Ultraflat single-crystal hexagonal boron nitride for wafer-scale integration of a 2D-compatible high-κ metal gate.

Hexagonal boron nitride (hBN) has emerged as a promising protection layer for dielectric integration in the next-generation large-scale integrated electronics. Although numerous efforts have been devoted to growing single-crystal hBN film, wafer-scale ultraflat hBN has still not been achieved. Here, we report the epitaxial growth of 4 in. ultraflat single-crystal hBN on Cu0.8Ni0.2(111)/sapphire wafers. The strong coupling between hBN and Cu0.8Ni0.2(111) suppresses the formation of wrinkles and ensures the seamless stitching of parallelly aligned hBN domains, resulting in an ultraflat single-crystal hBN film on a wafer scale. Using the ultraflat hBN as a protective layer, we integrate the wafer-scale ultrathin high-κ dielectrics onto two-dimensional (2D) materials with a damage-free interface. The obtained hBN/HfO2 composite dielectric exhibits an ultralow current leakage (2.36 × 10-6 A cm-2) and an ultrathin equivalent oxide thickness of 0.52 nm, which meets the targets of the International Roadmap for Devices and Systems. Our findings pave the way to the synthesis of ultraflat 2D materials and integration of future 2D electronics.

Directed differentiation of human embryonic stem cells into conjunctival epithelial cells.

Severe conjunctival damage can lead to extensive ocular cicatrisation, fornix shortening, and even ocular surface failure, resulting in significant vision impairment. Conjunctival reconstruction is the primary therapeutic strategy for these clinical conjunctival diseases. However, there have been limited studies on induced differentiation of conjunctival epithelial cells derived from stem cells. In this study, we established a chemical defined differentiation protocol from human embryonic stem cells (hESCs) into conjunctival epithelial cells. hES cell line H1 was used for differentiation, and RT-qPCR, immunofluorescence staining, Periodic-acid-Schiff staining (PAS), and transcriptome analysis were employed to identify the differentiated cells. Here, to imitate the development of the vertebrate conjunctiva, hESCs were induced using a three-step process involving first chetomin was used to induce ocular surface ectoderm, then nicotinamide was used to induce ocular surface epithelial progenitor cells, and finally epidermal growth factor, keratinocyte growth factor and other factors were used to differentiate mature conjunctival epithelial cells. hESC-derived conjunctival epithelial cells expressed mature conjunctival epithelial lineage markers (including PAX6, P63, K13). The presence of goblet cells was confirmed by positive PAS. Transcriptome analysis revealed that hESC-derived conjunctival epithelial cells possessed a more naïve phenotype, and exhibited greater proliferation capacity compared to mature human conjunctival epithelial cells, suggesting their potential as alternative seed cells for conjunctival reconstruction.

GOLM1 Promotes Pulmonary Fibrosis through Upregulation of NEAT1.

Idiopathic pulmonary fibrosis (IPF) is a lethal progressive disease with elusive molecular mechanisms and limited therapeutic options. Aberrant activation of fibroblasts is a central hallmark of lung fibrosis. Here, we report that Golgi membrane protein 1 (GOLM1, also known as GP73 or GOLPH2) was increased in the lungs of patients with pulmonary fibrosis and mice with bleomycin (BLM)-induced pulmonary fibrosis. Loss of GOLM1 inhibited proliferation, differentiation, and extracellular matrix deposition of fibroblasts, whereas overexpression of GOLM1 exerted the opposite effects. Similarly, worsening pulmonary fibrosis after BLM treatment was observed in GOLM1-knock-in mice, whereas BLM-treated Golm1-knockout mice exhibited alleviated pulmonary fibrosis and collagen deposition. Furthermore, we identified long noncoding RNA NEAT1 downstream of GOLM1 as a potential mediator of pulmonary fibrosis through increased GOLM1 expression. Depletion of NEAT1 inhibited fibroblast proliferation and extracellular matrix production and reversed the profibrotic effects of GOLM1 overexpression. Additionally, we identified KLF4 as a downstream mediator of GOLM1 signaling to NEAT1. Our findings suggest that GOLM1 plays a pivotal role in promoting pulmonary fibrosis through the GOLM1-KLF4-NEAT1 signaling axis. Targeting GOLM1 and its downstream pathways may represent a novel therapeutic strategy for treating pulmonary fibrosis.

Enhancing Protein Solubility via Glycosylation: From Chemical Synthesis to Machine Learning Predictions.

Glycosylation is a valuable tool for modulating protein solubility; however, the lack of reliable research strategies has impeded efficient progress in understanding and applying this modification. This study aimed to bridge this gap by investigating the solubility of a model glycoprotein molecule, the carbohydrate-binding module (CBM), through a two-stage process. In the first stage, an approach involving chemical synthesis, comparative analysis, and molecular dynamics simulations of a library of glycoforms was employed to elucidate the effect of different glycosylation patterns on solubility and the key factors responsible for the effect. In the second stage, a predictive mathematical formula, innovatively harnessing machine learning algorithms, was derived to relate solubility to the identified key factors and accurately predict the solubility of the newly designed glycoforms. Demonstrating feasibility and effectiveness, this two-stage approach offers a valuable strategy for advancing glycosylation research, especially for the discovery of glycoforms with increased solubility.

Association between the American Heart Association's new "Life's Essential 8" metrics and kidney stone.

PURPOSE: The incidence of kidney stone disease has increased worldwide, resulting in high medical costs and social burden. Kidney stone disease shares some common features with the risk factors of cardiovascular diseases (CVDs). We investigated the association between cardiovascular health (CVH) based on the Life's Essential 8 (LE8) score developed by the American Heart Association and the incidence of kidney stone disease. METHODS: We analyzed the data of 29,469 US adults aged 20 years or above from the National Health and Nutrition Examination Survey, 2007-2018. According to the LE8 score, CVH was divided into three categories: poor, intermediate, and ideal. Logistic regression was used to determine the association between CVH and the incidence of kidney stone disease by estimating odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: The average age of the participants was 48.6 years, and 50% of the participants were women. The numbers of participants with poor, intermediate, and ideal CVH were 4149, 19,782, and 5538, respectively. After adjusting for related confounding factors, ideal CVH was associated with a reduction in the odds of kidney stone occurrence as compared to poor CVH (adjusted OR [aOR]: 0.45, 95% CI: 0.35-0.57, p < 0.001). Moreover, if the ideal CVH metrics was ≥ 6, the odds of kidney stone occurrence decreased by up to 61% (aOR: 0.39, 95% CI: 0.30-0.51). CONCLUSIONS: In the present study, ideal CVH, a factor indicative of a healthy lifestyle, was associated with lower odds of kidney stone occurrence.

Optimizing stormwater runoff treatment: The role of two-stage tandem rain gardens.

Regarded as a superior urban stormwater management solution, rain gardens can effectively store rainfall runoff and purify water quality. However, the efficiency of traditional rain gardens (TRG) in regulating runoff and removing nitrogen and phosphorus varies under different hydrological conditions. In this study, the TRG was retrofitted to construct a two-stage tandem rain garden (TTRG). Based on the experimental monitoring of rain gardens under natural rainfall from 2011 to 2013, results indicated a significantly higher runoff reduction capacity for the TTRG compared to the traditional garden (p < 0.05), with average runoff and peak flow reduction rates increasing by 42.8% and 36.2%, respectively. Rainfall characteristics significantly impacted the runoff reduction of the TRG (p < 0.05), but not the TTRG (p > 0.05), demonstrating the enhanced control and stability of the TTRG in managing rainfall runoff. The concentration removal efficiency of nitrate nitrogen (NO3--N) was significantly improved (p < 0.05), whereas the total phosphorus (TP), ammonium nitrogen (NH3-N) and total nitrogen (TN) were not significantly changed (p > 0.05). The first-order kinetic model was used to fit the removal effect of different pollutants before and after retrofitting the rain garden, and the removal of NO3--N by the TTRG was better than that of the TRG. The TTRG showed significantly higher load removal efficiencies for TP, NO3--N, and NH3-N compared to TRG (p < 0.05), with average load removal rates increasing by 49.92%, 75.02%, and 14.81%, respectively. The TTRG can regulate urban rainfall runoff more efficiently and stably. By changing the water flow path in the rain garden, the TTRG has a better runoff reduction ability and pollutant purification effect.

Associations between oral health and depression and anxiety: A cross-sectional and prospective cohort study from the UK Biobank.

AIM: To investigate the associations between oral health and depression, anxiety and their comorbidity in the UK Biobank cohort. MATERIALS AND METHODS: Oral health problems were self-reported at baseline. Symptoms of depression and anxiety were assessed using the Mental Health Questionnaire (PHQ-4) in a cross-sectional study. In the cohort study, diagnoses of depression and anxiety disorders were based on hospital records. Logistic regression and Cox regression models were used to analyse the association between oral health and depression/anxiety. RESULTS: A total of 305,188 participants were included in the cross-sectional study, and multivariate analysis showed that periodontal disease was associated with depression and/or anxiety (odds ratio [OR]: 1.79, 95% confidence interval [CI]: 1.73-1.86). In the prospective cohort study involving 264,706 participants, periodontal disease was significantly associated with an increased risk of depression and/or anxiety (hazard ratio [HR]: 1.14, 95% CI: 1.10-1.19), depression (HR: 1.19, 95% CI: 1.13-1.25) and anxiety (HR: 1.13, 95% CI: 1.07-1.19). Periodontal disease was also significantly associated with comorbid depression and anxiety (HR: 1.27, 95% CI: 1.16-1.38). Multiple mediation analysis using baseline inflammatory factors showed that white blood cell count and C-reactive protein explained 3.07% and 3.15% of the association between periodontal disease and depression and anxiety, respectively. However, the results of longitudinal multiple mediation analysis of inflammatory factors at first follow-up (N = 10,673) were not significant. CONCLUSIONS: Periodontal disease was found to be consistently associated with an increased risk of depression, anxiety and their comorbidity.

The relationship between C-reactive protein/albumin ratio and mortality in hypertensive patients: A national cohort study.

BACKGROUND AND AIMS: The impact of inflammation on the prognosis of hypertension has received some attention. The current study examined the association between C-reactive protein to albumin ratio (CAR), a novel indicator of inflammatory response, and mortality in individuals with hypertension. METHODS AND RESULTS: A total of 9561 eligible individuals diagnosed with hypertension were included in the final analysis. CAR was calculated as ratio of C-reactive protein to serum albumin concentration. Patients were categorized into tertiles based on their baseline CAR levels. The Kaplan-Meier survival method was employed to compare the survival times of patients throughout the follow-up period. Multivariable analysis was conducted using the Cox proportional regression model. In the entire study population, 3262 (27%) experienced all-cause mortality. Patients in tertile 3 exhibited a higher risk of mortality (23% vs. 28% vs. 31%, P < 0.001) in comparison to those in the other tertiles. The findings from the multivariable Cox regression analysis demonstrated that when patients in tertile 1 were used as the reference group, the highest CAR tertile displayed a 60% increased risk of all-cause mortality (HR, 1.60 [95%CI, 1.23-2.09] P < 0.001). CONCLUSION: Among hypertensive patients, elevated CAR was found to be associated with an increased risk of all-cause mortality. Therefore, CAR might be used for risk stratification within this population, facilitating the implementation of closer follow-up and the optimization of treatment strategies.

Sleep deprivation induces corneal endothelial dysfunction by downregulating Bmal1.

BACKGROUND: Sleep deprivation (SD) is a common public health problem that contributes to various physiological disorders and increases the risk of ocular diseases. However, whether sleep loss can damage corneal endothelial function remains unclear. This study aimed to determine the effect and possible mechanism of SD on the corneal endothelium. METHODS: Male C57BL/6J mice were subjected to establish SD models. After 10 days, quantitative RT-PCR (qRT-PCR) and western blot or immunostaining for the expression levels of zonula occludens-1 (ZO-1), ATPase Na+/K + transporting subunit alpha 1 (Atp1a1), and core clock genes in the corneal endothelium were evaluated. Reactive oxygen species staining and mitochondrial abundance characterized the mitochondrial function. The regulatory role of Bmal1 was confirmed by specifically knocking down or overexpressing basic helix-loop-helix ARNT like 1 protein (Bmal1) in vivo. In vitro, a mitochondrial stress test was conducted on cultured human corneal endothelial cells upon Bmal1 knockdown. RESULTS: SD damaged the barrier and pump functions of mouse corneal endothelium, accompanied by mitochondrial dysfunction. Interestingly, SD dramatically downregulated the core clock gene Bmal1 expression level. Bmal1 knockdown disrupted corneal endothelial function, while overexpression of Bmal1 ameliorated the dysfunction induced by SD. Mitochondrial bioenergetic deficiency mediated by Bmal1 was an underlying mechanism for SD induced corneal endothelial dysfunction. CONCLUSION: The downregulation of Bmal1 expression caused by SD led to corneal endothelial dysfunction via impairing mitochondrial bioenergetics. Our findings offered insight into how SD impairs the physiological function of the corneal endothelium and expanded the understanding of sleep loss leading to ocular diseases.

Attitude and utilization of ChatGPT among registered nurses: A cross-sectional study.

AIM: This study explores the influencing factors of attitudes and behaviors toward use of ChatGPT based on the Technology Acceptance Model among registered nurses in Taiwan. BACKGROUND: The complexity of medical services and nursing shortages increases workloads. ChatGPT swiftly answers medical questions, provides clinical guidelines, and assists with patient information management, thereby improving nursing efficiency. INTRODUCTION: To facilitate the development of effective ChatGPT training programs, it is essential to examine registered nurses' attitudes toward and utilization of ChatGPT across diverse workplace settings. METHODS: An anonymous online survey was used to collect data from over 1000 registered nurses recruited through social media platforms between November 2023 and January 2024. Descriptive statistics and multiple linear regression analyses were conducted for data analysis. RESULTS: Among respondents, some were unfamiliar with ChatGPT, while others had used it before, with higher usage among males, higher-educated individuals, experienced nurses, and supervisors. Gender and work settings influenced perceived risks, and those familiar with ChatGPT recognized its social impact. Perceived risk and usefulness significantly influenced its adoption. DISCUSSION: Nurse attitudes to ChatGPT vary based on gender, education, experience, and role. Positive perceptions emphasize its usefulness, while risk concerns affect adoption. The insignificant role of perceived ease of use highlights ChatGPT's user-friendly nature. CONCLUSION: Over half of the surveyed nurses had used or were familiar with ChatGPT and showed positive attitudes toward its use. Establishing rigorous guidelines to enhance their interaction with ChatGPT is crucial for future training. IMPLICATIONS FOR NURSING AND HEALTH POLICY: Nurse managers should understand registered nurses' attitudes toward ChatGPT and integrate it into in-service education with tailored support and training, including appropriate prompt formulation and advanced decision-making, to prevent misuse.

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OBJECTIVES: To investigate the efficacy and safety of subcutaneous immunotherapy (SCIT) using dust mites in children with allergic asthma. METHODS: In a prospective randomized controlled study, 98 children with dust mite-induced allergic asthma were randomly divided into a control group (n=49) and an SCIT group (n=49). The control group received inhaled corticosteroid treatment, while the SCIT group additionally received a standardized three-year SCIT regimen. The two groups were compared based on peripheral blood eosinophil percentage, visual analogue score (VAS), total medication score, Asthma Control Test/Childhood Asthma Control Test scores, fractional exhaled nitric oxide (FeNO), and lung function before treatment, and at 6 months, 1 year, 2 years, and 3 years after treatment. Adverse reactions were recorded post-injection to evaluate the safety of SCIT. RESULTS: Compared with pre-treatment levels, the SCIT group showed a significant reduction in the percentage of peripheral blood eosinophils, VAS, total medication score, and FeNO, while lung function significantly improved, and asthma control levels were better 3 years after treatment (P<0.05). Compared with the control group, the SCIT group showed more significant improvement in all evaluated indicators 3 years after treatment (P<0.05). A total of 2 744 injections were administered, resulting in 157 cases (5.72%) of local adverse reactions and 4 cases (0.15%) of systemic adverse reactions, with no severe systemic adverse events. CONCLUSIONS: SCIT is an effective and safe treatment for allergic asthma in children.

Elevated urine albumin creatinine ratio increases cardiovascular mortality in coronary artery disease patients with or without type 2 diabetes mellitus: a multicenter retrospective study.

BACKGROUND: Albuminuria has been suggested as an atherosclerotic risk factor among the general population. However, whether this association will be amplified in patients with coronary artery disease (CAD) is unknown. It is also unknown whether diabetes mellitus confounds the association. We aim to analyse the prognosis of elevated urine albumin creatinine ratio (uACR) in the CAD population with or without type 2 diabetes mellitus (T2DM). METHODS: This multi-center registry cohort study included 5,960 patients with CAD. Patients were divided into T2DM and non-T2DM group, and baseline uACR levels were assessed on three grades (low: uACR < 10 mg/g, middle: 10 mg/g ≤ uACR < 30 mg/g, and high: uACR ≥ 30 mg/g). The study endpoints were cardiovascular mortality and all-cause mortality. RESULTS: During the median follow-up of 2.2 [1.2-3.1] years, 310 (5.2%) patients died, of which 236 (4.0%) patients died of cardiovascular disease. CAD patients with elevated uACR had a higher risk of cardiovascular mortality (middle: HR, 2.32; high: HR, 3.22) than those with low uACR, as well as all-cause mortality. Elevated uACR increased nearly 1.5-fold risk of cardiovascular mortality (middle: HR, 2.33; high: HR, 2.34) among patients without T2DM, and increased 1.5- fold to 3- fold risk of cardiovascular mortality in T2DM patients (middle: HR, 2.49; high: HR, 3.98). CONCLUSIONS: Even mildly increased uACR could increase the risk of cardiovascular mortality in patients with CAD, especially when combined with T2DM.

Independent effects of the triglyceride-glucose index on all-cause mortality in critically ill patients with coronary heart disease: analysis of the MIMIC-III database.

BACKGROUND: The triglyceride-glucose (TyG) index is a reliable alternative biomarker of insulin resistance (IR). However, whether the TyG index has prognostic value in critically ill patients with coronary heart disease (CHD) remains unclear. METHODS: Participants from the Medical Information Mart for Intensive Care III (MIMIC-III) were grouped into quartiles according to the TyG index. The primary outcome was in-hospital all-cause mortality. Cox proportional hazards models were constructed to examine the association between TyG index and all-cause mortality in critically ill patients with CHD. A restricted cubic splines model was used to examine the associations between the TyG index and outcomes. RESULTS: A total of 1,618 patients (65.14% men) were included. The hospital mortality and intensive care unit (ICU) mortality rate were 9.64% and 7.60%, respectively. Multivariable Cox proportional hazards analyses indicated that the TyG index was independently associated with an elevated risk of hospital mortality (HR, 1.71 [95% CI 1.25-2.33] P = 0.001) and ICU mortality (HR, 1.50 [95% CI 1.07-2.10] P = 0.019). The restricted cubic splines regression model revealed that the risk of hospital mortality and ICU mortality increased linearly with increasing TyG index (P for non-linearity = 0.467 and P for non-linearity = 0.764). CONCLUSIONS: The TyG index was a strong independent predictor of greater mortality in critically ill patients with CHD. Larger prospective studies are required to confirm these findings.

Single-molecule scale quantification reveals interactions underlying protein-protein interface: from forces to non-covalent bonds.

Protein-protein interactions (PPIs) between the B-cell lymphoma 2 (Bcl-2) family are considered a major driving force in cell cycle regulation and signaling. However, how this interfacial noncovalent interaction is achieved molecularly remains poorly understood. Herein, anti-apoptotic protein (Bcl-2) and pro-apoptotic protein (BAX) were used as models and their PPIs were explored for the first time using atomic force microscopy-based single-molecule force spectroscopy (SMFS) and in silico approaches. In addition, we used advanced analytical models, including multiple kinetic models, thermodynamic models, Poisson distributions, and contact angle molecular recognition to fully reveal the complexity of the BAX/Bcl-2 interaction interfaces. We propose that the binding kinetics between BAX/Bcl-2 are mainly mediated by specific (hydrogen bonding) and non-specific forces (hydrophobic interactions and electrostatic interactions) and show that the complicated multivalent binding interaction induces stable BAX/Bcl-2 complexes. This study enriches our understanding of the molecular mechanisms by which BAX interacts with Bcl-2. It provides valuable insights into the physical factors that need to be considered when designing PPI inhibitors.

Decreased plasma exposure of clopidogrel active metabolite in rats after long-term treatment with clopidogrel.

Clopidogrel (Clop) is oxidized by cytochrome P450s (CYPs) to an active thiol metabolite, Clop-AM, to inhibit platelet activation and aggregation. As an irreversible inhibitor of CYP2B6 and CYP2C19, clopidogrel may inhibit its own metabolism after long-term administration. The study compared the pharmacokinetic profiles of clopidogrel and its metabolites in rats receiving a single or a 2 week administration of Clop. The mRNA and protein levels of hepatic clopidogrel-metabolizing enzymes and their enzymatic activities were analyzed to explore their contribution to any altered plasma exposure of Clop and its metabolites. The results showed that long-term treatment with clopidogrel significantly decreased the AUC(0-t) and Cmax values of Clop-AM in rats, accompanied with markedly impaired catalytic activities of Clop-metabolizing CYPs including CYP1A2, CYP2B6, CYP2C9, CYP2C19, and CYP3A4. It suggests that consecutive administration of Clop to rats decreases hepatic CYPs activities, which may, in turn, inhibit clopidogrel metabolism and then reduce Clop-AM plasma exposure. Therefore, long-term treatment with clopidogrel has the potential to reduce its anti-platelet activity and to increase the risk of drug-drug interaction.

Effect of kidney disease on all-cause and cardiovascular mortality in patients undergoing coronary angiography.

Acute kidney injury (AKI) occurred in 12.8% of patients undergoing surgery and is associated with increased mortality. Chronic kidney disease (CKD) is a well-known risk for death and cardiovascular disease (CVD). Effects of AKI and CKD on patients undergoing coronary angiography (CAG) remain incompletely defined. The aim of our study was to investigate the relationship between acute and CKD and mortality in patients undergoing CAG. The cohort study included 49,194 patients in the multicenter cohort from January 2007 to December 2018. Cox regression analyses and Fine-Gray proportional subdistribution risk regression analysis are used to examine the association between kidney disease and all-cause and cardiovascular mortality. In the present study, 13,989 (28.4%) patients had kidney disease. During follow-up, 6144 patients died, of which 4508 (73.4%) were due to CVD. AKI without CKD (HR: 1.54, 95% CI: 1.36-1.74), CKD without AKI (HR: 2.02, 95% CI: 1.88-2.17), AKI with CKD (HR: 3.26, 95% CI: 2.90-3.66), and end-stage kidney disease (ESKD; HR: 5.63, 95% CI: 4.40-7.20) were significantly associated with all-cause mortality. Adjusted HR (95% CIs) for cardiovascular mortality was significantly elevated among patients with AKI without CKD (1.78 [1.54-2.06]), CKD without AKI (2.28 [2.09-2.49]), AKI with CKD (3.99 [3.47-4.59]), and ESKD (6.46 [4.93-8.46]). In conclusion, this study shows that acute or CKD is present in up to one-third of patients undergoing CAG and is associated with a substantially increased mortality. These findings highlight the importance of perioperative management of kidney function, especially in patients with CKD.Impact StatementWhat is already known on this subject? Acute kidney injury (AKI) occurred in 12.8% of patients undergoing surgery and is linked to a 22.2% increase in mortality. Chronic kidney disease (CKD) is a well-known risk for death and cardiovascular events. Effects of AKI and CKD on patients undergoing coronary angiography (CAG) remain incompletely defined.What do the results of this study add? This study shows that kidney disease is present in up to one-third of patients undergoing CAG and is associated with a substantially increased mortality. AKI and CKD are independent predicators for mortality in patients undergoing CAG.What are the implications of these findings for clinical practice and/or further research? These findings highlight the importance of perioperative management of kidney function, especially in patients with CKD.

Structural Characterization and Hypoglycemic Function of Polysaccharides from Cordyceps cicadae.

The polysaccharides isolated and purified from different parts of the medicinal fungus Cordyceps cicadae were identified, and three extracts displaying significant biological activities were selected for further study. The bacterium substance polysaccharides (BSP), spore powder polysaccharides (SPP), and pure powder polysaccharides (PPP) were separated, purified, and collected from the sclerotia, spores, and fruiting bodies of Cordyceps cicadae, respectively. The structures of Cordyceps cicadae polysaccharides were analyzed using gas chromatography, Fourier-transform infrared spectroscopy, methylation analysis, and one-dimensional (1H and 13C) nuclear magnetic resonance spectroscopy. Moreover, the hypoglycemic effect of Cordyceps cicadae polysaccharides was examined in both in vitro and in vivo models. BSP, SPP, and PPP significantly increased glucose absorption in HepG2 cells, and alleviated insulin resistance (IR) in the in vitro model. SPP was the most effective, and was therefore selected for further study of its hypoglycemic effect in vivo. SPP effectively improved body weight and glucose and lipid metabolism in type 2 diabetes model mice, in addition to exerting a protective effect on liver injury. SPP regulated the mRNA expression of key PI3K/Akt genes involved in the insulin signaling pathway. The hypoglycemic mechanism of SPP may reduce hepatic insulin resistance by activating the PI3K/Akt signaling pathway. Spore powder polysaccharides (SPP) extracted from Cordyceps cicadae effectively improved body weight and glucose and lipid metabolism in type 2 diabetes model mice, in addition to exerting a protective effect on liver injury. The mechanism underlying the hypoglycemic effect of SPP regulates the mRNA expression of key PI3K/Akt genes involved in the insulin signaling pathway to alleviate insulin resistance. Our results provide a theoretical basis for research into the hypoglycemic effect of Cordyceps cicadae, and lay the foundation for the development of functional products.

Extraction of Gold Based on Ionic Liquid Immobilized in UiO-66: An Efficient and Reusable Way to Avoid IL Loss Caused by Ion Exchange in Solvent Extraction.

Ionic liquids (ILs) have received considerable attention as a promising green solvent for extracting metal ions from aqueous solutions. However, the recycling of ILs remains difficult and challenging because of the leaching of ILs, which is caused by the ion exchange extraction mechanism and hydrolysis of ILs in acidic aqueous conditions. In this study, a series of imidazolium-based ILs were confined in a metal-organic framework (MOF) material (UiO-66) to overcome the limitations when used in solvent extraction. The effect of the various anions and cations of the ILs on the adsorption ability of AuCl4- was studied, and 1-hexyl-3-methylimidazole tetrafluoroborate ([HMIm]+[BF4]-@UiO-66) was used for the construction of a stable composite. The adsorption properties and mechanism of [HMIm]+[BF4]-@UiO-66 for Au(III) adsorption were also studied. The concentrations of tetrafluoroborate ([BF4]-) in the aqueous phase after Au(III) adsorption by [HMIm]+[BF4]-@UiO-66 and liquid-liquid extraction by [HMIm]+[BF4]- IL were 0.122 mg/L and 18040 mg/L, respectively. The results reveal that Au(III) coordinated with the N-containing functional groups, while [BF4]- was effectively confined in UiO-66, instead of undergoing anion exchange in liquid-liquid extraction. Electrostatic interactions and the reduction of Au(III) to Au(0) were also important factors determining the adsorption ability of Au(III). [HMIm]+[BF4]-@UiO-66 could be easily regenerated and reused for three cycles without any significant drop in the adsorption capacity.

Triglyceride-glucose index linked to all-cause mortality in critically ill patients: a cohort of 3026 patients.

BACKGROUND: Triglyceride-glucose (TyG) index as a reliable surrogate of insulin resistance (IR) has been shown to be related to adverse clinical outcomes in patients with acute coronary syndrome, heart failure, ischemic stroke and so on. However, the relationship between TyG index and all-cause mortality in intensive care unit (ICU) patients remains unknown. The purpose of this study was to investigate the correlation between TyG index and all-cause mortality to evaluate the impact of IR on the prognosis of this population. METHODS: This was a retrospective observational study that included 3026 patients who had an initial triglyceride and glucose data on the first day of ICU admission, and all data were extracted from the Medical Information Mart for Intensive Care III (MIMIC-III) database. These patients were grouped into quartiles (Q1-Q4) according to TyG index. The Kaplan-Meier analysis was used to compare all-cause mortality among the above four groups. Cox proportional hazards analyses were performed to examine the association between TyG index and all-cause mortality. RESULTS: During 10.46 years of follow-up, 1148 (37.9%) patients died, of which 350 (11.6%) occurred during the hospital stay and 258 (8.5%) occurred during the ICU stay. Kaplan-Meier analysis showed that the risk of all-cause mortality was significantly higher in patients with higher TyG index (log-rank P = 0.021). Multivariable Cox proportional hazards analyses showed that the TyG index was an independent risk predictor of ICU death (HR: 1.72, 95% CI 1.18-2.52, P = 0.005) and hospital death (HR: 2.19, 95% CI 1.59-3.03, P < 0.001), and each 1-unit increased in the TyG index, a 1.19-fold increase in the risk of death during the hospital stay. CONCLUSIONS: TyG index is strongly related to the all-cause mortality increasing in critically ill patients. This finding indicates that the TyG index might be useful in identifying people at high risk of ICU death and hospital death.

ERICH3: vesicular association and antidepressant treatment response.

Selective serotonin reuptake inhibitors (SSRIs) are standard of care for major depressive disorder (MDD) pharmacotherapy, but only approximately half of these patients remit on SSRI therapy. Our previous genome-wide association study identified a single-nucleotide polymorphism (SNP) signal across the glutamate-rich 3 (ERICH3) gene that was nearly genome-wide significantly associated with plasma serotonin (5-HT) concentrations, which were themselves associated with SSRI response for MDD patients enrolled in the Mayo Clinic PGRN-AMPS SSRI trial. In this study, we performed a meta-analysis which demonstrated that those SNPs were significantly associated with SSRI treatment outcomes in four independent MDD trials. However, the function of ERICH3 and molecular mechanism(s) by which it might be associated with plasma 5-HT concentrations and SSRI clinical response remained unclear. Therefore, we characterized the human ERICH3 gene functionally and identified ERICH3 mRNA transcripts and protein isoforms that are highly expressed in central nervous system cells. Coimmunoprecipitation identified a series of ERICH3 interacting proteins including clathrin heavy chain which are known to play a role in vesicular function. Immunofluorescence showed ERICH3 colocalization with 5-HT in vesicle-like structures, and ERICH3 knock-out dramatically decreased 5-HT staining in SK-N-SH cells as well as 5-HT concentrations in the culture media and cell lysates without changing the expression of 5-HT synthesizing or metabolizing enzymes. Finally, immunofluorescence also showed ERICH3 colocalization with dopamine in human iPSC-derived neurons. These results suggest that ERICH3 may play a significant role in vesicular function in serotonergic and other neuronal cell types, which might help explain its association with antidepressant treatment response.