freezing/self-healing capabilities by introducing ethylene glycol molecules,dynamic chemical bonding(disulfide bond),and supramolecular interaction(multi-hydrogen bond)into the polyacrylamide molecular chain.Thanks to the exceptional freeze resistance(84%capacity retention at-20℃)and intrinsic self-healing capabilities(95%capacity retention after 5 cutting/self-healing cycles),the obtained AF/SH-Hydrogel makes the zinc||manganese dioxide cell an economically feasible battery for the state-of-the-art applications.The Zn||AF/SH-Hydrogel||MnO_(2)device offers a near-theoretical specific capacity of 285 m A h g^(-1)at 0.1 A g^(-1)(Coulombic efficiency≈100%),as well as good self-healing capability and mechanical flexibility in an ice bath.This work provides insight that can be utilized to develop multifunctional hydrogel electrolytes for application in next generation of self-healable and freeze-resistance smart aqueous energy storage devices.
文摘Objective:To explore which pattern recognition receptors(PRRs)play a key role in the development of hand,foot,and mouth disease(HFMD)by analyzing PRR-associated genes.Methods:We conducted a comparative analysis of PRR-associated gene expression in human peripheral blood mononuclear cells(PBMCs)infected with enterovirus 71(EV-A71)which were derived from patients with HFMD of different severities and at different stages.A total of 30 PRR-associated genes were identified as significantly upregulated both over time and across different EV-A71 isolates.Subsequently,ELISA was employed to quantify the expression of the six most prominent genes among these 30 identified genes,specifically,BST2,IRF7,IFI16,TRIM21,MX1,and DDX58.Results:Compared with those at the recovery stage,the expression levels of BST2(P=0.027),IFI16(P=0.016),MX1(P=0.046)and DDX58(P=0.008)in the acute stage of infection were significantly upregulated,while no significant difference in the expression levels of IRF7(P=0.495)and TRIM21(P=0.071)was found between different stages of the disease.The expression levels of BST2,IRF7,IFI16 and MX1 were significantly higher in children infected with single pathogen than those infected with mixed pathogens,and BST2,IRF7,IFI16 and MX1 expression levels were significantly lower in coxsackie B virus(COXB)positive patients than the negative patients.Expression levels of one or more of BST2,IRF7,IFI16,TRIM21,MX1 and DDX58 genes were correlated with PCT levels,various white blood cell counts,and serum antibody levels that reflect disease course of HFMD.Aspartate aminotransferase was correlated with BST2,MX1 and DDX58 expression levels.Conclusions:PRR-associated genes likely initiate the immune response in patients at the acute stage of HFMD.
基金Supported by the Henan Province Medical Science and Technology Research Plan Joint Construction Project,No.LHGJ20210533Xinxiang Science and Technology Research Project,No.GG2020029.
文摘BACKGROUND Primary light chain amyloidosis is a rare and complex disease with complex clinical features and is highly susceptible to misdiagnosis and underdiagnosis in the early stages.CASE SUMMARY We report a case of a 47-year-old female patient whose only initial symptom was periorbital purpura,which was not taken seriously enough.As the disease progressed,pleural effusion gradually appeared,and after systematic diagnosis and treatment,she was diagnosed with“primary light chain amyloidosis”.She achieved rapid hematological remission after treatment with a daratumumab+bortezomib+cyclophosphamide+dexamethasone regimen.CONCLUSION Periorbital purpura can be the only initial symptom of primary light chain amyloidosis;we should pay attention to the cases where the initial clinical symptoms are only periorbital purpura.
文摘Objective:To investigate the clinicopathological characteristics and prognostic factors of early-stage breast cancer patients with indications for breast cancer susceptibility genes 1/2(BRCA1/2)genetic testing in China.Methods:Based on the indication criteria for BRCA genetic testing specified in the National Comprehensive Cancer Network(NCCN)clinical practice guidelines in oncology,genetic/familial high-risk assessment:Breast and ovarian(Version 2.2019),a retrospective analysis was performed on patients with early-stage invasive breast cancer treated at Breast Disease Center,Peking University First Hospital between January 2008 and December 2016.Clinicopathological characteristics of all patients were analyzed,and prognoses were calculated using the KaplanMeier method and a Cox proportionate hazards model.Results:A total of 906 early-stage breast cancer patients who had indications for BRCA genetic testing and had complete clinicopathological data and follow-up information were included in the study group,accounting for34.7%of all breast cancer patients treated in Breast Disease Center,Peking University First Hospital during the study period.Compared with breast cancer patients without indications for BRCA genetic testing,the overall survival(OS)and disease-free survival(DFS)of patients with indications were not significantly different.In the study group,patients with premenopausal status,high T stage,lymph node positive,estrogen receptor(ER)negative,Ki-67>20%and presence of a vascular tumor thrombus had worse prognosis.There were more family histories of gastrointestinal cancer in patients with related indications than in patients without such indications.Conclusions:Single-center data showed that more than 30%of patients with early-stage breast cancer had indications for BRCA genetic testing.There was no prognostic difference in patients with or without indications for BRCA genetic testing.Premenopausal status,high T stage,lymph node positive,ER negative,Ki-67>20%,and presence of a vascular tumor thrombus were associated with poor prognosis.
基金supported by the China Society for Drug Regulation(CSDR)Project:exploration of criteria for post-marketing risk assessment of medications using real-world data(DRM2021008)the Special Clinical Pharmacy Program of Shandong Medical Association(YXH2022ZX004)。
文摘BACKGROUND Butylphthalide(NBP)and edaravone(EDV)injection are common acute ischemic stroke medications in China,but there is a lack of large real-world safety studies on them.This study aimed to determine the incidence of adverse events,detect relevant safety signals,and assess the risk factors associated with these medications in real-world populations.METHODS In this study,data of acute ischemic stroke patients were extracted from the electronic medical record database of six tertiary hospitals between January 2019 and August 2021.Baseline confounders were eliminated using propensity score matching.The drugs’safety was estimated by comparing the results of 24 laboratory tests standards on liver function,kidney function,lipid level,and coagulation function.The drugs’relative risk was estimated by logistic regression.A third group with patients who did not receive NBP or EDV was constructed as a reference.Prescription sequence symmetry analysis was used to evaluate the associations between adverse events and NBP and EDV,respectively.RESULTS 81,292 patients were included in this study.After propensity score matching,the NBP,EDV,and third groups with 727patients in each group.Among the 15 test items,the incidence of adverse events was lower in the NBP group than in the EDV group,and the differences were statistically significant.The multivariate logistic regression equation revealed that NBP injection was not a promoting factor for abnormal laboratory test results,whereas EDV had statistically significant effects on aspartate transaminase,low-density lipoprotein cholesterol and total cholesterol.Prescription sequence symmetry analysis showed that NBP had a weak correlation with abnormal platelet count.EDV had a positive signal associated with abnormal results in gamma-glutamyl transferase,alanine aminotransferase,aspartate aminotransferase,prothrombin time,and platelet count.CONCLUSIONS In a large real-world population,NBP has a lower incidence of adverse events and a better safety profile than EDV or other usual medications.
基金funded by the National Natural Science Foundation of China (C31901702,and 32072175)the China Postdoctoral Science Foundation (2019M653535,2020T130395)+2 种基金the Fundamental Research Funds for the Central Universities of Shaanxi Normal University in China (GK202003083)the grants of Sci-Tech Innovation Team of Shaanxi Province (2019TD-035)the Development Program for Innovative Research Team of Shaanxi Normal University (GK202101006)。
文摘This study aimed to investigate the protective effects of fleshes from two Actinidia chinensis(ACF), pericarps from two A. chinensis(ACP), and fleshes with pericarps from two A. chinensis(ACFP)on high fructose(HF)-instigated dyslipidemia, hepatic steatosis, oxidative stress, insulin resistance, and fatty acid metabolism disorders in rats. In general, the above abnormalities were improved after 10 weeks intervention of ACF, ACP, and ACFP. Especially, ACFP considerably ameliorated HF-induced abnormal changes in body weight gain, serum TC, TG, LDL-C and HDL-C levels, as well as serum and hepatic SFAs, MUFAs and PUFAs contents. ACFP also alleviated HF-induced hyperglycemia and hyperinsulinemia, stabilized HF-caused increase in hepatic MDA and serum ALT, AST levels, and restored HF-declined hepatic T-SOD and GSH-Px activities. Besides, histopathology of the liver further endorsed the protective effects of ACFP on hepatocellular injury. Moreover, ACFP increased HF-dropped acetic, propionic and butyric acid levels. Overall, ACFP employs more efficacious protective effects against HF-induced metabolic disorders and liver damage than ACF and ACP. This study delivers a scientific foundation for developing kiwifruit(counting peel)-based dietary supplements for those with glucolipid-metabolic disorders and liver damage.
基金Project supported by the National Natural Science Foundation of China(Grant Nos.61773091,61603073,61601081,and 61501107)the Natural Science Foundation of Liaoning Province,China(Grant No.201602200)
文摘The emergence of Event-based Social Network(EBSN) data that contain both social and event information has cleared the way to study the social interactive relationship between the virtual interactions and physical interactions. In existing studies, it is not really clear which factors affect event similarity between online friends and the influence degree of each factor. In this study, a multi-layer network based on the Plancast service data is constructed. The the user’s events belongingness is shuffled by constructing two null models to detect offline event similarity between online friends. The results indicate that there is a strong correlation between online social proximity and offline event similarity. The micro-scale structures at multi-levels of the Plancast online social network are also maintained by constructing 0 k–3 k null models to study how the micro-scale characteristics of online networks affect the similarity of offline events. It is found that the assortativity pattern is a significant micro-scale characteristic to maintain offline event similarity. Finally, we study how structural diversity of online friends affects the offline event similarity. We find that the subgraph structure of common friends has no positive impact on event similarity while the number of common friends plays a key role, which is different from other studies. In addition, we discuss the randomness of different null models, which can measure the degree of information availability in privacy protection. Our study not only uncovers the factors that affect offline event similarity between friends but also presents a framework for understanding the pattern of human mobility.
基金supported by a grant from Zhejiang Province Public Welfare Technology Application Research Funding Project(GD22H036691).
文摘To the Editor:Hepatocellular carcinoma(HCC)is a prevalent form of gastrointestinal malignancies.The current combination of immunotherapy and other treatments improves overall survival compared to conventional therapies,but the immunosuppressive microenvironment of HCC is a significant barrier to the efficacy of immunothera-peutic drugs[1].Tumor immune escape is promoted by interactions among immunosuppressive cells,including tumor-associated macrophages,marrow-derived suppressor cells,tumor-associated neutrophils,cancer-associated fibroblasts,and tumor-infiltrating Tregs[2].
基金supported by Intergovernmental International Science and Technology Innovation Cooperation Project(2019YFE0100200)National Natural Science Foundation of China(22179101 and 52172266).
文摘Rechargeable Mg batteries(RMBs)are a promising large-scale energy-storage technology with low cost and high safety,but the performance is limited by the inferior kinetics of Mg-intercalation cathodes.In the present study,an octylamine-supporting interlayer expanded molybdenum diselenide(e-MoSe_(2))is synthesized and used as cathode for RMBs,in comparison with ordinary crystalline MoSe_(2).The octylamine molecules introduced show a strong interaction with the MoSe_(2)layers and increase the layer spacing significantly from 6.46 to 11.5Å.e-MoSe_(2)shows a high Mg-storage capacity of 238 mAh g^(-1)at 50 mA g^(-1)and a superior rate performance of 39 mAh g^(-1)at 10 A g1,far advantageous over crystalline MoSe_(2).e-MoSe_(2)also shows a considerably high structure stability during repeated magnesiation/demagnesiation,providing an outstanding cycling stability for 1000 cycles.Further electrochemical tests demonstrate the high Mg^(2+)diffusion coefficients in e-MoSe_(2).Theoretical computation indicates the interlayer expansion changes the Mg^(2+)diffusion paths from"hollow site→hollow site"to"hollow site→Se atom site→hollow site",largely decreasing the energy barrier and improving the Mg^(2+)diffusion kinetics.The present work highlights an efficient strategy for the improvement of Mg-storage performance for RMB cathodes.
文摘BACKGROUND Pancreatic cavernous hemangioma(pCH)is a rare type of benign vascular tumor.Making the right diagnosis is challenging due to low clinical suspicion and the lack of existing cross-sectional imaging tools to distinguish it from other pancreatic lesions.CASE SUMMARY We describe a male patient,age 18,who presented with a pCH.Computed tomography,magnetic resonance imaging,and ultrasound showed cystic space in the tail of the pancreas.A dark spot sign on the T2 weighted image sequence was observed.Clinically,a mucinous cystic neoplasm with hemorrhage was suspected preoperatively by combining imaging,and the operative indication was clear.The patient underwent a distal pancreatic tumor resection under laparoscopic control.Immunohistochemical staining for CD31 and CD34 was positive;D2-40 was positive in interstitial lymphatic vessels and negative in vascular epithelial cells;and calcium-binding protein was negative.The results support the diagnosis of pCH combined with chronic intracapsular spontaneous hemorrhage.No complications or recurrences were observed during the follow-up period.CONCLUSION Chronic spontaneous hemorrhage may occur in pCH,which may greatly influence the accuracy of diagnosis using imaging modalities.Surgical resection for uncertain pCH seems reasonable with a good outcome.
基金supported by grants from the National Natural Science Foundation of China(82000782,82270886,82070811)the Foster Program for NSFC at the Third Affiliated Hospital of Sun Yat-Sen University(2020G2RPYQN11,China)+3 种基金China International Medical Foundation(2018-N-01)the Science and Technology Plan Project of Guangzhou City(2024A03J0002,China)Key Area R&D Program of Guangdong Province(2019B020227003,China)Sci-Tech Research Development Program of Guangzhou City(202201020589,China).
文摘Glucagon-like peptide-1 receptor agonists(GLP-1 RAs)protect against diabetic cardiovascular diseases and nephropathy.However,their activity in diabetic retinopathy(DR)remains unclear.Our retrospective cohort study involving 1626 T2DM patients revealed superior efficacy of GLP-1 RAs in controlling DR compared to other glucose-lowering medications,suggesting their advantage in DR treatment.By single-cell RNA-sequencing analysis and immunostaining,we observed a high expression of GLP-1R in retinal endothelial cells,which was down-regulated under diabetic conditions.Treatment of GLP-1 RAs significantly restored the receptor expression,resulting in an improvement in retinal degeneration,vascular tortuosity,avascular vessels,and vascular integrity in diabetic mice.GO and GSEA analyses further implicated enhanced mitochondrial gene translation and mitochondrial functions by GLP-1 RAs.Additionally,the treatment attenuated STING signaling activation in retinal endothelial cells,which is typically activated by leaked mitochondrial DNA.Expression of STING mRNA was positively correlated to the levels of angiogenic and inflammatory factors in the endothelial cells of human fibrovascular membranes.Further investigation revealed that the cAMP-responsive element binding protein played a role in the GLP-1R signaling pathway on suppression of STING signaling.This study demonstrates a novel role of GLP-1 RAs in the protection of diabetic retinal vasculature by inhibiting STING-elicited inflammatory signals.
基金supported by Shandong Provincial Natural Science Foundation General Program(No.ZR2022MH213)Shandong Provincial Traditional Chinese Medicine Science and Technology Project General Program(No.M2023241)+1 种基金Jinan Clinical Medical Science and Technology Innovation Program(No.202328013)Qinghai Province High-end Innovative Talents Thousand Talents Program.
文摘Objective Obesity is a global health concern with management strategies encompassing bariatric surgery and anti-obesity drugs;however,concerns regarding complexities and side effects persist,driving research for more effective,low-risk strategies.The promotion of white adipose tissue(WAT)browning has emerged as a promising approach.Moreover,alisol B 23-acetate(AB23A)has demonstrated efficacy in addressing metabolic disorders,suggesting its potential as a therapeutic agent in obesity management.Therefore,in this study,we aimed to investigate the therapeutic potential of AB23A for mitigating obesity by regulating metabolic phenotypes and lipid distribution in mice fed a high-fat diet(HFD).Methods An obesity mouse model was established by administration of an HFD.Glucose and insulin metabolism were assessed via glucose and insulin tolerance tests.Adipocyte size was determined using hematoxylin and eosin staining.The expression of browning markers in WAT was evaluated using Western blotting and quantitative real-time polymerase chain reaction.Metabolic cage monitoring involved the assessment of various parameters,including food and water intake,energy metabolism,respiratory exchange rates,and physical activity.Moreover,oil red O staining was used to evaluate intracellular lipid accumulation.A bioinformatic analysis tool for identifying the molecular mechanisms of traditional Chinese medicine was used to examine AB23A targets and associated signaling pathways.Results AB23A administration significantly reduced the weight of obese mice,decreased the mass of inguinal WAT,epididymal WAT,and perirenal adipose tissue,improved glucose and insulin metabolism,and reduced adipocyte size.Moreover,treatment with AB23A promoted the expression of browning markers in WAT,enhanced overall energy metabolism in mice,and had no discernible effect on food intake,water consumption,or physical activity.In 3T3-L1 cells,AB23A inhibited lipid accumulation,and both AB23A and rapamycin inhibited the mammalian target of rapamycin-sterol regulatory element-binding protein-1(mTOR-SREBP1)signaling pathway.Furthermore,3-isobutyl-1-methylxanthine,dexamethasone and insulin,at concentrations of 0.25 mmol/L,0.25μmol/L and 1μg/mL,respectively,induced activation of the mTOR-SREBP1 signaling pathway,which was further strengthened by an mTOR activator MHY1485.Notably,MHY1485 reversed the beneficial effects of AB23A in 3T3-L1 cells.Conclusion AB23A promoted WAT browning by inhibiting the mTOR-SREBP1 signaling pathway,offering a potential strategy to prevent obesity.
