Uveal melanoma distant metastasis prediction system: A retrospective observational study based on machine learning.

Uveal melanoma (UM) patients face a significant risk of distant metastasis, closely tied to a poor prognosis. Despite this, there is a dearth of research utilizing big data to predict UM distant metastasis. This study leveraged machine learning methods on the Surveillance, Epidemiology, and End Results (SEER) database to forecast the risk probability of distant metastasis. Therefore, the information on UM patients from the SEER database (2000-2020) was split into a 7:3 ratio training set and an internal test set based on distant metastasis presence. Univariate and multivariate logistic regression analyses assessed distant metastasis risk factors. Six machine learning methods constructed a predictive model post-feature variable selection. The model evaluation identified the multilayer perceptron (MLP) as optimal. Shapley additive explanations (SHAP) interpreted the chosen model. A web-based calculator personalized risk probabilities for UM patients. The results show that nine feature variables contributed to the machine learning model. The MLP model demonstrated superior predictive accuracy (Precision = 0.788; ROC AUC = 0.876; PR AUC = 0.788). Grade recode, age, primary site, time from diagnosis to treatment initiation, and total number of malignant tumors were identified as distant metastasis risk factors. Diagnostic method, laterality, rural-urban continuum code, and radiation recode emerged as protective factors. The developed web calculator utilizes the MLP model for personalized risk assessments. In conclusion, the MLP machine learning model emerges as the optimal tool for predicting distant metastasis in UM patients. This model facilitates personalized risk assessments, empowering early and tailored treatment strategies.

Addressing healthy aging in China: Practices and prospects.

One important challenge for global development is aging. China is one of the world's countries with the highest elderly population and the most rapid aging; in 2022, the percentage of the population over 65 was 14.9%; by 2050, it is expected to rise to 26.1%. China's health security, elderly care, and healthcare services are facing serious challenges as a result of this aging trend. With 80% of provinces including medical and elderly care in national basic public health care programs, China has adopted a proactive national plan to combat population aging. Moreover, geriatric departments have been established at 69.3% of public general hospitals at secondary and higher tiers, 48% of provinces have devises preventive interventions for disability and dementia in the elderly, 48 percent of provinces are serving as test regions for medical care related to rehabilitation, and 49 cities are involved in long-term care insurance (LTCI) trials that encompass 170 million people. There are 4,259 medical and health care facilities that provide hospice care services, 152 hospice care pilot regions, and 87,000 pairs of contracts between medical and health care facilities and elderly care providers. These developments provide a strong basis, but there are still major obstacles to overcome. The Chinese Government is urged to adopt early preventive measures, offer more ongoing, practical, and cost-effective diagnostic and treatment services, allocate resources equitably, and use intelligent technologies to enhance elderly care. The ultimate goals are to lessen the financial burden, enhance the health of the elderly, and offer a vital global resource.

Analyzing psychological resilience in college students: A decision tree model.

In the evolving landscape of higher education, particularly in the post-pandemic era, it is crucial for college students to face societal challenges and achieve success by understanding and predicting psychological resilience. To deepen our understanding of psychological resilience, this study used a decision tree model to explore influencing factors. We surveyed 776 college students and collected data on demographic information, self-esteem, sense of school belonging, pro-environmental behavior, subjective well-being, internet game addiction, life autonomy, and academic procrastination using several scales. The decision tree model identified eight key predictors of psychological resilience, which are as follows in order of importance: self-esteem, sense of school belonging, pro-environmental behavior, subjective well-being, academic procrastination, life autonomy, internet game addiction, and academic achievement. This model's accuracy reached 73.985 %, emphasizing its potential utility in educational settings. The findings not only provide a novel and data-driven perspective to understand psychological resilience in college students compared to existing research but also provide practical guidance for educational practitioners and policymakers on how to develop psychological resilience in college students.

Nonclinical immunogenicity risk assessment for knobs-into-holes bispecific IgG1 antibodies.

Bispecific antibodies, including bispecific IgG, are emerging as an important new class of antibody therapeutics. As a result, we, as well as others, have developed engineering strategies designed to facilitate the efficient production of bispecific IgG for clinical development. For example, we have extensively used knobs-into-holes (KIH) mutations to facilitate the heterodimerization of antibody heavy chains and more recently Fab mutations to promote cognate heavy/light chain pairing for efficient in vivo assembly of bispecific IgG in single host cells. A panel of related monospecific and bispecific IgG1 antibodies was constructed and assessed for immunogenicity risk by comparison with benchmark antibodies with known low (Avastin and Herceptin) or high (bococizumab and ATR-107) clinical incidence of anti-drug antibodies. Assay methods used include dendritic cell internalization, T cell proliferation, and T cell epitope identification by in silico prediction and MHC-associated peptide proteomics. Data from each method were considered independently and then together for an overall integrated immunogenicity risk assessment. In toto, these data suggest that the KIH mutations and in vitro assembly of half antibodies do not represent a major risk for immunogenicity of bispecific IgG1, nor do the Fab mutations used for efficient in vivo assembly of bispecifics in single host cells. Comparable or slightly higher immunogenicity risk assessment data were obtained for research-grade preparations of trastuzumab and bevacizumab versus Herceptin and Avastin, respectively. These data provide experimental support for the common practice of using research-grade preparations of IgG1 as surrogates for immunogenicity risk assessment of their corresponding pharmaceutical counterparts.

Characterization of the Aroma Profile of Ginger Powder Produced by a Split-Stream Spray-Drying Process.

Freeze-dried ginger (Zingiber officinale) is renowned for its high quality, but it is expensive. As an alternative, spray drying can be explored for producing ginger powder. However, sugar rich feed solutions can lead to stickiness development during the process. Adding carrier materials increases costs and labeling. Accordingly, a split-stream spray-drying process was developed, where ginger fibers in their natural composition were reintroduced as a carrier material into the spray-drying process. The inlet and outlet temperatures were set at 220 and 80 °C, respectively, for optimal aroma retention. Using a stir bar sorptive extraction-gas chromatography-mass spectrometry-olfactometry, the results revealed that reintegrating ginger fibers significantly increased the concentration of eight key odorants. Although freeze-dried ginger retains more aroma, the total concentration of twenty-seven odorants in the developed spray-dried ginger was 1.9 times higher compared to frozen ginger.

Two new jatrophane diterpenoids from Euphorbia helioscopia with activity towards autophagic flux.

Nine jatrophane diterpenoids were isolated from the whole plant Euphorbia helioscopia, including two new ones, helioscopnins A (1) and B (2). Comprehensive spectroscopic data analysis and ECD calculations elucidated their structures, including absolute configurations. All compounds were evaluated for bioactivity towards autophagic flux by flow cytometry using HM mCherry-GFP-LC3 cells. Compounds 1, 3, 4, 5, 8, and 9 significantly increased autophagic flux.

Study on Nutrient Carrier of Mulch Based on Hydrogel @SiO2.

Soil conservation is one of the best methods to improve soil fertility and enhance crop growth efficiency. Replacing plastic mulch with biomass is an environmentally friendly strategy. Innovative encapsulated soil granules (ESGs) were developed using PVA/PC film as the wall material and rural soil as the core. The PVA/PC was synthesized using 60% protein polypeptide (PC) from leather waste scrap and 35% poly (vinyl alcohol) (PVA), which was optimized for water absorption expansion and water retention performance. The ESG-10 granulated with 10% PVA/PC exhibited good water absorption, moisture retention, and resistance to water solubility. As an auxiliary material for soil improvement, the amount of ESGs mixed with the topsoil at ratios of 0 g/m2, 200 g/m2, and 400 g/m2 was proportional to the soil insulation and moisture retention. In rapeseed cultivation, the experimental results indicated that the soil mulched with ESG-10 can maintain seedling vitality for a long time under low water content conditions.

Deletion of Tgm2 suppresses BMP-mediated hepatocyte-to-cholangiocyte metaplasia in ductular reaction.

Transglutaminase 2 (Tgm2) plays an essential role in hepatic repair following prolonged toxic injury. During cholestatic liver injury, the intrahepatic cholangiocytes undergo dynamic tissue expansion and remodelling, referred to as ductular reaction (DR), which is crucial for liver regeneration. However, the molecular mechanisms governing the dynamics of active cells in DR are still largely unclear. Here, we generated Tgm2-knockout mice (Tgm2-/-) and Tgm2-CreERT2-Rosa26-mTmG flox/flox (Tgm2CreERT2-R26T/Gf/f) mice and performed a three-dimensional (3D) collagen gel culture of mouse hepatocytes to demonstrate how Tgm2 signalling is involved in DR to remodel intrahepatic cholangiocytes. Our results showed that the deletion of Tgm2 adversely affected the functionality and maturity of the proliferative cholangiocytes in DR, thus leading to more severe cholestasis during DDC-induced liver injury. Additionally, Tgm2 hepatocytes played a crucial role in the regulation of DR through metaplasia. We unveiled that Tgm2 regulated H3K4me3Q5ser via serotonin to promote BMP signalling activation to participate in DR. Besides, we revealed that the activation or inhibition of BMP signalling could promote or suppress the development and maturation of cholangiocytes in DDC-induced DR. Furthermore, our 3D collagen gel culture assay indicated that Tgm2 was vital for the development of cholangiocytes in vitro. Our results uncovered a considerable role of BMP signalling in controlling metaplasia of Tgm2 hepatocytes in DR and revealed the phenotypic plasticity of mature hepatocytes.

Cross-sectional study of pharmacovigilance knowledge, attitudes, and practices based on structural equation modeling and network analysis: a case study of healthcare personnel and the public in Yunnan Province.

Background: This study focuses on understanding pharmacovigilance knowledge, attitudes, and practices (KAP) in Yunnan Province, employing Structural Equation Modeling (SEM) and network analysis. It aims to evaluate the interplay of these factors among healthcare personnel and the public, assessing the impact of demographic characteristics to inform policy and educational initiatives. Methods: A cross-sectional survey was conducted in Yunnan, targeting healthcare personnel and the public. Data collection was through questionnaires, with subsequent analysis involving correlation matrices, network visualization, and SEM. The data analysis utilized SPSS 27.0, AMOS 26.0, and Gephi software for network analysis. Results: This study evaluated pharmacovigilance KAP among 209 public participants and 823 healthcare personnel, uncovering significant differences. Public respondents scored averages of 4.62 ± 2.70 in knowledge, 31.99 ± 4.72 in attitudes, and 12.07 ± 4.96 in practices, while healthcare personnel scored 4.38 ± 3.06, 27.95 ± 3.34, and 7.75 ± 2.77, respectively. Statistically significant correlations across KAP elements were observed in both groups, highlighting the interconnectedness of these factors. Demographic influences were more pronounced among healthcare personnel, emphasizing the role of professional background in pharmacovigilance competency. Network analysis identified knowledge as a key influencer within the pharmacovigilance KAP network, suggesting targeted education as a vital strategy for enhancing pharmacovigilance engagement. Conclusion: The research reveals a less-than-ideal state of pharmacovigilance KAP among both healthcare personnel and the public in Yunnan, with significant differences between the two groups. SEM and network analysis confirmed a strong positive link among KAP components, moderated by demographics like age, occupation, and education level. These insights emphasize the need to enhance pharmacovigilance education and awareness, thereby promoting safer drug use.

TET2 regulation of alcoholic fatty liver via Srebp1 mRNA in paraspeckles.

Epigenetic modifications have emerged as key regulators of metabolism-related complex diseases including the alcoholic fatty liver disease (AFLD) prevalent chronic liver disorder with significant economic implications. Building upon previous research that emphasizes ten-eleven translocation (TET) proteins' involvement in adipocyte insulin sensitization and fatty acid oxidation, we explored the role of TET2 protein in AFLD pathogenesis which catalyzes 5-methylcytosine into 5-hydroxymethylcytosine in DNA/RNA. Our findings revealed that TET2 deficiency exacerbates AFLD progression. And TET2 influenced the expression and activity of sterol regulatory element binding protein 1 (SREBP1), a key regulator of hepatic lipid synthesis, by modulating Srebp1 mRNA retention. Employing RIP-qPCR and bisulfite sequencing techniques, we provided evidence of TET2-mediated epigenetic modifications on Srebp1 mRNA, thereby affecting lipid metabolism. Through elucidating the role of methylation in RNA nuclear retention via paraspeckles, our study enhances understanding of AFLD pathogenesis from an epigenetic perspective, paving the way for identifying potential therapeutic targets.

Comparison of Second-Generation Cryoballoon Ablation and Quantitative Radiofrequency Ablation Guided by Ablation Index for Atrial Fibrillation.

We compared the efficacy and complication rates of quantitative radiofrequency ablation guided by ablation index (RFCA-AI) with those of second-generation cryoballoon ablation (CBA-2). Consecutive patients (n = 230) with symptomatic atrial fibrillation (AF) undergoing a first ablation CBA-2 (92 patients) or RFCA-AI (138 patients) procedure were enrolled in this study. The late recurrence rate in the CBA-2 group was higher than that in the RFCA-AI group (P = .012). Subgroup analysis showed the same result in patients with paroxysmal AF (PAF) (P = .039), but no difference was found in patients with persistent AF (P = .21). The average operation duration in the CBA-2 group (85 [75-99.5] minutes) was shorter than that in the RFCA-AI group (100 [84.5-120] minutes) (P < .0001), but the average exposure time (17.36(13.87-22.49) vs 5.49(4.00-8.24) minutes) in the CBA-2 group and X-ray dose (223.25(149.15-336.95) vs 109.15(80.75-168.7) mGym) were significantly longer than those in RFCA-AI group (P < .0001). Multivariate logistic regression analysis showed that left atrial diameter (LAD), early recurrence, and methods of ablation (cryoballoon ablation) were independent risk factors for late recurrence after AF ablation. Early recurrence of AF and LAD were independent risk factors for predicting late recurrence after AF ablation.

E3 ubiquitin ligase NEDD4L inhibits epithelial-mesenchymal transition by suppressing the ß-catenin/HIF-1α positive feedback loop in chronic rhinosinusitis with nasal polyps.

Chronic rhinosinusitis with nasal polyp (CRSwNP) is a refractory inflammatory disease with epithelial-mesenchymal transition (EMT) as one of the key features. Since ubiquitin modification has been shown to regulate the EMT process in other diseases, targeting ubiquitin ligases may be a potential strategy for the treatment of CRSwNP. In this study we investigated whether certain E3 ubiquitin ligases could regulate the EMT process in CRSwNP, and whether these regulations could be the potential drug targets as well as the underlying mechanisms. After screening the potential drug target by bioinformatic analyses, the expression levels of three potential E3 ubiquitin ligases were compared among the control, eosinophilic nasal polyp (ENP) and non-eosinophilic nasal polyp (NENP) group in clinical samples, and the significant decrement of the expression level of NEDD4L was found. Then, IP-MS, bioinformatics and immunohistochemistry studies suggested that low NEDD4L expression may be associated with the EMT process. In human nasal epithelial cells (hNECs) and human nasal epithelial cell line RPMI 2650, knockdown of NEDD4L promoted EMT, while upregulating NEDD4L reversed this effect, suggesting that NEDD4L inhibited EMT in nasal epithelial cells. IP-MS and Co-IP studies revealed that NEDD4L mediated the degradation of DDR1. We demonstrated that NEDD4L inhibited the ß-catenin/HIF-1α positive feedback loop either directly (degrading ß-catenin and HIF-1α) or indirectly (mediating DDR1 degradation). These results were confirmed in a murine NP model in vivo. This study for the first time reveals the regulatory role of ubiquitin in the EMT process of nasal epithelial cells, and identifies a novel drug target NEDD4L, which has promising efficacy against both ENP and NENP by suppressing ß-catenin/HIF-1α positive feedback loop.

Associations between Phthalate Metabolite Concentrations in Follicular Fluid and Reproductive Outcomes among Women Undergoing in Vitro Fertilization/Intracytoplasmic Sperm Injection Treatment.

BACKGROUND: Phthalates have been reported to impair fertility in various studies. However, evidence exploring the associations between phthalate metabolites in follicular fluid (FF) and reproductive outcomes is lacking. OBJECTIVES: To investigate the associations between phthalate metabolite concentrations in FF and in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes among women recruited from a fertility clinic. METHODS: We included 641 women undergoing IVF/ICSI treatment from December 2018 to January 2020. The levels of eight phthalate metabolites, including monoethyl phthalate (MEP), mono-isobutyl phthalate (MiBP), mono-n-butyl phthalate (MBP), monobenzyl phthalate (MBzP), mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), were quantified in FF collected on the oocyte retrieval day. Associations between quartiles of individual phthalate metabolite concentrations and nine IVF/ICSI outcomes, including oocyte yield, mature oocyte number, two distinct pronuclei (2PN) zygote number, fertilization rate, blastocyst formation rate, implantation, clinical pregnancy, miscarriage, and live birth, were estimated with generalized linear models. The effects of phthalate mixtures on IVF/ICSI outcomes were assessed using Bayesian kernel machine regression (BKMR) models. RESULTS: After adjusting for relevant confounders, elevated quartiles of MBzP, MEHHP, and MEHP in FF were inversely associated with the numbers of retrieved oocytes, mature oocytes, and 2PN zygotes (all p for trends <0.10). In comparison with the lowest quartile, the highest quartile of molar sum of di(2-ethylhexyl) phthalate metabolites (ΣDEHP) was associated with a reduction of 9.1% [95% confidence interval (CI): -17.1%, -0.37%] and 10.3% (95% CI: -18.8%, -0.94%) in yielded oocyte and mature oocyte numbers, respectively. Furthermore, the BKMR models revealed inverse associations between phthalate mixtures and the numbers of retrieved oocytes and mature oocytes. We generally found null results for implantation, clinical pregnancy, miscarriage, and live birth. DISCUSSION: Certain phthalate metabolites in FF are inversely associated with the numbers of retrieved oocytes, mature oocytes, and 2PN zygotes among women undergoing IVF/ICSI treatment. https://doi.org/10.1289/EHP11998.

Spatiotemporal profile and ecological impacts of major and trace elements in surface sediments of marginal seas of the Arctic and Northern Pacific Oceans.

The status and ecological impacts of sedimentary elements of the marginal seas of Arctic and Northern Pacific Oceans was investigated during 2016 to 2018 by using inductively coupled plasma mass spectrometry. Industrial (0.006 mg kg-1-64.6 g kg-1), precious (0.003-43.8 mg kg-1), rare earth (0.006-112.9 mg kg-1), and heavy metal (0.009-398.9 mg kg-1) elements showed spatial variation, and temporal uniformity. The results indicated ΣREEs and light REEs enrichment compared to chondrite and heavy REEs, respectively, while nonsignificant positive and negative δCe and δEu anomalies existed, respectively. High contamination and extreme enrichment of priority control, industrial (As, Mo, Re, Sb), precious (Au, Ir, Pd, Pt, and Ru) and RE elements indicated potential moderate to high ecological and biological risks. The study highlighted the ecological importance and fragile nature of these ecosystems and calls for an urgent action to ensure sustainability of these ecosystems.

Integrated investigation and discovery of therapeutic targets for 3-hydroxybakuchiol against diabetes based on molecular docking studies and cell experiments.

BACKGROUND: Diabetes mellitus is a prevalent endocrine condition. We aimed to investigate the anti-diabetic effects of 3-hydroxybakuchiol (HYD) by exploring its potential targets and molecular mechanisms through bioinformatics analysis and cell experiments. METHODS: We performed an extensive search and screening of HYD and its potential targets for diabetes mellitus across various databases. Enrichment analyses were conducted using the ClusterProfiler package. PPI networks of the identified genes were constructed using STRING, and topological analysis was performed to identify core targets. The results were further confirmed through molecular docking. To validate the findings of our bioinformatics analysis, we conducted cell experiments using insulin resistance-induced HepG2 cells and C2C12 cells. RESULTS: We discovered 260 common targets of HYD and diabetes mellitus, which were primarily related to the MAPK signaling pathway, PI3K-Akt signaling pathway, and endocrine resistance. A topological analysis of the PPI network identified four core targets (HSP90AA1, AKT1, SRC, and MAPK1). Molecular docking studies further confirmed the strong binding ability between HYD and these core targets. In cell experiments, we observed that HYD enhanced glucose uptake and suppressed gluconeogenesis in HepG2 cells and C2C12 cells. This resulted in an improvement in glucose metabolism, potentially through the regulation of the PI3K-Akt pathway. CONCLUSIONS: This study provides valuable insights into the pharmacological effects of HYD on diabetes mellitus, suggesting its potential as a promising treatment option for the disease.

Associations between phthalate metabolites and cytokines in the follicular fluid of women undergoing in vitro fertilization.

Many studies have showed that phthalates have reproductive and embryonic toxicity, while the potential mechanisms are mostly unknown. Inflammation may play a mediating part in phthalate exposure and adverse reproductive endpoints. A cross-sectional survey was conducted to investigate the associations of phthalate metabolites with inflammatory cytokines in the follicular fluid (FF) of women undergoing in vitro fertilization (IVF). We determined the levels of eight phthalate metabolites and five cytokines in the FF of 76 women, including interleukin (IL)- 6, IL-8, IL-10, monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-α (TNF-α). The associations of individual phthalate exposure with cytokines in FF samples were explored by multiple linear regression. We further evaluated the combined effects of multiple phthalate exposures on FF levels of cytokines by using Bayesian kernel machine regression (BKMR) models. We found that there was a positive relationship between mono-ethyl phthalate (MEP) and IL-6 in the FF (percent change:12.4%; 95% CI: 1.3%, 24.9%). In contrast, elevated mono-benzyl phthalate (MBzP), mono(2-ethylhexyl) phthalate (MEHP) and %MEHP levels were associated with decreased MCP-1. In the BKMR models, phthalate metabolite mixtures were positively associated with TNF-α when the mixtures were lower than 65th percentile compared with their medians. In the stratified analyses, MEHP was inversely associated with MCP-1 among women with BMI ≥ 23 kg/m2 (test for interaction <0.05). Our results suggest that certain phthalate metabolites or their mixtures may alter levels of inflammatory cytokines in the FF, and further research is necessary to elucidate the mechanisms underlying the relationship between phthalates exposure, ovarian dysfunction and adverse pregnancy outcomes.

Unraveling the Role of Microalgae in Mitigating Antibiotics and Antibiotic Resistance Genes in Photogranules Treating Antibiotic Wastewater.

Harnessing the potential of specific antibiotic-degrading microalgal strains to optimize microalgal-bacterial granular sludge (MBGS) technology for sustainable antibiotic wastewater treatment and antibiotic resistance genes (ARGs) mitigation is currently limited. This article examined the performance of bacterial granular sludge (BGS) and MBGS (of Haematococcus pluvialis, an antibiotic-degrading microalga) systems in terms of stability, nutrient and antibiotic removal, and fate of ARGs and mobile genetic elements (MGEs) under multiclass antibiotic loads. The systems exhibited excellent performance under none and 50 µg/L mixed antibiotics and a decrease in performance at a higher concentration. The MBGS showed superior potential, higher nutrient removal, 53.9 mg/L/day higher chemical oxygen demand (COD) removal, and 5.2-8.2% improved antibiotic removal, notably for refractory antibiotics, and the system removal capacity was predicted. Metagenomic analysis revealed lower levels of ARGs and MGEs in effluent and biomass of MBGS compared to the BGS bioreactor. Particle association niche and projection pursuit regression models indicated that microalgae in MBGS may limit gene transfers among biomass and effluent, impeding ARG dissemination. Moreover, a discrepancy was found in the bacterial antibiotic-degrading biomarkers of BGS and MBGS systems due to the microalgal effect on the microcommunity. Altogether, these findings deepened our understanding of the microalgae's value in the MBGS system for antibiotic remediation and ARG propagation control.

Hepatocyte-specific Sox9 knockout ameliorates acute liver injury by suppressing SHP signaling and improving mitochondrial function.

BACKGROUND AND AIMS: Sex determining region Y related high-mobility group box protein 9 (Sox9) is expressed in a subset of hepatocytes, and it is important for chronic liver injury. However, the roles of Sox9+ hepatocytes in response to the acute liver injury and repair are poorly understood. METHODS: In this study, we developed the mature hepatocyte-specific Sox9 knockout mouse line and applied three acute liver injury models including PHx, CCl4 and hepatic ischemia reperfusion (IR). Huh-7 cells were subjected to treatment with hydrogen peroxide (H2O2) in order to induce cellular damage in an in vitro setting. RESULTS: We found the positive effect of Sox9 deletion on acute liver injury repair. Small heterodimer partner (SHP) expression was highly suppressed in hepatocyte-specific Sox9 deletion mouse liver, accompanied by less cell death and more cell proliferation. However, in mice with hepatocyte-specific Sox9 deletion and SHP overexpression, we observed an opposite phenotype. In addition, the overexpression of SOX9 in H2O2-treated Huh-7 cells resulted in an increase in cytoplasmic SHP accumulation, accompanied by a reduction of SHP in the nucleus. This led to impaired mitochondrial function and subsequent cell death. Notably, both the mitochondrial dysfunction and cell damage were reversed when SHP siRNA was employed, indicating the crucial role of SHP in mediating these effects. Furthermore, we found that Sox9, as a vital transcription factor, directly bound to SHP promoter to regulate SHP transcription. CONCLUSIONS: Overall, our findings unravel the mechanism by which hepatocyte-specific Sox9 knockout ameliorates acute liver injury via suppressing SHP signaling and improving mitochondrial function. This study may provide a new treatment strategy for acute liver injury in future.

Individual and joint associations of urinary phthalate metabolites with polycystic ovary and polycystic ovary syndrome: Results from the TREE cohort.

Phthalates are widespread endocrine disrupting chemicals that adversely affect female reproductive health. We aimed to investigate the individual and joint associations of phthalate exposures measured by repeated urinary metabolites with polycystic ovary (PCO) and polycystic ovary syndrome (PCOS) (96 PCO cases, 96 PCOS cases and 370 controls). In single-pollutant analyses, mono-isobutyl phthalate (MiBP), monobenzyl phthalate (MBzP) and the sum of di(2-ethylhexyl) phthalate (∑DEHP) were associated with increased prevalence of PCO. Mono(2-ethylhexyl) phthalate (MEHP), MBzP and ∑DEHP were associated with elevated prevalence of PCOS. In multiple-pollutant analyses, one-quartile increase of weighted quantile sum index in phthalate metabolite mixtures was associated with increased prevalence of PCO and PCOS, and MBzP was the most major contributor. Our findings suggest a potential role for phthalate exposures, both individually and in mixtures, in the development of PCO and PCOS.

Diagnostic accuracy of interleukin-2 receptor in sarcoidosis: a systematic review and meta-analysis.

INTRODUCTION: Soluble interleukin-2 receptor (sIL-2 R), a valuable diagnostic biomarker for sarcoidosis, has been reported with variable results. Based on the literatures currently accessible, a systematic review and meta-analysis of the diagnostic performance of serum sIL-2 R for sarcoidosis were performed. METHODS: Relevant studies investigating sIL-2 R for sarcoidosis diagnosis in several databases were searched and data on sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were pooled by STATA 16.0 software. Overall test performance was assessed using summary receiver operating characteristic curves and the area under the curve (AUC). Potential publication bias was assessed by Deeks test. RESULTS: We included eleven studies involving 1,424 subjects, with 1,099 cases of sarcoidosis and 325 of non-sarcoidosis. The pooled parameters of sIL-2 R in diagnosing sarcoidosis were summarized as follows: sensitivity, 0.85 (95% CI: 0.72-0.93); specificity, 0.88 (95% CI: 0.72-0.96); PLR, 7.3 (95% CI: 2.7-20.1); NLR, 0.17 (95% CI:0.08-0.36); DOR, 44 (95% CI: 8-231); and the AUC, 0.93 (95% CI: 0.90-0.95). No publication bias was identified (P = 0.64). CONCLUSIONS: Evidence suggests sIL-2 R performs well in diagnosing sarcoidosis. Nevertheless, results of sIL-2 R assay should be interpreted with other diagnostic examinations.