Fluorescence modulation of quantum dots in subsurface defects of optical elements by a linearly polarized light.

The limited excitation efficiency of quantum dots in the detection of subsurface defects in optical elements by quantum dot fluorescence gives rise to insufficient accuracy. To enhance the excitation efficiency of quantum dots, we studied the modulation of the polarization direction of linearly polarized incident light on quantum dot fluorescence. We first apply density matrix evolution theory to study the quantum dots interacting with linearly polarized incident light and emitting fluorescence. The fluorescence intensity exhibits cosine oscillations versus modulated laser polarization. It reaches a maximum value at the polarization angle zero, and then decreases as the angle becomes larger until π/2. The experimental results for the quantum dot in both solutions and subsurface defect of optical elements confirmed these results. For optical elements tagged with CdSe/ZnS quantum dots, the fluorescence intensity increases by 61.7%, and the area for the detected subsurface defects increases by 142.9%. Similarly, for C and InP/ZnS quantum dots, there are also increases in both the fluorescence intensity and the area of subsurface defects. Our study suggests that the subsurface defect detection in optical elements by the linearly polarized incident light could enhance the detection accuracy of subsurface defects in optical elements, and potentially achieve super-resolution imaging of subsurface defects.

Joint-tissue integrative analysis identifies high-risk genes for Parkinson's disease.

The loss of dopaminergic neurons in the substantia nigra and the abnormal accumulation of synuclein proteins and neurotransmitters in Lewy bodies constitute the primary symptoms of Parkinson's disease (PD). Besides environmental factors, scholars are in the early stages of comprehending the genetic factors involved in the pathogenic mechanism of PD. Although genome-wide association studies (GWAS) have unveiled numerous genetic variants associated with PD, precisely pinpointing the causal variants remains challenging due to strong linkage disequilibrium (LD) among them. Addressing this issue, expression quantitative trait locus (eQTL) cohorts were employed in a transcriptome-wide association study (TWAS) to infer the genetic correlation between gene expression and a particular trait. Utilizing the TWAS theory alongside the enhanced Joint-Tissue Imputation (JTI) technique and Mendelian Randomization (MR) framework (MR-JTI), we identified a total of 159 PD-associated genes by amalgamating LD score, GTEx eQTL data, and GWAS summary statistic data from a substantial cohort. Subsequently, Fisher's exact test was conducted on these PD-associated genes using 5,152 differentially expressed genes sourced from 12 PD-related datasets. Ultimately, 29 highly credible PD-associated genes, including CTX1B, SCNA, and ARSA, were uncovered. Furthermore, GO and KEGG enrichment analyses indicated that these genes primarily function in tissue synthesis, regulation of neuron projection development, vesicle organization and transportation, and lysosomal impact. The potential PD-associated genes identified in this study not only offer fresh insights into the disease's pathophysiology but also suggest potential biomarkers for early disease detection.

Sinapic acid modulates oxidative stress and metabolic disturbances to attenuate ovarian fibrosis in letrozole-induced polycystic ovary syndrome SD rats.

Sinapic acid (SA) is renowned for its many pharmacological activities as a polyphenolic compound. The cause of polycystic ovary syndrome (PCOS), a commonly encountered array of metabolic and hormonal abnormalities in females, has yet to be determined. The present experiment was performed to evaluate the antifibrotic properties of SA in rats with letrozole-induced PCOS-related ovarian fibrosis. SA treatment successfully mitigated the changes induced by letrozole in body weight (BW) (p < .01) and relative ovary weight (p < .05). Histological observation revealed that SA reduced the number of atretic and cystic follicles (AFs) and (CFs) (p < .01), as well as ovarian fibrosis, in PCOS rats. Additionally, SA treatment impacted the serum levels of sex hormones in PCOS rats. Luteinizing hormone (LH) and testosterone (T) levels were decreased (p < .01, p < .05), and follicle-stimulating hormone (FSH) levels were increased (p < .05). SA administration also decreased triglyceride (TG) (p < .01) and total cholesterol (TC) levels (p < .05) and increased high-density lipoprotein cholesterol (HDL-C) levels (p < .01), thereby alleviating letrozole-induced metabolic dysfunction in PCOS rats. Furthermore, SA treatment targeted insulin resistance (IR) and increased the messenger RNA (mRNA) levels of antioxidant enzymes in the ovaries of PCOS rats. Finally, SA treatment enhanced the activity of peroxisome proliferator-activated receptor-γ (PPAR-γ), reduced the activation of transforming growth factor-ß1 (TGF-ß1)/Smads, and decreased collagen I, α-smooth muscle actin (α-SMA), and connective tissue growth factor (CTGF) levels in the ovaries of PCOS rats. These observations suggest that SA significantly ameliorates metabolic dysfunction and oxidative stress and ultimately reduces ovarian fibrosis in rats with letrozole-induced PCOS.

Are vacuolar dynamics crucial factors for plant cell division and differentiation?

Vacuoles are the largest membrane-bound organelles in plant cells, critical for development and environmental responses. Vacuolar dynamics indicate reversible changes of vacuoles in morphology, size, or numbers. In this review, we summarize current understandings of vacuolar dynamics in different types of plant cells, biological processes associated with vacuolar dynamics, and regulators controlling vacuolar dynamics. Specifically, we point out the possibility that vacuolar dynamics play key roles in cell division and differentiation, which are controlled by the nucleus. Finally, we propose three routes through which vacuolar dynamics actively participate in nucleus-controlled cellular activities.

Dietary habits and nutrition status in esophageal cancer patients after esophageal reconstruction.

Background: Surgery is the cornerstone of the treatment of esophageal cancer (EC). This study is to evaluate the dietary habits and nutrition status in EC patients who underwent esophagectomy followed by esophageal reconstruction. Methods: This retrospective study included patients with EC who underwent esophagectomy followed by esophageal reconstruction in the Department of Thoracic Surgery I of Peking University Cancer Hospital between February 2014 and December 2018. The primary outcomes were dietary habits and nutrition status. The secondary outcomes were gastrointestinal symptoms and quality of life (QoL). Results: A total of 346 patients were included. At 30 months after the operation, 90.2% of the patients had recovered to regular dietary habits, 72.8% of patients had a restored frequency of preoperative regular food intake, 2.3% of the patients ate more than six times a day, and 0.6% had semi-liquid food because of bad teeth. The nutrition status remained stable after 6 months postoperatively and recovered slightly 1 year after the surgery. At 30 months after the operation, the most common gastrointestinal symptoms were reflux (38.4%), dysphagia (15.3%), hoarseness (11.8%), abdominal distension (6.6%), diarrhea (2.9%), and nausea and vomiting (2.3%). According to the European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire-OG 25 (EORTC QLQ-OG 25), the factors that affected the life quality of patients during follow-up were anxiety, reflux, and dietary limitations. Conclusions: Most patients with EC who underwent esophageal reconstruction recovered to regular dietary habits and stable nutrition status, while some may still suffer from gastrointestinal symptoms, anxiety, and dietary limitations.

Work-Related Stress and Psychological Distress among Law Enforcement Officers: The Carolina Blue Project.

Law enforcement is a stressful occupation that places significant psychological demands on those serving in this role. However, little is known about the severity of work-related stress and psychological distress among law enforcement officers (LEOs) in North Carolina (NC). This cross-sectional study examined the severity of work-related stress and psychological distress among 283 LEOs in NC. The Maslach Burnout Inventory, the Operational Police Stress Questionnaire, the Depression, Anxiety, and Stress Scale, and the Post-Traumatic Stress Disorder (PTSD) Checklist were used to assess burnout, operational police stress, depression, anxiety, stress, and PTSD among LEOs. Descriptive statistics, independent t-tests, Mann-Whitney U tests, one-way ANOVA, and Kruskal-Wallis tests were performed. Rural and male LEOs reported higher burnout levels related to depersonalization (i.e., increased mental distance from one's job) compared with their urban and female counterparts. LEOs exposed to toxic materials or performing patrol duties exhibited higher operational police stress levels than those who did not. Caucasian LEOs exhibited higher depression, anxiety, and stress than their African American counterparts. Rural LEOs and LEOs who were exposed to toxic materials displayed higher levels of PTSD than their counterparts. Our findings highlight the need for increased mental health support and better working environments for LEOs.

Emotional Eating and Cardiovascular Risk Factors in the Police Force: The Carolina Blue Project.

There is an association between emotional eating and cardiovascular disease (CVD) risk factors; however, little is known about this association in the police force. This study explores the associations between emotional eating and CVD risk factors in law enforcement officers in North Carolina. Four hundred and five officers completed The Emotional Eating Scale, and 221 of them completed the assessment for CVD-related markers. Descriptive statistics, Pearson's correlation, and multiple linear regression analyses were performed. Emotional eating in response to anger was significantly positively associated with body weight (ß = 1.51, t = 2.07, p = 0.04), diastolic blood pressure (ß = 0.83, t = 2.18, p = 0.03), and mean arterial pressure (ß = 0.84, t = 2.19, p = 0.03) after adjusting for age and use of blood pressure medicine. Emotional eating in response to depression was significantly positively associated with triglycerides (ß = 5.28, t = 2.49, p = 0.02), while the emotional eating in response to anxiety was significantly negatively associated with triglycerides (ß = -11.42, t = -2.64, p = 0.01), after adjusting for age and use of cholesterol medicine. Our findings offer new insights to address emotional eating and lower CVD risk in law enforcement officers.

[Research progress of novel functional materials in extraction of algal toxins].

Algal toxins are secondary metabolites produced by harmful algae; these metabolites are characterized with strong toxicity, diverse structure and bioaccumulation. Aquatic organisms that feed on harmful algae can accumulate algal toxins in their bodies, and the consumption of these organisms by humans can cause symptoms of paralysis, diarrhea, and even death. The onset of poisoning can occur within as little as 30 min; in many cases, no suitable antidote for algal toxins is available. Thus, algal toxins present significant threats to human health, the aquaculture industry, and aquatic ecosystems. Because the potential risks of algal toxins are a critical issue, these toxins have become a research hotspot. The water environment and various types of aquatic products should be monitored and analyzed to ensure their safety. However, because of possible matrix effects and the low content of algal toxins in actual samples, an efficient pretreatment method is necessary prior to instrumental analyses. Efficient sample pretreatment techniques can not only reduce or eliminate interferences from the sample matrix during analysis but also enrich the target analytes to meet the detection limit of the analytical instrument, thereby ensuring the sensitivity and accuracy of the detection method. In recent years, sample pretreatment techniques such as solid-phase extraction (SPE), solid-phase microextraction (SPME), magnetic SPE (MSPE), dispersive SPE (DSPE), and pipette tip-based SPE (PT-SPE) have gained wide attention in the field of algal-toxin separation and analysis. The performance of these pretreatment techniques largely depends on the characteristics of the extraction materials. Given the diverse physicochemical properties of algal toxins, including their different molecular sizes, hydrophobicity/hydrophilicity, and charges, the design and preparation of materials suitable for algal-toxin extraction is an essential undertaking. The optimal extraction material should be capable of reversible algal-toxin adsorption and preferably possess a porous structure with a large surface area to allow for high recovery rates and good interfacial contact with the toxins. Additionally, the extraction material should exhibit good chemical stability in the sample solution and elution solvent within the working pH range; otherwise, it may dissolve or lose its functional groups. Many research efforts have sought to develop novel adsorbent materials with these properties in the separation and analysis of algal toxins, focusing on carbon-based materials, metal organic frameworks (MOFs), covalent organic frameworks (COFs), molecularly imprinted polymers (MIPs), and their functionalized counterparts. Carbon-based materials, MOFs, and COFs have advantages such as large surface areas and abundant adsorption sites. These extraction materials are widely used in the separation and analysis of target substances in complex environmental, biological, and food samples owing to their excellent performance and unique microstructure. They are also the main adsorbents used for the extraction of algal toxins. These extraction materials play an essential role in the extraction of algal toxins, but they also present a number of limitations: (1) Carbon-based materials, MOFs, and COFs have relatively poor selective-adsorption ability towards target substances; (2) Most MOFs are unstable in aqueous solutions and challenging to apply during extraction from water-based sample solutions; (3) COFs mainly consist of lightweight elements, rendering them difficult to completely separate from sample solutions using centrifugal force, which limits their application range; (4) Although MIPs have good selectivity, issues such as template-molecule loss, slow mass-transfer rates, and low adsorption capacity must be addressed. Therefore, the design and preparation of novel functionalized extraction materials specifically tailored for algal toxins and studies on new composite extraction materials are highly desirable. This article collects representative literature from domestic and international research on algal-toxin analysis over the past decade, summarizes the relevant findings, categorizes the applications of novel functional materials in algal-toxin-extraction processes, and provides an outlook on their future development prospects.

Causal effect of interleukin (IL)-6 on blood pressure and hypertension: A mendelian randomization study.

To examine whether circulating interleukin-6 (IL-6) levels (CirIL6) have a causal effect on blood pressure using Mendelian randomization (MR) methods. We used data from genome-wide association studies (GWAS) of European ancestry to obtain genetic instruments for circulating IL-6 levels and blood pressure measurements. We applied several robust MR methods to estimate the causal effects and to test for heterogeneity and pleiotropy. We found that circulating IL-6 had a significant positive causal effect on systolic blood pressure (SBP) and pulmonary arterial hypertension (PAH), but not on diastolic blood pressure (DBP) or hypertension. We found that as CirIL6 genetically increased, SBP increased using Inverse Variance Weighted (IVW) method (for ukb-b-20175, ß = 0.082 with SE = 0.032, P = 0.011; for ukb-a-360, ß = 0.075 with SE = 0.031, P = 0.014) and weighted median (WM) method (for ukb-b-20175, ß = 0.061 with SE = 0.022, P = 0.006; for ukb-a-360, ß = 0.065 with SE = 0.027, P = 0.014). Moreover, CirIL6 may be associated with an increased risk of PAH using WM method (odds ratio (OR) = 15.503, 95% CI, 1.025-234.525, P = 0.048), but not with IVW method. Our study provides novel evidence that circulating IL-6 has a causal role in the development of SBP and PAH, but not DBP or hypertension. These findings suggest that IL-6 may be a potential therapeutic target for preventing or treating cardiovascular diseases and metabolic disorders. However, more studies are needed to confirm the causal effects of IL-6 on blood pressure and to elucidate the underlying mechanisms and pathways.

Optimizing ensemble U-Net architectures for robust coronary vessel segmentation in angiographic images.

Automated coronary angiography assessment requires precise vessel segmentation, a task complicated by uneven contrast filling and background noise. Our research introduces an ensemble U-Net model, SE-RegUNet, designed to accurately segment coronary vessels using 100 labeled angiographies from angiographic images. SE-RegUNet incorporates RegNet encoders and squeeze-and-excitation blocks to enhance feature extraction. A dual-phase image preprocessing strategy further improves the model's performance, employing unsharp masking and contrast-limited adaptive histogram equalization. Following fivefold cross-validation and Ranger21 optimization, the SE-RegUNet 4GF model emerged as the most effective, evidenced by performance metrics such as a Dice score of 0.72 and an accuracy of 0.97. Its potential for real-world application is highlighted by its ability to process images at 41.6 frames per second. External validation on the DCA1 dataset demonstrated the model's consistent robustness, achieving a Dice score of 0.76 and an accuracy of 0.97. The SE-RegUNet 4GF model's precision in segmenting blood vessels in coronary angiographies showcases its remarkable efficiency and accuracy. However, further development and clinical testing are necessary before it can be routinely implemented in medical practice.

Prognostic role of urinary ketone body in patients with sepsis-associated encephalopathy without hepatic failure: a retrospective cohort study.

Sepsis-associated encephalopathy (SAE) is defined as a dysfunction of the central nervous system experienced during sepsis with variable clinical features. The study aims to identify the prognostic role of urinary ketone bodies in relation to clinical outcomes in patients with SAE. The Medical Information Mart for Intensive Care III (MIMIC-III) database was used to conduct a retrospective cohort study. We recruited 427 patients with SAE admitted to the intensive care unit (ICU) from the MIMIC-III database. Patients with SAE were divided into a survival group (380 patients) and a non-survival group (47 patients). We used the Wilcoxon signed-rank test and the multivariate logistic regression analysis to analyze the relationship between the level of urinary ketone bodies and the clinical prognosis in patients with SAE. The primary outcome was the relationship between urinary ketone body levels and 28-day mortality of SAE. The secondary outcomes were the relationship between urinary ketone body levels and length of ICU stays, Simplified Acute Physiology Score II, Sequential Organ Failure Assessment (SOFA), Glasgow Coma Scale, mechanical ventilation, renal replacement therapy, and the use of vasopressors. The 28-day mortality of patients with SAE was 11.0%. Urinary ketone body levels were not significantly associated with the 28-day mortality of patients with SAE. Urinary ketone body levels were associated with SOFA score and the use of vasopressors in patients with SAE. The SOFA score was an independent risk factor for the 28-day mortality in patients with SAE. Urinary ketone body levels were significantly associated with SOFA score and the use of vasopressors in patients with SAE. Furthermore, the SOFA score can predict the prognosis of short-term outcomes of patients with SAE. Therefore, we should closely monitor the changes of urinary ketone bodies and SOFA score and intervene in time.

A haplotype-resolved gap-free genome assembly provides novel insight into monoterpenoid diversification in Mentha suaveolens 'Variegata'.

Mentha is a commonly used spice worldwide, which possesses medicinal properties and fragrance. These characteristics are conferred, at least partially, by essential oils such as menthol. In this study, a gap-free assembly with a genome size of 414.3 Mb and 31,251 coding genes was obtained for Mentha suaveolens 'Variegata'. Based on its high heterozygosity (1.5%), two complete haplotypic assemblies were resolved, with genome sizes of 401.9 and 405.7 Mb, respectively. The telomeres and centromeres of each haplotype were almost fully annotated. In addition, we detected a total of 41,135 structural variations. Enrichment analysis demonstrated that genes involved in terpenoid biosynthesis were affected by these structural variations. Analysis of volatile metabolites showed that M. suaveolens mainly produces piperitenone oxide rather than menthol. We identified three genes in the M. suaveolens genome which encode isopiperitenone reductase (ISPR), a key rate-limiting enzyme in menthol biosynthesis. However, the transcription levels of ISPR were low. Given that other terpenoid biosynthesis genes were expressed, M. suaveolens ISPRs may account for the accumulation of piperitenone oxide in this species. The findings of this study may provide a valuable resource for improving the detection rate and accuracy of genetic variants, thereby enhancing our understanding of their impact on gene function and expression. Moreover, our haplotype-resolved gap-free genome assembly offers novel insights into molecular marker-assisted breeding of Mentha.

GLA Mutations Suppress Autophagy and Stimulate Lysosome Generation in Fabry Disease.

Fabry disease (FD) is an X-linked recessive inheritance lysosomal storage disorder caused by pathogenic mutations in the GLA gene leading to a deficiency of the enzyme alpha-galactosidase A (α-Gal A). Multiple organ systems are implicated in FD, most notably the kidney, heart, and central nervous system. In our previous study, we identified four GLA mutations from four independent Fabry disease families with kidney disease or neuropathic pain: c.119C>A (p.P40H), c.280T>C (C94R), c.680G>C (p.R227P) and c.801+1G>A (p.L268fsX3). To reveal the molecular mechanism underlying the predisposition to Fabry disease caused by GLA mutations, we analyzed the effects of these four GLA mutations on the protein structure of α-galactosidase A using bioinformatics methods. The results showed that these mutations have a significant impact on the internal dynamics and structures of GLA, and all these altered amino acids are close to the enzyme activity center and lead to significantly reduced enzyme activity. Furthermore, these mutations led to the accumulation of autophagosomes and impairment of autophagy in the cells, which may in turn negatively regulate autophagy by slightly increasing the phosphorylation of mTOR. Moreover, the overexpression of these GLA mutants promoted the expression of lysosome-associated membrane protein 2 (LAMP2), resulting in an increased number of lysosomes. Our study reveals the pathogenesis of these four GLA mutations in FD and provides a scientific foundation for accurate diagnosis and precise medical intervention for FD.

Diabetes mellitus and Alzheimer's disease: Vacuolar adenosine triphosphatase as a potential link.

Globally, the incidence of diabetes mellitus (DM) and Alzheimer's disease (AD) is increasing year by year, causing a huge economic and social burden, and their pathogenesis and aetiology have been proven to have a certain correlation. In recent years, more and more studies have shown that vacuolar adenosine triphosphatases (v-ATPases) in eukaryotes, which are biomolecules regulating lysosomal acidification and glycolipid metabolism, play a key role in DM and AD. This article describes the role of v-ATPase in DM and AD, including its role in glycolysis, insulin secretion and insulin resistance (IR), as well as its relationship with lysosomal acidification, autophagy and ß-amyloid (Aß). In DM, v-ATPase is involved in the regulation of glucose metabolism and IR. v-ATPase is closely related to glycolysis. On the one hand, v-ATPase affects the rate of glycolysis by affecting the secretion of insulin and changing the activities of key glycolytic enzymes hexokinase (HK) and phosphofructokinase 1 (PFK-1). On the other hand, glucose is the main regulator of this enzyme, and the assembly and activity of v-ATPase depend on glucose, and glucose depletion will lead to its decomposition and inactivation. In addition, v-ATPase can also regulate free fatty acids, thereby improving IR. In AD, v-ATPase can not only improve the abnormal brain energy metabolism by affecting lysosomal acidification and autophagy but also change the deposition of Aß by affecting the production and degradation of Aß. Therefore, v-ATPase may be the bridge between DM and AD.

Sources and seasonal variations of nitrate in the coastal multiple-aquifer groundwater of Beihai, southern China.

Elevated nitrate (NO3-) loadings in groundwater may cause health effects in drinking water and nutrient enrichment of aquatic ecosystems. To reveal the sources and seasonal variations of NO3- in the coastal groundwater of Beihai, southern China, we carried out hydrochemical and isotopic (δ15N-δ18O in NO3-) investigations in the summer and winter, respectively, concerning multiple-aquifer groundwater, rainwater, seawater, and surface water. The sources of the main elements present in the waters were interpreted by ionic ratios. NO3- sources were identified by combined use of the δ15N values and δ18O values or NO3-/Na+ molar ratios, with estimations of the proportional contribution by the Bayesian stable isotope mixing model. Denitrification was interpreted along the flow paths. The results show groundwater main elements are originated primarily from silicate weathering, and secondarily from anthropogenic inputs and carbonate dissolution. Its qualities are largely affected by seawater intrusion along the coastline. Because of difference in the predominant minerals within the aquifers and in scale and extent of seawater intrusion, the groundwater displays distinct ionic ratio characters. NO3- concentrations are up to 33.9 mg/L, with higher loadings in the plains relative to along the coastline. Soil N, domestic sewage, rainwater, chemical fertilizers, and algae are NO3- sources, with average proportional contributions of 0.255, 0.221, 0.207, 0.202, and 0.116, respectively. In relation to the winter, higher production of NO3- from nitrification of soil N- and algae-derived ammonium induced by higher temperatures in the summer accounts for increases in groundwater NO3- loadings. In the rural areas, elevated loadings of NO3- in the winter may be due to larger infiltration fractions of sewage. Seasonal variations of atmospheric NO3- deposition and farming may also cause the dynamics. Our results improve the understanding of sources and seasonal dynamics of NO3- in coastal groundwater.

TRAF2 decrease promotes the TGF-ß-mTORC1 signal in MAFLD-HCC through enhancing AXIN1-mediated Smad7 degradation.

According to recent research, metabolic-associated fatty liver disease (MAFLD) has emerged as an important underlying etiology of hepatocellular carcinoma (HCC). However, the molecular mechanism of MAFLD-HCC is still unclear. Tumor necrosis factor receptor-associated factor 2 (TRAF2) is the key molecule to mediate the signal of inflammatory NF-κB pathway. This study aims to investigate the potential dysregulation of TRAF2 and its biological function in MAFLD-HCC. Huh7 TRAF2-/- demonstrated increased tumor formation ability compared to huh7 TRAF2+/+ when stimulated with transforming growth factor-ß (TGF-ß). The decisive role of TGF-ß in the development of MAFLD-HCC was confirmed through the specific depletion of TGF-ß receptor II gene in the hepatocytes (Tgfbr2ΔHep) of mice. In TRAF2-/- cells treated with TGF-ß, both the glycolysis rate and lipid synthesis were enhanced. We proved the signal of the mechanistic target of rapamycin complex 1 (mTORC1) could be activated in the presence of TGF-ß, and was enhanced in TRAF2-/- cells. The coimmunoprecipitation (co-IP) experiments revealed that TRAF2 fortified the Smurf2-mediated ubiquitination degradation of AXIN1. Hence, TRAF2 depletion resulted in increased Smad7 degradation induced by AXIN1, thus promoting the TGF-ß signal. We also discovered that PLX-4720 could bind with AXIN1 and restrained the tumor proliferation of TRAF2-/- in mice fed with high-fat diet (HFD). Our findings indicate that TRAF2 plays a significant role in the pathogenesis of MAFLD-HCC. The reduction of TRAF2 expression leads to the enhancement of the TGF-ß-mTORC1 pathway by facilitating AXIN1-mediated Smad7 degradation.

Impact of body mass index on adverse kidney events in diabetes mellitus patients: A systematic-review and meta-analysis.

BACKGROUND: The incidence of chronic kidney disease among patients with diabetes mellitus (DM) remains a global concern. Long-term obesity is known to possibly influence the development of type 2 diabetes mellitus. However, no previous meta-analysis has assessed the effects of body mass index (BMI) on adverse kidney events in patients with DM. AIM: To determine the impact of BMI on adverse kidney events in patients with DM. METHODS: A systematic literature search was performed on the PubMed, ISI Web of Science, Scopus, Ovid, Google Scholar, EMBASE, and BMJ databases. We included trials with the following characteristics: (1) Type of study: Prospective, retrospective, randomized, and non-randomized in design; (2) participants: Restricted to patients with DM aged ≥ 18 years; (3) intervention: No intervention; and (4) kidney adverse events: Onset of diabetic kidney disease [estimated glomerular filtration rate (eGFR) of < 60 mL/min/1.73 m2 and/or microalbuminuria value of ≥ 30 mg/g Cr], serum creatinine increase of more than double the baseline or end-stage renal disease (eGFR < 15 mL/min/1.73 m2 or dialysis), or death. RESULTS: Overall, 11 studies involving 801 patients with DM were included. High BMI (≥ 25 kg/m2) was significantly associated with higher blood pressure (BP) [systolic BP by 0.20, 95% confidence interval (CI): 0.15-0.25, P < 0.00001; diastolic BP by 0.21 mmHg, 95%CI: 0.04-0.37, P = 0.010], serum albumin, triglycerides [standard mean difference (SMD) = 0.35, 95%CI: 0.29-0.41, P < 0.00001], low-density lipoprotein (SMD = 0.12, 95%CI: 0.04-0.20, P = 0.030), and lower high-density lipoprotein (SMD = -0.36, 95%CI: -0.51 to -0.21, P < 0.00001) in patients with DM compared with those with low BMIs (< 25 kg/m2). Our analysis showed that high BMI was associated with a higher risk ratio of adverse kidney events than low BMI (RR: 1.22, 95%CI: 1.01-1.43, P = 0.036). CONCLUSION: The present analysis suggested that high BMI was a risk factor for adverse kidney events in patients with DM.

Short-term exposure to extreme temperature and outpatient visits for respiratory diseases among children in the northern city of China: a time-series study.

BACKGROUND: Although studies have indicated that extreme temperature is strongly associated with respiratory diseases, there is a dearth of studies focused on children, especially in China. We aimed to explore the association between extreme temperature and children's outpatient visits for respiratory diseases and seasonal modification effects in Harbin, China. METHODS: A distributed lag nonlinear model (DLNM) was used to explore the effect of extreme temperature on daily outpatient visits for respiratory diseases among children, as well as lag effects and seasonal modification effects. RESULTS: Extremely low temperatures were defined as the 1st percentile and 2.5th percentile of temperature. Extremely high temperatures were defined as the 97.5th percentile and 99th percentile of temperature. At extremely high temperatures, both 26 °C (97.5th) and 27 °C (99th) showed adverse effects at lag 0-6 days, with relative risks (RRs) of 1.34 [95% confidence interval (CI): 1.21-1.48] and 1.38 (95% CI: 1.24-1.53), respectively. However, at extremely low temperatures, both - 26 °C (1st) and - 23 °C (2.5th) showed protective effects on children's outpatient visits for respiratory diseases at lag 0-10 days, with RRs of 0.86 (95% CI: 0.76-0.97) and 0.85 (95% CI: 0.75-0.95), respectively. We also found seasonal modification effects, with the association being stronger in the warm season than in the cold season at extremely high temperatures. CONCLUSIONS: Our study indicated that extremely hot temperatures increase the risk of children's outpatient visits for respiratory diseases. Efforts to reduce the exposure of children to extremely high temperatures could potentially alleviate the burden of pediatric respiratory diseases, especially during the warm season.

Ferroptosis Contributes to Microvascular Dysfunction in Diabetic Retinopathy.

Ferroptosis is a new form of cell death characterized by iron-dependent lipid peroxidation. Whether ferroptosis is involved in retinal microvascular dysfunction under diabetic condition is not known. The expression of ferroptosis-related genes in patients with proliferative diabetic retinopathy and in diabetic mice was determined with RT-qPCR. Reactive oxygen species, iron content, lipid peroxidation products, and ferroptosis-associated proteins in the cultured human retinal microvascular endothelial cells (HRMECs) and in the retina of diabetic mice were examined. The association of ferroptosis with the functions of endothelial cells in vitro was evaluated. After administration of ferroptosis-specific inhibitor, Fer-1, the retinal microvasculature in diabetic mice was assessed. Characteristic changes of ferroptosis-associated markers, including GPX4, FTH1, long-chain acyl-CoA synthetase 4, TFRC, and cyclooxygenase-2, were detected in the retinal fibrovascular membrane of patients with proliferative diabetic retinopathy, cultured HRMECs, and the retina of diabetic mice. Elevated levels of reactive oxygen species, lipid peroxidation, and iron content were found in the retina of diabetic mice and in cultured HRMECs. Ferroptosis was found to be associated with HRMEC dysfunction under high-glucose condition. Inhibition of ferroptosis with specific inhibitor Fer-1 in diabetic mice significantly reduced the severity of retinal microvasculopathy. Ferroptosis contributes to microvascular dysfunction in diabetic retinopathy, and inhibition of ferroptosis might be a promising strategy for the therapy of early-stage diabetic retinopathy.

Inhibition of RhoGEF/RhoA alleviates regorafenib resistance and cancer stemness via Hippo signaling pathway in hepatocellular carcinoma.

Patients with hepatocellular carcinoma (HCC) are vulnerable to drug resistance. Although drug resistance has been taken much attention to HCC therapy, little is known of regorafenib and regorafenib resistance (RR). This study aimed to determine the drug resistance pattern and the role of RhoA in RR. Two regorafenib-resistant cell lines were constructed based on Huh7 and Hep3B cell lines. In vitro and in vivo assays were conducted to study RhoA expression, the activity of Hippo signaling pathway and cancer stem cell (CSC) traits. The data showed that RhoA was highly expressed, Hippo signaling was hypoactivated and CSC traits were more prominent in RR cells. Inhibiting RhoA could reverse RR, and the alliance of RhoA inhibition and regorafenib synergistically attenuated CSC phenotype. Furthermore, inhibiting LARG/RhoA increased Kibra/NF2 complex formation, prevented YAP from shuttling into the nucleus and repressed CD44 mRNA expression. Clinically, the high expression of RhoA correlated with poor prognosis. LARG, RhoA, YAP1 and CD44 show positive correlation with each other. Thus, inhibition of RhoGEF/RhoA has the potential to reverse RR and repress CSC phenotype in HCC.