Green light all the way: Triple modification synergistic modification effect to enhance the photoelectrochemical water oxidation performance of BiVO4 photoanode.

The recombination of photogenerated electron-hole pairs of the photoanode seriously impairs the application of bismuth vanadate (BiVO4) in photoelectrochemical water splitting. To address this issue, we prepared a Yb:BiVO4/Co3O4/FeOOH composite photoanode by employing drop-casting and soaking methods to attach Co3O4/FeOOH cocatalysts to the surface of ytterbium-doped BiVO4. The prepared Yb:BiVO4/Co3O4/FeOOH photoanode demonstrates a high photocurrent density of 4.89 mA cm-2 at 1.23 V versus the reversible hydrogen electrode (RHE), which is 5.1 times that of bare BiVO4 (0.95 mA cm-2). Detailed characterization and testing demonstrated that Yb doping narrows the band gap and significantly enhances the carrier density. Furthermore, Co3O4 serves as a hole transfer layer to expedite hole migration and diminish recombination, while FeOOH offers additional active sites and minimizes surface trap states, thus boosting stability. The synergistic effects of Yb doping and Co3O4/FeOOH cocatalyst significantly improved the reaction kinetics and overall performance of PEC water oxidation. This work provides a strategy for designing efficient photoanodes for PEC water oxidation.

Weighted gene co-expression network analysis and identification of ginsenoside biosynthesis candidate genes for ginseng adventitious roots under MeJA treatment.

BACKGROUND: Ginseng (Panax ginseng) is an herb with a long history and a wide range of applications. Ginsenoside is one of the most representative and active ginseng compounds, with various pharmacological effects. Therefore, the development of bioreactors using methyl jasmonate (MeJA) as an inducer for targeted ginsenoside production is of great commercial value. Combined with transcriptomic research tools, screenings to obtain candidate genes involved in ginsenoside biosynthesis are crucial for future discoveries about the molecular mechanism of MeJA-regulated ginsenoside biosynthesis. OBJECTIVE AND METHODS: In our study, the ginsenoside content of ginseng adventitious roots treated with MeJA at different times was analyzed. Transcriptome analysis was performed to investigate the effects of MeJA on changes in ginsenoside content in ginseng adventitious roots. RESULTS: The MeJA could significantly increase changes in the content of pro-ginsenodiol ginsenosides as well as pro-triol ginsenosides Rg3, Re, and Rf in ginseng adventitious roots. Differential gene expression analysis showed that a total of 14,009 differentially expressed genes were obtained from the screening of the present study. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that differentially expressed genes were mainly enriched under GO terms in response to stimuli, metabolic processes, and the regulation of biological processes, with significant annotation to the metabolic terms of terpenoids and polyketides. Two expression modules of genes highly related to ginsenoside biosynthesis were obtained via WGCNA. CONCLUSIONS: Our study provides a reference system for the targeted ginsenoside production using MeJA as an inducer, and also provides genetic and gene resources for subsequently validating genes related to the regulation of ginsenoside biosynthesis using weighted gene co-expression network analysis (WGCNA).

Navigating the Landscape of Coronary Microvascular Research: Trends, Triumphs, and Challenges Ahead.

Coronary microvascular dysfunction (CMD) refers to structural and functional abnormalities of the microcirculation that impair myocardial perfusion. CMD plays a pivotal role in numerous cardiovascular diseases, including myocardial ischemia with non-obstructive coronary arteries, heart failure, and acute coronary syndromes. This review summarizes recent advances in CMD pathophysiology, assessment, and treatment strategies, as well as ongoing challenges and future research directions. Signaling pathways implicated in CMD pathogenesis include adenosine monophosphate-activated protein kinase/Krüppel-like factor 2/endothelial nitric oxide synthase (AMPK/KLF2/eNOS), nuclear factor erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE), Angiotensin II (Ang II), endothelin-1 (ET-1), RhoA/Rho kinase, and insulin signaling. Dysregulation of these pathways leads to endothelial dysfunction, the hallmark of CMD. Treatment strategies aim to reduce myocardial oxygen demand, improve microcirculatory function, and restore endothelial homeostasis through mechanisms including vasodilation, anti-inflammation, and antioxidant effects. Traditional Chinese medicine (TCM) compounds exhibit therapeutic potential through multi-targeted actions. Small molecules and regenerative approaches offer precision therapies. However, challenges remain in translating findings to clinical practice and developing effective pharmacotherapies. Integration of engineering with medicine through microfabrication, tissue engineering and AI presents opportunities to advance the diagnosis, prediction, and treatment of CMD.

Comprehensive scRNA-seq analysis to identify new markers of M2 macrophages for predicting the prognosis of prostate cancer.

BACKGROUND: Prostate cancer (PCa) has become the highest incidence of malignant tumor among men in the world. Tumor microenvironment (TME) is necessary for tumor growth. M2 macrophages play an important role in many solid tumors. This research aimed at the role of M2 macrophages' prognosis value in PCa. METHODS: Single-cell RNA-seq (scRNA-seq) data and mRNA expression data were obtained from the Gene Expression Omnibus database (GEO) and The Cancer Genome Atlas (TCGA). Quality control, normalization, reduction, clustering, and cell annotation of scRNA-seq data were preformed using the Seruat package. The sub-populations of the tumor-associated macrophages (TAMs) were analysis and the marker genes of M2 macrophage were selected. Differentially expressed genes (DEGs) in PCa were identified using limma and the immune infiltration was detected using CIBERSORTx. Then, a weighted correlation network analysis (WGCNA) was constructed to identify the M2 macrophage-related modules and genes. Integration of the marker genes of M2 macrophage from scRNA-seq data analysis and hub genes from WGCNA to select the prognostic gene signature based on Univariate and LASSO regression analysis. The risk score was calculated, and the DEGs, biological function, immune characteristics related to risk score were explored. And a predictive nomogram was constructed. CCK8, Transwell, and wound healing were used to verify cell phenotype changes after co-cultured. RESULTS: A total of 2431 marker genes of M2 macrophage and 650 hub M2 macrophage-related genes were selected based on scRNA-seq data and WGCNA. Then, 113 M2 macrophage-related genes were obtained by overlapping the scRNA-seq data and WGCNA results. Nine M2 macrophage-related genes (SMOC2, PLPP1, HES1, STMN1, GPR160, ABCG1, MAZ, MYC, and EPCAM) were screened as prognostic gene signatures. M2 risk score was calculated, the DEGs, Immune score, stromal score, ESTIMATE score, tumor purity, and immune cell infiltration, immune checkpoint expression, and responses of immunotherapy and chemotherapy were identified. And a predictive nomogram was constructed. CCK8, Transwell invasion, and wound healing further verified that M2 macrophages promoted the proliferation, invasion, and migration of PCa (p < 0.05). CONCLUSIONS: We uncovered that M2 macrophages and relevant genes played key roles in promoting the occurrence, development, and metastases of PCa and played as convincing predictors in PCa.

Construction and application of "organ-system-centered" undergraduate nursing professional training model.

OBJECTIVE: The purpose of this study is to construct an organ system-centered undergraduate nursing professional training model and explore its application effect. METHODS: This study is divided into two steps. In the early stage, literature review and expert consultation were used to establish the training mode (curriculum and assessment standard) of nursing undergraduate specialty based on organ system reform. Secondly, a cross-sectional survey method was used to investigate the training quality of nursing students who graduated from Jinzhou Medical University from 2007 to 2017 under this model. RESULTS: A five-module curriculum system was established, including general courses, public basic courses, professional education courses, expanding elective courses and concentrated practical teaching. Under the teaching reform of organ system, the nursing graduates of Jinzhou Medical University, who are mainly employed in public hospitals, are generally not satisfied with their jobs, salaries, contents and prospects. Their overall satisfaction with their alma mater is very high; Graduates have certain independent core competence; Employers are basically satisfied with graduates. CONCLUSION: The training mode of undergraduate nursing specialty based on organ system reform basically meets the training requirements and objectives.

Identification of severe fever with thrombocytopenia syndrome virus isolates in the northwest of Hubei Province, China.

Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne viral disease that is increasingly affecting human being worldwide. The clinical manifestations and mortality rates of SFTS can vary depending on the geographic region and the specific genotype of the SFTS virus (SFTSV). From July 2022 to August 2023, we collected serum samples from 83 patients with suspected SFTSV infection in the northwest of Hubei Province, China. From which, 13 patients tested positive for SFTSV. Phylogenetic analysis of the SFTSV L, M, and S gene segments was performed using the maximum likelihood method to determine the genetic diversity of the isolates. At least 2 SFTSV genotypes (A and F) were identified in the northwest of Hubei Province. The clinical manifestations and laboratory findings on the first day of admission were investigated. Results showed that bleeding and disturbance of consciousness, and significant elevated AST and APTT, are valuable for assessing the prognosis for SFTS patients. This study disclosed the genomic sequences and genotypes of SFTSV spreading in the northwest of Hubei Province for the first time, providing information of genetically etiology for SFTS in the local district. Furthermore, certain symptoms and/or laboratory findings may indicate adverse clinical outcomes, highlighting the importance of identifying the symptoms and monitoring specific laboratory markers. Future research is needed to investigate the threshold values of these markers and to closely observe the indicative symptoms in order to early identify and timely management of critically ill patients within clinical settings.

Dysregulation of lncRNA TFAP2A-AS1 is involved in the pathogenesis of pulpitis by the regulation of microRNA-32-5p.

OBJECTIVE: This study was designed to evaluate TFAP2A-AS1 expression in the dental pulp of teeth with or without pulpitis and to determine the function of TFAP2A-AS1 in pulp cells. METHODS: GSE92681 was analyzed to filter out differentially expressed lncRNAs. Pulp samples from teeth with pulpitis and healthy teeth (control) were examined using real-time (RT) quantitative polymerase chain reaction (qPCR). Human dental pulp stem cells (hDPSCs) were cultured in a specific medium for osteogenic induction, or treated with lipopolysaccharide (LPS) to simulate inflammation. The viability and apoptosis of human DPSCs (hDPSCs) were determined by XTT assay and apoptosis detection kit. Inflammation was induced by LPS and assessed by measuring the expression and release of inflammatory cytokines after TFAP2A-AS1 knockdown. Osteogenic differentiation of hDPSCs was investigated by determining expression levels of osteogenic markers and alkaline phosphatase (ALP) activity after TFAP2A-AS1 overexpression. The downstream microRNA (miRNA) was predicted. Dual-luciferase reporter was used to confirm the binding between miR-32-5p and TFAP2A-AS1. RESULTS: The expression of TFAP2A-AS1 was evaluated in inflamed pulp using RT-qPCR. TFAP2A-AS1 had a discriminatory ability for healthy individuals and patients with pulpitis. The expression of TFAP2A-AS1 decreased upon the osteogenic differentiation of hDPSCs, and increased upon the LPS induction. TFAP2A-AS1 can reverse the osteogenic differentiation of hDPSCs, as evidenced by decreased levels of dentine sialophosphoprotein, dentin matrix protein-1, and ALP activity. TFAP2A-AS1 knockdown can promote cell proliferation of hDPSCs and relieve LPS-induced inflammation, as evidenced by decreased levels of TNF-α, IL-1ß, and IL-6. miR-32-5p was identified as a downstream miRNA of TFAP2A-AS1. CONCLUSION: This study demonstrated the expression and potential function of TFAP2A-AS1 in the human dental pulp. TFAP2A-AS1 can inhibit odontogenic differentiation but promote inflammation in pulp cells.

Strain- and sex-specific differences in intestinal microhemodynamics and gut microbiota composition.

Background: Intestinal microcirculation is a critical interface for nutrient exchange and energy transfer, and is essential for maintaining physiological integrity. Our study aimed to elucidate the relationships among intestinal microhemodynamics, genetic background, sex, and microbial composition. Methods: To dissect the microhemodynamic landscape of the BALB/c, C57BL/6J, and KM mouse strains, laser Doppler flowmetry paired with wavelet transform analysis was utilized to determine the amplitude of characteristic oscillatory patterns. Microbial consortia were profiled using 16S rRNA gene sequencing. To augment our investigation, a broad-spectrum antibiotic regimen was administered to these strains to evaluate the impact of gut microbiota depletion on intestinal microhemodynamics. Immunohistochemical analyses were used to quantify platelet endothelial cell adhesion molecule-1 (PECAM-1), estrogen receptor α (ESR1), and estrogen receptor ß (ESR2) expression. Results: Our findings revealed strain-dependent and sex-related disparities in microhemodynamic profiles and characteristic oscillatory behaviors. Significant differences in the gut microbiota contingent upon sex and genetic lineage were observed, with correlational analyses indicating an influence of the microbiota on microhemodynamic parameters. Following antibiotic treatment, distinct changes in blood perfusion levels and velocities were observed, including a reduction in female C57BL/6J mice and a general decrease in perfusion velocity. Enhanced erythrocyte aggregation and modulated endothelial function post-antibiotic treatment indicated that a systemic response to microbiota depletion impacted cardiac amplitude. Immunohistochemical data revealed strain-specific and sex-specific PECAM-1 and ESR1 expression patterns that aligned with observed intestinal microhemodynamic changes. Conclusions: This study highlights the influence of both genetic and sex-specific factors on intestinal microhemodynamics and the gut microbiota in mice. These findings also emphasize a substantial correlation between intestinal microhemodynamics and the compositional dynamics of the gut bacterial community.

Endometrial carcinoma with cervical stromal invasion: Three case reports.

BACKGROUND: Endometrial cancer is a kind of well-known tumors of female genitourinary system. Cervical stromal invasion is an adverse factor for poor prognosis of endometrial cancer. There is still controversy regarding the use of magnetic resonance imaging (MRI) in the diagnosis of cervical stromal invasion of endometrial cancer. The diagnosis of cervical stromal invasion varies significantly between different observers and institutions. We present a limited case series of the particular pattern of endometrial cancer, which infiltrates the cervical stroma and is often overlooked. CASE SUMMARY: We present three cases of endometrial carcinoma with cervical stromal invasion with cancer-free uterine cavity. One patient, a reproductive-aged woman, exhibited irregular menstruation and was diagnosed with endometrial polyps by hysteroscopy and segmental curettage. A MRI scan revealed polypoid nodules within the internal cervical orifice. The other two cases were postmenopausal women who presented with abnormal vaginal bleeding. Hysteroscopy and segmental curettage suggested atypical hyperplasia of the endometrium. MRI scans did not detect any malignant signs in the endometrium. In one case, a non-thickened endometrium was observed, while in another, hyperplasia of the endometrium was seen. Notably, none of these patients had malignant tumors identified in the uterine cavity via MRI scans. However, postoperative pathological results following hysterectomy consistently indicated cervical stromal invasion. CONCLUSION: Cervical stromal invasion is easily missed if no cancer is found in the uterine body on MRI. Immunohistochemistry of endoscopic curettage specimens should be conducted to avoid underestimation of the disease.

Individual and combined effects of famine exposure and obesity parameters on type 2 diabetes in middle-aged and older adults: A population-based cross-sectional study.

Malnutrition early in life may have adverse effects on health later in life. The relationship between malnutrition and obesity parameters (body mass index [BMI] and waist circumference [WC]) and type 2 diabetes is inconsistent. This study aimed to identify the effects of famine exposure and obesity parameters on type 2 diabetes individually or in combination among middle-aged and older adults in China. Data were extracted from the China Health and Retirement Longitudinal Study Wave1 in 2011. The sample involved 13,065 adults aged 45 to 90. The t- or F test was employed to compare age among groups. The chi-square test was utilized to compare baseline characteristics according to the categorical WC levels/BMI levels/famine exposure and examine between-group differences in type 2 diabetes (diabetes and non-diabetes). Odds ratio (OR) and 95% confidence interval (CI) were estimated by logistic regression models to estimate the individual and combined associations of BMI/WC levels and famine exposure with the prevalence of type 2 diabetes. In this study, 1559 (11.93%) individuals were exposed to Chinese famine during their fetal stage, 5132 (39.28%) and 4428 (33.89%) in childhood and adolescence/adulthood, respectively. Among BMI measurements, 3780 (28.93%) were overweight, and 1487 (11.38%) were obese, whereas WC measurements showed that 5408 (41.39%) were obesity. In addition, 831 (45.48%) males and 996 (54.52%) females reported type 2 diabetes. In multivariable-adjusted regression models, obesity parameters and famine exposure were independently associated with type 2 diabetes prevalence among all participants (P < .001). In the interaction analysis, there existed a trend of higher odds for prevalence of type 2 diabetes across all groups compared to the combination of no-exposed and normal BMI/WC level group (the most increase in odds, adolescence/adulthood-exposed group with central obesity in WC levels: OR 4.51 (95% CI = 3.42-5.95); adolescence/adulthood-exposed group with obesity in BMI levels: OR 5.84 (95% CI = 4.11-8.30; P for interaction <.001). The findings for females exhibited similar to the overall participants, when by gender stratification. Our results suggest famine exposure and obesity parameters have positive combined effects on type 2 diabetes in middle-aged and older adults in China.

Evaluation of the inhibitory effects of sitamaquine on Babesia infections.

The treatment strategies for either human or animal babesiosis have been established and used for many years. With the rising indications of drug resistance and adverse side effects, finding effective and alternative therapies is urgently needed. Sitamaquine (SQ) is an 8-aminoquinoline that was first synthesized as a part of the collaborative anti-malarial program that led to primaquine. In this study, we evaluated the inhibitory effects of SQ on Babesia spp. in vitro and in vivo. The half-maximal inhibitory concentration (IC50) on in vitro cultured Babesia gibsoni was 8.04 ± 1.34 µM. Babesia gibsoni parasites showed degenerative morphological changes following SQ treatment. The in vivo growth inhibitory effects of SQ were evaluated in BALB/c mice infected with B. microti and atovaquone (ATV)-resistant B. microti strain. Oral administration of SQ at a dose of 20 mg/kg significantly inhibited the growth of B. microti and ATV-resistant B. microti. Meanwhile, SQ also showed inhibitory effects on the growth of B. rodhaini, a lethal rodent Babesia species. All mice infected with B. rodhaini treated with SQ survived, whereas the mice in the control group succumbed to the disease. The results obtained in this study indicate that SQ has potent inhibition effects against Babesia spp., which support SQ as a prospective alternative candidate for babesiosis treatment.

Regulation of ginseng adventitious root growth in Panax ginseng by the miR156-targeted PgSPL24-09 transcription factors.

MicroRNA (miRNA) is a class of non-coding endogenous small-molecule, single-stranded RNAs, and it is involved in post-transcriptional gene expression regulation in plants and plays an important role in plant growth and development. Among them, miRNA156 regulates members of target SPL gene family and thus participates in plant growth and development, hormonal response and adversity stress. However, it has not been reported in ginseng. In this study, based on the previous analysis of the SPL gene family, the age-related and stably expressed SPL gene PgSPL24-09 was obtained in roots. The binding site of miRNA156 to this gene was analyzed using target gene prediction tools, and the interactions between miRNA156 and PgSPL24-09 gene were verified by dual luciferase reporter gene assay and RT-qPCR. At the same time, miRNA156 silencing vector and overexpression vector were constructed and transformed into ginseng adventitious roots and Arabidopsis thaliana to analyze the molecular mechanism of miRNA156-SPL module in regulating the growth of ginseng adventitious roots. This study provides a theoretical basis for the in-depth study of the molecular role of miRNAs in ginseng growth, and also lays the foundation for the study of the role of miRNA156-SPL module in regulating the growth and development of ginseng.

Study on the value of MRI in locating the internal OS of the cervix and influencing factors.

The position of the internal os of the cervix reported in the literature was inconsistent on MRI images. Additionally, the practical impactful data influencing the internal os located by MRI is limited. We aimed to confirm the position of the internal os of the cervix on MRI images, and the influencing factors locating the the internal os by MRI. A single-center retrospective study was conducted. Data from 175 patients who underwent total hysterectomy for stage I endometrial cancer were collected. The internal os of the cervix is positioned as the starting point for measuring the length of the cervix on MRI images. On dynamic contrast-enhanced MRI (DCE-MRI), the section formed by the enhancement difference between the uterus and cervix, and on T2-weighted imaging(T2WI), the section formed by the physiological curvature of the uterus and the low signal intensity of the cervical stroma were used as starting points. The results showed no statistically significant difference compared with the removed uterus specimens (p = 0.208, p = 0.571, p = 0.804). A history of cesarean section(p < 0.001), irregular vaginal bleeding for more than three months(p < 0.001), cervical adenomyosis(p = 0.043), and premenopause(p = 0.001) were not conducive to locating the internal os of the cervix by MRI. Our findings provide valuable information and confirm the position of the internal os of the cervix on MRI images, and the several important infuencing factors. We hope that some patients will benefit from our study.

Predictive role of depressive symptoms on frailty and its components in Chinese middle-aged and older adults: a longitudinal analysis.

BACKGROUND: To investigate the cross-sectional and longitudinal associations between depressive symptoms and the prevalence of frailty and its components in a nationally representative sample of middle-aged and older Chinese adults. METHOD: The China Health and Retirement Longitudinal Study (CHARLS) provided data on 2581 (after inclusion and exclusion criteria) adults aged ≥ 45 years. Every two years, face-to-face, computer-aided personal interviews (CAPI), and structured questionnaires were used to follow up with the respondents. The Chinese version of the Center for Epidemiologic Studies-Depression Scale (CES-D) was used to evaluate depressive symptoms, and the Fried criteria were used to measure frailty. The odds ratio (OR) and 95% confidence interval (CI) for the association of exposure (depressive symptoms at baseline) with the onset of the outcome (frailty and its components) in the individuals at baseline were analyzed by binary logistic regression. RESULTS: At baseline, 11.62% of participants had frailty, and 57.92% had depressive symptoms. In the cross-sectional analysis, depressive symptoms (OR = 5.222, 95%CI 3.665-7.442) were associated with frailty. In the longitudinal analysis, after adjusting for the full set of covariates among participants free of baseline frailty, depressive symptoms were significantly associated with incident frailty during the short term (OR = 2.193, 95%CI 1.324-3.631) and the long term (OR = 1.926, 95%CI 1.021-3.632). Meanwhile, depressive symptoms were associated with an increased risk of weakness (OR = 1.990, 95%CI 1.250-3.166), slowness (OR = 1.395, 95%CI 1.044-1.865), and exhaustion (OR = 2.827, 95%CI 2.150-3.719) onset during the short-term. Depressive symptoms were associated with an increased risk of exhaustion (OR = 2.869, 95%CI 2.004-4.109) onset during the long-term. CONCLUSION: Among middle-aged and older adults, depressive symptoms could predict frailty during 2 years of follow-up and 4 years of follow-up. When considering potential confounding factors, depressive symptoms were considered a predictor of weakness, slowness, and exhaustion. Interventions aimed at preventing depressive symptoms may be beneficial in reducing frailty and its components.

Impact of several sludge dewatering conditioners on municipal sludge pyrolysis properties, kinetics, by-products, and environmental risk assessment.

The pyrolysis characteristics of four different types of conditioned sludge were ascertained, and PAM, CaO, K2FeO4, and K2FeO4-CaO-PAM (KCP) conditioners were employed as sludge dewatering conditioners. The sludge pyrolysis reaction's activation energy (E) dropped with the addition of four conditioners. CaO, PAM, KCP, and K2FeO4 were the sequences of E needed for the pyrolysis of four different types of conditioned sludge. The addition of K2FeO4, CaO, and KCP resulted in an increase in the yields of H2 and CO. Except for the K2FeO4 conditioning sludge carbon, the pyrolytic carbon of the other three groups of samples showed an increase in S contents, while the pyrolytic carbon of the four groups of samples treated with conditioners clearly showed lower C and N contents compared to the raw sludge carbon. Protein-N made up the majority of N in sludge pyrolytic carbon. After adding conditioner, the level of organic sulfur decreased. Organic sulfur could then be broken down by K2FeO4 and CaO. The four conditioners efficiently mitigated the ecological and environmental risks posed by heavy metals. Alkynes were the most abundant result in pyrolytic volatiles of sludge pyrolysis; the other products included acids, alcohols, lipids, furans, ketones, phenols, hydrocarbons, N-components, and so on. All samples' acids, alcohols, and ketones from pyrolysis were decreased once the conditioner was added. The acid reduction rate reached 66.7 %, and the alkynes clearly increased during the KCP conditioned sludge's pyrolysis. The sulfur level of the bio-oil was decreased by all four conditioners. Everything mentioned above indicated that the KCP aided in the subsequent pyrolysis of the sludge, leading to the production of an advantageous pyrolysis bio-oil.

Tanshinone IIA Promoted Autophagy and Inhibited Inflammation to Alleviate Podocyte Injury in Diabetic Nephropathy.

Purpose: Tanshinone IIA (Tan-IIA) is widely used in patients with diabetic nephropathy (DN), but its protective effect on podocytes in DN has not been well studied. In this study, the effects of Tan-IIA on autophagy and inflammation of glomerular podocytes in DN were observed in vivo and in vitro, and the underlying mechanisms were investigated. Irbesartan, an angiotensin II receptor blocker, is a representative medication for the clinical treatment of DN. So irbesartan was chosen as a positive control drug. Methods: Eight-week-old male db/db mice were randomly divided into a DN group, an irbesartan group, and three groups receiving different doses of Tan-IIA. The control group consisted of the db/m littermate mice. Blood, urine, and kidney samples were taken from the mice after 12 weeks of continuous administration. Renal protection of Tan-IIA was evaluated using enzyme-linked immunosorbent assay kits, haematoxylin and eosin staining, transmission electron microscopy, Western blotting, and immunohistochemistry. In vitro, the protective effect of Tan-IIA on podocytes was explored using MPC5 cells cultured with high glucose. Results: Tan-IIA significantly improved renal pathological injury and relieved the renal dysfunction in DN. Compared with the DN group, Tan-IIA could up-regulate the expression of Synaptopodin, Podocin, LC3II/I and Beclin-1 (p < 0.05), and down-regulate the expression of p62, F4/80, NF-κB p65, IL-1ß, TNF-α and IL-6 (p < 0.05) both in vivo and in vitro, suggesting that Tan-IIA treatment alleviated podocyte injury by promoting autophagy and inhibiting inflammation during DN. The levels of p-PI3K/PI3K, p-Akt/Akt and p-mTOR/mTOR in Tan-IIA group were lower than those in DN group (p < 0.05), indicating that Tan-IIA inhibited the PI3K/Akt/mTOR signalling pathway in podocytes, which was a key pathway in regulating both autophagy and inflammation. Conclusion: Tan-IIA prevented podocyte injury in DN by fostering autophagy and inhibiting inflammation, at least in part via inhibition of the PI3K/Akt/mTOR signalling pathway.

Brain ischemia causes systemic Notch1 activity in endothelial cells to drive atherosclerosis.

Stroke leads to persistently high risk for recurrent vascular events caused by systemic atheroprogression that is driven by endothelial cell (EC) activation. However, whether and how stroke induces sustained pro-inflammatory and proatherogenic endothelial alterations in systemic vessels remain poorly understood. We showed that brain ischemia induces persistent activation, the upregulation of adhesion molecule VCAM1, and increased senescence in peripheral ECs until 4 weeks after stroke onset. This aberrant EC activity resulted from sustained Notch1 signaling, which was triggered by increased circulating Notch1 ligands DLL1 and Jagged1 after stroke in mice and humans. Consequently, this led to increased myeloid cell adhesion and atheroprogression by generating a senescent, pro-inflammatory endothelium. Notch1- or VCAM1-blocking antibodies and the genetic ablation of endothelial Notch1 reduced atheroprogression after stroke. Our findings revealed a systemic machinery that induces the persistent activation of peripheral ECs after stroke, which paves the way for therapeutic interventions or the prevention of recurrent vascular events following stroke.

Altered counts and mitochondrial mass of peripheral blood leucocytes in patients with chronic hepatitis B virus infection.

Hepatitis B virus (HBV) damages liver cells through abnormal immune responses. Mitochondrial metabolism is necessary for effector functions of white blood cells (WBCs). The aim was to investigate the altered counts and mitochondrial mass (MM) of WBCs by two novel indicators of mitochondrial mass, MM and percentage of low mitochondrial membrane potential, MMPlow%, due to chronic HBV infection. The counts of lymphocytes, neutrophils and monocytes in the HBV infection group were in decline, especially for lymphocyte (p = 0.034) and monocyte counts (p = 0.003). The degraded MM (p = 0.003) and MMPlow% (p = 0.002) of lymphocytes and MM (p = 0.005) of monocytes suggested mitochondrial dysfunction of WBCs. HBV DNA within WBCs showed an extensive effect on mitochondria metabolic potential of lymphocytes, neutrophils and monocytes indicated by MM; hepatitis B e antigen was associated with instant mitochondrial energy supply indicated by MMPlow% of neutrophils; hepatitis B surface antigen, antiviral therapy by nucleos(t)ide analogues and prolonged infection were also vital factors contributing to WBC alterations. Moreover, degraded neutrophils and monocytes could be used to monitor immune responses reflecting chronic liver fibrosis and inflammatory damage. In conclusion, MM combined with cell counts of WBCs could profoundly reflect WBC alterations for monitoring chronic HBV infection. Moreover, HBV DNA within WBCs may be a vital factor in injuring mitochondria metabolic potential.

TM9SF1 offers utility as an efficient predictor of clinical severity and mortality among acute respiratory distress syndrome patients.

Introduction: Acute respiratory distress syndrome (ARDS) is a major cause of death among critically ill patients in intensive care settings, underscoring the need to identify biomarkers capable of predicting ARDS patient clinical status and prognosis at an early time point. This study specifically sought to explore the utility and clinical relevance of TM9SF1 as a biomarker for the early prediction of disease severity and prognostic outcomes in patients with ARDS. Methods: This study enrolled 123 patients with severe ARDS and 116 patients with non-severe ARDS for whom follow-up information was available. The mRNA levels of TM9SF1 and cytokines in peripheral blood mononuclear cells from these patients were evaluated by qPCR. The predictive performance of TM9SF1 and other clinical indicators was evaluated using received operating characteristic (ROC) curves. A predictive nomogram was developed based on TM9SF1 expression and evaluated for its ability in the early prediction of severe disease and mortality in patients with ARDS. Results: TM9SF1 mRNA expression was found to be significantly increased in patients with severe ARDS relative to those with non-severe disease or healthy controls. ARDS severity increased in correspondence with the level of TM9SF1 expression (odds ratio [OR] = 2.43, 95% confidence interval [CI] = 2.15-3.72, P = 0.005), and high TM9SF1 levels were associated with a greater risk of mortality (hazard ratio [HR] = 2.27, 95% CI = 2.20-4.39, P = 0.001). ROC curves demonstrated that relative to other clinical indicators, TM9SF1 offered superior performance in the prediction of ARDS severity and mortality. A novel nomogram incorporating TM9SF1 expression together with age, D-dimer levels, and C-reactive protein (CRP) levels was developed and was used to predict ARDS severity (AUC = 0.887, 95% CI = 0.715-0.943). A separate model incorporating TM9SF1 expression, age, neutrophil-lymphocyte ratio (NLR), and D-dimer levels (C-index = 0.890, 95% CI = 0.627-0.957) was also developed for predicting mortality. Conclusion: Increases in ARDS severity and patient mortality were observed with rising levels of TM9SF1 expression. TM9SF1 may thus offer utility as a novel biomarker for the early prediction of ARDS patient disease status and clinical outcomes.