Down-regulation of CORO1C mediated by lncMALAT1/miR-133a-3p axis contributes to trophoblast dysfunction and preeclampsia.

INTRODUCTION: Placental trophoblast dysfunction has been proved to be closely related to the pathogenesis of preeclampsia. Coronaryxin-like actin-binding protein 1C (CORO1C) plays an important role in cell proliferation, apoptosis, invasion, and signal transduction, but its involvement in trophoblast dysfunction and preeclampsia remains uncertain. METHODS: The expression of CORO1C in placental tissues of preeclampsia (PE) pregnant women and pregnant mice PE model were detected by real-time quantitative polymerase chain reaction (RT-qPCR), western blotting (WB) and immunohistochemical (IHC) staining. Next, the proliferation, invasion, migration and apoptosis were performed to explore the functions of CORO1C in HTR8/SVneo cell. Furthermore, the expression of CORO1C were detected in lncMALAT1 knockdown and overexpression HTR-8/SVneo cell. And then we investigated the possible regulatory mechanism of lncMALAT1 on CORO1C through bioinformatics analysis, FISH assays, RIP assays, RNA pull down and dual luciferase reporter assays. Finally, we further validated that lncMALAT1 regulate the function of placental trophoblast cells through CORO1C. RESULTS: The expression of CORO1C was significantly decreased in the placenta of PE patients and mice model, and positively associated with neonatal birth weight. And we found that CORO1C inhibited trophoblast proliferation, migration and invasion. Furthermore, reduced expression of lncMALAT1 impaired CORO1C level, thereby resulting in trophoblast dysfunction. Mechanistically, the dysregulation of lncMALAT1 promoted the expression of miR-133a-3p, strongly enhancing its binding to the 3'UTR region of CORO1C mRNA for degradation. DISCUSSION: This study demonstrated that the dysregulation of CORO1C via lncMALAT1/miR-133a-3p axis impairs trophoblast function and contributes to preeclampsia pathogenesis, providing novel insights in PE therapy through modulating CORO1C level.

Foliar spraying exogenous ABA resists chilling stress on adzuki beans (Vigna angularis).

Adzuki bean, an important legume crop, exhibits poor tolerance to low temperatures. To investigate the effect of exogenous abscisic acid (ABA) on the physiological metabolism and yield resistance of adzuki bean under low-temperature stress, we conducted a potted experiment using Longxiaodou 4 (LXD 4) and Tianjinhong (TJH) as test materials and pre-sprayed with exogenous ABA at flowering stage continuously for 5 days with an average of 12°C and an average of 15°C, respectively. We found that, compared with spraying water, foliar spraying exogenous ABA increased the activities of antioxidants and the content of non-enzymatic antioxidants, effectively inhibited the increase of malondialdehyde (MDA), hydrogen peroxide (H2O2) content, O2-· production rate. Exogenous ABA induced the activation of endogenous protective mechanisms by increasing antioxidant enzymes activities such as superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT), as well as elevated levels of non-enzymatic antioxidants including ascorbic acid (ASA) and glutathione (GSH). Moreover, the yield loss of 5.81%-39.84% caused by chilling stress was alleviated by spraying ABA. In conclusion, foliar spraying exogenous ABA can reduce the negative effects of low-temperature stress on the yield of Adzuki beans, which is essential to ensure stable production of Adzuki beans under low-temperature conditions.

A Multimodal Meta-Analysis of Structural and Functional Alterations in the Brain of Knee Osteoarthritis Systematic Review.

BACKGROUND: Abnormalities of structural and functional brain regions might influence the persistence of knee pain, the progression, and the response to treatments in knee osteoarthritis (KOA). These complex alterations present a challenge to the understanding of its mechanism. OBJECTIVES: To meta-analyze the concurrence across structural and functional magnetic resonance imaging studies. STUDY DESIGN: Systematic review and meta-analysis. SETTING: This meta-analysis examined all voxel-based morphometric (VBM) and amplitude of low-frequency fluctuation (ALFF) studies involving the whole-brain alterations of KOA. METHODS: VBM and ALFF studies published up to May 7, 2023, were searched in the Web of Science, PubMed, EMBASE, Cochrane Library (CENTRAL), China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database, Chongqing VIP, Wanfang Database. Two independent researchers carried out study screening, quality assessment, clinical data extraction, and neuroimaging data extraction. The whole-brain voxel-based gray matter (GM) and brain activity data of KOA were collected from eligible studies and meta-analyzed using the anisotropic effect size-signed differential mapping (AES-SDM). RESULTS: Fourteen studies were included in this study. In VBM meta-analyses, a total of 481 patients were enrolled in this study (252 KOA and 229 healthy patients). In the ALFF meta-analysis, a total of 518 patients were enrolled in this study (265 KOA and 253 healthy patients). According to the meta-analysis, KOA had increased GM volume in the right inferior frontal gyrus and decreased GM volume in the bilateral superior frontal gyrus, as well as increased brain activity in the left inferior frontal gyrus and inferior temporal gyrus, and decreased brain activity in the left middle occipital gyrus, right supramarginal gyrus, right superior frontal gyrus, and right superior parietal gyrus compared with healthy patients. LIMITATIONS: Most of the ALFF studies included in this meta-analysis were conducted in China. Our findings are exclusively addressed by the VBM and ALFF studies. The meta-regression between the duration of KOA, pain intensity and abnormal gray matter, and functional activity of brain regions in patients with KOA were unable to be analyzed. CONCLUSION: The results of this meta-analysis indicate that patients with KOA present significant abnormalities in GM volume and functional activity. These findings contribute to a better understanding of the structural and functional abnormalities seen in patients with KOA.

Experiences of the Older Adults After Being Abused: A Qualitative Meta-synthesis.

Elder abuse is a global public health problem with severe social costs. Research on elder abuse has gradually increased; however, less attention has been paid to older adults' perceptions and experiences of abuse. This review aimed to integrate older adults' perceptions and experiences of abuse to provide a theoretical basis for developing interventions that meet their authentic needs. Six electronic databases were searched to include qualitative studies examining perceptions and experiences of abuse among adults aged 60 years or older, and 22 studies were included. This study used the Joanna Briggs Institute meta-aggregation approach to integrate the qualitative findings, which identified four themes: (a) changes resulting from elder abuse, (b) causes of abuse, (c) barrier factors and facilitating factors to the disclosure of abusive behavior, and (d) adopting different response strategies. The findings revealed that older adults experience persistent physical and psychological burdens and financial stress following abuse. Multiple factors influence the emergence of abuse and older adults search for help from the outside world, especially social support and perceptions of abuse. Older adults can deal with abuse by accepting the status quo or taking steps to change it. These findings have important implications for helping older adults prevent and cope with abuse experiences.

The potential presence of infection may be indicated through non-invasive prediction of procalcitonin and C-reactive protein levels within the initial three days after cervical cerclage: a retrospective case-control study.

PURPOSE: To identify which non-invasive infection indicators could better predict post-cervical cerclage (CC) infections, and on which days after CC infection indicators should be closely monitored. METHODS: The retrospective, single-center study included 619 single-pregnancy patients from January 2021 to December 2022. Patients were categorized into infected and uninfected groups based on physicians' judgments of post-CC infections. Registered information included patient characteristics, cervical insufficiency history, gestational age at CC, surgical method (McDonald/Shirodkar), purpose of CC, mid-pregnancy miscarriage/preterm birth, infection history or risk factors, and infection indices on days 1, 3, 5, and 7 after CC. Propensity score matching (PSM) was applied to reduce patient characteristic bias. Statistical analysis of C-reactive protein (CRP), white blood cell (WBC), neutrophil count (NEU), percentage of neutrophil count (NEU_P), interleukin-6 (IL-6), and procalcitonin (PCT) in the infected group compared with the uninfected group was performed using chi-square tests and t-tests. Receiver operating characteristic (ROC) curves were used to further assess the diagnostic value of CRP, PCT, and CRP-PCT in combination. RESULTS: Among the 619 included patients, 206 patients were matched using PSM and subsequently assessed. PCT values on day 1 and day 3 after CC exhibited significant differences between the two groups in two statistical ways (P < 0.01, P < 0.05). The CRP levels on day 1 were significantly higher in the infected group compared to the uninfected group in two statistical ways (P < 0.05). On day 3, the mean CRP value was significantly elevated in the infected group compared to the uninfected group (P < 0.05). Analyses of IL-6, WBC, NEU, and NEU_P did not yield clinically significant results. The area under the ROC curves for CRP, PCT, and CRP-PCT on day 1 and day 3 were all below 0.7. In the preventive CC group, the AUC values of CRP and CRP-PCT obtained on d1 were found to be higher than 0.7, indicating moderate diagnostic accuracy. CONCLUSION: For women after CC surgery, especially of preventive aim, increased serum CRP and PCT levels from post-CC day 1 to day 3 may signal a potential postoperative infection, warranting close monitoring.

Effects of hydroxyproline supplementation in low fish meal diets on collagen synthesis, myofiber development and muscular texture of juvenile Pacific white shrimp (Litopenaeus vannamei).

This experiment aimed to evaluate the impact of dietary hydroxyproline (Hyp) supplementation on the muscle quality of juvenile Pacific white shrimp (Litopenaeus vannamei) fed a low fishmeal diet. Six formulated diets included one high fishmeal (HF; 25% fishmeal content) and five low fishmeal diets (10% fishmeal content) with 0%, 0.2%, 0.4%, 0.6% and 0.8% Hyp (LF0, LF2, LF4, LF6 and LF8, respectively). Each diet was assigned to four replicates, and 40 shrimp (0.32 ± 0.00 g) per replicate were fed four times a day for 8 weeks. Dietary Hyp supplementation had little effects on growth performance, but increased the contents of Hyp, prolyl 4-hydroxylases (P4Hs), and collagen. The meat yield, springiness, hardness, chewiness, and cohesiveness of muscle were the highest in the LF4 group among the low fishmeal groups (P < 0.05). Cooking loss and freezing loss of muscle were the lowest in the LF4 group (P < 0.05). Dietary supplementation with 0.4% Hyp increased the myofiber density and decreased the myofiber diameter of muscle (P < 0.05). Supplementation of Hyp in the diet up-regulated the mRNA expression of smyhc5, smyhc15, col1a1, col1a2, igf-1f, tgf-ß and tor and down-regulated the mRNA expression of smyhc 1, smyhc 2, smyhc 6a (P < 0.05). Supplementation of Hyp in the diet up-regulated the protein expression of P-4E-BP1, P-AKT, AKT and P-AKT/AKT (P < 0.05). These results suggested that the addition of 0.4% Hyp to low fishmeal diets improved the muscle quality of L. vannamei.

Genetic deletion of zinc transporter ZnT3 induces progressive cognitive deficits in mice by impairing dendritic spine plasticity and glucose metabolism.

Zinc transporter 3 (ZnT3) is abundantly expressed in the brain, residing in synaptic vesicles, where it plays important roles in controlling the luminal zinc levels. In this study, we found that ZnT3 knockout in mice decreased zinc levels in the hippocampus and cortex, and was associated with progressive cognitive impairments, assessed at 2, 6, and 9-month of age. The results of Golgi-Cox staining demonstrated that ZnT3 deficiency was associated with an increase in dendritic complexity and a decrease in the density of mature dendritic spines, indicating potential synaptic plasticity deficit. Since ZnT3 deficiency was previously linked to glucose metabolism abnormalities, we tested the expression levels of genes related to insulin signaling pathway in the hippocampus and cortex. We found that the Expression of glucose transporters, GLUT3, GLUT4, and the insulin receptor in the whole tissue and synaptosome fraction of the hippocampus of the ZnT3 knockout mice were significantly reduced, as compared to wild-type controls. Expression of AKT (A serine/threonine protein kinase) and insulin-induced AKT phosphorylation was also reduced in the hippocampus of ZnT3 knockout mice. We hypothesize that the ZnT3 deficiency and reduced brain zinc levels may cause cognitive impairment by negatively affecting glycose metabolism via decreased expression of key components of insulin signaling, as well as via changes in synaptic plasticity. These finding may provide new therapeutic target for treatments of neurodegenerative disorders.

[Relationship between the percentage of energy intake from macronutrients and obesity among adult residents in 15 provinces of China in 1991-2018].

OBJECTIVE: To explore the relationship between the percentage of energy intake from macronutrients and obesity in Chinese adult residents, and analyze the cut-off values of macronutrients for predicting obesity. METHODS: Data was collected in China Health and Nutrition Survey(CHNS)in 1991-2018. Adults who participated in at least two waves of the surveys and were not obese at baseline were selected as the study subjects. Obesity was defined as body mass index(BMI)≥28.0 kg/m~2. Generalized estimating equation was used to analyze the relationship between the percentage of energy intake from macronutrients and BMI and obesity, and receiver operating characteristic curve(ROC) was used to analyze the cut-off values of percentage of energy intake from macronutrients to predict obesity. RESULTS: The percentage of energy intake from protein and fat of adult residents in 15 provinces(autonomous regions and municipalities) in China showed an increasing trend(P<0.01), and the percentage of energy intake from carbohydrate showed a decreasing trend(P<0.01) between 1991 and 2018. After adjusting for covariates, the group of percentage of energy intake from fat in 20%～30%(ß=0.05, 95%CI 0.01-0.08)and ≥30%(ß=0.15, 95%CI 0.11-0.18)were positively correlated with BMI compared with the group of percentage of energy intake from fat <20%, and the risk of obesity in 20%-30% and ≥ 30% was increased by 17%(OR=1.17, 95%CI 1.04-1.31)and 6%(OR=1.06, 95%CI 1.24-1.56), respectively. Compared with the group of the percentage of energy intake from carbohydrate < 50%, the group of 50% to 65%(ß=-0.08, 95% CI-0.11--0.05) and ≥ 65%(ß=-0.17, 95%CI-0.20--0.13) was negatively correlated with BMI, and the percentage of energy intake from carbohydrate ≥ 65% reduced the risk of obesity(OR=0.71, 95%CI 0.63-0.80). CONCLUSION: Carbohydrate intake was inversely correlated with the risk of obesity, and fat intake was positively correlated with the risk of obesity. Moderate intake of carbohydrates and reduced fat intake can prevent obesity.

Broadband Emission Induced by Band-Edge Carrier Reconfiguration in 2D Hybrid Lead Halide Perovskites.

Broadband emission in hybrid lead halide perovskites (LHPs) has gained significant attention due to its potential applications in optoelectronic devices. The origin of this broadband emission is primarily attributed to the interactions between electrons and phonons. Most investigations have focused on the impact of structural characteristics of LHPs on broadband emission, while neglecting the role of electronic mobility. In this work, the study investigates the electronic origins of broadband emission in a family of 2D LHPs. Through spectroscopic experiments and density functional theory calculations, the study unveils that the electronic states of the organic ligands with conjugate effect in LHPs can extend to the band edges. These band-edge carriers are no longer localized only within the inorganic layers, leading to electronic coupling with molecular states in the barrier and giving rise to additional interactions with phonon modes, thereby resulting in broadband emission. The high-pressure photoluminescence measurements and theoretical calculations reveal that hydrostatic pressure can induce the reconfiguration of band-edge states of charge carriers, leading to different types of band alignment and achieving macroscopic control of carrier dynamics. The findings can provide valuable guidance for targeted synthesis of LHPs with broadband emission and corresponding design of state-of-the-art optoelectronic devices.

EFHD2 regulates T cell receptor signaling and modulates T helper cell activation in early sepsis.

EFHD2 (EF-hand domain family, member D2) has been identified as a calcium-binding protein with immunomodulatory effects. In this study, we characterized the phenotype of Efhd2-deficient mice in sepsis and examined the biological functions of EFHD2 in peripheral T cell activation and T helper (Th) cell differentiation. Increased levels of EFHD2 expression accompanied peripheral CD4+ T cell activation in the early stages of sepsis. Transcriptomic analysis indicated that immune response activation was impaired in Efhd2-deficient CD4+ T cells. Further, Efhd2-deficient CD4+ T cells isolated from the spleen of septic mice showed impaired T cell receptor (TCR)-induced Th differentiation, especially Th1 and Th17 differentiation. In vitro data also showed that Efhd2-deficient CD4+ T cells exhibit impaired Th1 and Th17 differentiation. In the CD4+ T cells and macrophages co-culture model for antigen presentation, the deficiency of Efhd2 in CD4+ T cells resulted in impaired formation of immunological synapses. In addition, Efhd2-deficient CD4+ T cells exhibited reduced levels of phospho-LCK and phospho-ZAP70, and downstream transcription factors including Nfat, Nfκb and Nur77 following TCR engagement. In summary, EFHD2 may promote TCR-mediated T cell activation subsequent Th1 and Th17 differentiation in the early stages of sepsis by regulating the intensity of TCR complex formation.

The Supplementation of Berberine in High-Carbohydrate Diets Improves Glucose Metabolism of Tilapia (Oreochromis niloticus) via Transcriptome, Bile Acid Synthesis Gene Expression and Intestinal Flora.

Berberine is an alkaloid used to treat diabetes. This experiment aimed to investigate the effects of berberine supplementation in high-carbohydrate diets on the growth performance, glucose metabolism, bile acid synthesis, liver transcriptome, and intestinal flora of Nile tilapia. The six dietary groups were the C group with 29% carbohydrate, the H group with 44% carbohydrate, and the HB1-HB4 groups supplemented with 25, 50, 75, and 100 mg/kg of berberine in group H. The results of the 8-week trial showed that compared to group C, the abundance of Bacteroidetes was increased in group HB2 (p < 0.05). The cholesterol-7α-hydroxylase (CYP7A1) and sterol-27-hydroxylase (CYP27A1) activities were decreased and the expression of FXR was increased in group HB4 (p < 0.05). The pyruvate carboxylase (PC) and phosphoenolpyruvate carboxykinase (PEPCK) activities was decreased in group HB4 (p < 0.05). The liver transcriptome suggests that berberine affects carbohydrate metabolic pathways and primary bile acid synthesis pathways. In summary, berberine affects the glucose metabolism in tilapia by altering the intestinal flora structure, enriching differentially expressed genes (DEGs) in the bile acid pathway to stimulate bile acid production so that it promotes glycolysis and inhibits gluconeogenesis. Therefore, 100 mg/kg of berberine supplementation in high-carbohydrate diets is beneficial to tilapia.

Altered static and dynamic functional brain network in knee osteoarthritis: A resting-state functional magnetic resonance imaging study: Static and dynamic FNC in KOA.

This study aimed to investigate altered static and dynamic functional network connectivity (FNC) and its correlation with clinical symptoms in patients with knee osteoarthritis (KOA). One hundred and fifty-nine patients with KOA and 73 age- and gender-matched healthy subjects (HS) underwent resting-state functional magnetic resonance imaging (rs-fMRI) and clinical evaluations. Group independent component analysis (GICA) was applied, and seven resting-state networks were identified. Patients with KOA had decreased static FNC within the default mode network (DM), visual network (VS), and cerebellar network (CB) and increased static FNC between the subcortical network (SC) and VS (p < 0.05, FDR corrected). Four reoccurring FNC states were identified using k-means clustering analysis. Although abnormalities in dynamic FNCs of KOA patients have been found using the common window size (22 TR, 44 s), but the results of the clustering analysis were inconsistent when using different window sizes, suggesting dynamic FNCs might be an unstable method to compare brain function between KOA patients and HS. These recent findings illustrate that patients with KOA have a wide range of abnormalities in the static and dynamic FNCs, which provided a reference for the identification of potential central nervous therapeutic targets for KOA treatment and might shed light on the other musculoskeletal pain neuroimaging studies.

Acupuncture-Related Therapy for Knee Osteoarthritis: A Narrative Review of Neuroimaging Studies.

Acupuncture has been widely applied for treating knee osteoarthritis (KOA). Numerous studies have found that acupuncture can effectively alleviate KOA symptoms. With the advancement of neuroimaging techniques, integrating neuroimaging with in-depth investigations of acupuncture mechanisms has emerged as a hot topic in traditional Chinese medical neuroscience research. This review aimed to analyze the study design and main findings from neuroimaging studies of acupuncture-related therapy for KOA to provide a reference for future research. Original studies were sourced from English databases (PubMed, Embase, and Cochrane Library) and Chinese databases (Chinese National Knowledge Infrastructure, Chinese Biomedical Literature Database, the Chongqing VIP database, and Wanfang database). As a result, thirteen articles were ultimately included in this review. Functional magnetic resonance imaging was the most frequently used neuroimaging technique to explore cerebral responses to acupuncture-related therapy for KOA. Findings suggested that acupuncture-related therapy could regulate some brain regions in patients with KOA. Specifically, for acupuncture, it showed that the medial pain pathway and the limbic system were involved in the regulation of KOA. Meanwhile, moxibustion induced a wide range of functional activity throughout the entire brain.

Longitudinal Relationship between the Percentage of Energy Intake from Macronutrients and Overweight/Obesity among Chinese Adults from 1991 to 2018.

To investigate the prospective relationship between macronutrient intake and overweight/obesity, data were collected in the China Health and Nutrition Survey (CHNS) from 1991 to 2018. Adults who participated in at least two waves of the survey and were not obese at baseline were selected as the study subjects. A total of 14,531 subjects were finally included with complete data. Overweight/obesity was defined as a body mass index (BMI) ≥ 24.0 kg/m2. The generalized estimating equation (GEE) was used to analyze the relationship between the percentage of energy intake from macronutrients and BMI and overweight/obesity. The percentages of energy intake from protein and fat showed an increasing trend (p < 0.01), and the percentage of energy intake from carbohydrate showed a decreasing trend (p < 0.01) among Chinese adults between 1991 and 2018. Adjusting for covariates, the energy intake from fat was positively correlated with BMI, while the energy intake from carbohydrates was negatively correlated with BMI. The percentage of energy intake from non-high-quality protein and polyunsaturated fatty acids (PUFA) were positively correlated with overweight/obesity. In contrast, monounsaturated fatty acids (MUFA) and high-quality carbohydrates were negatively correlated with overweight/obesity. In short, fat, non-high-quality protein, saturated fatty acids (SFA), and PUFA were positively correlated with the risk of obesity, whereas higher carbohydrate, MUFA, and high-quality carbohydrate intake were associated with a lower risk of obesity. Obesity can be effectively prevented by appropriately adjusting the proportion of intake from the three major macronutrients.

Effects of Dietary Aflatoxin B1 on Hybrid Grouper (Epinephelus fuscoguttatus ♀ × Epinephelus lanceolatus ♂) Growth, Intestinal Health, and Muscle Quality.

This study investigated the effects of varying doses of dietary aflatoxin B1 (AFB1) on the growth, intestinal health, and muscle quality of hybrid grouper. Four diets with varying AFB1 concentrations (0, 30, 445, and 2,230 µg kg-1) were used. Elevating AFB1 concentrations led to a decline in growth indexes, specifically the weight gain rate and the specific growth rate, although the survival rate remained unchanged. Morphological indicators showed a dose-dependent decline with AFB1 exposure. Intestinal MDA content and hindgut reactive oxygen species (ROS) levels increased, while antioxidant indexes and digestive enzymes decreased with higher AFB1 levels. AFB1 negatively influenced hindgut tight junction protein and antioxidant-related gene expression while promoting inflammation-related gene expression. The presence of AFB1 in the experiment led to a decrease in beneficial intestinal bacteria, such as Prevotella, and an increase in harmful intestinal bacteria, such as Prevotellaceae_NK3B31_group. Muscle lipid and unsaturated fatty acid content significantly decreased, while muscle protein and liver AFB1 content increased dramatically with higher AFB1 concentrations. AFB1 caused myofibrillar cleavage and myofilament damage, leading to increased spaces between muscle fibers. In conclusion, diets with AFB1 levels exceeding 30 µg kg-1 inhibited hybrid grouper growth, while levels surpassing 445 µg kg-1 resulted in hindgut ROS accumulation, inflammation, elevated intestinal permeability, reduced digestive enzyme activity, and compromised muscle quality.

Chronic vascular pathogenesis results in the reduced serum Metrnl levels in ischemic stroke patients.

Metrnl is a secreted protein involved in neurite outgrowth, insulin sensitivity, immunoinflammatory responses, blood lipids and endothelial protection. In this study, we investigated the role of Metrnl in ischemic stroke. Fifty-eight ischemic stroke patients (28 inpatient patients within 2 weeks of onset and 30 emergency patients within 24 h of onset) and 20 healthy controls were enrolled. Serum Metrnl was measured by enzyme-linked immunosorbent assay. We showed that serum Metrnl levels were significantly reduced in both inpatient and emergency patient groups compared with the controls. Different pathological causes for ischemic stroke such as large artery atherosclerosis and small artery occlusion exhibited similar reduced serum Metrnl levels. Transient ischemic attack caused by large artery atherosclerosis without brain infarction also had lower serum Metrnl levels. Metrnl was correlated with some metabolic, inflammatory and clotting parameters. Reduced serum Metrnl was associated with the severity of intracranial arterial stenosis and the presence of ischemic stroke. In order to elucidate the mechanisms underlying the reduced serum Metrnl levels, we established animal models of ischemic stroke in normal mice, atherosclerotic apolipoprotein E-knockout mice and Metrnl-knockout mice by middle cerebral artery occlusion (MCAO) using intraluminal filament or electrocoagulation. We demonstrated that serum Metrnl levels were significantly lower in atherosclerosis mice than normal mice, whereas acute ischemic stroke injury in normal mice and atherosclerosis mice did not alter serum Metrnl levels. Metrnl knockout did not affect acute ischemic stroke injury and death. We conclude that reduced serum Metrnl levels are attributed to the chronic vascular pathogenesis before the onset of ischemic stroke. Metrnl is a potential target for prevention of ischemic stroke.

Effects of α-Lipoic Acid Supplementation on Growth Performance, Liver Histology, Antioxidant and Related Genes Expression of Hybrid Grouper (Epinephelus fuscoguttatus ♀ × E. lanceolatus ♂).

This study aimed to assess the impact of α-lipoic acid on the growth performance, antioxidant capacity and immunity in hybrid groupers (♀ Epinephelus fuscoguttatus × â™‚ E. lanceolatus) fed with a high-lipid diet. Groupers (8.97 ± 0.01 g) were fed six different diets, with α-lipoic acid content in diets being 0, 400, 800, 1200, 1600, and 2000 mg/kg, named S1, S2, S3, S4, S5, and S6, respectively. The results show that the addition of 2000 mg/kg α-lipoic acid in the diet inhibited the growth, weight gain rate (WGR), and specific growth rate (SGR), which were significantly lower than other groups. In serum, catalase (CAT) and superoxide dismutase (SOD) were significantly higher in the S5 group than in the S1 group. In the liver, CAT, SOD and total antioxidative capacity (T-AOC) levels were significantly increased in α-lipoic acid supplemented groups. α-lipoic acid significantly upregulated liver antioxidant genes sod and cat, anti-inflammatory factor interleukin 10 (il10) and transforming growth factor ß (tgfß) mRNA levels. Conclusion: the addition of 2000 mg/kg of α-lipoic acid inhibits the growth of hybrid groupers. In addition, 400-800 mg/kg α-lipoic acid contents improve the antioxidant capacity of groupers and have a protective effect against high-lipid-diet-induced liver oxidative damage.

Implications on growth performance, glucose metabolism, PI3K/AKT pathway, intestinal flora induced by dietary taurine in a high-carbohydrate diet for grass carp (Ctenopharyngodon idella).

An 8-week experiment was performed to investigate the influence on growth performance, plasma biochemistry, glucose metabolism and the insulin pathway of supplementation of dietary taurine to a high-carbohydrate diet for grass carp. In this study, fish were fed diets at one of two carbohydrate levels, 31·49 % (positive control) or 38·61 % (T00). The high-carbohydrate basal diet (T00), without taurine, was supplemented with 0·05 % (T05), 0·10 % (T10), 0·15 % (T15) or 0·20 % (T20) taurine, resulting in six isonitrogenous (30·37 %) and isolipidic (2·37 %) experimental diets. The experimental results showed that optimal taurine level improved significantly weight gain, specific growth rate (SGR), feed utilisation, reduced plasma total cholesterol levels, TAG and promoted insulin-like growth factor level. Glucokinase, pyruvate kinase and phosphoenolpyruvate carboxykinase activities showed a quadratic function model with increasing dietary taurine level, while hexokinase, fatty acid synthetase activities exhibited a positive linear trend. Optimal taurine supplementation in high-carbohydrate diet upregulated insulin receptor (Ir), insulin receptor substrate (Irs1), phosphatidylinositol 3-kinase (pi3k), protein kinase B (akt1), glycogen synthase kinase 3 ß (gs3kß) mRNA level and downregulated insulin-like growth factor (igf-1), insulin-like growth factor 1 receptor (igf-1R) and Fork head transcription factor 1 (foxo1) mRNA level. The above results suggested that optimal taurine level could improve growth performance, hepatic capacity for glycolipid metabolism and insulin sensitivity, thus enhancing the utilisation of carbohydrates in grass carp. Based on SGR, dietary optimal tributyrin taurine supplementation in grass carp was estimated to be 0·08 %.

Epidemiology Characteristics and Potential Clinical Value of Vulvar Human Papillomavirus in Chinese Women: A Multicenter Cross-Sectional Study.

CONTEXT.­: Noninvasive self-sampling is a convenient option that may be highly accepted by women for home-based detection, which could increase the screening rate for cervical cancer (CC) and reduce its incidence and mortality. OBJECTIVE.­: To compare the distribution of high-risk human papillomavirus (hr-HPV) between the vulva and cervix and to explore the clinical value of vulvar HPV detection in CC screening. DESIGN.­: The study was nested within a clinical trial on recombinant HPV 9-valent vaccine for women ages 20 to 45 years. Women with paired vulvar and cervical specimens were included and received cytology and HPV detection. The consistency of HPV detection between vulvar and cervical specimens was evaluated using Cohen κ statistics. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were used to evaluate the diagnostic accuracy of primary CC screening. The primary end points were cervical intraepithelial neoplasia (CIN) grade 2/3 or worse (CIN2+/3+). RESULTS.­: A total of 7999 women were enrolled, and 83/33 cases were diagnosed as CIN2+/CIN3+. The HPV-positive rate in vulvar specimens (1785 of 7999; 22.32%) was higher than that in cervical specimens (1390 of 7999; 17.38%), and there were no significant differences in the distribution of hr-HPV genotypes between the vulva and cervix in patients with CIN2+/CIN3+. Vulva-based HPV primary screening showed sensitivity, specificity, PPV, and NPV comparable to those for cervix-based HPV primary CC screening in the detection of CIN3+. CONCLUSIONS.­: The distribution of vulvar and cervical HPV was similar in patients with CIN2+/CIN3+. Vulva-based HPV primary CC screening had acceptable diagnostic efficacy and might be used as a modality for primary CC screening.

An integrated study of glutamine alleviates enteritis induced by glycinin in hybrid groupers using transcriptomics, proteomics and microRNA analyses.

Glutamine has been used to improve intestinal development and immunity in fish. We previously found that dietary glutamine enhances growth and alleviates enteritis in juvenile hybrid groupers (Epinephelus fuscoguttatus♀ × Epinephelus lanceolatus♂). This study aimed to further reveal the protective role of glutamine on glycinin-induced enteritis by integrating transcriptome, proteome, and microRNA analyses. Three isonitrogenous and isolipidic trial diets were formulated: a diet containing 10% glycinin (11S group), 10% glycinin diet supplemented with 2% alanine-glutamine (Gln group), and a diet containing neither glycinin nor alanine-glutamine (fishmeal, FM group). Each experimental diet was fed to triplicate hybrid grouper groups for 8 weeks. The analysis of intestinal transcriptomic and proteomics revealed a total of 570 differentially expressed genes (DEGs) and 169 differentially expressed proteins (DEPs) in the 11S and FM comparison group. Similarly, a total of 626 DEGs and 165 DEPs were identified in the Gln and 11S comparison group. Integration of transcriptome and proteome showed that 117 DEGs showed consistent expression patterns at both the transcriptional and translational levels in the Gln and 11S comparison group. These DEGs showed significant enrichment in pathways associated with intestinal epithelial barrier function, such as extracellular matrix (ECM)-receptor interaction, tight junction, and cell adhesion molecules (P < 0.05). Further, the expression levels of genes (myosin-11, cortactin, tenascin, major histocompatibility complex class I and II) related to these pathways above were significantly upregulated at both the transcriptional and translational levels (P < 0.05). The microRNA results showed that the expression levels of miR-212 (target genes colla1 and colla2) and miR-18a-5p (target gene colla1) in fish fed Gln group were significantly lower compared to the 11S group fish (P < 0.05). In conclusion, ECM-receptor interaction, tight junction, and cell adhesion molecules pathways play a key role in glutamine alleviation of hybrid grouper enteritis induced by high-dose glycinin, in which miRNAs and target mRNAs/proteins participated cooperatively. Our findings provide valuable insights into the RNAs and protein profiles, contributing to a deeper understanding of the underlying mechanism for fish enteritis.