Throughout the globe,diabetes mellitus(DM) is increasing in incidence with limited therapies presently available to prevent or resolve the significant complications of this disorder.DM impacts multiple organs and affe...Throughout the globe,diabetes mellitus(DM) is increasing in incidence with limited therapies presently available to prevent or resolve the significant complications of this disorder.DM impacts multiple organs and affects all components of the central and peripheral nervous systems that can range from dementia to diabetic neuropathy.The mechanistic target of rapamycin(m TOR) is a promising agent for the development of novel regenerative strategies for the treatment of DM.m TOR and its related signaling pathways impact multiple metabolic parameters that include cellular metabolic homeostasis,insulin resistance,insulin secretion,stem cell proliferation and differentiation,pancreatic β-cell function,and programmed cell death with apoptosis and autophagy.m TOR is central element for the protein complexes m TOR Complex 1(m TORC1) and m TOR Complex 2(m TORC2) and is a critical component for a number of signaling pathways that involve phosphoinositide 3-kinase(PI 3-K),protein kinase B(Akt),AMP activated protein kinase(AMPK),silent mating type information regulation 2 homolog 1(Saccharomyces cerevisiae)(SIRT1),Wnt1 inducible signaling pathway protein 1(WISP1),and growth factors.As a result,m TOR represents an exciting target to offer new clinical avenues for the treatment of DM and the complications of this disease.Future studies directed to elucidate the delicate balance m TOR holds over cellular metabolism and the impact of its broad signaling pathways should foster the translation of these targets into effective clinical regimens for DM.展开更多
Gastric cancer,a prevalent malignancy worldwide,ranks sixth in terms of frequency and third in fatality,causing over a million new cases and 769000 annual deaths.Predominant in Eastern Europe and Eastern Asia,risk fac...Gastric cancer,a prevalent malignancy worldwide,ranks sixth in terms of frequency and third in fatality,causing over a million new cases and 769000 annual deaths.Predominant in Eastern Europe and Eastern Asia,risk factors include family medical history,dietary habits,tobacco use,Helicobacter pylori,and Epstein-Barr virus infections.Unfortunately,gastric cancer is often diagnosed at an advanced stage,leading to a grim prognosis,with a 5-year overall survival rate below 5%.Surgical intervention,particularly with D2 Lymphadenectomy,is the mainstay for early-stage cases but offers limited success.For advanced cases,the National Comprehensive Cancer Network recommends chemotherapy,radiation,and targeted therapy.Emerging immunotherapy presents promise,especially for unresectable or metastatic cases,with strategies like immune checkpoint inhibitors,tumor vaccines,adoptive immunotherapy,and nonspecific immunomodulators.In this Editorial,with regards to the article“Advances and key focus areas in gastric cancer immunotherapy:A comprehensive scientometric and clinical trial review”,we address the advances in the field of immunotherapy in gastric cancer and its future prospects.展开更多
To determine the prevalence of metabolic syndrome (MetS) in Malaysian type 2 diabetic patients using WHO, NCEP ATP III, IDF and the new Harmonized definitions, and the concordance between these definitions. This study...To determine the prevalence of metabolic syndrome (MetS) in Malaysian type 2 diabetic patients using WHO, NCEP ATP III, IDF and the new Harmonized definitions, and the concordance between these definitions. This study involved 313 patients diagnosed with type 2 diabetes mellitus (T2DM) at two Malaysian tertiary hospitals. Socio-demographic data were assessed using a pre-tested interviewer-administered structured questionnaire. Anthropometric measurements were carried out according to standard protocols. Clinical and laboratory characteristics were examined. Kappa (k) statistics were used for the agreement between the four MetS definitions. The overall prevalence rates of MetS (95% CI) were 95.8% (93.6-98.1), 96.1% (94.0-98.3), 84.8% (80.8-88.9) and 97.7% (96.1-99.4) according to the WHO, NCEP ATP III, IDF and the Harmonized definitions, respectively. The Kappa statistics demonstrated a slight to substantial agreement between the definitions (k = 0.179-0.875, p k = 0.875, p hest specificity (100%) in identifying MetS. In conclusion, the new Harmonized criteria established the highest prevalence of MetS among the four definitions applied. There was a very good concordance between the WHO and NCEP ATP III criteria. The extremely high prevalence of MetS observed in type 2 diabetic patients indicates an impending pandemic of CVD risk in Malaysia. Aggressive treatment of MetS components is required to reduce cardiovascular risk in T2DM.展开更多
Acute care management of traumatic brain injury is focused on the prevention and reduction of secondary insults such as hypotension,hypoxia,intracranial hypertension,and detrimental inflammation.However,the imperative...Acute care management of traumatic brain injury is focused on the prevention and reduction of secondary insults such as hypotension,hypoxia,intracranial hypertension,and detrimental inflammation.However,the imperative to balance multiple clinical concerns simultaneously often results in therapeutic strategies targeted to address one clinical concern causing unintended effects in other remote organ systems.Recently the bidirectional communication between the gastrointestinal tract and the brain has been shown to influence both the central nervous system and gastrointestinal tract homeostasis in health and disease.A critical component of this axis is the microorganisms of the gut known as the gut microbiome.Changes in gut microbial populations in the setting of central nervous system disease,including traumatic brain injury,have been reported in both humans and experimental animal models and can be further disrupted by off-target effects of patient care.In this review article,we will explore the important role gut microbial populations play in regulating brain-resident and peripheral immune cell responses after traumatic brain injury.We will discuss the role of bacterial metabolites in gut microbial regulation of neuroinflammation and their potential as an avenue for therapeutic intervention in the setting of traumatic brain injury.展开更多
Mitochondrial dysfunction is a significant pathological alte ration that occurs in Parkinson's disease(PD),and the Thr61lle(T61I)mutation in coiled-coil helix coiled-coil helix domain containing 2(CHCHD2),a crucia...Mitochondrial dysfunction is a significant pathological alte ration that occurs in Parkinson's disease(PD),and the Thr61lle(T61I)mutation in coiled-coil helix coiled-coil helix domain containing 2(CHCHD2),a crucial mitochondrial protein,has been reported to cause Parkinson's disease.FIFO-ATPase participates in the synthesis of cellular adenosine triphosphate(ATP)and plays a central role in mitochondrial energy metabolism.However,the specific roles of wild-type(WT)CHCHD2 and T611-mutant CHCHD2 in regulating F1FO-ATPase activity in Parkinson's disease,as well as whether CHCHD2 or CHCHD2 T61I affects mitochondrial function through regulating F1FO-ATPase activity,remain unclea r.Therefore,in this study,we expressed WT CHCHD2 and T61l-mutant CHCHD2 in an MPP^(+)-induced SH-SY5Y cell model of PD.We found that CHCHD2 protected mitochondria from developing MPP^(+)-induced dysfunction.Under normal conditions,ove rexpression of WT CHCHD2 promoted F1FO-ATPase assembly,while T61I-mutant CHCHD2 appeared to have lost the ability to regulate F1FO-ATPase assembly.In addition,mass spectrometry and immunoprecipitation showed that there was an interaction between CHCHD2 and F1FO-ATPase.Three weeks after transfection with AAV-CHCHD2 T61I,we intraperitoneally injected 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine into mice to establish an animal model of chronic Parkinson's disease and found that exogenous expression of the mutant protein worsened the behavioral deficits and dopaminergic neurodegeneration seen in this model.These findings suggest that WT CHCHD2 can alleviate mitochondrial dysfunction in PD by maintaining F1F0-ATPase structure and function.展开更多
Pancreatic cancer is the third leading cause of cancer mortality in both men and women in the United States,with poor response to current standard of care,short progression-free and overall survival.Immunotherapies th...Pancreatic cancer is the third leading cause of cancer mortality in both men and women in the United States,with poor response to current standard of care,short progression-free and overall survival.Immunotherapies that target cytotoxic T lymphocyte antigen-4,programmed cell death protein-1,and programmed death-ligand 1 checkpoints have shown remarkable activities in several cancers such as melanoma,renal cell carcinoma,and nonsmall cell lung cancer due to high numbers of somatic mutations,combined with cytotoxic T-cell responses.However,single checkpoint blockade was ineffective in pancreatic cancer,highlighting the challenges including the poor antigenicity,a dense desmoplastic stroma,and a largely immunosuppressive microenvironment.In this review,we will summarize available clinical results and ongoing efforts of combining immune checkpoint therapies with other treatment modalities such as chemotherapy,radiotherapy,and targeted therapy.These combination therapies hold promise in unleashing the potential of immunotherapy in pancreatic cancer to achieve better and more durable clinical responses by enhancing cytotoxic T-cell responses.展开更多
The snow cover over the Taurus Mountains affects water supply, agriculture, and hydropower generation in the region. In this study, we analyzed the monthly Snow Cover Extent(SCE) from November to April in the Central ...The snow cover over the Taurus Mountains affects water supply, agriculture, and hydropower generation in the region. In this study, we analyzed the monthly Snow Cover Extent(SCE) from November to April in the Central Taurus Mountains(Bolkar, Aladaglar, Tahtali and Binboga Mountains) from 1981 to 2021. Linear trends of snow cover season(November to April) over the last 41 years showed decreases in SCE primarily at lower elevations. The downward trend in SCE was found to be more pronounced and statistically significant for only November and March. SCE in the Central Taurus Mountains has declined about-6.3% per decade for 2500-3000 m in November and about-6.0% per decade for 1000-1500 m and 3000+ m in March over the last 41 years. The loss of SCE has become evident since the 2000s, and the lowest negative anomalies in SCE have been observed in 2014, 2001, and 2007 in the last 41 years, which are consistent with an increase in air temperature and decreased precipitation. SCE was correlated with both mean temperature and precipitation, with temperature having a greater relative importance at all elevated gradients. Results showed that there is a strong linear relationship between SCE and the mean air temperature(r =-0.80) and precipitation(r = 0.44) for all elevated gradients during the snow season. The Arctic Oscillation(AO), the North Atlantic Oscillation(NAO), and the Mediterranean Oscillation(MO) winter indices were used to explain the year-to-year variability in SCE over the Central Taurus Mountains. The results showed that the inter-annual variability observed in the winter SCE on the Central Taurus Mountains was positively correlated with the phases of the winter AO, NAO and MO, especially below 2000 m elevation.展开更多
目的以雌性和雄性非肥胖糖尿病(nonobese diabetic,NOD)小鼠以及健康对照癌症研究所(institute for cancer research,ICR)小鼠为研究对象,比较分析初始、效应、记忆、耗竭以及调节性CD8^(+)T细胞分化亚群差异,探讨1型糖尿病(type 1 diab...目的以雌性和雄性非肥胖糖尿病(nonobese diabetic,NOD)小鼠以及健康对照癌症研究所(institute for cancer research,ICR)小鼠为研究对象,比较分析初始、效应、记忆、耗竭以及调节性CD8^(+)T细胞分化亚群差异,探讨1型糖尿病(type 1 diabetes,T1D)背景下的性别因素对CD8^(+)T细胞分化命运的影响。方法采用流式细胞术检测雌雄NOD小鼠脾脏、胰腺引流淋巴结(pancreatic draining lymph nodes,pLN)、胰腺浸润淋巴细胞(pancreas-infiltrating lymphocytes,PIL)、初始T细胞(naive T cells,T_(N))、中枢记忆T细胞(central memory T cells,T_(CM))、效应T细胞(effector T cells,T_(EFF))、效应前体样T细胞(effector precursor T cells,T_(EP))、耗竭T细胞(exhausted T cells,T_(EX))、耗竭前体T细胞(precursor exhausted T cells,T_(PEX))以及调节性T细胞(regulatory T cells,Tregs)等CD8^(+)T细胞分化亚群的频率和表型差异。结果与雄性NOD小鼠比较,雌性NOD小鼠pLN及PIL中IFN-γ^(+)、CD107a^(+)和CCL5^(+)CD8^(+)T_(EFF)频率显著升高(P<0.01,P<0.05,P<0.05),同时脾脏中CD8^(+)T_(N)、CD8^(+)T_(CM)、CD8^(+)T_(EX)、CD8^(+)T_(PEX)和CD122^(+)CD8^(+)Tregs亚群的频率均显著降低(P<0.01,P<0.01,P<0.01,P<0.01,P<0.001);而雌性和雄性ICR小鼠体内除CD122^(+)CD8^(+)Tregs差异变化与NOD小鼠一致(P<0.05),其余上述各CD8^(+)T细胞分化亚群无显著差异。结论雄激素可能通过抑制记忆T细胞向效应T细胞分化,同时促进效应T细胞功能耗竭,导致雌雄发病率差异。展开更多
Type 1 diabetes mellitus(T1DM) lacks insulin secretion due to autoimmune deficiency of pancreaticβ-cells.Protecting pancreatic islets and enhancing insulin secretion has been therapeutic approaches.Mannogalactoglucan...Type 1 diabetes mellitus(T1DM) lacks insulin secretion due to autoimmune deficiency of pancreaticβ-cells.Protecting pancreatic islets and enhancing insulin secretion has been therapeutic approaches.Mannogalactoglucan is the main type of polysaccharide from natural mushroom,which has potential medicinal prospects.Nevertheless,the antidiabetic property of mannogalactoglucan in T1DM has not been fully elucidated.In this study,we obtained the neutral fraction of alkali-soluble Armillaria mellea polysaccharide(AAMP-N) with the structure of mannogalactoglucan from the fruiting body of A.mellea and investigated the potential therapeutic value of AAMP-N in T1DM.We demonstrated that AAMP-N lowered blood glucose and improved diabetes symptoms in T1DM mice.AAMP-N activated unfolded protein response(UPR) signaling pathway to maintain ER protein folding homeostasis and promote insulin secretion in vivo.Besides that,AAMP-N promoted insulin synthesis via upregulating the expression of transcription factors,increased Ca^(2+) signals to stimulate intracellular insulin secretory vesicle transport via activating calcium/calmodulin-dependent kinase Ⅱ(CamkⅡ) and cAMP/PKA signals,and enhanced insulin secretory vesicle fusion with the plasma membrane via vesicle-associated membrane protein 2(VAMP2).Collectively,these studies demonstrated that the therapeutic potential of AAMP-N on pancreatic islets function,indicating that mannogalactoglucan could be natural nutraceutical used for the treatment of T1DM.展开更多
Tumor immunity proceeds through multiple processes, which consist of antigen presentation by antigen presenting cells(APCs) to educate effector cells and destruction by the effector cytotoxic cells. However, tumor imm...Tumor immunity proceeds through multiple processes, which consist of antigen presentation by antigen presenting cells(APCs) to educate effector cells and destruction by the effector cytotoxic cells. However, tumor immunity is frequently repressed at tumor sites. Malignantly transformed cells rarely survive the attack by the immune system, but cells that do survive change their phenotypes to reduce their immunogenicity. The resultant cells evade the attack by the immune system and form clinically discernible tumors. Tumor microenvironments simultaneously contain a wide variety of immune suppressive molecules and cells to dampen tumor immunity. Moreover, the liver microenvironment exhibits immune tolerance to reduce aberrant immune responses to massively-exposed antigens via the portal vein, and immune dysfunction is frequently associated with liver cirrhosis, which is widespread in hepatocellular carcinoma(HCC) patients. Immune therapy aims to reduce tumor burden, but it is also expected to prevent non-cancerous liver lesions from progressing to HCC, because HCC develops or recurs from noncancerous liver lesions with chronic inflammatory states and/or cirrhosis and these lesions cannot be cured and/or eradicated by local and/or systemic therapies. Nevertheless, cancer immune therapy should augment specific tumor immunity by using two distinct measures: enhancing the effector cell functions such as antigen presentation capacity of APCs and tumor cell killing capacity of cytotoxic cells, and reactivating the immune system in immune-suppressive tumor microenvironments. Here, we will summarize the current status and discuss the future perspective on immune therapy for HCC.展开更多
Milk fat globule membrane(MFGM),which contains abundant glycoproteins and phospholipids,exerts beneficial effects on intestinal health and immunomodulation.The aim of this study was to evaluate the protective effects ...Milk fat globule membrane(MFGM),which contains abundant glycoproteins and phospholipids,exerts beneficial effects on intestinal health and immunomodulation.The aim of this study was to evaluate the protective effects and possible underlying mechanisms of MFGM on cow’s milk allergy(CMA)in aβ-lactoglobulin(BLG)-induced allergic mice model.MFGM was supplemented to allergic mice induced by BLG at a dose of 400 mg/kg body weight.Results demonstrated that MFGM alleviated food allergy symptoms,decreased serum levels of lipopolysaccharide,pro-inflammatory cytokines,immunoglobulin(Ig)E,Ig G1,and Th2 cytokines including interleukin(IL)-4,while increased serum levels of Th1 cytokines including interferon-γand regulatory T cells(Tregs)cytokines including IL-10 and transforming growth factor-β.MFGM modulated gut microbiota and enhanced intestinal barrier of BLG-allergic mice,as evidenced by decreased relative abundance of Desulfobacterota,Rikenellaceae,Lachnospiraceae,and Desulfovibrionaceae,while increased relative abundance of Bacteroidetes,Lactobacillaceae and Muribaculaceae,and enhanced expressions of tight junction proteins including Occludin,Claudin-1 and zonula occludens-1.Furthermore,MFGM increased fecal short-chain fatty acids(SCFAs)levels,which elevated G protein-coupled receptor(GPR)43 and GPR109A expressions.The increased expressions of GPR43 and GPR109A induced CD103+dendritic cells accumulation and promoted Tregs differentiation in mesenteric lymph node to a certain extent.In summary,MFGM alleviated CMA in a BLG-induced allergic mice model through enhancing intestinal barrier and promoting Tregs differentiation,which may be correlated with SCFAs-mediated activation of GPRs.These findings suggest that MFGM may be useful as a promising functional ingredient against CMA.展开更多
According to clinical statistics,the mortality of patients with early brainstem hemorrhage is high.In this study,we established rat models of brainstem hemorrhage by injecting type Ⅶ collagenase into the right basote...According to clinical statistics,the mortality of patients with early brainstem hemorrhage is high.In this study,we established rat models of brainstem hemorrhage by injecting type Ⅶ collagenase into the right basotegmental pontine and investigated the pathological changes of early brainstem hemorrhage using multi-sequence magnetic resonance imaging and histopathological methods.We found that brainstem hematoma gradually formed in the injured rats over the first 3 days and then reduced after 7 days.The edema that occurred was mainly of the vasogenic type.No complete myelin sheath structure was found around the focus of the brainstem hemorrhage.The integrity and continuity of nerve fibers gradually deteriorated over the first 7 days.Neuronal degeneration was mild in the first 3 days and then obviously aggravated on the 7^(th)day.Inflammatory cytokines,interleukin-1β,and tumor necrosis factorαappeared on the 1st day after intracerebral hemorrhage,reached peak levels on the 3^(rd)day,and decreased from the 7^(th)day.Our findings show the characteristics of the progression of early brainstem hemorrhage.展开更多
As the average age of the world population increases,more people will face debilitating aging-associated conditions,including dementia and stroke.Not only does the incidence of these conditions increase with age,but t...As the average age of the world population increases,more people will face debilitating aging-associated conditions,including dementia and stroke.Not only does the incidence of these conditions increase with age,but the recovery afterward is often worse in older patients.Researchers and health professionals must unveil and understand the factors behind age-associated diseases to develop a therapy for older patients.Aging causes profound changes in the immune system including the activation of microglia in the brain.Activated microglia promote T lymphocyte transmigration leading to an increase in neuroinflammation,white matter damage,and cognitive impairment in both older humans and rodents.The presence of T and B lymphocytes is observed in the aged brain and correlates with worse stroke outcomes.Preclinical strategies in stroke target either microglia or the lymphocytes or the communications between them to promote functional recovery in aged subjects.In this review,we examine the role of the microglia and T and B lymphocytes in aging and how they contribute to cognitive impairment.Additionally,we provide an important update on the contribution of these cells and their interactions in preclinical aged stroke.展开更多
Rejection is one of the key factors that determine the long-term allograft function and survival in renal transplant patients. Reliable and timely diagnosis is important to treat rejection as early as possible. Allogr...Rejection is one of the key factors that determine the long-term allograft function and survival in renal transplant patients. Reliable and timely diagnosis is important to treat rejection as early as possible. Allograft biopsies are not suitable for continuous monitoring of rejection. Thus, there is an unmet need for non-invasive methods to diagnose acute and chronic rejection. Proteomics in urine and blood samples has been explored for this purpose in 29 studies conducted since 2003. This review describes the different proteomic approaches and summarizes the results from the studies that examined proteomics for the rejection diagnoses. The potential limitations and open questions in establishing proteomic markers for rejection are discussed, including ongoing trials and future challenges to this topic.展开更多
Our knowledge of renal cell carcinoma(RCC) is rapidly expanding. For those who diagnose and treat RCC, it is important to understand the new developments. In recent years, many new renal tumors have been described and...Our knowledge of renal cell carcinoma(RCC) is rapidly expanding. For those who diagnose and treat RCC, it is important to understand the new developments. In recent years, many new renal tumors have been described and defined, and our understanding of the biology and clinical correlates of these tumors is changing. Evolving concepts in Xp11 translocation carcinoma, mucinous tubular and spindle cell carcinoma, multilocular cystic clear cell RCC, and carcinoma associated with neuroblastoma are addressed within this review. Tubulocystic carcinoma, thyroid-like follicular carcinoma of kidney, acquired cystic disease-associated RCC, and clear cell papillary RCC are also described. Finally, candidate entities, including RCC with t(6;11) translocation, hybrid oncocytoma/chromophobe RCC, hereditary leiomyomatosis and RCC syndrome, and renal angiomyoadenomatous tumor are reviewed. Knowledge of these new entities is important for diagnosis, treatment and subsequent prognosis. This review provides a targeted summary of new developments in RCC.展开更多
Shale gas is an important component of unconventional oil and gas resources.Studying the imbibition behavior is helpful to optimize flowback parameters and enhance gas recovery.Recent imbibition studies have focused o...Shale gas is an important component of unconventional oil and gas resources.Studying the imbibition behavior is helpful to optimize flowback parameters and enhance gas recovery.Recent imbibition studies have focused on shale matrix,and the pressure conditions discussed were mostly atmospheric.The initial imbibition behavior begins from propped fractures to matrix,but there are few studies working on explaining the imbibition behavior in propped fractures or the phenomenon of many shale wells exhibit higher productivity after a“soaking”period.Therefore,propped fracture samples were designed for imbibition and migration experiments.In order to accurately study the mechanism and main influencing factors of fracturing fluid imbibition and migration in propped and unpropped shale fractures under high temperature and high pressure,a series of experiments based on nuclear magnetic resonance(NMR)were carried out.Results showed that NMR T2 spectra of all samples exhibited a bimodal distribution.The final imbibition volume of fracturing fluid was positively related to pressure and fracture width.The imbibition effect of fracturing fluid was more evident in matrix pores under high pressure.In the migration during soaking stage,the fracturing fluid gradually migrated from large pores to small pores and gradually displaced the shale gas from the matrix,thus allowing the water blocking in propped fractures to self-unlock to some extent.Gas permeability decreased in the imbibition stage,while it recovered in the migration stage to some extent.展开更多
transcription and expression,and its potential biological mechanisms.Methods Differentially expressed genes related to Hg exposure were identified and validated using gene expression microarray analysis and extended v...transcription and expression,and its potential biological mechanisms.Methods Differentially expressed genes related to Hg exposure were identified and validated using gene expression microarray analysis and extended validation.Hg-exposed cell models and PTEN lowexpression models were established in vitro using 293T cells.PTEN gene expression was assessed using qRT-PCR,and Western blotting was used to measure PTEN,AKT,and PI3K protein levels.IL-6 expression was determined by ELISA.Results Combined findings from gene expression microarray analysis,bioinformatics,and population expansion validation indicated significant downregulation of the PTEN gene in the high-concentration Hg exposure group.In the Hg-exposed cell model(25 and 10μmol/L),a significant decrease in PTEN expression was observed,accompanied by a significant increase in PI3K,AKT,and IL-6 expression.Similarly,a low-expression cell model demonstrated that PTEN gene knockdown led to a significant decrease in PTEN protein expression and a substantial increase in PI3K,AKT,and IL-6 levels.Conclusion This is the first study to report that Hg exposure downregulates the PTEN gene,activates the PI3K/AKT regulatory pathway,and increases the expression of inflammatory factors,ultimately resulting in kidney inflammation.展开更多
In 2023,two consecutive earthquakes exceeding a magnitude of 7 occurred in Türkiye,causing severe casualties and economic losses.The damage to critical urban infrastructure and building structures,including highw...In 2023,two consecutive earthquakes exceeding a magnitude of 7 occurred in Türkiye,causing severe casualties and economic losses.The damage to critical urban infrastructure and building structures,including highways,railroads,and water supply pipelines,was particularly severe in areas where these structures intersected the seismogenic fault.Critical infrastructure projects that traverse active faults are susceptible to the influence of fault movement,pulse velocity,and ground motions.In this study,we used a unique approach to analyze the acceleration records obtained from the seismic station array(9 strong ground motion stations)located along the East Anatolian Fault(the seismogenic fault of the MW7.8 mainshock of the 2023 Türkiye earthquake doublet).The acceleration records were filtered and integrated to obtain the velocity and displacement time histories.We used the results of an on-site investigation,jointly conducted by China Earthquake Administration and Türkiye’s AFAD,to analyze the distribution of PGA,PGV,and PGD recorded by the strong motion array of the East Anatolian Fault.We found that the maximum horizontal PGA in this earthquake was 3.0 g,and the maximum co-seismic surface displacement caused by the East Anatolian Fault rupture was 6.50 m.As the fault rupture propagated southwest,the velocity pulse caused by the directional effect of the rupture increased gradually,with the maximum PGA reaching 162.3 cm/s.We also discussed the seismic safety of critical infrastructure projects traversing active faults,using two case studies of water supply pipelines in Türkiye that were damaged by earthquakes.We used a three-dimensional finite element model of the PE(polyethylene)water pipeline at the Islahiye State Hospital and fault displacement observations obtained through on-site investigation to analyze pipeline failure mechanisms.We further investigated the effect of the fault-crossing angle on seismic safety of a pipeline,based on our analysis and the failure performance of the large-diameter Thames Water pipeline during the 1999 Kocaeli earthquake.The seismic method of buried pipelines crossing the fault was summarized.展开更多
This study aims to discuss anisotropic solutions that are spherically symmetric in the quintessence field,which describe compact stellar objects in the modified Rastall teleparallel theory of gravity.To achieve this g...This study aims to discuss anisotropic solutions that are spherically symmetric in the quintessence field,which describe compact stellar objects in the modified Rastall teleparallel theory of gravity.To achieve this goal,the Krori and Barua arrangement for spherically symmetric components of the line element is incorporated.We explore the field equations by selecting appropriate off-diagonal tetrad fields.Born-Infeld function of torsion f(T)=β√λT+1-1 and power law form h(T)=δTn are used.The Born-Infeld gravity was the first modified teleparallel gravity to discuss inflation.We use the linear equation of state pr=ξρto separate the quintessence density.After obtaining the field equations,we investigate different physical parameters that demonstrate the stability and physical acceptability of the stellar models.We use observational data,such as the mass and radius of the compact star candidates PSRJ 1416-2230,Cen X-3,&4U 1820-30,to ensure the physical plausibility of our findings.展开更多
基金supported by American Diabetes Association,American Heart Association,NIH NIEHS,NIH NIA,NIH NINDS,and NIH ARRA
文摘Throughout the globe,diabetes mellitus(DM) is increasing in incidence with limited therapies presently available to prevent or resolve the significant complications of this disorder.DM impacts multiple organs and affects all components of the central and peripheral nervous systems that can range from dementia to diabetic neuropathy.The mechanistic target of rapamycin(m TOR) is a promising agent for the development of novel regenerative strategies for the treatment of DM.m TOR and its related signaling pathways impact multiple metabolic parameters that include cellular metabolic homeostasis,insulin resistance,insulin secretion,stem cell proliferation and differentiation,pancreatic β-cell function,and programmed cell death with apoptosis and autophagy.m TOR is central element for the protein complexes m TOR Complex 1(m TORC1) and m TOR Complex 2(m TORC2) and is a critical component for a number of signaling pathways that involve phosphoinositide 3-kinase(PI 3-K),protein kinase B(Akt),AMP activated protein kinase(AMPK),silent mating type information regulation 2 homolog 1(Saccharomyces cerevisiae)(SIRT1),Wnt1 inducible signaling pathway protein 1(WISP1),and growth factors.As a result,m TOR represents an exciting target to offer new clinical avenues for the treatment of DM and the complications of this disease.Future studies directed to elucidate the delicate balance m TOR holds over cellular metabolism and the impact of its broad signaling pathways should foster the translation of these targets into effective clinical regimens for DM.
文摘Gastric cancer,a prevalent malignancy worldwide,ranks sixth in terms of frequency and third in fatality,causing over a million new cases and 769000 annual deaths.Predominant in Eastern Europe and Eastern Asia,risk factors include family medical history,dietary habits,tobacco use,Helicobacter pylori,and Epstein-Barr virus infections.Unfortunately,gastric cancer is often diagnosed at an advanced stage,leading to a grim prognosis,with a 5-year overall survival rate below 5%.Surgical intervention,particularly with D2 Lymphadenectomy,is the mainstay for early-stage cases but offers limited success.For advanced cases,the National Comprehensive Cancer Network recommends chemotherapy,radiation,and targeted therapy.Emerging immunotherapy presents promise,especially for unresectable or metastatic cases,with strategies like immune checkpoint inhibitors,tumor vaccines,adoptive immunotherapy,and nonspecific immunomodulators.In this Editorial,with regards to the article“Advances and key focus areas in gastric cancer immunotherapy:A comprehensive scientometric and clinical trial review”,we address the advances in the field of immunotherapy in gastric cancer and its future prospects.
文摘To determine the prevalence of metabolic syndrome (MetS) in Malaysian type 2 diabetic patients using WHO, NCEP ATP III, IDF and the new Harmonized definitions, and the concordance between these definitions. This study involved 313 patients diagnosed with type 2 diabetes mellitus (T2DM) at two Malaysian tertiary hospitals. Socio-demographic data were assessed using a pre-tested interviewer-administered structured questionnaire. Anthropometric measurements were carried out according to standard protocols. Clinical and laboratory characteristics were examined. Kappa (k) statistics were used for the agreement between the four MetS definitions. The overall prevalence rates of MetS (95% CI) were 95.8% (93.6-98.1), 96.1% (94.0-98.3), 84.8% (80.8-88.9) and 97.7% (96.1-99.4) according to the WHO, NCEP ATP III, IDF and the Harmonized definitions, respectively. The Kappa statistics demonstrated a slight to substantial agreement between the definitions (k = 0.179-0.875, p k = 0.875, p hest specificity (100%) in identifying MetS. In conclusion, the new Harmonized criteria established the highest prevalence of MetS among the four definitions applied. There was a very good concordance between the WHO and NCEP ATP III criteria. The extremely high prevalence of MetS observed in type 2 diabetic patients indicates an impending pandemic of CVD risk in Malaysia. Aggressive treatment of MetS components is required to reduce cardiovascular risk in T2DM.
文摘Acute care management of traumatic brain injury is focused on the prevention and reduction of secondary insults such as hypotension,hypoxia,intracranial hypertension,and detrimental inflammation.However,the imperative to balance multiple clinical concerns simultaneously often results in therapeutic strategies targeted to address one clinical concern causing unintended effects in other remote organ systems.Recently the bidirectional communication between the gastrointestinal tract and the brain has been shown to influence both the central nervous system and gastrointestinal tract homeostasis in health and disease.A critical component of this axis is the microorganisms of the gut known as the gut microbiome.Changes in gut microbial populations in the setting of central nervous system disease,including traumatic brain injury,have been reported in both humans and experimental animal models and can be further disrupted by off-target effects of patient care.In this review article,we will explore the important role gut microbial populations play in regulating brain-resident and peripheral immune cell responses after traumatic brain injury.We will discuss the role of bacterial metabolites in gut microbial regulation of neuroinflammation and their potential as an avenue for therapeutic intervention in the setting of traumatic brain injury.
基金supported by the National Natural Science Foundation of China(Youth Program),No.81901282(to XC)the National Natural Science Foundation of China,Nos.81401416(to PX),81870992(to PX),81870856(to XC and MZ)+3 种基金Guangdong Basic and Applied Basic Research Foundation the Science Foundation,No.2019A1515011189(to XC)Central Government Guiding Local Science and Technology Development Projects,No.ZYYD2022C17(to PX)Key Project of Guangzhou Health Commission,No.2019-ZD-09(to PX)Science and Technology Planning Project of Guangzhou,Nos.202102020029(to XC),202102010010(to PX)。
文摘Mitochondrial dysfunction is a significant pathological alte ration that occurs in Parkinson's disease(PD),and the Thr61lle(T61I)mutation in coiled-coil helix coiled-coil helix domain containing 2(CHCHD2),a crucial mitochondrial protein,has been reported to cause Parkinson's disease.FIFO-ATPase participates in the synthesis of cellular adenosine triphosphate(ATP)and plays a central role in mitochondrial energy metabolism.However,the specific roles of wild-type(WT)CHCHD2 and T611-mutant CHCHD2 in regulating F1FO-ATPase activity in Parkinson's disease,as well as whether CHCHD2 or CHCHD2 T61I affects mitochondrial function through regulating F1FO-ATPase activity,remain unclea r.Therefore,in this study,we expressed WT CHCHD2 and T61l-mutant CHCHD2 in an MPP^(+)-induced SH-SY5Y cell model of PD.We found that CHCHD2 protected mitochondria from developing MPP^(+)-induced dysfunction.Under normal conditions,ove rexpression of WT CHCHD2 promoted F1FO-ATPase assembly,while T61I-mutant CHCHD2 appeared to have lost the ability to regulate F1FO-ATPase assembly.In addition,mass spectrometry and immunoprecipitation showed that there was an interaction between CHCHD2 and F1FO-ATPase.Three weeks after transfection with AAV-CHCHD2 T61I,we intraperitoneally injected 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine into mice to establish an animal model of chronic Parkinson's disease and found that exogenous expression of the mutant protein worsened the behavioral deficits and dopaminergic neurodegeneration seen in this model.These findings suggest that WT CHCHD2 can alleviate mitochondrial dysfunction in PD by maintaining F1F0-ATPase structure and function.
文摘Pancreatic cancer is the third leading cause of cancer mortality in both men and women in the United States,with poor response to current standard of care,short progression-free and overall survival.Immunotherapies that target cytotoxic T lymphocyte antigen-4,programmed cell death protein-1,and programmed death-ligand 1 checkpoints have shown remarkable activities in several cancers such as melanoma,renal cell carcinoma,and nonsmall cell lung cancer due to high numbers of somatic mutations,combined with cytotoxic T-cell responses.However,single checkpoint blockade was ineffective in pancreatic cancer,highlighting the challenges including the poor antigenicity,a dense desmoplastic stroma,and a largely immunosuppressive microenvironment.In this review,we will summarize available clinical results and ongoing efforts of combining immune checkpoint therapies with other treatment modalities such as chemotherapy,radiotherapy,and targeted therapy.These combination therapies hold promise in unleashing the potential of immunotherapy in pancreatic cancer to achieve better and more durable clinical responses by enhancing cytotoxic T-cell responses.
文摘The snow cover over the Taurus Mountains affects water supply, agriculture, and hydropower generation in the region. In this study, we analyzed the monthly Snow Cover Extent(SCE) from November to April in the Central Taurus Mountains(Bolkar, Aladaglar, Tahtali and Binboga Mountains) from 1981 to 2021. Linear trends of snow cover season(November to April) over the last 41 years showed decreases in SCE primarily at lower elevations. The downward trend in SCE was found to be more pronounced and statistically significant for only November and March. SCE in the Central Taurus Mountains has declined about-6.3% per decade for 2500-3000 m in November and about-6.0% per decade for 1000-1500 m and 3000+ m in March over the last 41 years. The loss of SCE has become evident since the 2000s, and the lowest negative anomalies in SCE have been observed in 2014, 2001, and 2007 in the last 41 years, which are consistent with an increase in air temperature and decreased precipitation. SCE was correlated with both mean temperature and precipitation, with temperature having a greater relative importance at all elevated gradients. Results showed that there is a strong linear relationship between SCE and the mean air temperature(r =-0.80) and precipitation(r = 0.44) for all elevated gradients during the snow season. The Arctic Oscillation(AO), the North Atlantic Oscillation(NAO), and the Mediterranean Oscillation(MO) winter indices were used to explain the year-to-year variability in SCE over the Central Taurus Mountains. The results showed that the inter-annual variability observed in the winter SCE on the Central Taurus Mountains was positively correlated with the phases of the winter AO, NAO and MO, especially below 2000 m elevation.
文摘目的以雌性和雄性非肥胖糖尿病(nonobese diabetic,NOD)小鼠以及健康对照癌症研究所(institute for cancer research,ICR)小鼠为研究对象,比较分析初始、效应、记忆、耗竭以及调节性CD8^(+)T细胞分化亚群差异,探讨1型糖尿病(type 1 diabetes,T1D)背景下的性别因素对CD8^(+)T细胞分化命运的影响。方法采用流式细胞术检测雌雄NOD小鼠脾脏、胰腺引流淋巴结(pancreatic draining lymph nodes,pLN)、胰腺浸润淋巴细胞(pancreas-infiltrating lymphocytes,PIL)、初始T细胞(naive T cells,T_(N))、中枢记忆T细胞(central memory T cells,T_(CM))、效应T细胞(effector T cells,T_(EFF))、效应前体样T细胞(effector precursor T cells,T_(EP))、耗竭T细胞(exhausted T cells,T_(EX))、耗竭前体T细胞(precursor exhausted T cells,T_(PEX))以及调节性T细胞(regulatory T cells,Tregs)等CD8^(+)T细胞分化亚群的频率和表型差异。结果与雄性NOD小鼠比较,雌性NOD小鼠pLN及PIL中IFN-γ^(+)、CD107a^(+)和CCL5^(+)CD8^(+)T_(EFF)频率显著升高(P<0.01,P<0.05,P<0.05),同时脾脏中CD8^(+)T_(N)、CD8^(+)T_(CM)、CD8^(+)T_(EX)、CD8^(+)T_(PEX)和CD122^(+)CD8^(+)Tregs亚群的频率均显著降低(P<0.01,P<0.01,P<0.01,P<0.01,P<0.001);而雌性和雄性ICR小鼠体内除CD122^(+)CD8^(+)Tregs差异变化与NOD小鼠一致(P<0.05),其余上述各CD8^(+)T细胞分化亚群无显著差异。结论雄激素可能通过抑制记忆T细胞向效应T细胞分化,同时促进效应T细胞功能耗竭,导致雌雄发病率差异。
基金funded by the National Natural Science Foundation of China (32371341,31872674)the Scientific and Technologic Foundation of Jilin Province (20230202050NC)the Fundamental Research Funds for the Central Universities (CGZH202206)。
文摘Type 1 diabetes mellitus(T1DM) lacks insulin secretion due to autoimmune deficiency of pancreaticβ-cells.Protecting pancreatic islets and enhancing insulin secretion has been therapeutic approaches.Mannogalactoglucan is the main type of polysaccharide from natural mushroom,which has potential medicinal prospects.Nevertheless,the antidiabetic property of mannogalactoglucan in T1DM has not been fully elucidated.In this study,we obtained the neutral fraction of alkali-soluble Armillaria mellea polysaccharide(AAMP-N) with the structure of mannogalactoglucan from the fruiting body of A.mellea and investigated the potential therapeutic value of AAMP-N in T1DM.We demonstrated that AAMP-N lowered blood glucose and improved diabetes symptoms in T1DM mice.AAMP-N activated unfolded protein response(UPR) signaling pathway to maintain ER protein folding homeostasis and promote insulin secretion in vivo.Besides that,AAMP-N promoted insulin synthesis via upregulating the expression of transcription factors,increased Ca^(2+) signals to stimulate intracellular insulin secretory vesicle transport via activating calcium/calmodulin-dependent kinase Ⅱ(CamkⅡ) and cAMP/PKA signals,and enhanced insulin secretory vesicle fusion with the plasma membrane via vesicle-associated membrane protein 2(VAMP2).Collectively,these studies demonstrated that the therapeutic potential of AAMP-N on pancreatic islets function,indicating that mannogalactoglucan could be natural nutraceutical used for the treatment of T1DM.
基金Supported by(in part)Research Programs on the Innovative Development and Application for New Drugs for Hepatitis B(No.17fk0310116h0001) from the Japan Agency for Medical Research and Development(AMED)Extramural Collaborative Research Grant of Cancer Research Institute,Kanazawa University
文摘Tumor immunity proceeds through multiple processes, which consist of antigen presentation by antigen presenting cells(APCs) to educate effector cells and destruction by the effector cytotoxic cells. However, tumor immunity is frequently repressed at tumor sites. Malignantly transformed cells rarely survive the attack by the immune system, but cells that do survive change their phenotypes to reduce their immunogenicity. The resultant cells evade the attack by the immune system and form clinically discernible tumors. Tumor microenvironments simultaneously contain a wide variety of immune suppressive molecules and cells to dampen tumor immunity. Moreover, the liver microenvironment exhibits immune tolerance to reduce aberrant immune responses to massively-exposed antigens via the portal vein, and immune dysfunction is frequently associated with liver cirrhosis, which is widespread in hepatocellular carcinoma(HCC) patients. Immune therapy aims to reduce tumor burden, but it is also expected to prevent non-cancerous liver lesions from progressing to HCC, because HCC develops or recurs from noncancerous liver lesions with chronic inflammatory states and/or cirrhosis and these lesions cannot be cured and/or eradicated by local and/or systemic therapies. Nevertheless, cancer immune therapy should augment specific tumor immunity by using two distinct measures: enhancing the effector cell functions such as antigen presentation capacity of APCs and tumor cell killing capacity of cytotoxic cells, and reactivating the immune system in immune-suppressive tumor microenvironments. Here, we will summarize the current status and discuss the future perspective on immune therapy for HCC.
基金supported by the National Key Research and Development Program of China(Grant No.2019YFC1605000)National Natural Science Foundation of China(Grant No.31871806)the Beijing Livestock Industry Innovation Team(BAIC05-2023)。
文摘Milk fat globule membrane(MFGM),which contains abundant glycoproteins and phospholipids,exerts beneficial effects on intestinal health and immunomodulation.The aim of this study was to evaluate the protective effects and possible underlying mechanisms of MFGM on cow’s milk allergy(CMA)in aβ-lactoglobulin(BLG)-induced allergic mice model.MFGM was supplemented to allergic mice induced by BLG at a dose of 400 mg/kg body weight.Results demonstrated that MFGM alleviated food allergy symptoms,decreased serum levels of lipopolysaccharide,pro-inflammatory cytokines,immunoglobulin(Ig)E,Ig G1,and Th2 cytokines including interleukin(IL)-4,while increased serum levels of Th1 cytokines including interferon-γand regulatory T cells(Tregs)cytokines including IL-10 and transforming growth factor-β.MFGM modulated gut microbiota and enhanced intestinal barrier of BLG-allergic mice,as evidenced by decreased relative abundance of Desulfobacterota,Rikenellaceae,Lachnospiraceae,and Desulfovibrionaceae,while increased relative abundance of Bacteroidetes,Lactobacillaceae and Muribaculaceae,and enhanced expressions of tight junction proteins including Occludin,Claudin-1 and zonula occludens-1.Furthermore,MFGM increased fecal short-chain fatty acids(SCFAs)levels,which elevated G protein-coupled receptor(GPR)43 and GPR109A expressions.The increased expressions of GPR43 and GPR109A induced CD103+dendritic cells accumulation and promoted Tregs differentiation in mesenteric lymph node to a certain extent.In summary,MFGM alleviated CMA in a BLG-induced allergic mice model through enhancing intestinal barrier and promoting Tregs differentiation,which may be correlated with SCFAs-mediated activation of GPRs.These findings suggest that MFGM may be useful as a promising functional ingredient against CMA.
基金supported by the Natural Science Foundation of Xinjiang Uygur Autonomous Region, No. 2020D01A13 (to CWW)Chengdu Science and Technology Bureau, No. 2019-YF05-00511-SN (to MT)1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University, Nos. ZY2016102 (to MT), and ZY2016203 (to CY)
文摘According to clinical statistics,the mortality of patients with early brainstem hemorrhage is high.In this study,we established rat models of brainstem hemorrhage by injecting type Ⅶ collagenase into the right basotegmental pontine and investigated the pathological changes of early brainstem hemorrhage using multi-sequence magnetic resonance imaging and histopathological methods.We found that brainstem hematoma gradually formed in the injured rats over the first 3 days and then reduced after 7 days.The edema that occurred was mainly of the vasogenic type.No complete myelin sheath structure was found around the focus of the brainstem hemorrhage.The integrity and continuity of nerve fibers gradually deteriorated over the first 7 days.Neuronal degeneration was mild in the first 3 days and then obviously aggravated on the 7^(th)day.Inflammatory cytokines,interleukin-1β,and tumor necrosis factorαappeared on the 1st day after intracerebral hemorrhage,reached peak levels on the 3^(rd)day,and decreased from the 7^(th)day.Our findings show the characteristics of the progression of early brainstem hemorrhage.
基金supported by 16POST27490032 American Heart Association post-doctoral fellowshipNational Institute of Neurological Disorders and Stroke Exploratory Neuroscience Research Grant R21 NS114836-01A1 (to AC)
文摘As the average age of the world population increases,more people will face debilitating aging-associated conditions,including dementia and stroke.Not only does the incidence of these conditions increase with age,but the recovery afterward is often worse in older patients.Researchers and health professionals must unveil and understand the factors behind age-associated diseases to develop a therapy for older patients.Aging causes profound changes in the immune system including the activation of microglia in the brain.Activated microglia promote T lymphocyte transmigration leading to an increase in neuroinflammation,white matter damage,and cognitive impairment in both older humans and rodents.The presence of T and B lymphocytes is observed in the aged brain and correlates with worse stroke outcomes.Preclinical strategies in stroke target either microglia or the lymphocytes or the communications between them to promote functional recovery in aged subjects.In this review,we examine the role of the microglia and T and B lymphocytes in aging and how they contribute to cognitive impairment.Additionally,we provide an important update on the contribution of these cells and their interactions in preclinical aged stroke.
基金Supported by The Deutsche Forschungsgemeinschaft,No.GW 4/6-1
文摘Rejection is one of the key factors that determine the long-term allograft function and survival in renal transplant patients. Reliable and timely diagnosis is important to treat rejection as early as possible. Allograft biopsies are not suitable for continuous monitoring of rejection. Thus, there is an unmet need for non-invasive methods to diagnose acute and chronic rejection. Proteomics in urine and blood samples has been explored for this purpose in 29 studies conducted since 2003. This review describes the different proteomic approaches and summarizes the results from the studies that examined proteomics for the rejection diagnoses. The potential limitations and open questions in establishing proteomic markers for rejection are discussed, including ongoing trials and future challenges to this topic.
文摘Our knowledge of renal cell carcinoma(RCC) is rapidly expanding. For those who diagnose and treat RCC, it is important to understand the new developments. In recent years, many new renal tumors have been described and defined, and our understanding of the biology and clinical correlates of these tumors is changing. Evolving concepts in Xp11 translocation carcinoma, mucinous tubular and spindle cell carcinoma, multilocular cystic clear cell RCC, and carcinoma associated with neuroblastoma are addressed within this review. Tubulocystic carcinoma, thyroid-like follicular carcinoma of kidney, acquired cystic disease-associated RCC, and clear cell papillary RCC are also described. Finally, candidate entities, including RCC with t(6;11) translocation, hybrid oncocytoma/chromophobe RCC, hereditary leiomyomatosis and RCC syndrome, and renal angiomyoadenomatous tumor are reviewed. Knowledge of these new entities is important for diagnosis, treatment and subsequent prognosis. This review provides a targeted summary of new developments in RCC.
基金The authors gratefully acknowledge the support of the National Natural Science Foundation of China(Grant Nos.52174036,51774243,51904257,51874251)the Sichuan Province Science and Technology Program(Grant Nos.2021YJ0345,2022JDJQ0009,2022NSFSC0186).
文摘Shale gas is an important component of unconventional oil and gas resources.Studying the imbibition behavior is helpful to optimize flowback parameters and enhance gas recovery.Recent imbibition studies have focused on shale matrix,and the pressure conditions discussed were mostly atmospheric.The initial imbibition behavior begins from propped fractures to matrix,but there are few studies working on explaining the imbibition behavior in propped fractures or the phenomenon of many shale wells exhibit higher productivity after a“soaking”period.Therefore,propped fracture samples were designed for imbibition and migration experiments.In order to accurately study the mechanism and main influencing factors of fracturing fluid imbibition and migration in propped and unpropped shale fractures under high temperature and high pressure,a series of experiments based on nuclear magnetic resonance(NMR)were carried out.Results showed that NMR T2 spectra of all samples exhibited a bimodal distribution.The final imbibition volume of fracturing fluid was positively related to pressure and fracture width.The imbibition effect of fracturing fluid was more evident in matrix pores under high pressure.In the migration during soaking stage,the fracturing fluid gradually migrated from large pores to small pores and gradually displaced the shale gas from the matrix,thus allowing the water blocking in propped fractures to self-unlock to some extent.Gas permeability decreased in the imbibition stage,while it recovered in the migration stage to some extent.
基金supported by the Jiangsu Province’s Outstanding Medical Academic Leader Program[CXTDA2017029]and the Jiangsu Provincial Key Medical Discipline[ZDXK202249].
文摘transcription and expression,and its potential biological mechanisms.Methods Differentially expressed genes related to Hg exposure were identified and validated using gene expression microarray analysis and extended validation.Hg-exposed cell models and PTEN lowexpression models were established in vitro using 293T cells.PTEN gene expression was assessed using qRT-PCR,and Western blotting was used to measure PTEN,AKT,and PI3K protein levels.IL-6 expression was determined by ELISA.Results Combined findings from gene expression microarray analysis,bioinformatics,and population expansion validation indicated significant downregulation of the PTEN gene in the high-concentration Hg exposure group.In the Hg-exposed cell model(25 and 10μmol/L),a significant decrease in PTEN expression was observed,accompanied by a significant increase in PI3K,AKT,and IL-6 expression.Similarly,a low-expression cell model demonstrated that PTEN gene knockdown led to a significant decrease in PTEN protein expression and a substantial increase in PI3K,AKT,and IL-6 levels.Conclusion This is the first study to report that Hg exposure downregulates the PTEN gene,activates the PI3K/AKT regulatory pathway,and increases the expression of inflammatory factors,ultimately resulting in kidney inflammation.
基金funded by the China National Key Research and Development Program(No.2022YFC3003505)the Fundamental Research Fund for the Central Public-interest Scientific Institutes(No.DQJB23Y01)+1 种基金the National Natural Science Foundation of China(No.52278540)the Fundamental Research Fund for the Central Public-interest Scientific Institutes(No.DQJB22B28).
文摘In 2023,two consecutive earthquakes exceeding a magnitude of 7 occurred in Türkiye,causing severe casualties and economic losses.The damage to critical urban infrastructure and building structures,including highways,railroads,and water supply pipelines,was particularly severe in areas where these structures intersected the seismogenic fault.Critical infrastructure projects that traverse active faults are susceptible to the influence of fault movement,pulse velocity,and ground motions.In this study,we used a unique approach to analyze the acceleration records obtained from the seismic station array(9 strong ground motion stations)located along the East Anatolian Fault(the seismogenic fault of the MW7.8 mainshock of the 2023 Türkiye earthquake doublet).The acceleration records were filtered and integrated to obtain the velocity and displacement time histories.We used the results of an on-site investigation,jointly conducted by China Earthquake Administration and Türkiye’s AFAD,to analyze the distribution of PGA,PGV,and PGD recorded by the strong motion array of the East Anatolian Fault.We found that the maximum horizontal PGA in this earthquake was 3.0 g,and the maximum co-seismic surface displacement caused by the East Anatolian Fault rupture was 6.50 m.As the fault rupture propagated southwest,the velocity pulse caused by the directional effect of the rupture increased gradually,with the maximum PGA reaching 162.3 cm/s.We also discussed the seismic safety of critical infrastructure projects traversing active faults,using two case studies of water supply pipelines in Türkiye that were damaged by earthquakes.We used a three-dimensional finite element model of the PE(polyethylene)water pipeline at the Islahiye State Hospital and fault displacement observations obtained through on-site investigation to analyze pipeline failure mechanisms.We further investigated the effect of the fault-crossing angle on seismic safety of a pipeline,based on our analysis and the failure performance of the large-diameter Thames Water pipeline during the 1999 Kocaeli earthquake.The seismic method of buried pipelines crossing the fault was summarized.
基金funded by the National Natural Science Foundation of China (Grant No. 11975145)
文摘This study aims to discuss anisotropic solutions that are spherically symmetric in the quintessence field,which describe compact stellar objects in the modified Rastall teleparallel theory of gravity.To achieve this goal,the Krori and Barua arrangement for spherically symmetric components of the line element is incorporated.We explore the field equations by selecting appropriate off-diagonal tetrad fields.Born-Infeld function of torsion f(T)=β√λT+1-1 and power law form h(T)=δTn are used.The Born-Infeld gravity was the first modified teleparallel gravity to discuss inflation.We use the linear equation of state pr=ξρto separate the quintessence density.After obtaining the field equations,we investigate different physical parameters that demonstrate the stability and physical acceptability of the stellar models.We use observational data,such as the mass and radius of the compact star candidates PSRJ 1416-2230,Cen X-3,&4U 1820-30,to ensure the physical plausibility of our findings.
