Recent advances in the adjunctive management of diabetic foot ulcer: Focus on noninvasive technologies.

Diabetic foot ulcer (DFU) is one of the most costly and serious complications of diabetes. Treatment of DFU is usually challenging and new approaches are required to improve the therapeutic efficiencies. This review aims to update new and upcoming adjunctive therapies with noninvasive characterization for DFU, focusing on bioactive dressings, bioengineered tissues, mesenchymal stem cell (MSC) based therapy, platelet and cytokine-based therapy, topical oxygen therapy, and some repurposed drugs such as hypoglycemic agents, blood pressure medications, phenytoin, vitamins, and magnesium. Although the mentioned therapies may contribute to the improvement of DFU to a certain extent, most of the evidence come from clinical trials with small sample size and inconsistent selections of DFU patients. Further studies with high design quality and adequate sample sizes are necessitated. In addition, no single approach would completely correct the complex pathogenesis of DFU. Reasonable selection and combination of these techniques should be considered.

Fabrication of Single-Crystal Violet Phosphorus Flakes For Ultrasensitive Photodetection.

Violet phosphorus (VP) has attracted a lot of attention for its unique physicochemical properties and emerging potential in photoelectronic applications. Although VP has a van der Waals (vdW) structure similar to that of other 2D semiconductors, direct synthesis of VP on a substrate is still challenging. Moreover, optoelectronic devices composed of transfer-free VP flakes have not been demonstrated. Herein, a bismuth-assisted vapor phase transport technique is designed to grow uniform single-crystal VP flakes on the SiO2 /Si substrate directly. The size of the crystalline VP flakes is an order of magnitude larger than that of previous liquid-exfoliated samples. The photodetector fabricated with the VP flakes shows a high responsivity of 12.5 A W-1 and response/recovery time of 3.82/3.03 ms upon exposure to 532 nm light. Furthermore, the photodetector shows a small dark current (<1 pA) that is beneficial to high-sensitivity photodetection. As a result, the detectivity is 1.38 × 1013 Jones that is comparable with that of the vdW p-n heterojunction detector. The results reveal the great potential of VP in optoelectronic devices as well as the CVT technique for the growth of single-crystal semiconductor thin films.

Melamine Polymerization Promotes Compact Phosphorus/Carbon Composite for High-Performance and Safe Lithium Storage.

Phosphorus is regarded as a promising material for high-performance lithium-ion batteries (LIBs) due to its high theoretical capacity, appropriate lithiation potential, and low lithium-ion diffusion barrier. Phosphorus/carbon composites (PC) are engineered to serve as high-capacity high-rate anodes; the interaction between phosphorus and carbon, long-term capacity retention, and safety problems are important issues that must be well addressed simultaneously. Herein, an in situ polymerization approach to fabricate a poly-melamine-hybridized (pMA) phosphorus/carbon composite (pMA-PC) is employed. The pMA hybridization enhances the density and electrical conductivity of the PC, improves the structural integrity, and facilitates stable electron transfer within the pMA-PC composite. Moreover, the pMA-PC composite exhibits efficient adsorption of lithium polysulfides, enabling stable transport of Li+ ions. Therefore, the pMA-PC anode demonstrates a high specific charging capacity of 1,381 mAh g-1 at 10 A g-1, and a great capacity retention of 86.7% at 1 A g-1 over 500 cycles. The synergistic effect of phosphorus and nitrogen further confers excellent flame retardant properties to the pMA-PC anode, including self-extinguishing in 2.5 s, and a much lower combustion temperature than PC. The enhanced capacity and safety performance of pMA-PC show potential in future high-capacity and high-rate LIBs.

CVOT Summit Report 2023: new cardiovascular, kidney, and metabolic outcomes.

The 9th Cardiovascular Outcome Trial (CVOT) Summit: Congress on Cardiovascular, Kidney, and Metabolic Outcomes was held virtually on November 30-December 1, 2023. This reference congress served as a platform for in-depth discussions and exchange on recently completed outcomes trials including dapagliflozin (DAPA-MI), semaglutide (SELECT and STEP-HFpEF) and bempedoic acid (CLEAR Outcomes), and the advances they represent in reducing the risk of major adverse cardiovascular events (MACE), improving metabolic outcomes, and treating obesity-related heart failure with preserved ejection fraction (HFpEF). A broad audience of endocrinologists, diabetologists, cardiologists, nephrologists and primary care physicians participated in online discussions on guideline updates for the management of cardiovascular disease (CVD) in diabetes, heart failure (HF) and chronic kidney disease (CKD); advances in the management of type 1 diabetes (T1D) and its comorbidities; advances in the management of CKD with SGLT2 inhibitors and non-steroidal mineralocorticoid receptor antagonists (nsMRAs); and advances in the treatment of obesity with GLP-1 and dual GIP/GLP-1 receptor agonists. The association of diabetes and obesity with nonalcoholic steatohepatitis (NASH; metabolic dysfunction-associated steatohepatitis, MASH) and cancer and possible treatments for these complications were also explored. It is generally assumed that treatment of chronic diseases is equally effective for all patients. However, as discussed at the Summit, this assumption may not be true. Therefore, it is important to enroll patients from diverse racial and ethnic groups in clinical trials and to analyze patient-reported outcomes to assess treatment efficacy, and to develop innovative approaches to tailor medications to those who benefit most with minimal side effects. Other keys to a successful management of diabetes and comorbidities, including dementia, entail the use of continuous glucose monitoring (CGM) technology and the implementation of appropriate patient-physician communication strategies. The 10th Cardiovascular Outcome Trial Summit will be held virtually on December 5-6, 2024 ( http://www.cvot.org ).

ENPP2/Autotaxin: The potential drug target for alcoholic liver disease identified through Mendelian randomization analysis.

BACKGROUND AND AIMS: At present, there is still a lack of radical drug targets for intervention in alcoholic liver disease (ALD), and drug discovery through randomized controlled trials is a lengthy, risky, and expensive undertaking, so we aimed to identify effective drug targets based on human genetics. METHODS: We used Mendelian randomization (MR) and Bayesian colocalization analysis to investigate 2639 genes encoding druggable proteins and examined the causal effects on ALD (PMID 34737426: 456348 European with 451 cases and 455 897 controls). In addition, we conducted the mediation analysis to explore the potential mechanism using the genome-wide association study (GWAS) data of blood biomarkers as mediators. RESULTS: We finally identified the drug target: ENPP2/Autotaxin and genetically proxied ENPP2/Autotaxin was causally associated with the risk of ALD (OR = 2.28, 95% CI: 1.64 to 3.16, p = 7.49E-7). In addition, we found that the effect of ENPP2/Autotaxin on ALD may be partly mediated by effector memory CD8+ T cell (the proportion of mediation effect: 8.49%). CONCLUSIONS: Our integrative analysis suggested that genetically determined levels of circulating ENPP2/Autotaxin have a causal effect on ALD risk and are a promising drug target.

Beinaglutide for weight management in Chinese individuals with overweight or obesity: A phase 3 randomized controlled clinical study.

AIM: To investigate the efficacy and safety of beinaglutide as an adjunct to lifestyle intervention among non-diabetic Chinese individuals with overweight or obesity. METHODS: This multicentre, randomized, double-blind, placebo-controlled trial (ChiCTR1900023428) included 427 Chinese adults with a body mass index of 28 kg/m2 or higher (obesity) or 24-27.9 kg/m2 (overweight) with weight-related complications. Patients were randomized in a 2:1 ratio to receive 0.2 mg of beinaglutide (subcutaneous) thrice daily or placebo for 16 weeks. Co-primary endpoints were body weight change and the proportion of patients with a weight reduction of 5% or more. RESULTS: Mean body weight change from baseline to week 16 was -6.0% and -2.4% in the beinaglutide (n = 282) and placebo (n = 138) groups, respectively; the mixed model repeated measures difference was -3.6% (95% confidence interval: -4.6% to -2.6%; P < .0001). At week 16, more beinaglutide-treated patients achieved a weight reduction of 5% or more (58.2% vs. 25.4% [placebo], odds ratio: 4.4; P < .0001) and of 10% or more (21.3% vs. 5.1% [placebo], odds ratio: 5.5; P < .0001). Beinaglutide also resulted in greater waist circumference reduction (difference: -1.81 cm; P < .01). The weight regain rate 12 weeks after beinaglutide treatment was 0.78%. Nausea (transient and mild-to-moderate) was the most common adverse event in the beinaglutide group (49.3% vs. 7.1% [placebo]). More patients receiving beinaglutide discontinued treatment because of adverse events (5.9% vs. 0.7% [placebo]). Pancreatitis or an increased resting heart rate was not observed in the beinaglutide group. CONCLUSION: Beinaglutide combined with lifestyle intervention resulted in significant and clinically meaningful weight reduction with good tolerance in non-diabetic Chinese individuals with overweight or obesity.

Efficacy of noiiglutide injection on body weight in obese Chinese adults without diabetes: A multicentre, randomized, double-blind, placebo-controlled, phase 2 trial.

AIM: To evaluate the effect of noiiglutide as an adjunct to lifestyle intervention on the reduction in body weight and tolerability in obese Chinese adults without diabetes. MATERIALS AND METHODS: In this 24-week, randomized, double-blind, placebo-controlled phase 2 trial, 254 obese adults with a body mass index of 28.0-40.0 kg/m2 and without diabetes were enrolled. Participants were initially randomized in a 1:1:1 ratio to one of three dose levels: 0.12, 0.24, or 0.36 mg of the study treatment. Within each dose level, participants were further randomized in a 3:1 ratio to receive either subcutaneous injection of noiiglutide or a matching placebo. The primary endpoint was the change in body weight from baseline to week 24. RESULTS: Across all noiiglutide dosage levels, least squares mean reductions in body weight from baseline to week 24 ranged from 8.03 to 8.50 kg, compared with 3.65 kg in the placebo group (all p-values <.0001). In the noiiglutide groups (0.12, 0.24, 0.36 mg/day), a significantly higher proportion of participants achieved a weight loss ≥5% (68.8%, 60.0%, 73.0%) and ≥10% (37.5%, 36.9%, 39.7%), compared with the pooled placebo group (≥5%: 29.0%; ≥10%: 8.1%). Gastrointestinal adverse events, such as nausea, diarrhoea and vomiting, were more common in all noiiglutide groups (15.4%-30.2%, 18.8%-22.2%, 15.6%-18.5%) than in the pooled placebo group (8.1%, 6.5%, 0%). CONCLUSIONS: In obese Chinese adults without diabetes, once-daily subcutaneous noiiglutide significantly reduced body week at week 24 compared with placebo, and had a manageable safety profile, primarily involving gastrointestinal disorders.

Body size, insulin sensitivity, metabolic health and risk of cardiovascular disease in Chinese adults: Insights from the China Cardiometabolic Disease and Cancer Cohort (4C) study.

AIMS: To assess the excess risk of cardiovascular disease (CVD) associated with different criteria for metabolic health, and the interplay of body size, insulin sensitivity and metabolic health with CVD risk. MATERIALS AND METHODS: We conducted a prospective study involving 115 638 participants from the China Cardiometabolic Disease and Cancer Cohort (4C) Study. Metabolic health was defined using three different definitions: (1) insulin sensitivity defined by homeostatic model assessment of insulin resistance index; (2) absence of metabolic syndrome according to the National Cholesterol Education Program Adult Treatment Panel III criteria; and (3) simultaneous absence of metabolic abnormalities (diabetes, hypertension, dyslipidaemia). The primary endpoint was a composite of incident CVD events comprising the first occurrence of myocardial infarction, stroke, heart failure, or cardiovascular death. RESULTS: During a mean 3.61-year follow-up period, obese individuals with insulin sensitivity (multivariable-adjusted hazard ratio [HR] 1.69, 95% confidence interval [CI] 1.37-2.08), or without metabolic syndrome (HR 1.46, 95% CI 1.13-1.89) still exhibited increased CVD risks, when compared to their normal-weight counterparts. Otherwise, those with obesity but simultaneous absence of metabolic abnormalities demonstrated similar CVD risk compared to normal-weight individuals (HR 0.91, 95% CI 0.53-1.59). CVD risk increased with the number of abnormalities across body mass index categories, regardless of insulin sensitivity. CONCLUSIONS: This study emphasizes the need for refined definitions of metabolic health and advocates for meticulous screening for metabolic abnormalities to reduce cardiovascular risks, even in individuals with normal weight and insulin sensitivity.

Enhanced Catalytic Activity of Crystalline Phosphorus Nanosheets Fabricated via Solvothermal Phase Transformation.

The newly reported crystalline phosphorus nanosheets (cryst-P NSs) exhibit promising features for industrial applications, including outstanding air-water stability and facile large-scale production. However, their complex crystallization impedes a priori tailoring. Herein, the temporal evolution of cryst-P NSs was investigated with the optimized synthesis parameters. The occurrence of self-assembly and solid-state rearrangement unveiled the existence of an intermediate phase as the bulk crystalline precursor and the predominance of nonclassical crystallization pathway(s). With the upgraded synthesis protocol simultaneously strengthening the merits of cryst-P NSs, their catalytic performances were evaluated in various electro- and/or photocatalytic reactions spanning hydrogen and oxygen evolution, full water splitting, CO2 reduction, and organic pollutant decomposition. Superior catalytic activities and orders of magnitude longer lifetimes were consistently discerned compared with the widely employed black phosphorus nanosheets with similar size and thickness. The exciting discoveries in both fundamental crystallization and catalytic applications drastically thrust the comprehension of elemental phosphorus, shedding light on the encouraging capabilities of solvothermal synthesis strategies in the design and systematic tailoring of phosphorus materials.

Regulation of SiO2 Nanoparticles on the Adsorptive Fractionation of Dissolved Organic Matter by Goethite.

SiO2 nanoparticles (SiO2NPs) are most widely available and coexisting with DOM at the mineral-water interface; however, the role of SiO2NPs in DOM fractionation and the underlying mechanisms have not been fully understood. Using Fourier transform ion cyclotron resonance mass spectrometry, combined with Fourier transform infrared spectroscopy and X-ray adsorption fine structure spectroscopy, was employed to investigate the adsorptive fractionation of litter layer-derived DOM on goethite coexisting with SiO2NPs under different pH conditions. Results indicated that the inhibitory effect of the coexisting SiO2NPs on OM sorbed by goethite was waning as environmental pH increased due to the reduced steric interactions and the concurrent elevated hydrogen bonding/hydrophobic partitioning interactions on the goethite surface. We observed the coexisting SiO2NPs inhibited the adsorption of high carboxylic-containing condensed aromatic/aromatics compounds on goethite under different pH conditions while improving the adsorption of highly unsaturated aliphatic/phenolic and carbohydrate-like compounds in an alkaline and/or circumneutral environment. More nitrogen-containing structures may favor the adsorption of phenolic and nonaromatic compounds to goethite by counteracting the negative effect of SiO2NPs. These findings suggest that DOM sequestration may be significantly regulated by the coexisting SiO2NPs at the mineral-water interface, which may further influence the carbon-nitrogen cycling and contaminant fate in natural environments.

A black phosphorus nanosheet-based RNA delivery system for prostate cancer therapy by increasing the expression level of tumor suppressor gene PTEN via CeRNA mechanism.

BACKGROUND: Prostate cancer (PCa) has a high incidence in men worldwide, and almost all PCa patients progress to the androgen-independent stage which lacks effective treatment measures. PTENP1, a long non-coding RNA, has been shown to suppress tumor growth through the rescuing of PTEN expression via a competitive endogenous RNA (ceRNA) mechanism. However, PTENP1 was limited to be applied in the treatment of PCa for the reason of rapid enzymatic degradation, poor intracellular uptake, and excessively long base sequence to be synthesized. Considering the unique advantages of artificial nanomaterials in drug loading and transport, black phosphorus (BP) nanosheet was employed as a gene-drug carrier in this study. RESULTS: The sequence of PTENP1 was adopted as a template which was randomly divided into four segments with a length of about 1000 nucleotide bases to synthesize four different RNA fragments as gene drugs, and loaded onto polyethyleneimine (PEI)-modified BP nanosheets to construct BP-PEI@RNA delivery platforms. The RNAs could be effectively delivered into PC3 cells by BP-PEI nanosheets and elevating PTEN expression by competitive binding microRNAs (miRNAs) which target PTEN mRNA, ultimately exerting anti-tumor effects. CONCLUSIONS: Therefore, this study demonstrated that BP-PEI@RNAs is a promising gene therapeutic platform for PCa treatment.

Renaissance of elemental phosphorus materials: properties, synthesis, and applications in sustainable energy and environment.

The polymorphism of phosphorus-based materials has garnered much research interest, and the variable chemical bonding structures give rise to a variety of micro and nanostructures. Among the different types of materials containing phosphorus, elemental phosphorus materials (EPMs) constitute the foundation for the synthesis of related compounds. EPMs are experiencing a renaissance in the post-graphene era, thanks to recent advancements in the scaling-down of black phosphorus, amorphous red phosphorus, violet phosphorus, and fibrous phosphorus and consequently, diverse classes of low-dimensional sheets, ribbons, and dots of EPMs with intriguing properties have been produced. The nanostructured EPMs featuring tunable bandgaps, moderate carrier mobility, and excellent optical absorption have shown great potential in energy conversion, energy storage, and environmental remediation. It is thus important to have a good understanding of the differences and interrelationships among diverse EPMs, their intrinsic physical and chemical properties, the synthesis of specific structures, and the selection of suitable nanostructures of EPMs for particular applications. In this comprehensive review, we aim to provide an in-depth analysis and discussion of the fundamental physicochemical properties, synthesis, and applications of EPMs in the areas of energy conversion, energy storage, and environmental remediation. Our evaluations are based on recent literature on well-established phosphorus allotropes and theoretical predictions of new EPMs. The objective of this review is to enhance our comprehension of the characteristics of EPMs, keep abreast of recent advances, and provide guidance for future research of EPMs in the fields of chemistry and materials science.

Data-Driven Controlled Synthesis of Oriented Quasi-Spherical CsPbBr3 Perovskite Materials.

Controlled synthesis of lead-halide perovskite crystals is challenging yet attractive because of the pivotal role played by the crystal structure and growth conditions in regulating their properties. This study introduces data-driven strategies for the controlled synthesis of oriented quasi-spherical CsPbBr3, alongside an investigation into the synthesis mechanism. High-throughput rapid characterization of absorption spectra and color under ultraviolet illumination was conducted using 23 possible ligands for the synthesis of CsPbBr3 crystals. The links between the absorption spectra slope (difference in the absorbance at 400 nm and 450 nm divided by a wavelength interval of 50 nm) and crystal size were determined through statistical analysis of more than 100 related publications. Big data analysis and machine learning were employed to investigate a total of 688 absorption spectra and 652 color values, revealing correlations between synthesis parameters and properties. Ex situ characterization confirmed successful synthesis of oriented quasi-spherical CsPbBr3 perovskites using polyvinylpyrrolidone and Acacia. Density functional theory calculations highlighted strong adsorption of Acacia on the (110) facet of CsPbBr3. Optical properties of the oriented quasi-spherical perovskites prepared with these data-driven strategies were significantly improved. This study demonstrates that data-driven controlled synthesis facilitates morphology-controlled perovskites with excellent optical properties.

Interfacial Engineering Enables Perovskite Heteroepitaxial Growth on Black Phosphorus for Flexible X-ray Detectors.

2D materials with atomic-scale thickness and mechanical robustness are required for flexible devices. The superior optoelectronic properties and high-Z atoms in metal halide perovskites render them desirable for X-ray detection, but the intrinsic brittleness is an obstacle hampering the applications in flexible detectors. Herein, an interfacial engineering strategy is demonstrated for the epitaxial growth of methylammonium lead bromide (MAPbBr3 ) on black phosphorus (BP) for flexible X-ray detectors. The mechanically robust, high-quality heterostructure consisting of a Pb transition layer is synthesized for the two-way bridging of BP and MAPbBr3 . Excellent optoelectronic properties such as a high X-ray sensitivity of 1,609 ± 122 µC Gy-1  cm-2 (80 times higher than that of the commercial amorphous Se), a fast response time of 40 ± 5 ms, as well as a low detection limit of 3 µGys-1 (about a fifteenth of the medical chest X-ray dose rate) are achieved from the simple and planar direct X-ray detector fabricated on an organic filter membrane. More importantly, these flat and simple devices are bendable and mechanically durable by exhibiting only 10% photocurrent degradation after 200 bending cycles. The novel heterostructure has great potential in large-area, flexible, and sensitive X-ray detection applications.

Prevalence and risk factors of diabetic peripheral neuropathy: A population-based cross-sectional study in China.

AIMS: To assess the prevalence of diabetic peripheral neuropathy (DPN) and its risk factors in the type 2 diabetes mellitus (T2DM) population. METHODS: This cross-sectional study enroled patients with T2DM between July and December 2017 from 24 provinces in China. Diabetic peripheral neuropathy and its severity were assessed by the Toronto clinical scoring system, neuropathy symptoms score (NSS) and neuropathy disability score. The prevalence of DPN and its risk factors were analysed. RESULTS: A total of 14,908 patients with T2DM were enroled. The prevalence of DPN was 67.6%. Among 10,084 patients with DPN, 4808 (47.7%), 3325 (33.0%), and 1951 (19.3%) had mild, moderate, and severe DPN, respectively. The prevalence of DPN in females was higher than in males (69.0% vs. 66.6%, P = 0.002). The prevalence of DPN increased with age and course of diabetes and decreased with body mass index (BMI) and education level (all P for trend <0.05). The comorbidities and complications in patients with DPN were higher than in those without DPN, including hypertension, myocardial infarction, diabetic retinopathy, and diabetic nephropathy (all P < 0.001). Age, hypertension, duration of diabetes, diabetic retinopathy, diabetic nephropathy, glycated haemoglobin, high-density lipoprotein cholesterol, and lower estimated glomerular filtration rate were positively associated with DPN, while BMI, education level, fasting C-peptide, and uric acid were negatively associated with DPN. CONCLUSIONS: Among patients with T2DM in China, the prevalence of DPN is high, especially in the elderly, low-income, and undereducated patients.

Comprehensive analysis identifies cuproptosis-related gene DLAT as a potential prognostic and immunological biomarker in pancreatic adenocarcinoma.

BACKGROUND: Cuproptosis is a regulated cell death form associated with tumor progression, clinical outcomes, and immune response. However, the role of cuproptosis in pancreatic adenocarcinoma (PAAD) remains unclear. This study aims to investigate the implications of cuproptosis-related genes (CRGs) in PAAD by integrated bioinformatic methods and clinical validation. METHODS: Gene expression data and clinical information were downloaded from UCSC Xena platform. We analyzed the expression, mutation, methylation, and correlations of CRGs in PAAD. Then, based on the expression profiles of CRGs, patients were divided into 3 groups by consensus clustering algorithm. Dihydrolipoamide acetyltransferase (DLAT) was chosen for further exploration, including prognostic analysis, co-expression analysis, functional enrichment analysis, and immune landscape analysis. The DLAT-based risk model was established by Cox and LASSO regression analysis in the training cohort, and then verified in the validation cohort. Quantitative reverse transcriptase polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC) assays were performed to examine the expression levels of DLAT in vitro and in vivo, respectively. RESULTS: Most CRGs were highly expressed in PAAD. Among these genes, increased DLAT could serve as an independent risk factor for survival. Co-expression network and functional enrichment analysis indicated that DLAT was engaged in multiple tumor-related pathways. Moreover, DLAT expression was positively correlated with diverse immunological characteristics, such as immune cell infiltration, cancer-immunity cycle, immunotherapy-predicted pathways, and inhibitory immune checkpoints. Submap analysis demonstrated that DLAT-high patients were more responsive to immunotherapeutic agents. Notably, the DLAT-based risk score model possessed high accuracy in predicting prognosis. Finally, the upregulated expression of DLAT was verified by RT-qPCR and IHC assays. CONCLUSIONS: We developed a DLAT-based model to predict patients' clinical outcomes and demonstrated that DLAT was a promising prognostic and immunological biomarker in PAAD, thereby providing a new possibility for tumor therapy.

Whole fresh fruit intake and risk of incident diabetes in different glycemic stages: a nationwide prospective cohort investigation.

PURPOSE: Fruit intake is beneficial to several chronic diseases, but controversial in diabetes. We aimed to investigate prospectively the associations of whole fresh fruit intake with risk of incident type 2 diabetes (T2D) in subjects with different glucose regulation capacities. METHODS: The present study included 79,922 non-diabetic participants aged ≥ 40 years from an ongoing nationwide prospective cohort in China. Baseline fruit intake information was collected by a validated food frequency questionnaire. Plasma HbA1c, fasting and 2 h post-loading glucose levels were measured at both baseline and follow-up examinations. Cox proportional hazards models were used to calculate hazard ratio (HR) and 95% confidence intervals (CI) for incident diabetes among participants with normal glucose tolerance (NGT) and prediabetes, after adjusted for multiple confounders. Restricted cubic spline analysis was applied for dose-response relation. RESULTS: During a median 3.8-year follow-up, 5886 (7.36%) participants developed diabetes. Overall, we identified a linear and dose-dependent inverse association between dietary whole fresh fruit intake and risk of incident T2D. Each 100 g/d higher fruit intake was associated with 2.8% lower risk of diabetes (HR 0.972, 95%CI [0.949-0.996], P = 0.0217), majorly benefiting NGT subjects with 15.2% lower risk (HR 0.848, 95%CI [0.766-0.940], P = 0.0017), while not significant in prediabetes (HR 0.981, 95%CI 0.957-4.005, P = 0.1268). Similarly, the inverse association was present in normoglycemia individuals with a 48.6% lower risk of diabetes when consuming fruits > 7 times/week comparing to those < 1 time/week (HR 0.514, 95% CI [0.368-0.948]), but not in prediabetes (HR 0.883, 95% CI [0.762-1.023]). CONCLUSION: These findings suggest that higher frequency and amount of fresh fruit intake may protect against incident T2D, especially in NGT, but not in prediabetes, highlighting the dietary recommendation of higher fresh fruit consumption to prevent T2D in normoglycemia population.

Biodegradable FePS3 nanoplatform for efficient treatment of osteosarcoma by combination of gene and NIR-II photothermal therapy.

As a common tumor with high incidence, osteosarcoma possesses extremely poor prognosis and high mortality. Improving the survival of osteosarcoma patients is still a great challenge due to the precipice of advancement in treatment. In this study, a combination strategy of gene therapy and photothermal therapy (PTT) is developed for efficient treatment of osteosarcoma. Two-dimensional (2D) FePS3 nanosheets are synthesized and functionalized by poly-L-lysine-PEG-folic acid (PPF) to fabricate a multifunctional nanoplatform (FePS@PPF) for further loading microRNAs inhibitor, miR-19a inhibitor (anti-miR-19a). The photothermal conversion efficiency of FePS@PPF is up to 47.1% under irradiation by 1064 nm laser. In vitro study shows that anti-miR-19a can be efficiently internalized into osteosarcoma cells through the protection and delivery of FePS@PPF nanaocarrier, which induces up-regulation of PTEN protein and down-regulation p-AKT protein. After intravenous injection, the FePS@PPF nanoplatform specifically accumulates to tumor site of osteosarcoma-bearing mice. The in vitro and in vivo investigations reveal that the combined PTT-gene therapy displays most significant tumor ablation compared with monotherapy. More importantly, the good biodegradability promotes FePS@PPF to be cleared from body avoiding potential toxicity of long-term retention. Our work not only develops a combined strategy of NIR-II PTT and gene therapy mediated by anti-miR-19a/FePS@PPF but also provides insights into the design and applications of other nanotherapeutic platforms.

The Impact of Sedentary Behavior on Renal Function Decline in 132,123 Middle Aged and Older Adults: A Nationwide Cohort Study.

BACKGROUND Prior studies suggest that sedentary behavior is a well-known risk factor for cardiometabolic diseases. However, the longitudinal association between overall siting time and kidney function decline is not known. MATERIAL AND METHODS We performed a nationwide prospective cohort study in individuals aged more than 40 years enrolled in the China Cardiometabolic Disease and Cancer Cohort (4C) study. A total of 132 123 individuals were included in this study. Sitting time was measured with the short version of the International Physical Activity Questionnaire (IPAQ). Kidney function decline was defined as an eGFR <60 mL/min/1.73 m² or more than a 30% decrease in eGFR from baseline. Multivariate Cox proportional hazards regression analyses were conducted to estimate the adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) of the relation between kidney function decline and sitting time. RESULTS During a mean follow-up of 3.8 years, 3890 (2.9%) participants experienced kidney function decline. Longer sitting time was significantly associated with the risk of kidney function decline (aHR, 1.136; 95% CI, 1.036-1.247, P=0.007, comparing participants with baseline sitting time in the lowest quartile with those in the highest quartile) after adjustment for potential confounders. CONCLUSIONS Longer sitting time was independently and prospectively associated with a higher risk of kidney function decline. Sedentary behavior might represent a modifiable risk factor for chronic kidney disease (CKD) prevention.

Irisin attenuates ethanol-induced behavioral deficits in mice through activation of Nrf2 and inhibition of NF-κB pathways.

This study aims to investigate the effect of irisin on ethanol-induced behavioral deficits and explore the underlying mechanisms. A mouse model of ethanol addiction/withdrawal was constructed through chronic ethanol administration. Depressive-like behaviors were evaluated by the tail suspension test and forced swimming test, and anxiety-like behaviors were evaluated by the marble-burying test and elevated plus maze test. The expression of Nrf2 was measured by western blotting. Levels of inflammatory mediators (NF-κB, TNF-α, IL-1ß and IL-6) and oxidative stress factors (ROS, MDA, GSH and SOD) were detected by ELISA. The ethanol-induced PC12/BV2 cell injury model was used to elucidate whether the effect of irisin on ethanol-induced neurological injury was related to anti-inflammatory and antioxidant mechanisms. Ethanol-induced ethanol preference and emotional deficits were improved by chronic irisin treatment; however, these improvements were partly reversed by cotreatment with the Nrf2 inhibitor ML385. Further results implied that the improvement effect of irisin on behavioral abnormalities may be related to its anti-inflammatory and antioxidant effects. In detail, irisin inhibited ethanol-induced abnormal expression of ROS and MDA and upregulated the expression of GSH and SOD. Meanwhile, irisin treatment inhibited ethanol-induced overexpression of NF-κB, TNF-α, IL-1ß and IL-6 in the hippocampus and cerebral cortex. The regulation of oxidative stress factors by irisin was reversed after ML385 treatment. In the in vitro study, overexpression of oxidative stress factors in ethanol-treated PC12 cells was inhibited by irisin treatment; however, the prevention was reversed after the knockdown of Nrf2 siRNA. Moreover, ethanol-induced overexpression of inflammatory mediators in BV2 cells was also inhibited by irisin treatment. Irisin improved depressive and anxiety-like behaviors induced by ethanol addiction/withdrawal in mice, and this protection was greatly associated with the NF-κB-mediated anti-inflammatory signaling pathway and Nrf2-mediated antioxidative stress signaling pathway.