Effects of the prenatal and postnatal nurturing environment on the phenotype and gut microbiota of mice with polycystic ovary syndrome induced by prenatal androgen exposure: a cross-fostering study.

The gut microbiome is implicated in the pathogenesis of polycystic ovary syndrome (PCOS), and prenatal androgen exposure is involved in the development of PCOS in later life. Our previous study of a mouse model of PCOS induced by prenatal dihydrotestosterone (DHT) exposure showed that the reproductive phenotype of PCOS appears from puberty, followed by the appearance of the metabolic phenotype after young adulthood, while changes in the gut microbiota was already apparent before puberty. To determine whether the prenatal or postnatal nurturing environment primarily contributes to these changes that characterize prenatally androgenized (PNA) offspring, we used a cross-fostering model to evaluate the effects of changes in the postnatal early-life environment of PNA offspring on the development of PCOS-like phenotypes and alterations in the gut microbiota in later life. Female PNA offspring fostered by normal dams (exposed to an abnormal prenatal environment only, fostered PNA) exhibited less marked PCOS-like phenotypes than PNA offspring, especially with respect to the metabolic phenotype. The gut microbiota of the fostered PNA offspring was similar to that of controls before adolescence, but differences between the fostered PNA and control groups became apparent after young adulthood. In conclusion, both prenatal androgen exposure and the postnatal early-life environment created by the DHT injection of mothers contribute to the development of PCOS-like phenotypes and the alterations in the gut microbiota that characterize PNA offspring. Thus, both the pre- and postnatal environments represent targets for the prevention of PCOS and the associated alteration in the gut microbiota in later life.

Cellular senescence of granulosa cells in the pathogenesis of polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women of reproductive age, but its pathology has not been fully characterized and the optimal treatment strategy remains unclear. Cellular senescence is a permanent state of cell-cycle arrest that can be induced by multiple stresses. Senescent cells contribute to the pathogenesis of various diseases, owing to an alteration in secretory profile, termed 'senescence-associated secretory phenotype' (SASP), including with respect to pro-inflammatory cytokines. Senolytics, a class of drugs that selectively eliminate senescent cells, are now being used clinically, and a combination of dasatinib and quercetin (DQ) has been extensively used as a senolytic. We aimed to investigate whether cellular senescence is involved in the pathology of PCOS and whether DQ treatment has beneficial effects in patients with PCOS. We obtained ovaries from patients with or without PCOS, and established a mouse model of PCOS by injecting dehydroepiandrosterone. The expression of the senescence markers p16INK4a, p21, p53, γH2AX, and senescence-associated ß-galactosidase (SA-ß-gal); and the SASP-related factor interleukin (IL)-6; were significantly higher in the ovaries of patients with PCOS and PCOS mice than in controls. To evaluate the effects of hyperandrogenism and DQ on cellular senescence in vitro, we stimulated cultured human granulosa cells (GCs) with testosterone and treated them with DQ. The expression of markers of senescence and a SASP-related factor was increased by testosterone, and DQ reduced this increase. DQ reduced the expression of markers of senescence and a SASP-related factor in the ovaries of PCOS mice and improved their morphology. These results indicate that cellular senescence occurs in PCOS. Hyperandrogenism causes cellular senescence in GCs in PCOS and senolytic treatment reduces the accumulation of senescent GCs and improves ovarian morphology under hyperandrogenism. Thus, DQ might represent a novel therapy for PCOS.

Simulation of vertical migration behaviors of heavy metals in polluted soils from arid regions in northern China under extreme weather.

Heavy metal migration behaviors and mechanisms in soils are important for pollution control and remediation. However, there are few related studies in arid areas under extreme weather patterns. In this study, we developed a one-dimensional continuous point source unsaturated solute transport model, and utilized Hydrus-1D to simulate the transport of Cu, As and Zn, in the pack gas zones of soils within the impact areas of two typical mining areas in Inner Mongolia. The results show that the soil has a significant interception capacity, with a short heavy metal vertical migration distance of ≤100 cm. Soil texture and heavy metal sorption affinity are two key factors that influence heavy metal transport. In soils with high contents of sands but low contents of clays, heavy metals have large mobility and thus migrate deeper and are more evenly distributed in the soil profile. The migration of different heavy metals in the same soil also varies considerably, with large migration depth for metals having low binding affinities onto soils. Scenario analysis for extreme drought and rainfall shows that, rainfall amount and intensity are positively correlated with heavy metal transport depth and negatively correlated with the peak concentration. Increasing rainfall/intensity results in a more uniform distribution of heavy metals, and lower profile concentrations owing to enhanced horizontal dispersion of surface runoff. When the total amount and intensity of rainfall remain constant, continuous or intermittent rainfall only affects the transport process but has almost no effect on the final pollutant concentration redistribution in the soil. These results provide theoretical data for estimating the degree of heavy metal pollution, and help design control and remediation strategies for polluted soils.

PhageScope: a well-annotated bacteriophage database with automatic analyses and visualizations.

Bacteriophages are viruses that infect bacteria or archaea. Understanding the diverse and intricate genomic architectures of phages is essential to study microbial ecosystems and develop phage therapy strategies. However, the existing phage databases are short of meticulous annotations. To this end, we propose PhageScope (https://phagescope.deepomics.org), an online phage database with comprehensive annotations. PhageScope harbors a collection of 873 718 phage sequences from various sources. Applying fifteen state-of-the-art tools to perform systematic annotations and analyses, PhageScope provides annotations on genome completeness, host range, lifestyle information, taxonomy classification, nine types of structural and functional genetic elements, and three types of comparative genomic studies for curated phages. Additionally, PhageScope incorporates automatic analyses and visualizations for curated and customized phages, serving as an efficient platform for phage study.

The Role of Cellular Senescence in Cyclophosphamide-Induced Primary Ovarian Insufficiency.

Young female cancer patients can develop chemotherapy-induced primary ovarian insufficiency (POI). Cyclophosphamide (Cy) is one of the most widely used chemotherapies and has the highest risk of damaging the ovaries. Recent studies elucidated the pivotal roles of cellular senescence, which is characterized by permanent cell growth arrest, in the pathologies of various diseases. Moreover, several promising senolytics, including dasatinib and quercetin (DQ), which remove senescent cells, are being developed. In the present study, we investigated whether cellular senescence is involved in Cy-induced POI and whether DQ treatment rescues Cy-induced ovarian damage. Expression of the cellular senescence markers p16, p21, p53, and γH2AX was upregulated in granulosa cells of POI mice and in human granulosa cells treated with Cy, which was abrogated by DQ treatment. The administration of Cy decreased the numbers of primordial and primary follicles, with a concomitant increase in the ratio of growing to dormant follicles, which was partially rescued by DQ. Moreover, DQ treatment significantly improved the response to ovulation induction and fertility in POI mice by extending reproductive life. Thus, cellular senescence plays critical roles in Cy-induced POI, and targeting senescent cells with senolytics, such as DQ, might be a promising strategy to protect against Cy-induced ovarian damage.

Evaluation of renal ischemia-reperfusion injury using CEUS in mice.

BACKGROUND: Renal ischemia-reperfusion injury (IRI) frequently occurs clinically. We investigated the value of contrast-enhanced ultrasonography (CEUS) in the evaluation of renal IRI levels in mice. METHODS: Thirty-six healthy adult male C57BL/6 mice (20-22 g) were randomly divided into the sham, 10 min, 20 min, 30 min, 40 min, and 50 min groups based on the time of renal warm ischemia by blocking the left renal pedicle, approved by the Institutional Animal Ethics Committee. Time-intensity curve (TIC)-derived parameters such as peak enhancement (PE) and wash-in perfusion index (WiPI) were produced using CEUS at 1 h and 24 h after IRI. The severity of kidney injury was detected by the renal tubular necrosis rate which was analyzed by hematoxylin and eosin staining at 24 h after IRI. The Spearman correlation coefficient was used to describe the correlations between PE and WiPI values and the renal tubular necrosis rate. RESULTS: The PE and WiPI values decreased after IRI in the groups with a warm ischemia time ≥ 20 min. The renal tubular necrosis rate was significantly correlated with the PE value at 1 h (ρ = -0.802) and 24 h (ρ = -0.861) after IRI and the WiPI value at 1 h (ρ = -0.814) and 24 h (ρ = -0.853) after IRI (all p < 0.001). CONCLUSION: TIC-derived parameters, including PE and WiPI values, can be used to evaluate the severity of renal IRI in mice. CEUS is a safe and effective technology for the detection of renal IRI. RELEVANCE STATEMENT: CEUS can evaluate the severity of renal ischemia-reperfusion injury by peak enhancement and wash-in perfusion index values selected from various time-intensity curve-derived parameters. KEY POINTS: • Contrast-enhanced ultrasonography can evaluate the level of renal ischemia-reperfusion injury. • Peak enhancement and wash-in perfusion index are correlated with the renal tubular necrosis rate. • CEUS can detect changes in unilateral renal function without radiation.

Low-cost UAV detection via WiFi traffic analysis and machine learning.

In recent years, unmanned aerial vehicles (UAVs) have undergoing experienced remarkable advancements. Nevertheless, the growing utilization of UAVs brings forth potential security threats to the public, particularly in private and sensitive locales. To address these emerging hazards, we introduce a low-cost, three-stage UAV detection framework for monitoring invading UAVs in vulnerable zones. This framework devised through an exhaustive investigation of the Chinese UAV market. Various scenarios were examined to evaluate the effectiveness of the framework, and it was subsequently implemented on a portable board. Experiments demonstrated that the proposed framework can detect invading UAVs at an early stage, even in stealthy mode. As such, the framework has the potential to be applied in the formulation of a portable surveillance system for a UAV-restricted region.

Lumbar Spine Infection with Eikenella corrodens Presented as Abdominal Pain: A Case Report and Literature Review.

Background: Eikenella corrodens is a part of the inherent flora on the surface of human mucosa. It usually does not cause disease unless the patient has been bitten, injured or surgically infected. Lumbar spine infection caused by Eikenella corrodens usually presents with conventional symptoms such as low back pain and fever. Herein, we report a case of lumbar intervertebral space infection with Eikenella corrodens presented as abdominal pain. Case Presentation: A 38-year-old man with no medical history of note presented with abdominal pain. Initially, local doctors suspected that the patient had abdominal disease. However, abdominal diseases were ruled out and only lumbar spine infection was confirmed. Then, the patient was misdiagnosed as lumbar tuberculosis. Finally, anaerobic culture and metagenomic next-generation sequencing confirmed the Eikenella corrodens, which was rarely involved in lumbar intervertebral space infection. The patient recovered after operation and antibiotic therapy. Conclusion: This case indicated a rare symptom of lumbar spine infection, abdominal cramping, which is caused by Eikenella corrodens. Blood culture had low sensitivity as a diagnostic method for Eikenella corrodens, but lesion sample culture or metagenomic next-generation sequencing had high sensitivity for early diagnosis.

Roles of endoplasmic reticulum stress in the pathophysiology of polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among reproductive-age women, affecting up to 15% of women in this group, and the most common cause of anovulatory infertility. Although its etiology remains unclear, recent research has revealed the critical role of endoplasmic reticulum (ER) stress in the pathophysiology of PCOS. ER stress is defined as a condition in which unfolded or misfolded proteins accumulate in the ER because of an imbalance in the demand for protein folding and the protein-folding capacity of the ER. ER stress results in the activation of several signal transduction cascades, collectively termed the unfolded protein response (UPR), which regulates various cellular activities. In principle, the UPR restores homeostasis and keeps the cell alive. However, if the ER stress cannot be resolved, it induces programmed cell death. ER stress has recently been recognized to play diverse roles in both physiological and pathological conditions of the ovary. In this review, we summarize current knowledge of the roles of ER stress in the pathogenesis of PCOS. ER stress pathways are activated in the ovaries of both a mouse model of PCOS and in humans, and local hyperandrogenism in the follicular microenvironment associated with PCOS is responsible for activating these. The activation of ER stress contributes to the pathophysiology of PCOS through multiple effects in granulosa cells. Finally, we discuss the potential for ER stress to serve as a novel therapeutic target for PCOS.

Improving the eating quality of brown rice by defatting combined with hydrothermal treatment.

Aiming at consumer acceptability of brown rice such as cooking difficulty and coarse taste, the effects of defatting and hydrothermal treatment alone or in combination on the texture and sensory score of cooked brown rice were studied, and the improvement mechanism was explored through cooking quality and microscopic morphology. The results showed that defatting combined with hydrothermal treatment could significantly improve the quality of brown rice, the hardness and chewiness of treated cooked brown rice decreased respectively from 20.385 N and 10.221 N to 14.494 N and 6.886 N, and the sensory score increased from 68.90 to 83.50. The room temperature water absorption rate of the treated brown rice increased from 10.72 % to 29.71 %, which was much higher than that of polished rice. The cooking quality of the treated brown rice was obviously improved, the optimal cooking time decreased from 30.33 min to 22.67 min, and the heating water absorption, volume expansion rate and solid loss increased from 147.32 %, 255.20 % and 13.35 mg/g to 219.15 %, 400.39 % and 22.49 mg/g, respectively. Scanning electron microscope showed that defatting combined with hydrothermal treatment significantly increased cracks and micropores of brown rice grains, which may be the intrinsic reason for the improvement in room temperature water absorption rate and cooking quality of brown rice and thus eating quality of cooked brown rice. The results are of great significance for promoting the staple consumption of whole-grain brown rice with broad application prospects.

A network meta-analysis to evaluate the efficacy of traditional Chinese medicine on intestinal flora in patients with gastrointestinal cancer.

Background and Purpose: Traditional Chinese medicine (TCM) can regulate intestinal flora so as to affect the occurrence, progression, and prognosis of gastrointestinal cancer. According to clinical studies, TCM oral administration, TCM external treatment, and TCM injections, can adjust intestinal flora disorders in patients with gastrointestinal cancer. This network meta-analysis aims to evaluate the effect of three treatments on the intestinal flora in gastrointestinal cancer patients. Methods: This meta-analysis was registered in PROSPERO (CRD42022332553). Six electronic databases, namely CNKI, Wanfang, CSTJ, PubMed, Cochrane Library, and EMBASE, were searched from their inception to 1 April 2022. We identified randomized controlled trials (RCT) used to compare the efficacy of three TCM treatment methods-oral administration, external therapy and injections-on the intestinal flora in gastrointestinal cancer patients. The main outcome indicators were Bifidobacteria, Lactobacilli, Escherichia coli, and Enterococci. Stata (15.1) and the Cochrane risk of bias assessment tool were employed. Results: We identified 20 eligible RCTs with a total of 1,774 patients. According to network meta-analysis results, TCM injection plus common treatment (CT) or oral administration of TCM plus CT was superior to CT alone for supporting Bifidobacterium. In supporting Lactobacillus, TCM injection plus CT demonstrated more obvious effect relative to oral administration of TCM plus CT; TCM injection plus CT was more effective than CT only; and oral administration of TCM plus CT was superior to CT only.The inhibitory effect of TCM injection plus CT on Escherichia coli was better compared with CT only. In terms of inhibiting Enterococci, oral administration of TCM plus CT was superior to CT only.The difference in efficacy among the above treatments was statistically significant. In the SUCRA probability ranking, TCM injection plus CT had the best ranking curve among the three treatments and was the most effective in supporting Bifidobacteria (Sucra = 90.08%), Lactobacilli (Sucra = 96.4%), and regulating Escherichia coli (Sucra = 86.1%) and Enterococci (Sucra = 87.1%). Conclusion: TCM injections plus CT is the most effective therapy in balancing the intestinal flora of gastrointestinal cancer patients. However, the current results deserve further validation through high-quality research. Systematic Review Registration: http://www.prisma-statement.org/, identifier 10.1136/bmj.n71.

Global research trends and foci of artificial intelligence-based tumor pathology: a scientometric study.

BACKGROUND: With the development of digital pathology and the renewal of deep learning algorithm, artificial intelligence (AI) is widely applied in tumor pathology. Previous researches have demonstrated that AI-based tumor pathology may help to solve the challenges faced by traditional pathology. This technology has attracted the attention of scholars in many fields and a large amount of articles have been published. This study mainly summarizes the knowledge structure of AI-based tumor pathology through bibliometric analysis, and discusses the potential research trends and foci. METHODS: Publications related to AI-based tumor pathology from 1999 to 2021 were selected from Web of Science Core Collection. VOSviewer and Citespace were mainly used to perform and visualize co-authorship, co-citation, and co-occurrence analysis of countries, institutions, authors, references and keywords in this field. RESULTS: A total of 2753 papers were included. The papers on AI-based tumor pathology research had been continuously increased since 1999. The United States made the largest contribution in this field, in terms of publications (1138, 41.34%), H-index (85) and total citations (35,539 times). We identified the most productive institution and author were Harvard Medical School and Madabhushi Anant, while Jemal Ahmedin was the most co-cited author. Scientific Reports was the most prominent journal and after analysis, Lecture Notes in Computer Science was the journal with highest total link strength. According to the result of references and keywords analysis, "breast cancer histopathology" "convolutional neural network" and "histopathological image" were identified as the major future research foci. CONCLUSIONS: AI-based tumor pathology is in the stage of vigorous development and has a bright prospect. International transboundary cooperation among countries and institutions should be strengthened in the future. It is foreseeable that more research foci will be lied in the interpretability of deep learning-based model and the development of multi-modal fusion model.

Notch Signaling Induced by Endoplasmic Reticulum Stress Regulates Cumulus-Oocyte Complex Expansion in Polycystic Ovary Syndrome.

Endoplasmic reticulum (ER) stress activated in granulosa cells contributes to the pathophysiology of polycystic ovary syndrome (PCOS). In addition, recent studies have demonstrated that Notch signaling plays multiple roles in the ovary via cell-to-cell interactions. We hypothesized that ER stress activated in granulosa cells of antral follicles in PCOS induces Notch signaling in these cells, and that activated Notch signaling induces aberrant cumulus-oocyte complex (COC) expansion. Expression of Notch2 and Notch-target transcription factors was increased in granulosa cells of PCOS patients and model mice. ER stress increased expression of Notch2 and Notch-target transcription factors in cultured human granulosa-lutein cells (GLCs). Inhibition of Notch signaling abrogated ER stress-induced expression of genes associated with COC expansion in cultured human GLCs, as well as ER stress-enhanced expansion of cumulus cells in cultured murine COCs. Furthermore, inhibition of Notch signaling reduced the areas of COCs in PCOS model mice with activated ER stress in the ovary, indicating that Notch signaling regulates COC expansion in vivo. Our findings suggest that Notch2 signaling is activated in granulosa cells in PCOS and regulates COC expansion. It remains to be elucidated whether aberrant COC expansion induced by the ER stress-Notch pathway is associated with ovulatory dysfunction in PCOS patients.

Development and Validation of Survival Nomograms in Patients with Primary Bladder Lymphoma.

BACKGROUND: The existing studies on primary bladder lymphoma (PBL) are retrospective analyses based on individual cases or small series studies, and the research on PBL is not unified and in-depth enough at present because of the scarcity of PBL and the lack of relevant literature. This study is designed to develop and validate nomograms for overall survival (OS) and cancer-specific survival (CSS) prediction in patients with PBL. METHODS: According to the Surveillance, Epidemiology, and End Results (SEER) database, 405 patients diagnosed with PBL from 1975 to 2016 were collected and randomly assigned to training (n = 283) and validation (n = 122) cohort. After the multivariable Cox regression, the OS and CSS nomograms were developed. The discrimination, calibration and clinical usefulness of the nomograms were assessed and validated, respectively, by the training and validation cohort. Furthermore, all of the patients were reclassified into high- and low-risk groups and their survival were compared through Kaplan-Meier method and log-rank test. RESULTS: Age, subtype, Ann Arbor stage, radiation and chemotherapy were identified as independent prognostic factors for OS and age, sex, and subtype for CSS, then corresponding nomograms predicting the 3- and 5-year survival were constructed. The presented nomograms demonstrated good discrimination and calibration, which the C-index in the training and validation cohort were 0.744 (95% confidence interval [CI], 0.705-0.783) and 0.675 (95% CI, 0.603-0.747) for OS nomogram and 0.692 (95% CI, 0.632-0.752) and 0.646 (95% CI, 0.549-0.743) for CSS nomogram, respectively. Furthermore, the nomograms can be used to effectively distinguish Patients with PBL at high risk of death. The clinical usefulness of the nomograms was visually displayed by decision curve analysis. CONCLUSION: We updated the baseline characteristics of patients with PBL and constructed OS and CSS nomograms to predict their 3- and 5-year survival. Using these nomograms, it would be convenient to individually predict the prognosis of patients with PBL and provide guidance for clinical treatment.

The oncogenic miR-27a/BTG2 axis promotes obesity-associated hepatocellular carcinoma by mediating mitochondrial dysfunction.

Obesity is closely related to the initiation and development of hepatocellular carcinoma (HCC). The regulatory mechanism of obesity-associated HCC remains unclear. HepG2 cells treated with palmitic acid (PA) and diethylnitrosamine (DEN)-induced HCC mice fed a high-fat diet (HFD) were established. The expression of miR-27a and B-cell translocation gene 2 (BTG2) mRNA and protein were detected via qPCR and western blotting. Prediction software and luciferase assays were employed to verify the miR-27a/BTG2 axis. The biological effects of HepG2 cells were evaluated with ORO staining, MTT assays, Transwell assays, Mito-Timer, and Mito-SOX staining. Significantly upregulated miR-27a and downregulated BTG2 mRNA and protein were observed in HepG2 cells and liver tissues of HCC mice. Overexpressing miR-27a (mi-miR-27a) markedly promoted cellular lipid accumulation, proliferation, and invasion, accompanied by aggravated mitochondrial dysfunction (increased fading and ROS products of mitochondria) in HepG2 cells. Additionally, these effects were further reinforced in HepG2 cells treated with mi-miR-27a and PA. BTG2 was identified as a direct target and was negatively regulated by miR-27a. Similarly, BTG2 knockdown (sh-BTG2) had effects identical to those of mi-miR-27a on HepG2 cells. Additionally, PA evidently enhanced these effects of sh-BTG2 in HepG2 cells. Moreover, BTG2 overexpression effectively reversed the effects of miR-27a, including lipotropic and oncogenic effects, and simultaneously promoted mitochondrial imbalance in HepG2 cells. Thus, obesity-associated miR-27a acts as an oncogene to promote lipid accumulation, proliferation, and invasion by negatively regulating BTG2-mediated mitochondrial dysfunction in HCC.

CircRNA608-microRNA222-PINK1 axis regulates the mitophagy of hepatic stellate cells in NASH related fibrosis.

BACKGROUND: Increasing evidences have confirmed the relationship between mitophagy and nonalcoholic steatohepatitis (NASH). The exact mechanism of upstream circular RNAs (circRNAs) regulating PTEN-induced putative kinase 1 (PINK1) mediated mitophagy and its contribution to NASH-related liver fibrosis was explored in our study. METHODS: Primary hepatic stellate cells (PHSCs) from C57BL/6 mice transfected with small interfering RNAs against PINK1 (si-PINK1) and negative control (si-NC) were prepared to perform circRNA sequence. Differentially expressed circRNAs, bioinformatic analysis and predicting software were performed to select axis of circ608/miR-222/PINK1. The expressions of circ608/miR-222/PINK1 were verified by RT-qPCR. The mitochondrial function was evaluated by immunofluorescence staining of COX4 and LC3B. RESULTS: PINK1-mediated mitophagy was inhibited in NASH-related liver fibrosis mice. CircRNA sequence revealed there were 37 DE-circRNAs between si-PINK1 PHSCs and si-NC PHSCs. Bioinformatic analysis showed these DE-circRNAs were related to enriched signaling pathways (such as Wnt, Rap1, mTOR, Hippo) regulating liver fibrosis and mitophagy. Circ608 was significantly down-regulated in lipotoxic HSCs and in livers of NASH-related liver fibrosis mice. MiR222 was identified to be the target miRNA of circ608 and was negatively regulated by circ608 in lipotoxic HSCs. MiR222 also had a binding site with PINK1 and could negatively regulate PINK1. So, the axis of circ608-miR222-PINK1 was proved to participate in NASH-related liver fibrosis by regulating mitophagy. These results illustrated that circ608 might promote PINK1-mediated mitophagy though inhibiting miR222 in lipotoxic HSCs. CONCLUSION: Circ608 could promote PINK1-mediated mitophagy of HSCs though inhibiting miR222 in NASH-related liver fibrosis.

Association between vitamin D3 levels and insulin resistance: a large sample cross-sectional study.

Previous studies have shown that vitamin D3 may be a potential factor in insulin resistance, but the relationship between vitamin D3 and insulin resistance still remains controversial. At present, more research is needed to explore the relationship between vitamin D3 and insulin resistance. The samples from 2009 to 2018 in NHANES database were analyzed to Investigate the relationship and the potential mechanism. We performed a cross-sectional study of five periods in the NHANES database. Finally, 9298 participants were selected through strict inclusion and exclusion criteria, Multivariate logistic regression analysis and curve fitting were conducted to explore the relationship between vitamin D3 level and insulin resistance. Moreover, subgroup analysis was used to further prove the association. The results revealed that there was a strong association between vitamin D3 and insulin resistance (OR 0.82, 95% CI 0.72-0.93). However, subgroup analyses indicated that this correlation varied between individuals and races. There was a negative correlation between vitamin D3 level and insulin resistance, which provides a new proof for exploring the influencing factors of insulin resistance. More well-designed studies are still needed to further elaborate on these associations.

Hepatocyte-derived exosomal miR-27a activateshepatic stellate cells through the inhibitionof PINK1-mediated mitophagy in MAFLD.

The role of exosome-mediated mitophagy in the crosstalk between hepatocytes (HCs) and hepatic stellate cells (HSCs) in metabolic-associated fatty liver disease (MAFLD) remains unknown. Serum exosomal miR-27a levels were markedly increased and positively correlated with liver fibrosis in MAFLD patients and mice. Exosomal miR-27a was released from lipotoxic HCs and specifically transmitted to recipient-activated HSCs. PINK1, the key target of miR-27a, primarily mediates mitophagy. Overexpression of miR-27a or knockdown of PINK1 or lipotoxic HC-exosomal miR-27a impaired mitochondria (inhibiting mitophagy, respiration, membrane potential, and transcription while promoting reactive oxygen species production) in activated HSCs and stimulated HSC-derived fibroblasts (promoting activation and proliferation while inhibiting autophagy). High exosomal miR-27a serum levels and a lack of hepatic PINK1-mediated mitophagy were directly related to liver fibrosis in MAFLD mice. Lipotoxic HC exosome transplantation aggravated the degree of PINK1-mediated mitophagy suppression, steatohepatitis, lipidosis, and fibrosis in the livers of MAFLD mice with cirrhosis. Both in vitro and in vivo, exosomes derived from miR-27a-knockdown HCs could not facilitate the abovementioned deteriorating effects. In conclusion, lipotoxic HC-exosomal miR-27a plays a pivotal role in inhibiting mitophagy and in promoting MAFLD-related liver fibrosis by negatively regulating PINK1 expression.

Temporal relationship between alterations in the gut microbiome and the development of polycystic ovary syndrome-like phenotypes in prenatally androgenized female mice.

It has been recently recognized that prenatal androgen exposure is involved in the development of polycystic ovary syndrome (PCOS) in adulthood. In addition, the gut microbiome in adult patients and rodents with PCOS differs from that of healthy individuals. Moreover, recent studies have suggested that the gut microbiome may play a causative role in the pathogenesis of PCOS. We wondered whether prenatal androgen exposure induces gut microbial dysbiosis early in life and is associated with the development of PCOS in later life. To test this hypothesis, we studied the development of PCOS-like phenotypes in prenatally androgenized (PNA) female mice and compared the gut microbiome of PNA and control offspring from 4 to 16 weeks of age. PNA offspring showed a reproductive phenotype from 6 weeks and a metabolic phenotype from 12 weeks of age. The α-diversity of the gut microbiome of the PNA group was higher at 8 weeks and lower at 12 and 16 weeks of age, and the ß-diversity differed from control at 8 weeks. However, a significant difference in the composition of gut microbiome between the PNA and control groups was already apparent at 4 weeks. Allobaculum and Roseburia were less abundant in PNA offspring, and may therefore be targets for future interventional studies. In conclusion, abnormalities in the gut microbiome appear as early as or even before PCOS-like phenotypes develop in PNA mice. Thus, the gut microbiome in early life is a potential target for the prevention of PCOS in later life.

Associations of TG/HDL Ratio with the Risk of Prediabetes and Diabetes in Chinese Adults: A Chinese Population Cohort Study Based on Open Data.

BACKGROUND: In the global chronic diseases, type 2 diabetes shows a significant upward trend, and there are more people before prediabetes (impaired glucose tolerance). Many patients with impaired glucose tolerance and undiagnosed diabetes do not know that their glucose metabolism system has been in a state of disorder. Every year, about 5% to 10% of prediabetics develop diabetes. One of the important achieving factors may be the increase in blood lipids. However, it is not clear whether the triglyceride/high-density lipoprotein ratio is associated with impaired glucose tolerance and diabetes in the Chinese population. Therefore, we investigated the relationship between triglyceride/high-density lipoprotein and impaired glucose tolerance and diabetes in the Chinese population. METHODS: We conducted a retrospective cohort study using data from the health screening program. The study included 116,855 participants from 32 locations in China, all of whom were adults over 20. Participants measured fasting blood glucose levels at each visit and collected information about their diabetes history. Impaired glucose tolerance was diagnosed as fasting blood glucose ≥6.00 mmol and self-reported diabetes mellitus. The patient was measured on the date of diagnosis or on his last visit (whichever comes first). RESULTS: The results showed that, after adjusting the potential confounding factors, the ratio of TG/HDL was positively correlated with the occurrence of prediabetes and diabetes, and there was a saturation effect. The inflection points were 1.04 and 1.33, respectively. The effect value and 95% confidence interval before and after the inflection point of impaired glucose tolerance patients were 1.57 and (1.42, 1.73) and 1.03 and (1.01, 1.05), respectively. The effect value and 95% confidence interval before and after the inflection point in patients with diabetes were 2.07 and (1.80, 2.39) and 1.08 and (1.04, 1.12).