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The endophytic fungus Diaporthe sp. is known to contain many secondary metabolites, but fatty acid derivatives have rarely been found. In this study, four new fatty acid derivatives (1–4), together with four known compounds (5–8), were isolated from Diaporthe sp., which was obtained from the stem of Ligularia fischeri. The absolute configurations of the new compounds 1–4 were deduced based on spectroscopic technique and J-based coupling constant analysis. Moreover, compound 1 exhibited cytotoxic activities against HCT-8 and MCF-7 cancer cells, and compounds 3 and 4 showed modest selectivity for HCT-8 cells by MTT assay. [ABSTRACT FROM AUTHOR]

Backgrounds. Acute kidney injury (AKI) is a prevalent nonneurological complication in patients with traumatic brain injury (TBI). We designed this study to explore the association between serum uric acid (SUA) level and the occurrence of AKI following TBI. Methods. This is a retrospective single-center study. A total of 479 patients admitted with TBI were included in this study. We utilized SUA and other risk factors for AKI to construct a predictive model by performing multivariate logistic regression. 374 patients and 105 patients were, respectively, divided into a training set and validation set. The predictive value of the single SUA and constructed model was evaluated by drawing a receiver operating characteristic (ROC) curve. AKI was diagnosed according to the KIDGO criteria. Results. 79 (21.12%) patients were diagnosed with AKI in the training cohort. The patients in the AKI group are older than those in the non-AKI group (p = 0.01). And the Glasgow Coma Scale (GCS) of the AKI group was lower than that of the non-AKI group (p < 0.001). In a multivariate logistic regression analysis, we found that heart rate (p = 0.041), shock (p = 0.018), serum creatinine (p < 0.001), and serum uric acid (SUA) (p < 0.001) were significant risk factors for AKI. Bivariate correlation analyses showed that serum creatinine was moderately positively correlated with SUA (r = 0.523 , p < 0.001). Finally, the area under the receiver operating characteristic curve (AUC) of SUA for predicting AKI in the training set and validation set was 0.850 (0.805-0.895) and 0.869 (0.801-0.938), respectively. Conclusions. SUA is an effective risk factor for AKI following TBI. Combining SUA with serum creatinine could more accurately identify TBI patients with high risk of developing AKI. [ABSTRACT FROM AUTHOR]

Oxymatrine (OMTR) is widely used for the treatment of chronic hepatitis B (CHB) in China. Several reports revealed that combination of OMTR and lamivudine reduced the incidence of tyrosine- (Y-) methionine- (M-) aspartic acid- (D-) aspartic acid (D) (YMDD) mutations in CHB patients. The aim of this study was to evaluate the clinical value of oxymatrine in preventing lamivudine induced YMDD mutation using meta-analysis of data from published randomized controlled trials (RCTs) and to provide some useful information for clinical treatment and future research of YMDD mutation. The Cochrane Central Register of Controlled Trials, Medline, Science Citation Index, EMBASE, China National Knowledge Infrastructure, Wanfang Database, and China Biomedical Database were searched to identify RCTs that evaluated the incidence of YMDD-motif mutation to lamivudine therapy and lamivudine plus OMTR therapies in CHB patients. Data analysis was carried out with the use of RevMan 5.3.2. The literature search yielded 324 studies, and 16 RCTs matched the selection criteria. Overall, the incidence of YMDD mutation was significantly lower in patients treated with lamivudine plus OMTR than in patients treated with lamivudine alone (11.14% versus 28.18%; RR: 0.41; 95% CI: 0.33–0.52; p<0.05). The exact outcome needs to perform rigorously designed, multicenter, and large randomized controlled trials. [ABSTRACT FROM AUTHOR]

Summary: Background: The relationship between sugar‐free beverage (SFB) intake and childhood obesity among Chinese children is unknown. Objectives: To describe the status of SFB consumption among children and adolescents in China and assess the association between SFB intake and different types of obesity. Methods: The study was based on the baseline data of an ongoing cohort project named Evaluation and Monitoring on School‐based Nutrition and Growth in Shenzhen (EMSNGS). Food frequency questionnaires were used to collect information on SFB consumption in 3227 students aged 9–17. Physical and clinical examinations were conducted by trained investigators and clinicians. Multivariable binary logistic regression models were performed to assess the association between SFB intake and general obesity, overweight/obesity, abdominal obesity, metabolically unhealthy overweight (MUOW)/metabolically unhealthy obesity (MUO). Results: The median age of the participants was 13.28 years. Among the participants, 55.2% were boys, and 66.1% were adolescents. The median SFB consumption was 16.67 mL/d. After adjusting for potential confounding factors, each 100 mL increase in daily SFB intake was associated with an increased risk of overweight/obesity (OR = 1.14; 95%CI: 1.06–1.23), abdominal obesity (OR = 1.12; 95%CI: 1.03–1.23), and MUOW/MUO (OR = 1.12; 95%CI: 1.02–1.21), respectively. Stratified analyses showed that family income may have an impact on the association between SFB intake and overweight/obesity (P for interaction = 0.021) and abdominal obesity (P for interaction = 0.031). Conclusion: SFB intake was positively associated with childhood obesity in Chinese children, particularly among individuals with high‐income families. [ABSTRACT FROM AUTHOR]

Background. The association between atherogenic index of plasma (AIP) and hyperuricemia remains indistinct. This study was aimed to examine the relationship between AIP and hyperuricemia among the middle-aged and the elderly Chinese population. Methods. Datasets were retrieved from the China Health and Retirement Longitudinal Study (CHARLS) survey conducted in 2011 and 2015. 13,021 participants in the CHARLS in 2011 and 7,017 participants involved both in 2011 and 2015 were included, respectively. The measurement of AIP and hyperuricemia was based on the test of fasting blood. Association between AIP and hyperuricemia was assessed by logistic regression, and the nonlinear association was examined by restricted cubic splines (RCS). The cutoff point of AIP was calculated using receiver operator curve (ROC). 1 : 1 propensity score matching (PSM) was adopted to further explore the relationship between AIP and hyperuricemia. Results. In the section of a cross-sectional study, a positive association between AIP and hyperuricemia was found. The odds ratios (ORs) of hyperuricemia were 1.00 (reference), 1.52 (1.10–2.10), 1.80 (1.31–2.47), and 3.81 (2.84–5.11). Nonlinear association was not detected using RCS analysis. There were 664 hyperuricemia cases during the four years follow-up. The hyperuricemia prevalence was 9.5%. In the fully adjusted longitudinal analysis, the ORs for hyperuricemia across the quartiles of AIP were 1.00 (reference), 1.00 (0.74–1.37), 1.59 (1.20–2.11), and 2.55 (1.94–3.35), respectively. In the longitudinal analysis after PSM, the OR of hyperuricemia were 1.91 (1.45, 2.51) and 1.92 (1.45, 2.54) in the univariate and multivariate model, respectively. Conclusion. AIP can predict the prevalence of hyperuricemia in the Chinese middle-aged and elderly population. [ABSTRACT FROM AUTHOR]

Simple Summary: Hepatocellular carcinoma (HCC) has the highest incidence and mortality rate in the Asian population. However, it is unclear how ethnic genetic variability affects this. Our research shows that hsa-miR-100-5p, a miRNA associated with HCC prognosis, improves prognosis in Asians. In contrast, Polo-like kinase 1 (PLK1), inhibited by hsa-miR-100-5p, worsens HCC prognosis in Asians. A single-nucleotide polymorphism (SNP) named rs27770, located in the 3′UTR of PLK1, has a significantly higher frequency of the G allele in the East Asian population. The A>G change in rs27770 affects the PLK1 mRNA secondary structure and alters the hsa-miR-100-5p/PLK1 interaction by creating an additional seedless binding site. This could make hsa-miR-100-5p more favorable for HCC prognosis in the Asian population. Our findings could help explain why the Asian population is more susceptible to HCC. Hepatocellular carcinoma (HCC) has the highest incidence and mortality in the Asian population, and race is an independent risk factor affecting survival time in liver cancer. Micro RNAs (miRNAs) are remarkably dysregulated in HCC and closely associated with HCC prognosis. Recent studies show that genetic variability between ethnic groups may result in differences in the specificity of HCC miRNA biomarkers. Here, we reveal a high expression level of hsa-miR-100-5p, an HCC prognosis-related miRNA, which improves HCC prognosis in the Asian Population with Polo-like kinase 1 (PLK1) variant rs27770A>G. In this study, we discovered that hsa-miR-100-5p was downregulated in various HCC cell lines. While mimics transient transfection and mouse liver cancer model confirmed the interaction between hsa-miR-100-5p and PLK1, a stratified analysis based on the Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) data suggest both low hsa-miR-100-5p expression level and high PLK1 expression level associated with poor HCC prognosis, especially in the Asian population. According to the 1000 Genomes Project database, the SNP rs27770 located in 3′UTR of PLK1 had a significantly higher G allele frequency in the East Asian population. Bioinformatics analysis suggested that rs27770 A>G affects PLK1 mRNA secondary structure and alters the hsa-miR-100-5p/PLK1 interaction by forming an additional seedless binding site. This racial variation caused PLK1 to be more vulnerable to hsa-miR-100-5p inhibition, resulting in hsa-miR-100-5p being more favorable for HCC prognosis in the Asian population. [ABSTRACT FROM AUTHOR]

Objective This study aims to estimate the prevalence of anti-mitochondrial antibody subtype M2 (AMA-M2) and assess its consistency with AMA in a general population. Methods A total of 8954 volunteers were included to screen AMA-M2 using enzyme-linked immunosorbent assay. Sera with AMA-M2 >50 RU/mL were further tested for AMA using an indirect immunofluorescence assay. Results The population frequency of AMA-M2 positivity was 9.67%, of which 48.04% were males and 51.96% were females. The AMA-M2 positivity in males had a peak and valley value of 7.81% and 16.88% in those aged 40 to 49 and ≥70 years, respectively, whereas it showed a balanced age distribution in females. Transferrin and immunoglobulin M were the risk factors for AMA-M2 positivity and exercise was the only protective factor. Of 155 cases with AMA-M2 >50 RU/mL, 25 cases were AMA-positive, with a female-to-male ratio of 5.25:1. Only 2 people, with very high AMA-M2 of 760 and >800 RU/mL, met the diagnostic criteria of primary biliary cholangitis (PBC), making the prevalence of PBC 223.36 per million in southern China. Conclusion We found that AMA-M2 has a low coincidence rate with AMA in the general population. A new decision-making point for AMA-M2 is needed to improve consistency with AMA and diagnostic accuracy. [ABSTRACT FROM AUTHOR]

Background: Persistent psychological distress associated with the coronavirus disease 2019 (COVID-19) pandemic has been well documented. This study aimed to identify pre-COVID brain functional connectome that predicts pandemic-related distress symptoms among young adults. Methods: Baseline neuroimaging studies and assessment of general distress using the Depression, Anxiety and Stress Scale were performed with 100 healthy individuals prior to wide recognition of the health risks associated with the emergence of COVID-19. They were recontacted for the Impact of Event Scale-Revised and the Posttraumatic Stress Disorder Checklist in the period of community-level outbreaks, and for follow-up distress evaluation again 1 year later. We employed the network-based statistic approach to identify connectome that predicted the increase of distress based on 136-region-parcellation with assigned network membership. Predictive performance of connectome features and causal relations were examined by cross-validation and mediation analyses. Results: The connectome features that predicted emergence of distress after COVID contained 70 neural connections. Most within-network connections were located in the default mode network (DMN), and affective network-DMN and dorsal attention network-DMN links largely constituted between-network pairs. The hippocampus emerged as the most critical hub region. Predictive models of the connectome remained robust in cross-validation. Mediation analyses demonstrated that COVID-related posttraumatic stress partially explained the correlation of connectome to the development of general distress. Conclusions: Brain functional connectome may fingerprint individuals with vulnerability to psychological distress associated with the COVID pandemic. Individuals with brain neuromarkers may benefit from the corresponding interventions to reduce the risk or severity of distress related to fear of COVID-related challenges. [ABSTRACT FROM AUTHOR]

Background. Several studies have focused on the prognostic role of microRNA 222 in glioma. But different conclusions were drawn by these studies. We aimed to systematically evaluate the role of microRNA 222 in glioma by conducting a meta-analysis. Methods. A systematic literature search until January 2020 was conducted in Web of Science, EMBASE, Cochrane Library, PubMed, and China National Knowledge Infrastructure. The general characteristics and relevant data of nine articles were extracted. Hazard ratios (HRs) with 95% confidence intervals (CIs) were applied to evaluate the prognostic role of microRNA 222 in glioma. The primary outcomes were overall survival (OS) and disease-free survival (DFS). Results. Nine articles (11 data sets) with 1564 patients were included. We systematically evaluated the role of microRNA 222 for OS and DFS in glioma patients (HR for OS = 1.72 ; 95% CI, 1.31-2.26; p = 0.001 ; HR for DFS = 1.02 ; 95% CI, 0.86-1.22; p = 0.032). Subgroup analyses were performed according to the sources of patients, the types of the samples, the stages of the tumors, the methods for detecting the microRNA 222, and the sample size. No significant publication bias was found. Conclusion. In conclusion, our study provided evidence that a high expression of microRNA 222 was related to worse overall survival in glioma patients. However, given the limited study number, more high-quality studies are warranted in the future. [ABSTRACT FROM AUTHOR]

Background. There is a yearly increase in pain after neck surgery, which is accompanied by high consumption of opioids. However, the opioid addiction epidemic is one of the most serious public health problems worldwide. Therefore, it is important to find suitable alternatives for opioids. Acupuncture therapy has been found effective for some types of pain control. This protocol aims to evaluate the efficacy and safety of acupuncture therapy in the treatment of pain after neck surgery. Methods and Analysis. We will search eight electronic databases from their inception to April 2022. Only randomized controlled trials (RCTs) using manual acupuncture, auricular acupuncture, or electroacupuncture as major therapy will be included, regardless of whether the study was published in Chinese or English. The selection of studies and data extraction will be independently completed by at least two experienced reviewers with a master's degree. The methodological quality of the included studies will be assessed by the Cochrane risk-of-bias tool. For the meta-analysis, Review Manager Statistical (RevMan V.5.3) software will be used. The results will be presented as the risk ratio (RR) for the binary data and the mean difference (MD) or standardized mean difference (SMD) for the continuous data. Ethics and Dissemination. This protocol for a systematic review will be submitted to a peer-reviewed journal for publication and presented at a relevant conference, and there is no need to obtain formal ethical approval. Trial Registration Number. PROSPERO registration number CRD42021281722. [ABSTRACT FROM AUTHOR]

The perceptions and attitudes of commuters toward the behavioral thresholds for commuting time are of great significance for understanding their commuting patterns and possible changes in those patterns. This study focuses on the tolerance threshold of commuting time and presents the empirical evidences using the data from Kunming, China. The descriptive statistics of the tolerance thresholds of commuting time are presented. The statistical results demonstrate that the tolerance threshold of commuting time peaks at the interval of [30,40) min and the actual commuting time of 44.3% commuters is approximately equal to or exceeds the tolerance threshold. Furthermore, the determinants of the tolerance threshold of commuting time are identified using an ordered logistic model. The results demonstrate that age, gender, education level, household income, the presence of children, travel mode and residential location have a significant impact on the tolerance threshold of commuting time. [ABSTRACT FROM AUTHOR]

Background: The TM4 (UBAC2) protein, which contains 4 transmembrane domains and one ubiquitin binding domain, is mainly expressed in cell and nuclear membranes. The current research aimed to explore the role of TM4 in metabolic inflammation and to examine whether the ubiquitin–proteasome inhibitor PS-341 could regulate the function of TM4. Methods: The metabolic phenotypes of TM4 knockout (KO) mice were studied. We next explored the association between the polymorphisms of TM4 and obesity in a Chinese Han population. TM4 expression in the visceral fat of obese patients who underwent laparoscopic cholecystectomy was also analysed. Finally, the effect of PS-341 on the degradation and function of the TM4 protein was investigated in vivo and in vitro. Results: TM4 KO mice developed obesity, hepatosteatosis, hypertension, and glucose intolerance under a high-fat diet. TM4 counterregulated Nur77, IKKβ, and NF-kB both in vivo and in vitro. The TM4 SNP rs147851454 is significantly associated with obesity after adjusting for age and sex (OR 1.606, 95% CI 1.065–2.422 P = 0.023) in 3394 non-diabetic and 1862 type 2 diabetic adults of Han Chinese. TM4 was significantly downregulated in the visceral fat of obese patients. PS-341 induced TM4 expression through inhibition of TM4 degradation in vitro. In db/db mice, PS-341 administration led to downregulation of Nur77/IKKβ/NF-κB expression in visceral fat and liver, and alleviation of hyperglycaemia, hypertension, and glucose intolerance. The hyperinsulinaemic-euglycaemic clamp demonstrated that PS-341 improved the glucose infusion rate and alleviated insulin resistance in db/db mice. Conclusions: PS-341 alleviates chronic low-grade inflammation and improves insulin sensitivity through inhibition of TM4 degradation. [ABSTRACT FROM AUTHOR]

Background Fetal alcohol spectrum disorder is an immense public health problem. In vitro studies support the hypothesis that L1 cell adhesion molecule ( L1) is a target for ethanol ( EtOH) developmental neurotoxicity. L1 is critical for the development of the central nervous system. It functions through signal transduction leading to phosphorylation and dephosphorylation of tyrosines on its cytoplasmic domain. The function of L1 is also dependent on trafficking through lipid rafts ( LRs). Our hypothesis is that L1 is a target for EtOH neurotoxicity in vivo. Our objective is to demonstrate changes in L1 phosphorylation/dephosphorylation and LR association in vivo. Methods Rat pups on postnatal day 6 are administered 4.5, 5.25, and 6 g/kg of EtOH divided into 2 doses 2 hours apart, then killed. Cerebella are rapidly frozen for assay. Blood is analyzed for blood EtOH concentration. L1 tyrosine phosphorylation is determined by immunoprecipitation and dephosphorylation of tyrosine 1176 determined by immunoblot. LRs are isolated by sucrose density gradient, and the distribution of L1 in LRs is determined. Results EtOH at all doses reduced the relative amount of Y1176 dephosphorylation as well as the relative amount of L1 phosphorylated on other tyrosines. The proportion of L1 present in LRs is significantly increased in pups who received 6 g/kg EtOH compared to intubated controls. Conclusions L1 is a target for EtOH developmental neurotoxicity in vivo. [ABSTRACT FROM AUTHOR]

Scutellarin (1) possesses protective effects against neuronal injury, while 6-O-methyl-scutellarein (3), as the main metabolite of scutellarin in vivo, has not been reported about its protective effects previously. The present study mainly investigated whether the neural injury caused by ischemia/reperfusion would be influenced by different doses of 6-O-methyl-scutellarein (3). The results of behavioral, neurological, and histological examinations indicated that 6-O-methyl-scutellarein (3) could improve neuronal injury, and exhibit significant difference among the various doses. More importantly, 6-O-methyl-scutellarein (3) had better protective effects than scutellarin in rat cerebral ischemia. [ABSTRACT FROM AUTHOR]

Background Fetal alcohol spectrum disorder, the leading known cause of mental retardation, is caused by alcohol exposure during pregnancy. One mechanism of ethanol (EtOH) teratogenicity is the disruption of the functions of L1 cell adhesion molecule (L1). These functions include enhancement of neurite outgrowth, trafficking through lipid rafts, and signal transduction. Recent data have shown that choline supplementation of rat pups reduces the effects of EtOH on neurobehavior. We sought to determine whether choline could prevent the effect of EtOH on L1 function using a simple experimental system. Methods Cerebellar granule neurons ( CGN) from postnatal day 6 rat pups were cultured with and without supplemental choline, and the effects on L1 signaling, lipid raft distribution, and neurite outgrowth were measured in the presence or absence of EtOH. Results Choline significantly reduced the effect of EtOH on L1 signaling, the distribution of L1 in lipid rafts and L1-mediated neurite outgrowth. However, choline supplemented EtOH-exposed cultures remained significantly different than controls. Conclusions Choline pretreatment of CGN significantly reduces the disruption of L1 function by EtOH, but does not completely return L1 function to baseline. This experimental system will enable discovery of the mechanism of the neuroprotective effect of choline. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Methyl helicterate is a triterpenoid isolated from Helicteres angustifolia (Sterculiaceae), one of the valuable traditional Chinese herbs. Antifibrotic activities of H. angustifolia have been extensively proved. Aim of the study: The purpose of this study was to investigate the effect of methyl helicterate (MH) on liver fibrosis in rats induced by carbon tetrachloride (CCl4) and to explore its underlying mechanism. Materials and methods: Hepatic fibrosis was induced in male Sprague–Dawley (SD) rats by intragastric administration with 2ml/kg CCl4 (mixed 1:1 in peanut oil) twice a week for 12 weeks. To evaluate the effect of MH (16.72, 33.45, 66.90mg/kg) on hepatic fibrosis, liver function, histological study and hepatic fibrosis evaluation were performed. Liver function was assessed by determining the serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (Alb) and total protein (TP). The biomarkers such as hydroxyproline (Hyp), hyaluronic acid (HA), type III precollagen (PCIII) and laminin (LN) were examined for the evaluation of hepatic fibrosis. The underlying mechanism was investigated by measuring oxidative stress level and detecting the expression of TGF-β1 mRNA and Smad3 protein. Results: MH (33.45, 66.90mg/kg) treatment significantly inhibited the loss of body weight and the increase of liver index in rats induced by CCl4. MH also improved the liver function as indicated by decreasing serum enzymatic activities of ALT, AST, TP and Alb (P<0.05). Histological results indicated that MH alleviated liver damage and reduced the formation of fibrous septa. Moreover, MH significantly decreased liver Hyp, HA, LN and PCIII (P<0.05). Research on mechanism showed that MH could markedly reduce liver malondialdehyde (MDA) concentration, increase activities of liver superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and inhibit the expression of TGF-β1 mRNA and Smad3 protein (P<0.05). Conclusions: Our findings indicated that MH can inhibit CCl4-induced hepatic fibrosis, which may be ascribed to its radical scavenging action, antioxidant activity, and modulation of TGF-β-Smad3 signaling pathway. [Copyright &y& Elsevier]