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Abstract The aqueous interface-rich system has been proposed to act as a trigger and a reservoir for reactive radicals, playing a crucial role in chemical reactions. Although much is known about the redox reactivity of water microdroplets at “droplets-in-gas” interfaces, it remains poorly understood for “bubbles-in-water” interfaces that are created by feeding gas through the porous membrane of the gas diffusion electrode. Here we reveal the spontaneous generation of highly reactive redox radical species detected by using electron paramagnetic resonance under such conditions without applying any bias and loading any catalysts. In combination with ultraviolet-visible spectroscopy, the redox feature has been further verified through several probe molecules. Unexpectedly, introducing crown ether allows to isolate and stabilize both water radical cations and hydrated electrons thus substantially increasing redox reactivity. Our finding suggests a reactive microenvironment at the interface of the gas diffusion electrode owing to the coexistence of oxidative and reductive species.

Abstract Background Non-suicidal self-injury (NSSI) has exhibited an increasing trend in recent years and is now globally recognized as a major public health problem among adolescents and young adults. Negative life events (NLEs) are positively associated with NSSI. We sought to explore (1) whether sex plays a role in the risk of NLEs leading to NSSI and (2) the role played by mental health (MH). Methods We adopted a multi-stage cluster sampling method to select college students across four grades from May to June 2022. Generalized linear models were used to evaluate the relationships between NLEs, sex, MH and NSSI, presented as incidence-rate ratios (RRs) with 95% confidence intervals (CIs). We examined the complex relationship between these variables using the PROCESS method for moderation analysis. Results Following the exclusion of data that did not meet the study requirements, data from 3,578 students (mean age: 20.53 [± 1.65] years) were included. Poisson regression results indicate that high-level NLEs (RR = 0.110, 95%CI: 0.047–0.173) are associated with increased NSSI. Furthermore, interaction effects were observed among sex, NLEs and NSSI. MH and sex moderated the relationship between NLEs and NSSI. Conclusion Identifying risk factors for NSSI is also important when exploring the interaction between NLEs and MH given the potential for NSSI to significantly increase the risk of later psychopathological symptoms and substance abuse problems. In addition, the significance of sex differences in risk factors for NSSI should be determined. This study evaluated how the impact of NLEs on NSSI can be reduced among adolescents from multiple perspectives.

Abstract Background Artificial light at night (ALAN) is a common phenomenon and contributes to the severe light pollution suffered by more than 80% of the world's population. This study aimed to evaluate the relationship between outdoor ALAN exposure and cardiovascular health (CVH) in patients with diabetes and the influence of various modifiable factors. Methods A survey method based on the China Diabetes and Risk Factor Monitoring System was adopted. Study data were extracted for 1765 individuals with diabetes in Anhui Province. Outdoor ALAN exposure (nW/cm2/sr) within 1000 m of each participant's residential address was obtained from satellite imagery data, with a resolution of ~1000 m. Health risk behaviors (HRBs) were measured via a standardized questionnaire. A linear regression model was employed to estimate the relationship between outdoor ALAN, HRBs, and CVH. Results Participants' mean age was 59.10 ± 10.0 years. An association was observed between ALAN and CVH in patients with diabetes (β = 0.205) and exercise (β = −1.557), moderated by HRBs, or metabolic metrics. There was an association between ALAN, ALAN, vegetable intake, and CVH. Conclusions Exploring the relationship between ALAN exposure and cardiovascular and metabolic health provides policy data for improving light pollution strategies and reducing the risk of cardiovascular and metabolic disease in patients with diabetes.

Background Serum corin has been associated with stroke in observational studies, but the underlying causality is uncertain. This study examined the causal association between corin and stroke through Mendelian randomization study. Methods and Results In the Gusu cohort, serum corin was assayed at baseline, and stroke incidents were prospectively obtained during 10 years of follow‐up. Single‐nucleotide polymorphisms (SNPs) in CORIN were genotyped by MassArray for 2310 participants (mean age, 53 years; 39% men). Seventeen SNPs passed the Hardy–Weinberg test and were considered the potential instruments. Only 1 SNP (rs2271037) determined variability of serum corin was significantly associated with stroke even after adjusting for conventional risk factors (hazard ratio [HR], 1.36 [95% CI, 1.00–1.85]). The weighted genetic risk score generated from the SNP‐corin associations was significantly associated with stroke (HR, 2.01 [95% CI, 1.15–3.51]). Using this genetic risk score as the instrument, 1‐sample Mendelian randomization analysis found a significant HR of stroke per‐SD higher log2‐transformed corin (HR, 1.37 [95% CI, 1.07–1.76]). The inverse variance–weighted analysis based on the SNP‐corin and SNP‐stroke associations found that the HR of stroke pre‐SD higher log2‐transformed corin was 5.92 (95% CI, 2.23–15.72). The effect estimates stayed consistent regardless of an individual SNP being removed from the instruments. An almost identical effect estimate was also confirmed by multiple other 2‐sample Mendelian randomization methods. Conclusions Genetically determined variations of serum corin concentration were significantly associated with the risk of stroke in Chinese adults. Elevated serum corin may be a risk factor for stroke.

Purpose: Osteoporosis is linked to impaired function of osteoblasts, and decreased expression of METTL14 may result in abnormal differentiation of these bone-forming cells. However, the specific impact of METTL14 on osteoblast differentiation and its underlying mechanisms are not yet fully understood. Methods and results: This study discovered a positive correlation between METTL14 expression and bone formation in specimens from osteoporosis patients and ovariectomized (OVX) mice. Additionally, METTL14 targeting of SLC25A3 contributed to the restoration of mitochondrial ROS levels and mitochondrial membrane potential in osteoblasts and promoted osteoblast differentiation. Moreover, in vivo experiments showed that METTL14 enhanced bone formation, and therapeutic introduction of METTL14 countered the decrease in bone formation in OVX mice. Conclusions: Overall, these findings emphasize the crucial role of the METTL14/SLC25A3 signaling axis in osteoblast activity, suggesting that this axis could be a potential target for improving osteoporosis.

Abstract Exhausted CD8+ T lymphocytes and tumor-associated macrophages play critical roles in determining cancer prognosis and the efficacy of immunotherapy. Our study revealed a negative correlation between exhausted CD8+ T lymphocytes and prognosis in thyroid carcinoma (THCA). Consensus clustering divided patients into two subgroups of exhaustion with different prognoses, as defined by marker genes of exhausted CD8+ T cells. Subsequently, we constructed an eight-gene prognostic signature, and developed a risk score named the exhaustion-related gene score (ERGS) to forecast both prognosis and immunotherapy response in THCA. Bulk RNA sequencing analysis revealed a higher prevalence of M2 macrophages, indicative of an immunosuppressive tumor microenvironment (TME), in the high-ERGS group. Single-cell RNA sequencing showed that SPP1+ macrophages and CD14+ monocytes infiltrations were positively associated with higher ERGS. Functionally, it was determined that SPP1+ macrophages exert an immunosuppressive role, while CD14+ monocytes were implicated in promoting tumor progression and angiogenesis. Analysis of cell–cell interactions between SPP1+ macrophages and T cells highlighted the activation of the SPP1-CD44 and MIF-CD74 axes, both of which could foster an immunosuppressive TME. Therapeutic strategies that target SPP1+ macrophages, CD14+ monocytes, and the SPP1-CD44 and MIF-CD74 axes may potentially improve the prognosis and amplify the immunotherapy response in THCA patients.

Abstract The present study aims to assess the treatment outcome of patients with diabetes and tuberculosis (TB-DM) at an early stage using machine learning (ML) based on electronic medical records (EMRs). A total of 429 patients were included at Chongqing Public Health Medical Center. The random-forest-based Boruta algorithm was employed to select the essential variables, and four models with a fivefold cross-validation scheme were used for modeling and model evaluation. Furthermore, we adopted SHapley additive explanations to interpret results from the tree-based model. 9 features out of 69 candidate features were chosen as predictors. Among these predictors, the type of resistance was the most important feature, followed by activated partial throm-boplastic time (APTT), thrombin time (TT), platelet distribution width (PDW), and prothrombin time (PT). All the models we established performed above an AUC 0.7 with good predictive performance. XGBoost, the optimal performing model, predicts the risk of treatment failure in the test set with an AUC 0.9281. This study suggests that machine learning approach (XGBoost) presented in this study identifies patients with TB-DM at higher risk of treatment failure at an early stage based on EMRs. The application of a convenient and economy EMRs based on machine learning provides new insight into TB-DM treatment strategies in low and middle-income countries.

Abstract Diabetic foot ulcer (DFU), a serious complication of diabetes, remains a clinical challenge. MicroRNAs affect inflammation and may have therapeutic value in DFU. Here, we find that an miR-221-3p mimic reduces the inflammatory response and increases skin wound healing rates in a mouse model of diabetes, whereas miR-221-3p knockout produced the opposite result. In human keratinocytes cells, miR-221-3p suppresses the inflammatory response induced by high glucose. The gene encoding DYRK1A is a target of miR-221-3p. High glucose increases the expression of DYRK1A, but silencing DYRK1A expression decreases high glucose–induced inflammatory cytokine release via dephosphorylation of STAT3, a substrate of DYRK1A. Application of miR-221-3p mimic to human keratinocytes cells not only decreases DYRK1A expression but also inhibits high glucose–induced production of inflammatory cytokines to promote wound healing. This molecular mechanism whereby miR-221-3p regulates inflammation through the DYRK1A/STAT3 signaling pathway suggests targets and therapeutic approaches for treating DFU.

BackgroundMitochondrial dysfunction plays a crucial role in Type 2 Diabetes Mellitus (T2DM) and its complications. However, the genetic pathophysiology remains under investigation. Through multi-omics Mendelian Randomization (MR) and colocalization analyses, we identified mitochondrial-related genes causally linked with T2DM and its complications.MethodsSummary-level quantitative trait loci data at methylation, RNA, and protein levels were retrieved from European cohort studies. GWAS summary statistics for T2DM and its complications were collected from the DIAGRAM and FinnGen consortiums, respectively. Summary-data-based MR was utilized to estimate the causal effects. The heterogeneity in dependent instrument test assessed horizontal pleiotropy, while colocalization analysis determined whether genes and diseases share the same causal variant. Enrichment analysis, drug target analysis, and phenome-wide MR were conducted to further explore the biological functions, potential drugs, and causal associations with other diseases.ResultsIntegrating evidence from multi-omics, we identified 18 causal mitochondrial-related genes. Enrichment analysis revealed they were not only related to nutrient metabolisms but also to the processes like mitophagy, autophagy, and apoptosis. Among these genes, Tu translation elongation factor mitochondrial (TUFM), 3-hydroxyisobutyryl-CoA hydrolase (HIBCH), and iron-sulfur cluster assembly 2 (ISCA2) were identified as Tier 1 genes, showing causal links with T2DM and strong colocalization evidence. TUFM and ISCA2 were causally associated with an increased risk of T2DM, while HIBCH showed an inverse causal relationship. The causal associations and colocalization effects for TUFM and HIBCH were validated in specific tissues. TUFM was also found to be a risk factor for microvascular complications in T2DM patients including retinopathy, nephropathy, and neuropathy. Furthermore, drug target analysis and phenome-wide MR underscored their significance as potential therapeutic targets.ConclusionsThis study identified 18 mitochondrial-related genes causally associated with T2DM at multi-omics levels, enhancing the understanding of mitochondrial dysfunction in T2DM and its complications. TUFM, HIBCH, and ISCA2 emerge as potential therapeutic targets for T2DM and its complications.

The protein dynamical transition at ~200 K, where the biomolecule transforms from a harmonic, non-functional form to an anharmonic, functional state, has been thought to be slaved to the thermal activation of dynamics in its surface hydration water. Here, by selectively probing the dynamics of protein and hydration water using elastic neutron scattering and isotopic labeling, we found that the onset of anharmonicity in the two components around 200 K is decoupled. The one in protein is an intrinsic transition, whose characteristic temperature is independent of the instrumental resolution time, but varies with the biomolecular structure and the amount of hydration, while the one of water is merely a resolution effect.

The myostatin (MSTN) gene exhibits significant nucleotide sequence variations in sheep, impacting growth characteristics and muscular traits of the body. However, its influence on specific growth traits in some sheep remains to be further elucidated. This study utilized single nucleotide polymorphism sequence analysis to investigate the role of the MSTN gene in meat production performance across four sheep breeds: Charolais sheep, Australian White sheep, crossbreeds of Australian White and Small-tailed Han, and crossbreeds of Charolais and Small-tailed Han. At a SNP locus of the MSTN gene, the C2361T site was identified, with three genotypes detected: CC, CT, and TT, among which CC predominated. Gene substitution effect analysis revealed that replacing C with T could elevate the phenotypic value. Comparative analysis of data from different genotypes within the same breed highlighted the superiority of CC and TT genotypes in phenotypic values, underscoring the significance of specific genotypes in influencing key traits. Contrasting the performance of different genotypes across breeds, Charolais sheep and Charolais Han hybrids demonstrated superiority across multiple indicators, offering valuable insights for breeding new sheep varieties. Analysis of gender effects on growth characteristics indicated that ewes exhibited significantly wider chest, waist, and hip widths compared to rams, while rams displayed better skeletal growth and muscle development. Additionally, the MSTN gene also exerted certain effects on lamb growth characteristics, with the CC genotype closely associated with weight. These findings not only contribute crucial insights for sheep breeding but also pave the way for future research exploring the interaction of this gene with others.

The milk proteins from samples of 13 different animals were identified utilizing 4D-Label-Free proteomics technology, leading to the identification of a substantial number of proteins. Among the various samples, Chinese people (CHP) milk proteins exhibited the highest count, with 1149 distinct proteins. Simultaneously, we identified common proteins present in these animal milk. It's notable presence in goat milk contributes to enhancing infant infection resistance, showcasing the beneficial role of lactoperoxidase. Galectin-3 binding protein (Gal-3BP) and tetraspanin in human milk are significantly higher than those in other animals, which determine the prominent antiviral effect of human milk and the important processes related to cell transduction. Furthermore, human milk, camel milk, goat milk and sheep milk proved to be rich sources of milk fat globule membrane (MFGM) proteins. The insights obtained from this study can serve as a foundational framework for exploring the role of different animal milk proteins in disease treatment and the composition of infant formula.

Abstract Background Body mass index (BMI) is an important risk factor for hypertension in diabetic patients. However, the underlying mechanisms remain poorly understood. Although liver-derived biological intermediates may play irreplaceable roles in the pathophysiology of diabetes, few studies have explored them in the association between BMI and hypertension in diabetes. Objective To investigate the role of liver enzymes in mediating the relationship between BIM exposure and hypertension in type 2 diabetes mellitus (T2DM). Methods We included a total of 1765 participants from the China National Diabetic Chronic Complications Study Cohort. Associations between liver enzymes and hypertension were estimated using multivariable regression models. The function of liver indicators in the relationship between BMI and hypertension was assessed using mediation analysis. Mediation analysis was conducted, taking into account age, diabetes duration, current smoking, fasting plasma glucose level, glycated hemoglobin, anti-diabetic therapy, and family history of diseases, including diabetes, hypertension, obesity, and hyperlipidemia. Results For men, the association of BMI with hypertension was partially mediated by alanine aminotransferase (ALT), with a proportion of mediation was 68.67%, by aspartate aminotransferase (AST) was 27.02%, and by γ-glutamyltransferase (GGT) was 38.58%, by AST/ALT was 63.35%; for women, the proportion mediated by ALT was 36.93%, and by AST was 37.47%, and GGT was 44.60%, and AST/ALT was 43.73% for BMI (all P

The interaction between protein and water plays a pivotal role in shaping the structure, dynamics, and function of biomacromolecules. A comprehensive understanding of this intricate interplay necessitates a systematic evaluation of interaction strength and its consequential impact on the dynamics of proteins and water across diverse protein systems. Despite numerous works on understanding the dynamics of water and proteins and the coupling between them, there are still unanswered questions. Here, we combine neutron scattering and isotope labeling to probe the dynamics of proteins and their hydration water in a variety of protein systems. We consider proteins of different structures and varying thermostability as well as proteins within living cells with distinct growth temperatures. Simultaneous characterization of protein and hydration water dynamics across diverse systems was achieved. Moreover, we performed water sorption isothermal measurements on three representative proteins to correlate the observed dynamics with the strength of the interaction energies governing each system. The experimental results underscore that proteins manifesting stronger attractive interactions with water display diffusionlike dynamics with higher flexibility upon hydration, concomitant with a reduced mobility in hydration water. Significantly, our findings suggest that, in fact, it is the interaction between protein and its hydration water that facilitates the transfer of mobility from water to protein, with stronger interactions correlating to greater protein flexibility and slower hydration water diffusion.

Objectives: This study analyzed the synergistic development of the Traditional Chinese Medicine (TCM) service trade within the Greater Bay Area (GBA) in China, aiming to provide suggestions and references for the development of TCM service trade around the world. Methods: Taking the typical and representative Guangdong, Hong Kong and Macao Greater Bay Area as the research object, this paper focused on four modes of “cross-border supply, offshore consumption, commercial presence, and movement of natural persons”, and explored the current situation of TCM service trade from four macroscopic aspects: political, economic, social, and technological, through case studies. The challenges in the development of TCM service trade were analyzed. Results: Our study found that the degree of synergistic openness of Guangdong, Hong Kong and Macao needs to be improved. The integration of trade in TCM services is the integration of TCM services with tourism. However, there is a relative lack of human resources in TCM in Hong Kong and Macao, with weak competitiveness of service bases. The resources of TCM services are still under-utilized, and the GBA market of TCM services lacks momentum. Conclusions: We have come to the conclusion that the GBA need to promptly improve the unified standard system of TCM service trade. Actively building cultivating a “Bay Area GBA brand” for TCM service trade, steadily building a social climate in support of TCM service trade and vigorously promote the development of TCM service trade through digital technology, thus promoting the synergistic development of TCM service trade within the GBA.

Abstract Background Numerous factors influence the growth and development of cashmere. Existing research on cashmere has predominantly emphasized a single omics level. Integrating multi-omics analyses can offer a more comprehensive understanding by encompassing the entire spectrum. This study more accurately and comprehensively identified the key factors influencing cashmere fineness using multi-omics analysis. Methods This study used skin tissues of coarse cashmere type (CT_LCG) and fine cashmere type Liaoning cashmere goats (FT_LCG) for the analysis. This study employed an integrated approach involving transcriptomics, translatomics, proteomics, and metabolomics to identify substances associated with cashmere fineness. The findings were validated using parallel reaction monitoring (PRM) and multiple reaction monitoring (MRM) techniques. Results The GO functional enrichment analysis identified three common terms: multicellular organismal process, immune system process, and extracellular region. Furthermore, the KEGG enrichment analysis uncovered the involvement of the arachidonic acid metabolic pathway. Protein expression trends were verified using PRM technology. The expression trends of KRT79, as confirmed by PRM, were consistent with those observed in TMT proteomics and exhibited a positive regulatory effect on cashmere fineness. Metabolite expression trends were confirmed using MRM technology. The expression trends of 9 out of 15 validated metabolites were in agreement with those identified in the non-targeted metabolomics analysis. Conclusions This study employed multi-omics analysis to identify key regulators of cashmere fineness, including PLA2G12A, KRT79, and prostaglandin B2. The findings of this study offer valuable data and establish a theoretical foundation for conducting comprehensive investigations into the molecular regulatory mechanisms and functional aspects of cashmere fineness.

Abstract Objectives Depression among adolescents is a global concern. Adverse childhood experiences (ACEs) have been correlated with negative physical and mental health such as obesity and depression; however, increasing evidence has suggested that their correlation might be moderated by BMI and resilience. In this study, we aim to explore (1) whether resilience moderate the risk of mental health by ACEs; (2) whether BMI is a moderator of this relationship. Study Design Adolescents were obtained from 4 grade college students by a multi-stage convenience sampling method in the period of May to Jun, 2022. Methods We use the Connor-Davidson Resilience scale, Depression, Anxiety and Stress Scale-21 Item (DASS-21) questionnaires to measure the ACEs, BMI, resilience and mental health. The primary exposure was ACEs and the primary outcome was mental health; while resilience and BMI were moderators. Multivariable linear regression model was used to establish the relationship of ACEs, resilience and BMI against mental health status. Moderate analysis was employed by PROCESS method to explore the relationship between these variables. Results A total of 3600 individuals were initially enrolled, after excluding 22 with invalid questionnaires, 3578 adolescents were finally included. The mean age was (20.53 ± 1.65) years old. After adjusted for covariates, multivariable linear regression suggest that the high level ACEs (, β =0.58, , 95%CI:0.54,0.62, P

BackgroundObservational studies show that liver enzymes are diabetes risk factors. However, previous observational investigations on the relationship between liver enzymes and diabetic microvascular complications produced contradictory results. The purpose of this research is to examine the independent causal effects of liver enzymes on diabetic microvascular complications.MethodsUnivariable Mendelian randomization (UVMR) and multivariable Mendelian randomization (MVMR) were utilized to disentangle the causal effects. The genome-wide association study (GWAS) summary-level statistics were collected from the UK biobank and the FinnGen consortium. Single nucleotide polymorphisms (SNPs) were selected as genetic instruments with genome-wide significance (p < 5 ×10-8). Five UVMR approaches, including inverse variance weighted (IVW), Bayesian weighted Mendelian randomization, MR-Pleiotropy Residual Sum and Outlier (MR-PRESSO), weighted median, and MR-Egger, and three MVMR approaches, including the extended versions of IVW, MR-Egger, and the Q-minimization methods, were performed to evaluate the causal effects. The robustness of the MR results was further confirmed using several sensitivity analyses.ResultsUVMR revealed that a genetically predisposed per standard deviation increase in serum alanine aminotransferase (ALT) level increased the risk of diabetic retinopathy (DR) in type 2 diabetes mellitus (T2DM) (IVW OR = 1.489, 95% CI = 1.206-1.772, p = 0.006). Likewise, serum aspartate aminotransferase (AST) levels showed similar results (IVW OR = 1.376, 95% CI = 1.115-1.638, p = 0.017). Furthermore, these effects were consistent after controlling for glycemia and blood pressure using MVMR analysis. Additionally, sensitivity analyses further strengthened the causality. However, no significant associations were found between alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), and diabetic microvascular complications.ConclusionsRobust evidence was demonstrated for an independent causal effect of serum ALT or AST concentration on the risk of DR in T2DM. Further investigations are necessary to elucidate the potential biological mechanisms and confirm their clinical significance for early prevention and intervention.

Developing cost-effective and reliable solid-state sodium batteries with superior performance is crucial for stationary energy storage. A key component in facilitating their application is a solid-state electrolyte with high conductivity and stability. Herein, we employed aliovalent cation substitution to enhance ionic conductivity while preserving the crystal structure. Optimized substitution of Y3+ with Zr4+ in Na5YSi4O12 introduced Na+ ​ion vacancies, resulting in high bulk and total conductivities of up to 6.5 and 3.3 ​mS ​cm−1, respectively, at room temperature with the composition Na4.92Y0.92Zr0.08Si4O12 (NYZS). NYZS shows exceptional electrochemical stability (up to 10 ​V vs. Na+/Na), favorable interfacial compatibility with Na, and an excellent critical current density of 2.4 ​mA ​cm−2. The enhanced conductivity of Na+ ​ions in NYZS was elucidated using solid-state nuclear magnetic resonance techniques and theoretical simulations, revealing two migration routes facilitated by the synergistic effect of increased Na+ ​ion vacancies and improved chemical environment due to Zr4+ substitution. NYZS extends the list of suitable solid-state electrolytes and enables the facile synthesis of stable, low-cost Na+ ion silicate electrolytes.

Lipids are essential organic components in milk and have been associated with various health benefits for newborns. However, a comprehensive analysis of lipid profiles across multiple species and levels has been lacking. In this study, we employed liquid chromatography-tandem mass spectrometry (LC-MS/MS) to accurately determine the absolute content of lipid molecules. It revealed that ruminants exhibit a higher concentration of short-chain fatty acids compared to non-ruminants. Additionally, we identified ALC (camel), MGH (horse), and DZD (donkey) as species that display similarities to components found in human milk fat. Remarkably, it reveals that porcine milk fat is characterized by long chain lengths, low saturation, and a high proportion of essential fatty acids. PS (22:5_18:2) could potentially serve as a biomarker in porcine milk. These unique characteristics present potential opportunities for the utilization of porcine milk. Overall, our findings provide valuable insights into the lipidomics profiles of milk from different species.

The development of direct-acting antivirals to combat COVID-19 remains an important goal. Here the authors design covalent inhibitors that target the papain-like protease from SARS-CoV-2. The most promising inhibitor blocks viral replication in mammalian cells.

Breast milk plays a crucial role in the taste development of infants, which cannot be replicated by other mammalian milk or formulas. This study aimed to identify and characterize the flavor substances in 15 different types of milk and analyze the differences among them. The results showed that human milk contained high levels of esters, particularly fatty acid ethyl esters, which contribute to its unique flavor. The four substances that had the highest flavor contribution in all species were identified as 2,3-butanedione, trimethylamine, isophorone, and acetaldehyde. Furthermore, the analysis of differences revealed that thermal-oxidation of lipids could explain the variation between human milk and other species in terms of flavor compounds. The key differential flavor compounds identified in milk from all species were trimethylamine, propanal, 1-pentanol, pyridine 2-methyl, and 2-butanone. These findings can potentially aid in developing formulas that better meet the taste needs of infants.

Immobilization of biomolecules into porous materials could lead to enhanced performance in terms of stability and easier separation for their reuse. Here authors gain insights into the spatial arrangement of green fluorescent protein entrapped in a mesoporous MOF by situ small-angle neutron scattering.

Abstract Background Osteoporosis (OP) and diabetes mellitus (DM) are two major healthcare issues in the world. Numerous population based-studies have reported an increased prevalence of OP among individuals with DM, though, estimates vary significantly. Purpose The objective of this study is to estimate the prevalence of OP in patients with DM. Methods To identify relevant literature, PubMed, Embase, Medline, CBM and Cochrane Library were searched for studies published from inception till July 2022, The search was conducted, and studies were included without countries and language restrictions. For full-text articles included in the study, the references were also independently searched. Random inverse variance-weighted models were used by Stata version 17.0 to estimate the prevalence of OP in patients with diabetes across studies. The heterogeneity was examined with I2 via the χ2 test on Cochrane’s Q statistic. Subgroup analysis and meta-regression were used to explore potential sources of heterogeneity. Egger’s test was used to assess publication bias. Results A high OP prevalence of 27.67% (95% confidence interval (CI) 21.37-33.98%) was found in a pooled analysis of 21 studies involving 11,603 T2DM patients. Methodological value of the included articles was high, with only three medium-quality studies and no low-quality studies. A significantly high heterogeneity (I2 = 98.5%) was observed. Conclusions Worldwide, a high prevalence of OP was found in patients with T2DM. Therefore, strong measures to prevent and treat osteoporosis in diabetic patients are required. Trial registration This study has been registered on PROSPERO, number CRD42021286580 .

We aimed to determine the role of thyroid-stimulating hormone (TSH) of postmenopausal type 2 diabetes mellitus (T2DM) women with normal thyroid function in identifying ultrasound-diagnosed nonalcoholic fatty liver disease (NAFLD). The association between ultrasound-diagnosed NAFLD and biochemical parameters of 376 patients was analyzed among overall patients and in different age groups (≤60 years; 60–70 years; >70 years). The receiver operating characteristic curve (ROC) was used to analyze the diagnostic ability of TSH for ultrasound-diagnosed NAFLD. The prevalence of ultrasound-diagnosed NAFLD in postmenopausal T2DM women was 44.1%. Multivariate logistic regression analysis showed that the levels of BMI (OR = 0.843, 95%CI: 0.779–0.913), HbA1c (OR = 0.836, 95%CI: 0.738–0.946), TG (OR = 0.539, 95%CI: 0.408–0.712), ALT (OR = 0.979, 95%CI: 0.962–0.995) were independent risk factors of NAFLD. BMI and TG were related to the NFALD risk of patients in the three age groups. HOMA-IR and HbA1c were independent risk factors of NAFLD among patients aged ≤60 years and 60–70 years, respectively. The TSH with the best diagnostic ability was among ≤60 years old patients (sensitivity = 0.486; specificity = 0.730). Higher BMI, abnormal glucose and lipid metabolism had a higher risk for developing NFALD, and TSH diagnosis is more meaningful in relatively young patients.

ObjectiveOur aim was to evaluate the association between midday napping, combined sleep quality, and insulin resistance surrogates and the risk of hypertension in patients with type 2 diabetes mellitus (T2DM).MethodsData were collected using a standardized questionnaire. Binary logistic regression was performed to estimate the odds ratio (OR) and 95% confidence interval (CI) for the risk of hypertension. Systolic and diastolic blood pressure were grouped as categorical variables and unpaired two-sided Student’s t-test and Spearman correlation analysis were performed to estimate the association between different blood pressure levels and insulin resistance surrogates.ResultsThe overall prevalence rate of hypertension was 50%. Age (OR = 1.056, 95% CI:1.044–1.068), poor sleep quality (OR = 1.959, 95% CI:1.393–2.755), hyperlipidemia (OR = 1.821, 95% CI:1.462–2.369), family history of hypertension (OR = 2.811, 95% CI:2.261–3.495), and obesity (OR = 5.515, 95% CI:1.384–21.971) were significantly associated with an increased risk of hypertension. Midday napping for 1–30 min was negatively correlated with the risk of hypertension (OR = 0.534, 95% CI:0.305–0.936, P

Background: Evidence demonstrated that vitamin D insufficiency was involved in insulin resistance (IR) pathogenesis and associated with tuberculosis. However, the association of vitamin D and IR in patients with latent tuberculosis infection (LTBI) remains unclear. This study aims to evaluate the association between vitamin D and insulin resistance in US adults with LTBI. Method: National Health and Nutrition Examination Survey (NHANES) participants ≥ 20 years during the years 2011–2012 with positive QuantiFERON®-TB Gold-In-Tube (QFT) or tuberculin skin testing (TST) were enrolled in present study. Participants with LTBI were divided into 2 groups: (1) vitamin D insufficiency group (n = 267), and (2) vitamin D sufficiency group (n = 437). Results: Weighted analysis of all the population in the study showed that serum 25(OH)D inversely correlated with HOMA-IR (r = −0.14, P = 0.008). The vitamin D insufficiency group had higher fasting insulin (17.5 (1.38) vs. 15.29 (3.1), respectively, P = 0.0013) and HOMA-IR (5.0 (0.4) vs. 4.5 (1), respectively, P = 0.013) than the vitamin D sufficiency group. In adjusted analysis, vitamin D levels was independently associated with insulin resistance (adjusted OR [aOR] 2.74; 95% CI, 1.01–7.48, p = 0.0489). Conclusions: Taken together, our study suggested that serum 25(OH) D concentrations were inversely and independently associated with HOMA-IR in LTBI.

Conventional exploding foil initiator (EFI) in ignition or detonation applications hosts many performance advantages, but was hindered by the bulky, inaccurate, inefficient and expensive shortcomings. We highlight a novel micro-chip exploding foil initiator (McEFI) using printed circuit board (PCB) technology. The structural parameters were determined based on energy coupling relationship at the component interfaces. Next, the prototype McEFI has been batch-fabricated using PCB technology, with a monolithic structure of 7.0 mm (l) × 4.5 mm (w) × 4.0 mm (δ). As expected, this PCB-McEFI illustrated the successful firing validations for explosives pellets. This paper has addressed the cost problem in both military munitions and civil markets wherever reliable, insensitive and timing-dependent ignition or detonation are involved.

Abstract Background Diabetes is a global concern among adults. Previous studies have suggested an association between different screening methods and diabetes; however, increasing evidence has suggested the importance of early screening for diabetes mellitus (DM) and its influencing factors. In this study, we aimed to explore whether the non-invasive detection of advanced glycation end products (AGEs) in the early screening of DM in the Chinese community and whether body mass index (BMI) and metabolic indexes could moderate this relationship. Methods Three community health service centers in Hefei that signed the medical consortium agreement with the First Affiliated Hospital of Anhui Medical University were selected to screen the population aged 30–90 years in each community using a multi-stage cluster sampling method from January 2018 to January 2019. Univariate analysis of variance was used to compare the differences in general data, biochemical indexes, skin AGEs levels, and blood glucose among groups. In addition, a multivariable logistic regression analysis was performed. Results A total of 912 patients with a community health physical examination and no history of diabetes were selected, excluding those with missing values > 5%. Finally, 906 samples were included in the study with an effective rate of 99.3%. The prevalence in the normal, impaired glucose tolerance, and DM groups were 79.8%, 10.0%, and 10.2%, respectively. By dividing AGE by quartile, AGE accumulation was classified as ≤ P25, P25–P50, P50–P75, and > P75. Higher AGE accumulation (χ 2 = 37.95), BMI (χ 2 = 12.20), systolic blood pressure (SBP) (χ 2 = 8.46), triglyceride (TG) (χ 2 = 6.23), and older age (χ 2 = 20.11) were more likely to have a higher prevalence of fasting blood glucose (FBG). The analyses revealed significant correlations between AGE accumulation, BMI, TG, total cholesterol (TC), and FBG (P

Abstract Background DUAL I China, one of the DUAL trials, assessed efficacy/safety of insulin degludec/liraglutide (IDegLira) in Chinese adults with type 2 diabetes (T2D) not controlled by oral antidiabetic drugs (OADs). Methods This phase 3a, treat‐to‐target multicenter trial randomized participants (glycated hemoglobin [HbA1c] 53.0‐85.8 mmol/mol; previous metformin ± another OAD) 2:1:1 to IDegLira (n = 361), degludec (n = 179), or liraglutide (n = 180). Primary endpoint was change in HbA1c after 26 weeks. Secondary endpoints included: HbA1c

BackgroundThe purpose of the study was to evaluate characteristics and risk of cardiovascular disease (CVD) according to age at diagnosis and disease duration among adults with diabetes mellitus (DM).MethodsThe association between age at diagnosis, diabetes duration and CVD were examined in 1,765 patients with DM. High risk of estimated ten-year atherosclerotic cardiovascular disease (ASCVD) was performed by the Prediction for ASCVD Risk in China (China-PAR) project. Data were compared with analysis of variance and χ2 test, respectively. Multiple logistic regression was used to determine the risk factors of CVD.ResultsThe mean age at diagnosis (± standard deviation) was 52.91 ± 10.25 years and diabetes duration was 8.06 ± 5.66 years. Subjects were divided into early-onset DM group (≤43 years), late-onset DM group (44 to 59 years), elderly-onset DM group (≥60 years) according to age at diagnosis. Diabetes duration was classified by 5 years. Both early-onset and longest diabetes duration (>15 years) had prominent hyperglycaemia. Diabetes duration was associated with the risk of ischemic stroke (odds ratio (OR), 1.091) and coronary artery disease (OR, 1.080). Early-onset group (OR, 2.323), and late-onset group (OR, 5.199), and hypertension (OR, 2.729) were associated with the risk of ischemic stroke. Late-onset group (OR, 5.001), disease duration (OR, 1.080), and hypertension (OR, 2.015) and hyperlipidemia (OR, 1.527) might increase the risk of coronary artery disease. Aged over 65 (OR, 10.192), central obesity (OR, 1.992), hypertension (OR, 18.816), cardiovascular drugs (OR, 5.184), antihypertensive drugs (OR, 2.780), and participants with disease duration >15 years (OR, 1.976) were associated with the high risk of estimated ten-year ASCVD in participants with DM.ConclusionAge at diagnosis, diabetes duration, hypertension and hyperlipidemia were independent risks of CVD. Longest (>15 years) diabetes duration increased the high risk of ten-year ASCVD prediction among Chinese patients with DM. It’s urgent to emphasize the importance of age at diagnosis and diabetes duration to improve primary complication of diabetes.

BackgroundAutoimmune thyroid disease (AITD) is induced by various factors, including inheritability, which regulates gene expression. Multiple loci correlated with AITD have been discovered utilizing genome-wide association studies (GWASs). Nevertheless, demonstrating the biological relevance and function of these genetic loci is difficult.MethodsThe FUSION software was utilized to define genes that were expressed differentially in AITD using a transcriptome-wide association study (TWAS) method in accordance with GWAS summary statistics from the largest genome-wide association study of 755,406 AITD individuals (30,234 cases and 725,172 controls) and levels of gene expression from two tissue datasets (blood and thyroid). Further analyses were performed such as colocalization, conditional, and fine-mapping analyses to extensively characterize the identified associations, using functional mapping and annotation (FUMA) to conduct functional annotation of the summary statistics of 23329 significant risk SNPs (P < 5 × 10−8) recognized by GWAS, together with summary-data-based mendelian randomization (SMR) for identifying functionally related genes at the loci in GWAS.ResultsThere were 330 genes with transcriptome-wide significant differences between cases and controls, and the majority of these genes were new. 9 of the 94 unique significant genes had strong, colocalized, and potentially causal correlations with AITD. Such strong associations included CD247, TPO, KIAA1524, PDE8B, BACH2, FYN, FOXK1, NKX2-3, and SPATA13. Subsequently, applying the FUMA approach, novel putative AITD susceptibility genes and involved gene sets were detected. Furthermore, we detected 95 probes that showed strong pleiotropic association with AITD through SMR analysis, such as CYP21A2, TPO, BRD7, and FCRL3. Lastly, we selected 26 genes by integrating the result of TWAS, FUMA, and SMR analysis. A phenome-wide association study (pheWAS) was then carried out to determine the risk of other related or co-morbid phenotypes for AITD-related genes.ConclusionsThe current work provides further insight into widespread changes in AITD at the transcriptomic level, as well as characterized the genetic component of gene expression in AITD by validating identified genes, establishing new correlations, and uncovering novel susceptibility genes. Our findings indicate that the genetic component of gene expression plays a significant part in AITD.

ObjectiveAs the physical activator of natriuretic peptides, corin has been associated with stroke, but the underlying mechanism is not very clear. Here, we examined whether the CORIN promoter’s methylation, an epigenetic DNA modification, was associated with the risk of stroke in two independent samples.MethodsA total of 1771 participants including 853 stroke cases and 918 healthy controls were included as a discovery sample and 2,498 community members with 10 years of follow-up were included as a replication sample. DNA methylation of the CORIN promoter was quantified by target bisulfite sequencing in both samples. We first examined the single CpG association, followed by a gene-based analysis of the joint association between multiple CpG methylation and stroke, adjusting for conventional risk factors.ResultsThe single CpG association analysis found that hypermethylation at all of the 9 CpG sites assayed was significantly associated with lower odds of prevalent stroke in the discovery sample (all p

BackgroundUsing bibliometric method to analyze the research status and development trend of extracorporeal membrane oxygenation (ECMO), we aim to provide clinicians, scientists, and stakeholders with the most up-to-date and comprehensive overview of ECMO research.Materials and methodsUsing Excel and VOSviewer, the literature on ECMO was systematically analyzed regarding publication trends, journal source, foundation, countries, institutions, core authors, research hotspots, and market distribution.ResultsThere were five important time nodes in the research process of ECMO, including the success of the first ECMO operation, the establishment of ELSO, and the outbreak of influenza A/H1N1 and COVID-19. The R&D centers of ECMO were the United States, Germany, Japan, and Italy, and the attention to ECMO was gradually increasing in China. The products most used in the literature were from Maquet, Medtronic, and LivaNova. Medicine enterprises attached great importance to the funding of ECMO research. In recent years, the literature has mainly focused on the following aspects: the treatment of ARDS, the prevention of coagulation system-related complications, the application in neonatal and pediatric patients, mechanical circulatory support for cardiogenic shock, and ECPR and ECMO during the COVID-19 pandemic.ConclusionThe frequent epidemic occurrence of viral pneumonia and the technical advancement of ECMO in recent years have caused an increase in clinical applications. The hot spots of ECMO research are shown in the treatment of ARDS, mechanical circulatory support for cardiogenic shock, and the application during the COVID-19 pandemic.

Mature milk, as a nutrient-rich endogenous metabolite, has various beneficial effects on the human body. In order to investigate the specific nutrients provided by different dairy products to humans, we used UHPLC-Q-TOF MS to analyze the highly significantly differentially expressed metabolites in 13 species of mammalian mature milk, which were grouped into 17 major metabolite classes with 1992 metabolites based on chemical classification. KEGG shows that 5 pathways in which differentially significant metabolites are actively involved are ABC transporters, Purine metabolism, Pyrimidine metabolism, Phosphotransferase system, Galactose metabolism. The study found that pig milk and goat milk are closer to human milk and contain more nutrients that are beneficial to human health, followed by camel milk and cow milk. In the context of dairy production, the development of goat milk is more likely to meet human needs and health.

Three covalent hybrid inhibitors of SARS-CoV-2 main protease (Mpro) have been designed and compared to Pfizer’s nirmatrelvir (PF-07321332), providing atomic and thermodynamic details of their binding to the enzyme, and antiviral potency.

Objective. We aim to evaluate the impact of diabetes management shared care clinic (DMSCC) on glycated hemoglobin A1c (HbA1c) compliance and self-management abilities in patients with type 2 diabetes mellitus (T2DM). Methods. This study was a prospective cohort study of patients with T2DM participating in the DMSCC. At baseline and after management, the HbA1c levels were measured, the HbA1c compliance rate were calculated, and the Summary of Diabetes Self-Care Activities-6 (SDSCA-6), Diabetes Empowerment Scale-DAWN Short Form (DES-DSF), and Problem Areas in Diabetes Scale—Five-item Short Form (PAID-5) were completed. These pre- and post-management data were compared. Results. A total of 124 eligible patients were enrolled. After the diabetes management of DMSCC, the average HbA1c decreased and the HbA1c compliance rate increased significantly (P

BackgroundCardiovascular disease (CVD) has become a major cause of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). Although there is also evidence that multifactorial interventions to control blood glucose, blood pressure, and lipid profiles can reduce macrovascular complications and mortality in patients with T2DM, the link between these risk factors has not been established.MethodsOn 10 December 2018, 1,920 people in four cities in Anhui Province were included. Latent category analysis (LCA) was used to explore the clustering mode of HRBs (health risk behaviors). The primary exposure was HRBs and exercise and diet interventions, and the primary outcome was CVD and other variables, including zMS, triglyceride-glucose index (TyG), TyG-WC (waist circumference), TyG-BMI, TG/HDL, and cardiovascular health (CVH). A multivariable logistic regression model was used to establish the relationship between HRBs, exercise, diet interventions, and CVD. Moderate analysis and mediation moderation analysis were employed by the PROCESS method to explore the relationship between these variables. Sensitivity analysis explored the robustness of the model.ResultsThe mean age was 57.10 ± 10.0 years old. Overall, CVD affects approximately 19.9% of all persons with T2DM. Macrovascular complications of T2DM include coronary heart disease, myocardial infarction (MI), cardiac insufficiency, and cerebrovascular disease. Elderly age (χ2 = 22.70), no occupation (χ2 = 20.97), medium and high socioeconomic status (SES) (χ2 = 19.92), higher level of TyG-WC (χ2 = 6.60), and higher zMS (χ2 = 7.59) were correlated with high CVD. Many metabolic indices have shown a connection with T2DM combined with CVD, and there was a dose−response relationship between HRB co-occurrence and clustering of HRBs and zMS; there was a dose−response relationship between multifactorial intervention and CVH. In the mediation moderation analysis, there was an association between HRB, gender, TyG, TyG-BMI, and CVD. From an intervention management perspective, exercise and no diet intervention were more significant with CVD; moreover, there was an association between intervention management, gender, zMS, TyG-WC, TyG-BMI, TG/HDL, and CVD. Finally, there was an association between sex, CVH, and CVD. Sensitivity analysis demonstrated that our results were robust.ConclusionsCVD is one of the common complications in patients with type 2 diabetes, and its long-term outcome will have more or less impact on patients. Our findings suggest the potential benefits of scaling up multifactorial and multifaceted interventions to prevent CVD in patients with T2DM.

BackgroundDiabetes and obesity in adults are global issues. Obesity and type 2 diabetes mellitus (T2DM) are increasingly categorized under the umbrella term “diabesity.” Health risk factors (HRFs), which include altering sleep habits and reducing sugar-sweetened beverages (SSBs) consumption, have emerged as relatively novel and crucial strategies for preventing and treating diabetes.ObjectiveWe aimed to explore: 1) whether SSBs could affect diabesity in China’s community; 2) whether HRFs could moderate this relationship; and 3) whether a three-way interaction exists between HRFs, SSBs, and diabesity.MethodsOn December 10, 2018, we investigated diabetes complications in four cities in Anhui Province and obtained basic and lifestyle information using a detailed questionnaire. The primary exposure was SSBs and outcomes were body mass index (BMI) and waist circumference (WC), while glycated hemoglobin (HbA1c) and sleep patterns (including duration and disorders) were considered moderators.ResultsOverall, 1920 participants were enrolled, and those who did not complete the questionnaire were excluded. Finally, this study included 1765 participants, with a response rate of 92.0%. The mean age was (57.10 ± 10.0) years. Patients with lower educational levels were more likely to have a lower prevalence of WC (χ2 = 2.73) and BMI (χ2 = 3.47), and some HRFs were positively correlated with WC and BMI. Additionally, SSBs were significantly associated with BMI (β = 1.29) and WC (β = 2.97), and there was also differences based on sex, some HRFs, such as HbA1c, FBG and TG, showed higher levels in male participants, whereas TC level was higher in female participants. In the moderation analysis, sleep patterns were also associated with total cholesterol, triglyceride, and BMI. Furthermore, there were three-way interaction effects among HbA1c, sleep patterns, and SSBs on total cholesterol, triglyceride, BMI, and WC. Moreover, sensitivity analysis demonstrated that our results were robust.ConclusionSSBs positively correlated with patterns dose-dependently. Moreover, SSBs could also be associated with sleep patterns, and blood glucose levels were correlated with diabesity. A three-way interaction effect was discovered between SSBs, sleep patterns, blood glucose levels, and patterns. Therefore, understanding the diabesity caused by SSBs and other HRFs can help prevent its occurrence.

SARS-CoV-2 emerged at the end of 2019 to cause an unprecedented pandemic of the deadly respiratory disease COVID-19 that continues to date. The viral main protease (Mpro) is essential for SARS-CoV-2 replication and is therefore an important drug target. Understanding the catalytic mechanism of Mpro, a cysteine protease with a catalytic site comprising the noncanonical Cys145–His41 dyad, can help in guiding drug design. Here, a 2.0 Å resolution room-temperature X-ray crystal structure is reported of a Michaelis-like complex of Mpro harboring a single inactivating mutation C145A bound to the octapeptide Ac-SAVLQSGF-CONH2 corresponding to the nsp4/nsp5 autocleavage site. The peptide substrate is unambiguously defined in subsites S5 to S3′ by strong electron density. Superposition of the Michaelis-like complex with the neutron structure of substrate-free Mpro demonstrates that the catalytic site is inherently pre-organized for catalysis prior to substrate binding. Induced fit to the substrate is driven by P1 Gln binding in the predetermined subsite S1 and rearrangement of subsite S2 to accommodate P2 Leu. The Michaelis-like complex structure is ideal for in silico modeling of the SARS-CoV-2 Mpro catalytic mechanism.

Triggered spark-gap switch is a popular discharge switch for pulse power systems. Previous studies have focused on planarizing this switch using thin film techniques in order to meet the requirements of compact size in the systems. Such switches are one-shot due to electrodes being too thin to sufficiently resist spark-erosion. Additionally, these switches did not employ any structures in securing internal gas composition, resulting in inconsistent performance under harsh atmospheres. In this work, a novel planar triggered spark-gap switch (PTS) with a hermetically sealed cavity was batched-prepared with printed circuit board (PCB) technology, to achieve reusability with low cost. The proposed PTS was inspected by micro-computed tomography to ensure PCB techniques meet the requirements of machining precision. The results from electrical experiments demonstrated that PCB PTS were consistent and reusable with lifespan over 20 times. The calculated switch voltage and circuit current were consistent with those derived from real-world measurements. Finally, PCB PTS was used to introduce hexanitrostilbene (HNS) pellets in a pulse power system to verify its performance.

Abstract Background Diabetes mellitus (DM) causes excess risk of fracture at varied sites. Whereas, the difference between the roles of types 1 DM (T1DM) and 2 DM (T2DM) diabetes in the risk of fractures remains limited and inconclusive. We, therefore, conducted a meta-analysis to assess the differences for the associations of T1DM and T2DM with the risk of fractures. Methods We systematically searched PubMed, Embase, and the Cochrane library for eligible studies until May 2021. The odds ratios (ORs) with 95% confidence intervals (CIs) were used to calculate the pooled effect estimates for the associations of T1DM and T2DM with the risk of fractures using the random-effects model. An indirect comparison results for the ratio of OR (ROR) with 95% CI were also applied to assess the difference between T1DM and T2DM with the risk of fractures. Results Twenty-two cohort studies involving a total of 6,484,851 individuals were selected for meta-analysis. We noted that T1DM was associated with an increased risk of all fractures (OR: 1.72; 95% CI 1.36–2.19; P

ObjectiveThe aim of this study was to study the relationship between modified dietary inflammatory index (MDII) score with osteoporosis (OP) in adult Americans.MethodsData were extracted from the United States National Health and Nutrition Examination Survey (NHANES) (2007–2008, 2009–2010, 2013–2014, and 2017–2018). In this cross-sectional study, 5,446 participants were included and analyzed. Potential dietary inflammatory was assessed by MDII score (24-h recall), a composite method computed according to the relationship between nutrients and systemic pro-inflammatory cytokine level, and was further classified into tertiles. Weighted multivariable logistic regression analysis was employed to examine the associations between OP and MDII scores.ResultsIn weighted multivariable-adjusted logistic regression models, the highest tertile of MDII score was associated with an increased risk of OP [odds ratio (OR): 1.73, 95% confidence interval (95 CI%): 1.14–2.63]. In participants aged above 59 years, a higher MDII score showed a higher risk of OP (OR: 1.92; 95 CI%: 1.16–3.15). In the sex-stratified models, the results remained significant only among women (OR: 1.80; 95% CI: 1.02–3.17). In the menopausal status stratified model, after adjusting potential confounding variables, the association between the MDII score, either as a categorical (OR: 1.88; 95% CI: 1.07–3.13) or continuous variables (OR: 1.19; 95%CI: 1.02–1.38), and OP risk was significant among postmenopausal women.ConclusionOur study indicates that a higher MDII score (pro-inflammatory effect) is significantly associated with an increased risk of OP in US adults, especially among those postmenopausal women more than 60 years. This study further supports that those dietary changes have the potential to prevent OP.

Thyroid cancer (TC) is the leading cause and mortality of endocrine malignancies worldwide. Tumourigenesis involves multiple molecules including circular RNAs (circRNAs). circRNAs with covalently closed single-stranded structures have been identified as a type of regulatory RNA because of their high stability, abundance, and tissue/developmental stage-specific expression. Accumulating evidence has demonstrated that various circRNAs are aberrantly expressed in thyroid tissues, cells, exosomes, and body fluids in patients with TC. CircRNAs have been identified as either oncogenic or tumour suppressor roles in regulating tumourigenesis, tumour metabolism, metastasis, ferroptosis, and chemoradiation resistance in TC. Importantly, circRNAs exert pivotal effects on TC through various mechanisms, including acting as miRNA sponges or decoys, interacting with RNA-binding proteins, and translating functional peptides. Recent studies have suggested that many different circRNAs are associated with certain clinicopathological features, implying that the altered expression of circRNAs may be characteristic of TC. The purpose of this review is to provide an overview of recent advances on the dysregulation, functions, molecular mechanisms and potential clinical applications of circRNAs in TC. This review also aimes to improve our understanding of the functions of circRNAs in the initiation and progression of cancer, and to discuss the future perspectives on strategies targeting circRNAs in TC.

Researchers pursuing the development of third-generation solar cells, which typically include quantum dot-sensitized solar cells (QDSSCs), dye-sensitized solar cells (DSSCs), perovskite solar cells (PSCs), and organic solar cells (OSCs), continue to prioritize low cost, simple preparation, high efficiency, and stability. Polyoxometalates (POMs) are a class of inorganic anionic metallic oxygen cluster compounds with abundant charge, skeleton structure, and excellent physical and chemical properties, such as strong electron acceptability, adjustable energy band structure, and reversible multi-electron redox properties. They are also inexpensive and environmentally friendly. Owing to these exceptional characteristics, POMs are used as building blocks for synthesizing other nanomaterials. Notably, leveraging the extraordinary characteristics of POMs to reduce costs and improve the efficiency and stability of solar cells is an effective strategy for addressing the current energy crisis. In this review, we summarize the research progress of various POM molecules and their derived POM-based nanomaterials in enhancing the performance of third-generation solar cells. Promising development prospects of POMs in the field of photovoltaic devices are also highlighted.

Abstract Exosomes are lipid bilayer vesicles released from cells as a mechanism of intracellular communication. Containing information molecules of their parental cells and inclining to fuse with targeted cells, exosomes are valuable in disease diagnosis and drug delivery. The realization of their clinic applications still faces difficulties, such as lacking technologies for fast purification and functional reading. The advancement of nanotechnology in recent decades makes it promising to overcome these difficulties. In this article, we summarized recent progress in utilizing the physiochemical properties of nanoparticles (NPs) to enhance exosome purification and detection sensitivity or to derive novel technologies. We also discussed the valuable applications of exosomes in NPs‐based drug delivery. Till now most studies in these fields are still at the laboratory research stage. Translation of these bench works into clinic applications still has a long way to go.

Background: Atrial natriuretic peptide (ANP) has been associated with cardiovascular disease (CVD) and related risk factors, but the clinical application is limited and the underlying mechanisms are not very clear. Here, we aimed to examine whether proANP and its coding gene methylation were associated with CVD in the Chinese population. Methods: Serum proANP and peripheral blood DNA methylation of natriuretic peptide A gene ('NPPA') promoter was quantified at baseline for 2,498 community members (mean aged 53 years, 38% men) in the Gusu cohort. CVD events were obtained during 10 years of follow-up. A competing-risks survival regression model was applied to examine the prospective associations of proANP and 'NPPA' promoter methylation with incident CVD. Results: During follow-up, 210 participants developed CVD events, 50 participants died from non-cardiovascular causes, and 214 participants were lost. Per 1-nmol/L increment of serum proANP was associated with a 22% (HR = 1.22, 95%CI: 1.03–1.44, 'P' = 0.025) higher risk of CVD during follow-up. Of the 9 CpG sites assayed, per 2-fold increment of DNA methylation at CpG3 (located at Chr1:11908299) was significantly associated with a half lower risk of CVD (HR = 0.50, 95%CI: 0.30–0.82, 'P' = 0.006). The gene-based analysis found that DNA methylation of the 9 CpGs at 'NPPA' promoter as a whole was significantly associated with incident CVD ('P' < 0.05). Conclusions: Increased proANP and hypomethylation at 'NPPA' promoter at baseline predicted an increased future risk of CVD in Chinese adults. Aberrant DNA methylation of the 'NPPA' gene may participate in the mechanisms of CVD.

ObjectiveTo evaluate the value of non-invasive detection of advanced glycation end products (AGEs) in the early screening of type 2 diabetes mellitus (T2DM) in the community of China.MethodsFrom January 2018 to January 2019, a total of 912 patients with community health physical examination and no history of T2DM were selected, excluding the results of missing value > 5%. Finally, 906 samples were included in the study, with a response rate of 99.3%. Non-invasive diabetic detection technology was used to detect AGEs in the upper arm skin of all participants, AGE accumulations were classified as ≤P25, P25∼P50, P50∼P75, and >P75; HbA1c, insulin, C-peptide, total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), creatinine, urea, and other indicators were measured at the same time. Univariate analysis of variance was used to compare the differences in general data, biochemical indexes, skin AGE levels, and blood glucose among groups, and logistic regression analysis and latent category analysis were performed.ResultsIn univariate analysis, SBP, FBG, HbA1c, and age were correlated with higher AGE (p < 0.01); TG, TC, HDL, UA, and gender were not positively correlated with AGE (p < 0.01). After controlling for covariates (waist circumference, hip circumference), AGE accumulation was interacted with other variables. The results of latent category analysis (LCA) showed that the health risk factors (HRFs), including age, systolic blood pressure, HbA1c, FBG, triglyceride, total cholesterol, HDL-C, and uric acid, were divided as three groups, and AGE is divided into four categories according to the quartile method, which were low risk (≤P25), low to medium risk (P25∼P50), medium to high (P50∼P75), and high risk (>P75), respectively. The association between the quartile AGE and risk factors of the OR values was 1.09 (95% CI: 1.42, 2.86), 2.61 (95% CI: 1.11, 6.14), and 5.41 (95% CI: 2.42, 12.07), respectively. The moderation analysis using the PROCESS program was used to analyze whether BMI moderated the link between risk factors and AGE accumulation. There was also a significant three-way interaction among HRFs, BMI, and gender for AGE accumulation in the total sample (β = -0.30).ConclusionNon-invasive skin detection of AGEs has a certain application value for the assessment of T2DM risk and is related to a variety of risk factors.

BackgroundFurin has been associated with diabetes but the underlying mechanisms are unclear. As a mediator linking fixed genome and dynamic environment, DNA methylation of its coding gene FURIN may be involved. Here, we aimed to examine the prospective association between DNA methylation in FURIN promoter and incident diabetes during 4 years of follow-up in Chinese adults.MethodsDNA methylation levels in FURIN promoter were quantified by target bisulfite sequencing using peripheral blood from 1836 participants in the Gusu cohort who were free of diabetes at baseline. To examine the association between DNA methylation levels in FURIN promoter and incident diabetes, we constructed a logistic regression model adjusting for the conventional factors. Multiple testing was controlled by adjusting for the total number of CpG sites assayed using the false-discovery rate approach.ResultsAmong the 1836 participants free of diabetes at baseline, 109 (5.94%) participants developed diabetes during the average of 4 years of follow-up. Hypermethylation at two of the eight CpG sites assayed in the FURIN promoter was associated with an increased risk of diabetes, after multivariable adjustment and multiple testing correction. Every 5% increment in methylation levels at CpG1 and CpG2 were associated with a 22% (OR=1.22, 95%CI: 1.05-1.43, P=0.009, q=0.038) and 39% (OR=1.39, 95%CI: 1.08-1.77, P=0.009, q=0.038) higher risk of incident diabetes, respectively. The gene-based association analysis revealed that DNA methylation at multiple CpG loci was jointly associated with incident diabetes (P