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Climatic warming can shift community composition driven by the colonization-extinction dynamics of species with different thermal preferences; but simultaneously, habitat fragmentation can mediate species responses to warming. As this potential interactive effect has proven difficult to test empirically, we collected data on birds over 10 years of climate warming in a reservoir subtropical island system that was formed 65 years ago. We investigated how the mechanisms underlying climate-driven directional change in community composition were mediated by habitat fragmentation. We found thermophilization driven by increasing warm-adapted species and decreasing cold-adapted species in terms of trends in colonization rate, extinction rate, occupancy rate and population size. Critically, colonization rates of warm-adapted species increased faster temporally on smaller or less isolated islands; cold-adapted species generally were lost more quickly temporally on closer islands. This provides support for dispersal limitation and microclimate buffering as primary proxies by which habitat fragmentation mediates species range shift. Overall, this study advances our understanding of biodiversity responses to interacting global change drivers.

目的探讨线粒体酸5（mitochonic acid-5，MA-5）是否可以减轻脂多糖（lipopolysaccharide，LPS）诱导的脓毒症急性肾损伤以及可能的机制。方法细胞实验：将肾小管细胞分为正常组、MA-5（10 µmol/L）组、LPS（10 mg/L）刺激组和LPS+MA-5治疗组，通过细胞计数试剂盒8法评估细胞活力、流式细胞术评估细胞凋亡率；活性氧（reactive oxygen species，ROS）检测试剂盒检测ROS含量；三磷酸腺苷（adenosine triphosphate，ATP）检测试剂盒检测ATP水平；蛋白质印迹法（western blot，Wb）检测沉默信息调节因子3（silence information regulator 3，SIRT3）蛋白、线粒体动力学相关蛋白［动力相关蛋白1（dynamin-related protein 1，DRP1）、视神经萎缩因子1（optic atrophy 1，OPA1）］和细胞凋亡相关蛋白［B细胞淋巴瘤2（B-cell lymphoma-2，Bcl-2）、Bcl-2相关X蛋白（Bcl-2 associated X protein，Bax）］的表达水平。动物实验：将32只成年雄性小鼠按照统计学中完全随机设计的方法分为正常组、MA-5组、LPS组和LPS+MA-5组，每组8只。LPS（10 mg/kg）腹腔注射建立脓毒症急性肾损伤模型，随后腹腔注射MA-5（50 mg/kg）治疗，24 h后进行取材。通过检测血肌酐（serum creatinine，Scr）、血尿素氮（blood urea nitrogen，BUN）评估肾功能；分别应用HE染色观察肾组织病理变化，透射电镜观察肾组织线粒体超微结构，二氢乙锭荧光染色观察肾组织ROS水平，免疫组化法检测肾组织中Sirt3表达水平以及Wb检测肾组织中Sirt3、OPA1、Drp1、Bcl-2和Bax蛋白的表达水平。结果在体外，相较于LPS（10 mg/L）刺激组，LPS+MA-5治疗组肾小管上皮细胞凋亡率［（9.21 ± 0.34）%比（16.49 ± 0.52）%］显著减少（P

Introduction: Intrahepatic cholangiocarcinoma (iCCA) is the second most common primary liver cancer after hepatocellular carcinoma. Through data mining of publicly available iCCA transcriptomic datasets from the Gene Expression Omnibus, we identified SFN as the most significantly up-regulated gene in iCCA compared to normal tissue, focusing on the Gene Ontology term ''cell proliferation'' (GO:0008283). SFN encodes the 14-3-3σ protein, also known as stratifin, which plays crucial roles in various cellular processes. Materials and methods: Immunohistochemistry was used to assess stratifin expression in 182 patients with localized iCCAs undergoing surgical resection. Patients were divided into low and high expression groups, and the association between stratifin expression and clinicopathological features was analyzed. Univariate and multivariate survival analyses were performed to assess overall survival (OS), disease-specific survival (DSS), local recurrence-free survival (LRFS), and metastasis-free survival (MeFS). Results: Elevated stratifin expression in iCCAs was significantly associated with the absence of hepatitis, positive surgical margins, advanced primary tumor stages, and higher histological grades (all p ≤ 0.011). Survival analyses demonstrated a significant negative association between stratifin expression and all prognostic indicators, including OS, DSS, LRFS, and MeFS (all p ≤ 0.0004). Multivariate analysis revealed that stratifin overexpression was significantly correlated with poorer outcomes in terms of DSS, LRFS, and MeFS (all p

Objective To explore the correlation between urinary mitochondrial DNA（mtDNA） and the severity and prognosis of primary membranous nephropathy（PMN）.MethodsA total of 56 patients were definitely diagnosed as PMN through renal biopsy from May 2022 to June 2023. Clinical and laboratory data were recorded. Morning mid-stream urine samples were collected for detecting the copy numbers of cytochrome-c oxidase-3（COX3） and NADH dehydrogenase subunit-1（ND1） genes in mtDNA. The correlation between baseline mtDNA copy number and nephrotic syndrome（NS） was examined through univariate and multivariate Logistic regression models. During follow-ups, Kaplan-Meier survival curves were plotted for analyzing the differential remission outcomes between high and low urinary mtDNA copy number groups.Results COX3 and ND1 copy numbers spiked in medium-risk group[COX3 = 5.532（5.318, 5.797）, ND1 = 5.575（5.270, 5.815）] and high-risk group [COX3 = 5.575（5.270, 5.815）, ND1 = 5.575（5.270, 5.815）] as compared with low-risk group[COX3 = 5.362（5.194, 5.508）, ND1 = 5.386（5.272, 5.528）]（P＜0.05）.COX3 and ND1 copy numbers were correlated positively with 24-hour urinary protein（P = 0.031, P = 0.041） and negatively with albumin（P = 0.032, P = 0.005）. The predictive value of COX3 and ND1 copy numbers in PMN with NS was examined with receiver operating characteristic（ROC） curve. And grouping was based upon optimal cutoff values of COX3 and ND1 copy numbers. The results indicated that the risk of nephrotic syndrome（NS） was higher in group with elevated COX3 and ND1 copy numbers versus group with lower copy numbers（Model 1: OR = 3.51, P = 0.019; OR = 2.89, P = 0.024）. After adjusting for age, gender, systolic blood pressure, diastolic blood pressure, anti-PLA2R antibodies and eGFR, the risk of NS remains higher in group with elevated COX3 and ND1 copy numbers（Model 3: OR = 2.65, P = 0.031; OR = 2.17, P = 0.029）. In terms of disease remission, Kaplan-Meier survival curve analysis revealed no significant correlation between COX3 and ND1 copy numbers and remission outcomes of PMN（log-rank test P = 0.630, P = 0.208）.ConclusionUrinary mtDNA is significantly higher in PMN patients of medium/high-risk group than those of low-risk group. Urinary mtDNA is associated with an elevated risk of NS in PMN patients, However, its predictive effect on disease remission requires further studies.

Objective To gain a deeper understanding of molecular mechanisms underlying acute kidney injury （AKI）, explore traditional Chinese medicine strategies for managing AKI, employ bioinformatics to analyze key genes associated with AKI and predict potential Chinese herbal medicines with therapeutic effects. Methods The AKI gene expression microarray dataset GSE30718 were downloaded from the database of Gene Expression Omnibus （GEO） and GEO2R online tool was utilized for analysis. Simultaneously, AKI target genes were obtained from the Comparative Toxicogenomics Database （CTD） and the intersection of these datasets yielded the differential expression genes （DEGs） associated with AKI. Enrichment analysis and protein-protein interaction analysis were performed on DEGs. Cytoscape software was employed for identifying key genes. Subsequently, a medical information retrieval platform （Coremine Medical） was utilized for searching for traditional Chinese medicines corresponding to these key genes with the most frequently occurring ones identified. Then the database of BATMAN-TCM was employed for detailed analysis of molecular mechanisms involved in their therapeutic effects on AKI. Results For 206 DEGs, functional enrichment analysis confirmed their involvements in extracellular matrix regulation, immune-inflammatory responses and transcriptional regulation. FN1, Alb, COL1A1, JUN, TGFB1, FOS, PXDN, COL1A2, EGF and TIMP1 were identified as key genes for AKI. The potential traditional Chinese medicines for treating AKI included Danshen （Salvia Miltiorrhiza）, Renshen （Radix Ginseng）, Danggui （Angelica Sinensis） and Sanqi （Radix Notoginseng）. And Danshen had the highest frequency. The primary signaling pathway associated with Danshen's therapeutic effects on AKI was signaling pathway of phosphatidylinositide 3-kinase/protein kinase B （PI3K/AKT）. Conclusion This study has identified 10 key genes involved in AKI and their associated traditional Chinese medicines. Specific analysis of Danshen's molecular mechanisms in treating AKI provides new insights for clinical interventions and establishes theoretical rationales for subsequent researches.

ABSTRACT: Mule ducks accumulate a large amount of fat in their livers when fed high-energy feed, which is predominantly used for producing fatty livers. Nevertheless, there is limited research on the molecular mechanisms underlying the formation of fatty liver in mule ducks. Fatty acid translocase (CD36) is a sensor for fatty acids and lipid metabolism regulator, which may play a crucial role in the accumulation of fat in the liver of mule ducks. In this study, Overexpression and CD36 gene interference for 24 h was followed by induction of liver cells with 400 µmol/L palmitic acid (PA) for 24 h. The results demonstrated that CD36 overexpression increased hepatic triglyceride content, lipid droplet deposition, oxidative stress, and cell apoptosis. However, interference with CD36 had the opposite effect. CD36 overexpression suppressed the expression of AMPK and CPT-1A genes but enhanced the expression of ACC1 and LKB1 genes, with interference yielding contrasting results. Additionally, the expression of CD36 inhibited the AMPK pathway, reduced AMPK phosphorylation, downregulated AMPK protein expression, and upregulated SREBP1 protein expression. This promoted palmitic acid-induced hepatocyte fat accumulation. In summary, CD36 promotes palmitic acid-induced fat accumulation in primary mule duck liver cells through the AMPK signaling pathway.

Objective To observe the expression of silent information regulator 3 （Sirt3）, detect the level of aerobic glycolysis in renal fibrosis model and explore the role of Sirt3 in renal interstitial fibrosis. Methods Wild-type and Sirt3 gene knockout mice were utilized for constructing a renal fibrosis model by unilateral ureteral obstruction （UUO） and contralateral kidneys were used as sham surgery control group. The pathological changes of kidney were observed after hematoxylin-eosin （HE） and Masson stain. The expressions of Sirt3, signature proteins associated with fibrosis （fibronectin & collagen-I）, key enzymes of aerobic glycolysis [hexokinase-II （HXK-II） & pyruvate kinase M2 （PKM2）] and caspase-3 were evaluated by Western blot. Apoptotic level of renal tubular epithelial cells （RTECs） was assessed by terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling （TUNEL） stain. Human renal tubular epithelial cells （HK-2） were divided into control and si-Sirt3 groups and exposed to transforming growth factor-β1 （TGF-β1）. Western blot was utilized for detecting the expressions of fibronectin, collagen-I, HXK-II and PKM2. Flow cytometry was employed for detecting apoptosis. Results Apoptosis and aerobic glycolysis accelerated significantly during in vivo and in vitro fibrotic reactions. Sirt3 became markedly down-regulated. Sirt3 gene knockout further aggravated renal tubular epithelial cell apoptosis and abnormal aerobic glycolysis and promoted renal interstitial fibrosis. Conclusions Sirt3 may alleviate renal interstitial fibrosis through suppressing aerobic glycolysis of RTECs. It plays some protective role in chronic kidney disease （CKD）.

As a clinical syndrome with systemic manifestations, acute kidney injury (AKI) is characterized by a sharp decline in glomerular filtration rate, high morbidity and mortality. However, the pathogenesis of AKI has remained elusive. Mitochondrial dysfunction plays an important role in its progression. And silence information regulator 3 (SIRT3), a major deacetylase regulator of mitochondrial target proteins, ameliorates AKI through regulating mitochondrial biosynthesis, improving mitochondrial dynamics, inducing mitochondrial autophagy and reducing oxidative stress to maintain mitochondrial homeostasis. Elucidating the underlying mechanism of SIRT3-mediated mitochondrial homeostasis in AKI is of great significance for managing AKI and improving patient outcomes.

ObjectiveTo compare the clinical efficacy and safety of two regimens of rituximab (RTX) for idiopathic membranous nephropathy (IMN).MethodsA total of 79 IMN patients were recruited from December 01, 2019 to December 31, 2021. RTX two-dose regimen group (n=49): two infusions of 1g at 2-week intervals; if nephrotic albuminuria persisted during a 6-month follow-up, the regimen could be repeated once. RTX four-dose regimen group (n=30): four infusions of 375 mg/m2 at 1-week intervals. Both groups had a combination of low-dose glucocorticoid. The differences of 24-hour urinary protein, serum albumin, blood creatinine, peripheral blood CD19+ cell count, anti-PLA2R antibody titer, disease remission rate and adverse reactions were compared between two groups before and at different timepoints post-treatment.ResultsNo significant inter-group differences existed in gender, age, body mass index, blood pressure, 24-hour urinary protein, serum albumin, blood creatinine, eGFR, anti-PLA2R antibody or peripheral blood CD19+ cell count pre-treatment (P>0.05). At Month 12, 24-hour urinary protein declined markedly in 2 groups as compared with pre-treatment (P0.05). In terms of serum creatinine, total renal function of 2 groups remained stable without statistical significance (P>0.05). Anti-PLA2R-Ab level declined markedly in two groups post-treatment as compared with pre-treatment and the difference was not statistically significant (P>0.05). In terms of disease remission, total effective rate reached 75.95% at Month 12 and clinical remission rate of RTX two-dose regimen group was significantly higher than that of RTX four-dose regimen group (85.71% vs 60%). And the difference was statistically significant (P0.05).ConclusionWith a higher clinical remission rate without a higher incidence of adverse reactions, high-dose RTX regimen is more suitable for treating IMN. However, adverse reactions causing severe hypokalemia deserve greater attention.

ABSTRACT: Mule ducks tend to accumulate abundant fat in their livers via feeding, which leads to the formation of a fatty liver that is several times larger than a normal liver. However, the mechanism underlying fatty liver formation has not yet been elucidated. Fibroblast growth factor 1 (FGF1), a member of the FGF superfamily, is involved in cellular lipid metabolism and mitosis. This study aims to investigate the regulatory effect of FGF1 on lipid metabolism disorders induced by complex fatty acids in primary mule duck liver cells and elucidate the underlying molecular mechanism. Hepatocytes were induced by adding 1,500:750 µmol/L oleic and palmitic acid concentrations for 36 h, which were stimulated with FGF1 concentrations of 0, 10, 100, and 1000 ng/mL for 12 h. The results showed that FGF1 significantly reduced the hepatic lipid droplet deposition and triglyceride content induced by complex fatty acids; it also reduced oxidative stress; decreased reactive oxygen species fluorescence intensity and malondialdehyde content; upregulated the expression of antioxidant factors nuclear factor erythroid 2 related factor 2 (Nrf2), HO-1, and NQO-1; significantly enhanced liver cell activity; promoted cell cycle progression; inhibited cell apoptosis; upregulated cyclin-dependent kinase 1 (CDK1) and BCL-2 mRNA expression; and downregulated Bax and Caspase-3 expression. In addition, FGF1 promoted AMPK phosphorylation, activated the AMPK pathway, upregulated AMPK gene expression, and downregulated the expression of SREBP1 and ACC1 genes, thereby alleviating excessive fat accumulation in liver cells induced by complex fatty acids. In summary, FGF1 may alleviate lipid metabolism disorders induced by complex fatty acids in primary mule duck liver cells by activating the AMPK signaling pathway.

This research investigated the anticancer properties of punicalagin, a prominent bioactive polyphenol extracted from Punica granatum L, in human gastric cancer cell lines. Normal and gastric cancer cells were exposed to different doses of punicalagin for various durations. Punicalagin exhibited cytotoxic effects on gastric cancer cells in a dose- and time-dependent fashion, while sparing normal gastric epithelial cells. It is noteworthy that among the 3 gastric cancer cells, HGC-27 cells were more resistant to punicalagin than 23,132/87 and AGS cells. Furthermore, punicalagin triggered apoptosis in gastric cancer cells, evidenced by a rise in both early and late apoptotic cell percentages. Western blot analysis further revealed that punicalagin elevated the levels of activated caspase-3. Conversely, punicalagin curtailed cell invasion and reduced the expression of MMP-2, MMP-9, Snail, and Slug. From a mechanistic standpoint, Western blotting indicated that punicalagin might inhibit the Erk and NF-κB pathways, leading to apoptosis induction and the inhibition of cell invasion in gastric cancer cells. These results indicate that punicalagin promotes apoptosis and inhibits cell invasion in gastric cancer cells by activating caspase-3 and suppressing MMP-2, MMP-9, Snail, and Slug through the inhibition of the Erk and NF-κB pathways.

Abstract Cholangiocarcinoma is the most common malignant bile duct tumor in Southeast Asia. The special location of cholangiocarcinoma leads to it being difficult to diagnose. Currently, the progress in clinical prognosis outcomes remains abysmal owing to the lack of definitive diagnostic criteria. Therefore, uncovering the potential markers for cholangiocarcinoma is a pressing issue. Ubiquitin-conjugating enzyme E2 C (UBE2C) is a critical ubiquitination enzyme; it is involved in the tumorigenesis of various malignancies and affects the patient’s prognosis. However, there is currently no relevant literature to indicate whether UBE2C is related to the clinical survival outcome of cholangiocarcinoma patients. In this report, we mined the published cholangiocarcinoma transcriptome data set (GSE26566), compared it with the ubiquitination-associated gene (GO:0016567), and identified that UBE2C was highly expressed in cholangiocarcinoma tumor tissue. Moreover, high expression of UBE2C was markedly correlated with surgical margin, primary tumor, histological variants, and histological grade. More specifically, high expression of UBE2C was negatively associated with overall survival, disease-specific survival, local recurrence-free survival, and metastasis-free survival in patients with cholangiocarcinoma. Our findings demonstrate that UBE2C may provide a potential therapeutic marker and prognostic factor for cholangiocarcinoma patients.

Background: Co-stimulatory and co-inhibitory molecules are critical to T cell responses and involved in the pathogenesis of systemic lupus erythematosus (SLE). This study aimed to comprehensively analyze the surface expression of these molecules in various phenotypic immune cells, comparing the differences between various levels of the severity in SLE and control groups. Methods: Peripheral blood mononuclear cells (PBMCs) were isolated using Ficoll-Paque from blood samples of severe SLE patients (treatment with immunosuppressants), mild SLE patients (excluding those with persistent proteinuria or thrombocytopenia), and healthy controls (n = 10 each). PBMCs were stimulated for 48 h. The cells were stained with anti-CD3, CD4, CD28, PD-1, and CTLA-4 antibodies and analyzed by flow cytometry. Differences between groups were assessed using the Kruskal–Wallis test and Mann–Whitney U-test, with median values and statistical significance (p < 0.05) reported. Results: The results showed that CD28 expression was significantly higher in SLE patients compared to controls, with the highest levels in mild SLE. However, CD3+ CD28+ and CD4+ CD28+ cells were more prevalent in controls (p = 0.032 and 0.017, respectively). Mild SLE patients exhibited the highest CTLA-4 expression, with significant differences from severe SLE and controls (p = 0.030 and 0.037, respectively). PD-1 expression was lowest in severe SLE but highest in mild SLE within CD3+ CD4+ cells (p = 0.001). After 48 h of activation, CD4+ CTLA4+ and CD3+ CTLA4+ expression levels were significantly higher in controls compared to SLE groups. Conclusions: Our study highlighted that the expression of CD28, CTLA-4, and PD-1 in lymphocytes and specific T cell subsets was various according the severity of SLE in patients, underscoring their roles in disease pathogenesis.