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Abstract Background The plasma uric acid to albumin ratio (UAR) is considered as a novel indicator for Inflammation. However, the association between UAR and coronary slow flow phenomenon (CSFP) remains unclear. Methods A total of 1328 individuals with chronic coronary syndrome (CCS) receiving coronary angiography (CAG) and found no obvious obstructive stenosis (

Objectives: Intrinsic capacity (IC), a multidimensional construct encompassing mental and physical capacities, has been established in the aging framework by the World Health Organization. However, the detailed relationship between IC and Chinese sleep patterns (nighttime sleep and post-lunch naps) remains inadequately elucidated. Methods: Participants in this study were individuals aged ≥45 years residing in China, included in the China Health and Retirement Longitudinal Study (CHARLS). We analyzed 4 years of CHARLS data from the first wave (May 2011–March 2012) to the second wave (July 2015–January 2016). Data from these waves were utilized for longitudinal analysis. Self-reported data included nighttime sleep and nap duration, along with other baseline characteristics. The IC evaluation involved physical examinations and blood tests. Initially, linear regression was used to assess the relationship between total sleep duration, nighttime sleep duration, nap duration, and IC change between the two waves that were determined by marginal effects (ME) and their corresponding 95% confidence intervals (CIs). Regression splines were employed to explore potential nonlinear associations. Subgroup and sensitivity analyses were conducted to investigate the heterogeneity of IC change under specific conditions and the robustness of our results. Mediation analysis was performed to identify potential factors mediating the relationship between sleep patterns and IC change. Results: Both excessive (>10 h) (total, ME: −1.12; 95% CI: −1.61, −0.64; nighttime, ME: −1.44; 95% CI: −2.29, −0.59) and insufficient (

Purpose: This study aimed to explore the effects of quercetin on cholesterol metabolism and cisplatin sensitivity in oral squamous cell carcinoma (OSCC) cell line (CAL27) and investigate the potential molecular mechanisms. Methods: CAL27 cells were exposed to quercetin or cisplatin after upregulation or downregulation of AGR2. The expression of proteins and genes associated with cholesterol metabolism were assessed. The levels of cholesterol and LDL were also measured, and the cisplatin sensitivity of CAL27 cells was analyzed. Results: RNA high-throughput sequencing revealed that after treatment with quercetin, the expression of AGR2 was significantly reduced in cisplatin-resistant CAL27 cells (CAL-27R), which was associated with lipid metabolism. AGR2 deletion ameliorated but its overexpression exacerbated cisplatin resistance and cholesterol metabolism, evidenced by changes in SQLE, HMGCS, LDLR, and n-SREBP2 expression and cholesterol and LDL levels. Moreover, AGR2 promoted cisplatin resistance by activating the AKT signaling pathway and enhancing SREBP2-mediated cholesterol metabolism. Quercetin increased cisplatin sensitivity by repressing cholesterol metabolism but suppressed the AGR2/AKT/SREBP2 signaling pathway in a concentration-dependent manner. These effects were partly reversed by AGR2 overexpression and AKT activation. Conclusion: Our findings demonstrated that quercetin inhibits cholesterol metabolism and cisplatin resistance in CAL27 cells by modulating the AGR2/AKT/SREBP2 axis.

Objective: To explore the effect of oleuropein on sepsis-induced acute lung injury (ALI) in vitro and in vivo and investigate the underlying mechanism. Methods: In an lipopolysaccharide (LPS)-mediated cell model of sepsis-induced ALI and a cecal ligation and puncture-induced mouse model of septic ALI, CCK-8 assay and flow cytometry analysis were used to detect cell activity and apoptosis. ELISA and relevant assay kits were used to measure the levels of inflammatory cytokines and oxidative stress, respectively. Western blot was applied to determine the expression of apoptosis- and AMP-activated protein kinase (AMPK)/nuclear factor erythroid 2-related factor-2 (Nrf-2)/heme oxygenase-1 (HO-1) signaling-associated proteins. JC-1 staining, adenosine triphosphate (ATP) assay kit, and MitoSOX Red assays were performed to detect mitochondrial membrane potential, ATP content, and mitochondrial ROS formation, respectively. Moreover, lung injury was evaluated by measuring lung morphological alternations, lung wet-to-dry ratio, myeloperoxidase content, and total protein concentration. Results: Oleuropein reduced inflammatory reaction, oxidative damage, and apoptosis, and ameliorated mitochondrial dysfunction in LPS-exposed BEAS-2B cells and mice with septic ALI. Besides, oleuropein activated the AMPK/Nrf-2/HO-1 signaling pathway. However, these effects of oleuropein were abrogated by an AMPK inhibitor compound C. Conclusions: Oleuropein can protect against sepsis-induced ALI in vitro and in vivo by activating the AMPK/Nrf-2/HO-1 signaling, which might be a potential therapeutic agent for the treatment of sepsis-induced ALI.

BackgroundAcetaminophen is a commonly used medication, yet its recommendation for patients with comorbid conditions of gout and hypertension is contradictory, and the impact of its usage on clinical outcomes in real-world practical settings remains uncertain. The aim of this study was to investigate the association between acetaminophen administration and clinical outcomes in critically ill patients with gout and hypertension, utilizing real-world data.MethodsA retrospective cohort study was conducted based on the MIMIC-IV (Medical Information Mart in Intensive Care-IV) database. Adult critically ill patients with gout and hypertension were included in the analysis. The exposure was acetaminophen use during ICU stay. The primary outcome was in-hospital mortality. The secondary endpoints were frequent hospitalization, 30-day, and 60-day all-cause mortality, and incidence of hypertensive emergencies. Propensity score matching (PSM) was conducted at a 1:1 ratio. Multivariable analyses were used to adjust for confounders.ResultsThe pre-matched and propensity score-matched cohorts included 2448 and 1012 patients, respectively. In the PSM analysis, in-hospital mortality was 9.7% (49/506) in the acetaminophen use group and 12.1% (61/506) in the no use group. Acetaminophen use was associated with a decrease in-hospital mortality (hazard ratio [HR], 0.62; 95% CI, 0.41–0.92; P = 0.018). In terms of secondary endpoints, after PSM, there was no statistically significant difference for both 30-day and 60-day all-cause mortality reductions in the acetaminophen use group, and HRs were 0.78 (95% CI 0.55–1.11; P = 0.175), and 0.75 (95% CI 0.55–1.02; P = 0.069), respectively. According to the analysis of dosage and treatment group, the use of APAP within the dosage range of 2–4 g and within 3–5 days of treatment significantly reduced the mortality rate of the entire cohort and PSM cohort, with statistical differences. Subgroup analysis demonstrated that lower in-hospital mortality was consistent across different baselines (age, gender, BMI, liver disease, and renal disease), with no interactions in all subgroups (interaction p-values >0.05), thereby affirming the robustness and reliability of the findings.ConclusionAcetaminophen use was associated with lower in-hospital mortality in critically ill patients with gout and hypertension. Prospective studies are needed to verify this finding.

Abstract Over the years, microbiome research has achieved tremendous advancements driven by culture‐independent meta‐omics approaches. Despite extensive research, our understanding of the functional roles and causal effects of the microbiome on phenotypes remains limited. In this study, we focused on the rumen metaproteome, combining it with metatranscriptome and metabolome data to accurately identify the active functional distributions of rumen microorganisms and specific functional groups that influence feed efficiency. By integrating host genetics data, we established the potentially causal relationships between microbes‐proteins/metabolites‐phenotype, and identified specific patterns in which functional groups of rumen microorganisms influence host feed efficiency. We found a causal link between Selenomonas bovis and rumen carbohydrate metabolism, potentially mediated by bacterial chemotaxis and a two‐component regulatory system, impacting feed utilization efficiency of dairy cows. Our study on the nutrient utilization functional groups in the rumen of high‐feed‐efficiency dairy cows, along with the identification of key microbiota functional proteins and their potentially causal relationships, will help move from correlation to causation in rumen microbiome research. This will ultimately enable precise regulation of the rumen microbiota for optimized ruminant production.

Abstract It is long been suggested that one‐carbon metabolism (OCM) is associated with Alzheimer's disease (AD), whereas the potential mechanisms remain poorly understood. Taking advantage of chemical biology, that mitochondrial serine hydroxymethyltransferase (SHMT2) directly regulated the translation of ADAM metallopeptidase domain 10 (ADAM10), a therapeutic target for AD is reported. That the small‐molecule kenpaullone (KEN) promoted ADAM10 translation via the 5′ untranslated region (5′UTR) and improved cognitive functions in APP/PS1 mice is found. SHMT2, which is identified as a target gene of KEN and the 5′UTR‐interacting RNA binding protein (RBP), mediated KEN‐induced ADAM10 translation in vitro and in vivo. SHMT2 controls AD signaling pathways through binding to a large number of RNAs and enhances the 5′UTR activity of ADAM10 by direct interaction with GAGGG motif, whereas this motif affected ribosomal scanning of eukaryotic initiation factor 2 (eIF2) in the 5′UTR. Together, KEN exhibits therapeutic potential for AD by linking OCM with RNA processing, in which the metabolic enzyme SHMT2 “moonlighted” as RBP by binding to GAGGG motif and promoting the 5′UTR‐dependent ADAM10 translation initiation.

Abstract This prospective randomized controlled trial investigated the clinical value of sigmoid colon water exchange (SWE) colonoscopy by comparing it with air insufflation (AI) colonoscopy in terms of the patient’s pain score, insertion time, and screening quality. Consecutive patients who underwent colonoscopy without sedation were randomized into an AI group (n = 267) or an SWE group (n = 255). Patient characteristics, history of abdominal or pelvic surgery, maximum pain score, insertion time, cecal intubation rate, polyp detection rate, and the need for maneuvers were recorded. There was no significant between-group difference in insertion time, cecal intubation rate, assisted maneuvers (abdominal pressure, changing patients’ position), or polyp detection rate (P > 0.05). The mean maximum pain score was significantly lower in the SWE group than in the AI group. (3.57 ± 2.01 vs. 4.69 ± 1.83, P 24), the maximum pain scores were lower in the SWE group than in the AI group (3.67 ± 1.95 vs. 4.88 ± 1.80, P

Salinity tolerance is an important physiological index for crop breeding. Roots are typically the first plant tissue to withstand salt stress. In this study, we found that the tomato (Solanum lycopersicum) trehalose-6-phosphate phosphatase (SlTPP4) gene is induced by abscisic acid (ABA) and salt, and is mainly expressed in roots. Overexpression of SlTPP4 in tomato enhanced tolerance to salt stress, resulting in better growth performance. Under saline conditions, SlTPP4 overexpression plants demonstrated enhanced sucrose metabolism, as well as increased expression of genes related to salt tolerance. At the same time, expression of genes related to ABA biosynthesis and signal transduction was enhanced or altered, respectively. In-depth exploration demonstrated that SlTPP4 enhances Casparian band development in roots to restrict the intake of Na+. Our study thus clarifies the mechanism of SlTPP4-mediated salt tolerance, which will be of great importance for the breeding of salt-tolerant tomato crops.

ObjectiveAt present, the structure of knowledge in the field of childhood thyroid cancer is not clear enough, and scholars lack a sufficient understanding of the developing trends in this field, which has led to a shortage of forward-looking outputs. The purpose of this research is to help scholars construct a complete knowledge framework and identify current challenges, opportunities, and development trends.MethodsWe searched the literature in the Web of Science Core Collection database on August 7, 2023 and extracted key information from the top 100 most cited articles, such as the countries, institutions, authors, themes, and keywords. We used bibliometric tools such as bibliometrix, VOSviewer, and CiteSpace for a visualization analysis and Excel for statistical descriptions.ResultsThe top 100 most cited articles fluctuated over time, and the research was concentrated in European countries, the United States, and Japan, among which scientific research institutions and scholars from the United States made outstanding contributions. Keyword analysis revealed that research has shifted from simple treatment methods for pediatric thyroid cancer (total thyroidectomy) and inducing factors (the Chernobyl power station accident) to the clinical applications of genetic mutations (such as the BRAF and RET genes) and larger-scale genetic changes (mutation studies of the DICER1 gene). The thematic strategy analysis showed an increasing trend towards the popularity of fusion oncogenes, while the popularity of research on traditional treatments and diagnostics has gradually declined.ConclusionExtensive research has been conducted on the basic problems of pediatric thyroid cancer, and there has been significant outputs in the follow-up and cohort analysis of conventional diagnostic and treatment methods. However, these methods still have certain limitations. Therefore, scholars should focus on exploring fusion genes, the clinical applications of molecular targets, and novel treatment methods. This study provides a strong reference for scholars in this field.

Objective To identify risk factors associated with hypothalamic obesity after craniopharyngioma resection in children. Methods The clinical data as well as imaging and operation details of 34 children with craniopharyngioma who met the inclusion criteria from June 2015 to September 2022 in Beijing Children's Hospital, Capital Medical University were collected for retrospective analysis. The body mass index (BMI) at last follow-up were recorded to identify hypothalamic obesity, univariate and multivariate Logistic regression analyses were used to screen the risk factors. Results A total of 47.06% (16/34) of children experiened hypothalamic symptoms, including obesity and increased appetite, lethargy and mood abnormalities after surgery. Logistic regression analysis showed that symptomatic endocrine abnormalities (OR = 31.453, 95%CI: 1.009-980.082; P = 0.049) and impairment of the hypothalamus of Puget Ⅱ grade (OR = 48.844, 95%CI: 1.053-2264.975; P = 0.047) were risk factors for postoperative hypothalamic obesity. Conclusions There is a high incidence of hypothalamic obesity after childhood - onset craniopharyngioma resection, symptomatic endocrine abnormalities and impairment of the hypothalamus of Puget Ⅱ grade are risk factors. Early identification of risk factors and early adoption of reasonable and effective interventon measures can improve the long-term quality of life in children.