The association between visceral fat obesity and prefrailty in Chinese older adults: a cross-sectional study.

BACKGROUND: The prevalence of obesity is escalating. Previous research has concentrated on the link between frailty and obesity; however, the association between prefrailty and obesity has been less studied. Prefrailty screening and intervention may prevent or postpone frailty in older persons. OBJECTIVE: The study was to investigate into the relationship between prefrailty and several obesity indicators in Chinese community-dwelling older individuals. METHODS: This research employed the Frailty Screening Index to investigate the frailty phenotype of people living in Shanghai. Bioelectrical impedance analysis was used for evaluating body composition. RESULTS: There were 510 participants (39.0%) with high visceral adipose areas. Participants with a high visceral adipose area showed a higher risk of prefrailty (adjusted OR, 1.53; 95% CI, 1.19-1.96), according to multivariate models. When body mass index (BMI) and visceral fat area (VFA) were combined, it was discovered that having an overweight BMI with normal VFA was a protective factor for prefrailty (corrected OR, 0.62; 95% CI, 0.43-0.90), but having a normal weight but excess VFA increased the risk of prefrailty (corrected OR, 1.87; 95% CI, 1.15-3.03). CONCLUSION: Visceral fat obesity is an independent risk factor for prefrailty in Chinese older adults. Implementing targeted interventions, such as dietary modifications, increased physical activity, and other lifestyle changes, could play a crucial role in reducing the risk of prefrailty and improving overall health outcomes in this population.

Experimental Realization of Self-Contained Quantum Refrigeration.

A fundamental challenge in quantum thermodynamics is the exploration of inherent dimensional constraints in thermodynamic machines. In the context of two-level systems, the most compact refrigerator necessitates the involvement of three entities, operating under self-contained conditions that preclude the use of external work sources. Here, we build such a smallest refrigerator using a nuclear spin system, where three distinct two-level carbon-13 nuclei in the same molecule are involved to facilitate the refrigeration process. The self-contained feature enables it to operate without relying on net external work, and the unique mechanism sets this refrigerator apart from its classical counterparts. We evaluate its performance under varying conditions and systematically scrutinize the cooling constraints across a spectrum of scenarios, which sheds light on the interplay between quantum information and thermodynamics.

Coxsackievirus A10 impairs nail regeneration and induces onychomadesis by mimicking DKK1 to attenuate Wnt signaling.

Coxsackievirus A10 (CV-A10) infection, a prominent cause of childhood hand-foot-and-mouth disease (HFMD), frequently manifests with the intriguing phenomenon of onychomadesis, characterized by nail shedding. However, the underlying mechanism is elusive. Here, we found that CV-A10 infection in mice could suppress Wnt/ß-catenin signaling by restraining LDL receptor-related protein 6 (LRP6) phosphorylation and ß-catenin accumulation and lead to onychomadesis. Mechanistically, CV-A10 mimics Dickkopf-related protein 1 (DKK1) to interact with Kringle-containing transmembrane protein 1 (KRM1), the CV-A10 cellular receptor. We further found that Wnt agonist (GSK3ß inhibitor) CHIR99021 can restore nail stem cell differentiation and protect against nail shedding. These findings provide novel insights into the pathogenesis of CV-A10 and related viruses in onychomadesis and guide prognosis assessment and clinical treatment of the disease.

Linking artificial sweetener intake with kidney function: insights from NHANES 2003-2006 and findings from Mendelian randomization research.

Background: The current investigation examines the association between artificial sweetener (AS) consumption and the likelihood of developing chronic kidney disease (CKD), along with its impact on kidney function. Methods: We utilized data from the National Health and Nutrition Examination Survey from 2003-2006 to conduct covariance analysis and weighted adjusted logistic regression, aiming to assess the association between artificial sweetener intake and CKD risk, as well as kidney function indicators. Subsequently, we employed Mendelian randomization methods to validate the causal relationship between the intake of artificial sweeteners, CKD risk, and kidney function indicators. Instrumental variable analysis using inverse-variance weighting and Robust adjusted profile score were the primary analytical methods employed. Results: A total of 20,470 participants were included in the study, with 1,257 participants ultimately included in the analysis. In all adjusted logistic regression models, no significant association was found between the intake of artificial sweeteners and CKD risk. Similarly, the summary odds ratios (OR) for each unit change in genetically predicted CKD risk were 2.14 (95% CI: 0.83, 5.21, p = 0.092), 1.41 (95% CI: 0.54, 3.63, p = 0.482), and 1.50 (95% CI: 0.50, 4.52, p = 0.468) for the impact of artificial sweeteners added to cereals, tea, and coffee, respectively. It was only observed that adding artificial sweeteners to coffee was associated with a modest reduction in urinary albumin-to-creatinine ratio (OR = 0.94, 95% CI: -0.108, -0.022, p = 0.003), the effect appeared to be relatively small and may not directly impact the individual level. Conclusion: Our study does not support a causal relationship between artificial sweetener intake and the risk of CKD. However, due to the limitations and potential confounding factors, these findings need to be further validated through larger sample sizes in observational studies and Mendelian randomization analyses.

Effects of Plant Polysaccharides Combined with Boric Acid on Digestive Function, Immune Function, Harmful Gas and Heavy Metal Contents in Faeces of Fatteners.

The experiment aimed to investigate the effects of plant polysaccharides combined with boric acid on digestive function, immune function and harmful gas and heavy metal contents in the faeces of fatteners. For this study, 90 healthy crossbred fatteners were selected and randomly divided into five groups: the control group was fed with a basal diet (Con); experimental group I was fed with basal diet + 40 mg/kg boric acid (BA); experimental group II was fed with basal diet + 40 mg/kg boric acid + 400 mg/kg Astragalus polysaccharides (BA+APS); experimental group III was fed with basal diet + 40 mg/kg boric acid + 200 mg/kg Ganoderma lucidum polysaccharides (BA+GLP); and experimental group IV was fed with basal diet + 40 mg/kg boric acid + 500 mg/kg Echinacea polysaccharides (BA+EPS). Compared with Con, the average daily gain (ADG), the trypsin activities in the duodenum and jejunum, the IL-2 levels in the spleen, the T-AOC activities and GSH-Px contents in the lymph node of fattening were increased in the BA group (p < 0.05), but malondialdehyde content in the lymph and spleen, and the contents of NH3, H2S, Hg, Cu, Fe and Zn in the feces and urine were decreased (p < 0.05). Compared with the BA, the ADG, gain-to-feed ratio (G/F), the trypsin and maltase activities in the duodenum and jejunum were increased in the BA+APS (p < 0.05), and the T-SOD activities in the spleen and T-AOC activities in the lymph node were also increased (p < 0.05), but the H2S level was decreased in the feces and urine (p < 0.05). Compared with the BA, the ADG, G/F and the trypsin and maltase activities in the duodenum were increased in the BA+GLP and BA+EPS (p < 0.05), the activities of maltase and lipase in the duodenum of fatteners in the BA+GLP and the activities of trypsin, maltase and lipase in the BA+EPS were increased (p < 0.05). Gathering everything together, our findings reveal that the combined addition of boric acid and plant polysaccharides in the diet of fatteners synergistically improved their growth performance and immune status. That may be achieved by regulating the activity of intestinal digestive enzymes, improving the antioxidant function and then promoting the digestion and absorption of nutrients. Furthermore, the above results reduce the emission of harmful gases and heavy metals in feces and urine.

High specific surface area carbon aerogel derived from starch for methylene blue adsorption and supercapacitors.

Starch based carbon aerogel has attracted significant attention due to the wide source, environmental friendliness and low price of raw materials. Here, starch based carbon aerogel was fabricated by graft reaction and cross-linking reaction of starch. The network structure of starch hydrogel was optimized through graft and cross-linking reaction. After freeze drying and high temperature carbonization, the obtained carbon aerogel that carbonized at 800 °C showed a specific surface area of 1508 m2·g-1 without activation which is far higher than that of other unactivated carbon aerogels. The starch based carbon aerogel carbonized at 800 °C exhibited superior methylene blue adsorption ability with a maximum adsorption capacity of 963.5 mg·g-1 as a result of its rich surface functional groups, high specific surface area, and reasonable pore size distribution. Furthermore, the carbon aerogel carbonized at 700 °C exhibited excellent electrochemical performance with a specific capacitance of 180.1 F·g-1 at a current density of 1 A·g-1as electrode materials for supercapacitors. Overall, this work provides a new method to prepare high performance starch based carbon aerogel.

Integrative analysis of transcriptome, DNA methylome and chromatin accessibility reveals candidate therapeutic targets in hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease and is characterized by primary left ventricular hypertrophy usually caused by mutations in sarcomere genes. The mechanism underlying cardiac remodeling in HCM remains incompletely understood. An investigation of HCM through integrative analysis at multi-omics levels will be helpful for treating HCM. DNA methylation and chromatin accessibility, as well as gene expression, were assessed by nucleosome occupancy and methylome sequencing (NOMe-seq) and RNA-seq, respectively, using the cardiac tissues of HCM patients. Compared with those of the controls, the transcriptome, DNA methylome and chromatin accessibility of the HCM myocardium showed multifaceted differences. At the transcriptome level, HCM hearts returned to the fetal gene program through decreased sarcomeric and metabolic gene expression and increased extracellular matrix gene expression. In the DNA methylome, hypermethylated and hypomethylated differentially methylated regions (DMRs) were identified in HCM. At the chromatin accessibility level, HCM hearts showed changes in different genome elements. Several transcription factors (TFs), including SP1 and EGR1, exhibited a fetal-like pattern of binding motifs in nucleosome-depleted regions (NDRs) in HCM. In particular, the inhibition of SP1 or EGR1 in an HCM mouse model harboring sarcomere mutations markedly alleviated the HCM phenotype of the mutant mice and reversed fetal gene reprogramming. Overall, this study not only provides a high precision multi-omics map of HCM heart tissue but also sheds light on the therapeutic strategy by intervening the fetal gene reprogramming in HCM.

DEAD-box helicase 17 (DDX17) protects cardiac function by promoting mitochondrial homeostasis in heart failure.

DEAD-box helicase 17 (DDX17) is a typical member of the DEAD-box family with transcriptional cofactor activity. Although DDX17 is abundantly expressed in the myocardium, its role in heart is not fully understood. We generated cardiomyocyte-specific Ddx17-knockout mice (Ddx17-cKO), cardiomyocyte-specific Ddx17 transgenic mice (Ddx17-Tg), and various models of cardiomyocyte injury and heart failure (HF). DDX17 is downregulated in the myocardium of mouse models of heart failure and cardiomyocyte injury. Cardiomyocyte-specific knockout of Ddx17 promotes autophagic flux blockage and cardiomyocyte apoptosis, leading to progressive cardiac dysfunction, maladaptive remodeling and progression to heart failure. Restoration of DDX17 expression in cardiomyocytes protects cardiac function under pathological conditions. Further studies showed that DDX17 can bind to the transcriptional repressor B-cell lymphoma 6 (BCL6) and inhibit the expression of dynamin-related protein 1 (DRP1). When DDX17 expression is reduced, transcriptional repression of BCL6 is attenuated, leading to increased DRP1 expression and mitochondrial fission, which in turn leads to impaired mitochondrial homeostasis and heart failure. We also investigated the correlation of DDX17 expression with cardiac function and DRP1 expression in myocardial biopsy samples from patients with heart failure. These findings suggest that DDX17 protects cardiac function by promoting mitochondrial homeostasis through the BCL6-DRP1 pathway in heart failure.

Mosaic RBD nanoparticle elicits immunodominant antibody responses across sarbecoviruses.

Nanoparticle vaccines displaying mosaic receptor-binding domains (RBDs) or spike (S) from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or other sarbecoviruses are used in preparedness against potential zoonotic outbreaks. Here, we describe a self-assembling nanoparticle using lumazine synthase (LuS) as the scaffold to display RBDs from different sarbecoviruses. Mosaic nanoparticles induce sarbecovirus cross-neutralizing antibodies comparable to a nanoparticle cocktail. We find mosaic nanoparticles elicit a B cell receptor repertoire using an immunodominant germline gene pair of IGHV14-3:IGKV14-111. Most of the tested IGHV14-3:IGKV14-111 monoclonal antibodies (mAbs) are broadly cross-reactive to clade 1a, 1b, and 3 sarbecoviruses. Using mAb competition and cryo-electron microscopy, we determine that a representative IGHV14-3:IGKV14-111 mAb, M2-7, binds to a conserved epitope on the RBD, largely overlapping with the pan-sarbecovirus mAb S2H97. This suggests mosaic nanoparticles expand B cell recognition of the common epitopes shared by different clades of sarbecoviruses. These results provide immunological insights into the cross-reactive responses elicited by mosaic nanoparticles against sarbecoviruses.

1,25(OH)2D3 inhibits pancreatic stellate cells activation and promotes insulin secretion in T2DM.

PURPOSE: To evaluate the effect and mechanism of 1,25(OH)2D3 on pancreatic stellate cells (PSCs) in type 2 diabetes mellitus (T2DM). METHODS: A mouse model of T2DM was successfully established by high-fat diet (HFD) /streptozotocin (STZ) and administered 1,25(OH)2D3 for 3 weeks. Fasting blood glucose (FBG), glycated hemoglobin A1c (GHbA1c), insulin (INS) and glucose tolerance were measured. Histopathology changes and fibrosis of pancreas were examined by hematoxylin and eosin staining and Masson staining. Mouse PSCs were extracted, co-cultured with mouse insulinoma ß cells (MIN6 cells) and treated with 1,25(OH)2D3. ELISA detection of inflammatory factor expression. Tissue reactive oxygen species (ROS) levels were also measured. Immunofluorescence or Western blotting were used to measure fibrosis and inflammation-related protein expression. RESULTS: PSCs activation and islets fibrosis in T2DM mice. Elevated blood glucose was accompanied by significant increases in serum inflammatory cytokines and tissue ROS levels. 1,25(OH)2D3 attenuated islet fibrosis by reducing hyperglycemia, ROS levels, and inflammatory factors expression. Additionally, the co-culture system confirmed that 1,25(OH)2D3 inhibited PSCs activation, reduced the secretion of pro-inflammatory cytokines, down-regulated the expression of fibrosis and inflammation-related proteins, and promoted insulin secretion. CONCLUSION: Our findings identify that PSCs activation contributes to islet fibrosis and ß-cell dysfunction. 1,25(OH)2D3 exerts beneficial effects on T2DM potentially by inhibiting PSCs activation and inflammatory response, highlighting promising control strategies of T2DM by vitamin D.

Increased antibody titers but induced T cell AICD and apoptosis response in COVID-19 convalescents by inactivated vaccine booster.

It is urgently needed to evaluate the necessity and benefits of booster vaccination against the coronavirus 2 of the severe acute respiratory syndrome (SARS-CoV-2) Omicron to facilitate clinical decision-making for 2019 coronavirus disease (COVID-19) convalescents. We conducted a multicenter, prospective clinical trial (registration number: ChiCTR2100045810) in the first patients with COVID-19 from 28 January 2020 to 20 February 2020 to assess the long-term durability of neutralizing antibodies against live Omicron BA.5 and further assess the efficiency and safety of CoronaVac in the convalescent group. A total of 96 COVID-19 convalescents were enrolled in this study. Neutralizing antibody titers in convalescents were significantly reduced in 9-10 months. A dose-refreshing vaccination in 28 convalescents with an antibody titer below 96 significantly induced neutralizing antibodies against live Omicron by 4.84-fold. Meanwhile, the abundance of naive T cells increased dramatically, and TEMRA and TEM cells gradually decreased after vaccination. Activation-induced cell death and apoptosis-related genes were significantly elevated after vaccination in all T-cell subtypes. One-dose booster vaccination was effective in inducing a robust antibody response against SARS-CoV-2 Omicron in COVID-19 convalescents with low antibody titers. However, vaccine-mediated T-cell consumption and regeneration patterns may be detrimental to the antiviral response.IMPORTANCEThe globally dominant coronavirus 2 of the severe acute respiratory syndrome (SARS-CoV-2) Omicron variant raises the possibility of repeat infections among 2019 coronavirus disease (COVID-19) convalescents with low neutralizing antibody titers. The importance of this multicenter study lies in its evaluation of the long-term durability of neutralizing antibodies in COVID-19 convalescents and the efficacy of a booster vaccination against the live Omicron. The findings suggest that a one-dose booster vaccination is effective in inducing a robust antibody response against SARS-CoV-2 Omicron in convalescents with low antibody titers. However, the study also highlights the potential detrimental effects on the antiviral response due to vaccine-mediated T-cell consumption and regeneration patterns. These results are crucial for facilitating clinical decision-making for COVID-19 convalescents and informing public health policies regarding booster vaccinations.