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Interleukin‐4 (IL‐4)/IL‐4 receptor alpha (IL‐4Rα) signalling pathways play important roles in the complex process of bone formation and bone remodelling. However, whether IL‐4/IL‐4Rα participates in skeletogenesis during embryonic development is not completely understood. We used the anti‐IL‐4Rα monoclonal antibody (anti‐IL‐4Rα mAb) as a powerful investigational tool to evaluate the potential roles of IL‐4/IL‐4Rα in the chondrogenic differentiation of rat bone marrow mesenchymal stem cells (BMSCs) in vitro. Simultaneously, we explored the effect of IL‐4/IL‐4Rα on bone ossification during rat embryo‐fetal development. In this study, we found that, compared to the control group, IL‐4 can significantly promote the chondrogenic differentiation of BMSCs. Furthermore, following exposure to anti‐IL‐4Rα mAb in pregnant rats, unexpected phenomena were observed in fetal bone development, including non‐ossification of the fetal sternum, an incomplete ossification centre in long bones and a reduced number of ossification points in digit (toe) bones. To further investigate the underlying mechanism of the phenotype, we studied the rat sternum as the target organ, starting from different time points of sternum development in the embryonic stage. The results indicated that the retardation mainly occurred in the middle and late stages of embryonic development. This retardation was characterized by the inhibition of the differentiation process of mesenchymal stem cells into chondrocytes, resulting in reduced angiogenesis near the ossification centre, failure of osteoblasts to invade the centre of the cartilage body with the blood vessels and delayed formation of the primary ossification centre (POC). Overall, our study demonstrated the significant function of IL‐4/IL‐4Rα in chondrogenic differentiation of BMSCs and bone ossification during embryo‐fetal development. [ABSTRACT FROM AUTHOR]

Age‐related declines in self‐renewal and multipotency of bone marrow mesenchymal stem cells (BMSCs) limit their applications in tissue engineering and clinical therapy. Thus, understanding the mechanisms behind BMSC senescence is crucial for maintaining the rejuvenation and multipotent differentiation capabilities of BMSCs. This study reveals that impaired USP26 expression in BMSCs leads to mitochondrial dysfunction, ultimately resulting in aging and age‐related declines in the self‐renewal and multipotency of BMSCs. Specifically, decreased USP26 expression results in decreased protein levels of Sirtuin 2 due to its ubiquitination degradation, which leads to mitochondrial dysfunction in BMSCs and ultimately resulting in aging and age‐related declines in self‐renewal and multilineage differentiation potentials. Additionally, decreased USP26 expression in aging BMSCs is a result of dampened hypoxia‐inducible factor 1α (HIF‐1α) expression. HIF‐1α facilitates USP26 transcriptional expression by increasing USP26 promoter activity through binding to the ‐191 — ‐198 bp and ‐262 — ‐269 bp regions on the USP26 promoter. Therefore, the identification of USP26 as being correlated with aging and age‐related declines in self‐renewal and multipotency of BMSCs, along with understanding its expression and action mechanisms, suggests that USP26 represents a novel therapeutic target for combating aging and age‐related declines in the self‐renewal and multipotent differentiation of BMSCs. [ABSTRACT FROM AUTHOR]

Introduction: We investigated the genetic determinants of variation in the hemoglobin glycation index (HGI), an emerging biomarker for the risk of diabetes complications. Methods: We conducted a genome-wide association study (GWAS) for HGI in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial (N = 7,913) using linear regression and additive genotype encoding on variants with minor allele frequency greater than 3%. We conducted replication analyses of top findings in the Atherosclerosis Risk in Communities (ARIC) study with inverse variance-weighted meta-analysis. We followed up with stratified GWAS analyses by sex and self-reported race. Results: In ACCORD, we identified single nucleotide polymorphisms (SNPs) associated with HGI, including a peak with the strongest association at the intergenic SNP rs73407935 (7q11.22) (P = 5.8e−10) with a local replication in ARIC. In black individuals, the variant rs10739419 on chromosome 9 in the Whirlin (WHRN) gene formally replicated (meta- P = 2.2e−9). The SNP-based heritability of HGI was 0.39 (P < 1e−10). HGI had significant sex-specific associations with SNPs in or near GALNT11 in women and HECW2 in men. Finally, in Hispanic participants, we observed genome-wide significant associations with variants near USF1 and NXNL2/SPIN1. Discussion: Many HGI-associated SNPs were distinct from those associated with fasting plasma glucose or HbA1c, lending further support for HGI as a distinct biomarker of diabetes complications. The results of this first evaluation of the genetic etiology of HGI indicate that it is highly heritable and point to heterogeneity by sex and race. [ABSTRACT FROM AUTHOR]

Heteroatom configuration, lattice engineering, and cation–anion modulation are important factors affecting the performance of catalysts for water splitting. However, simultaneously achieving multi-scale regulation of the catalyst represents a formidable challenge. For this problem, we constructed S, N, O triple-doped carbon/Co8FeS8 catalysts with SO42−-riched and lattice distortion (SNO-C/Co8FeS8) via a deep eutectic solvent (DES) strategy. SNO-C/Co8FeS8 demonstrates outstanding performance in both the oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) with overpotentials of 230 mV and 120 mV at a current density of 10 mA cm−2, respectively. Additionally, the theoretical calculations reveal that the remarkable HER/OER dual-function catalytic activity of SNO-C/Co8FeS8 primarily stems from the synergistic electronic modulation of sulfate and the carbon matrix on Fe and Co sites. This regulation optimizes the binding of the adsorption capacity of the intermediate, thereby accelerating the kinetics of the HER and OER. This study presents a multi-scale regulation catalyst strategy for fabricating high-performance electrocatalysts. [ABSTRACT FROM AUTHOR]

The deterioration and deformation of brittle rock generally appear in railway tunnels with the operation of large buried deep tunnel. To investigate the macro-micro fracture and acoustic emission evolution characteristics of brittle rock, this paper conducted the uniaxial compression, scanning electron microscope (SEM), and acoustic emission (AE) signal monitoring under different loading rates. The results showed that the loading rate has an obvious enhancement effect on mechanical parameters. The increased loading rate extends the elastic deformation and improves the bearing strength, elastic modulus and deformation modulus. The fracture patterns include shear fracture, composite fracture, and tension fracture. The oblique shear fracture is transformed into composite fracture and tension fracture with the loading rate increasing. The microscopic fracture shows that increasing loading rate inhibits the evolution of oblique shear fractures and promotes the expansion of tensile fractures. The roughness level of tensile fractures is significantly lower than that of oblique shear fracture and composite fracture. The AE parameters and deformation behavior are characterized by simultaneous evolution. The AE amplitude changes from low-level and low-density distribution to high-level and high-density distribution as the loading rate increases. The AE activity intensity of tensile fracture is significantly greater than that of oblique shear fracture and composite fracture. The warning timeliness of cumulative AE events and cumulative AE energy is generally earlier than the AE b-value under the same loading rate, and the early warning timeliness of cumulative AE events is similar to that of cumulative AE energy. [ABSTRACT FROM AUTHOR]

Background/Objectives: Metabolomics provides insights into the biological underpinnings of disease development and treatment. This systematic review investigated the impact of acupuncture on metabolite levels and associated metabolic pathways using a metabolomic approach. Methods: Five databases (i.e., PubMed, Embase, Scopus, CINAHL, and Cochrane Central) were searched using terms such as "acupuncture" and "metabolites" to retrieve relevant journal articles published through January 2024. Studies utilizing mass spectrometry or nuclear magnetic resonance were included. Risk of bias was evaluated using the Cochrane Risk of Bias tool and the Newcastle–Ottawa scale. Metabolic pathway analysis was conducted using MetaboAnalyst 6.0 to identify common significant pathways affected by acupuncture. Additionally, subgroup pathway enrichment analysis identified metabolites significantly altered in more than two studies. Results: Among 4019 articles, 22 studies met inclusion criteria, examining changes in metabolomic biomarkers before and after acupuncture for various diseases and symptoms. A total of 226 metabolites showed significant changes, with 14 common metabolites altered in more than two studies (glutamine, androsterone glucuronide, choline, citric acid, decanoylcarnitine, estrone, glutathione, glycine, hypoxanthine, lactic acid, pyruvic acid, serine, proline, and sn-glycero-3-phosphocholine). Common pathways affected by acupuncture were glycine, serine, and threonine metabolism, glutathione metabolism, arginine biosynthesis, and glyoxylate and dicarboxylate metabolism. Conclusions: This review provides insights of the metabolomic mechanisms underlying acupuncture, highlighting its impact on specific metabolic pathways. Recognizing these changes can enhance acupuncture's effectiveness and support the development of personalized treatments. The findings underscore metabolomics as a valuable tool for understanding and optimizing acupuncture for various diseases and symptoms. [ABSTRACT FROM AUTHOR]

Introduction: Due to the high cost and complexity, the oral glucose tolerance test is not adopted as the screening method for identifying diabetes patients, which leads to the misdiagnosis of patients with isolated post‐challenge hyperglycemia (IPH), that is., patients with normal fasting plasma glucose (<7.0 mmoL/L) and abnormal 2‐h postprandial blood glucose (≥11.1 mmoL/L). We aimed to develop a model to differentiate individuals with IPH from the normal population. Methods: Data from 54301 eligible participants were obtained from the Risk Evaluation of Cancers in Chinese Diabetic Individuals: a longitudinal (REACTION) study in China. Data from 37740 participants were used to develop the diagnostic system. External validation was performed among 16561 participants. Three machine learning algorithms were used to create the predictive models, which were further evaluated by various classification algorithms to establish the best predictive model. Results: Ten features were selected to develop an IPH diagnosis system (IPHDS) based on an artificial neural network. In external validation, the AUC of the IPHDS was 0.823 (95% CI 0.811–0.836), which was significantly higher than the AUC of the Taiwan model [0.799 (0.786–0.813)] and that of the Chinese Diabetes Risk Score model [0.648 (0.635–0.662)]. The IPHDS model had a sensitivity of 75.6% and a specificity of 74.6%. This model outperformed the Taiwan and CDRS models in subgroup analyses. An online site with instant predictions was deployed at https://app‐iphds‐e1fc405c8a69.herokuapp.com/. Conclusions: The proposed IPHDS could be a convenient and user‐friendly screening tool for diabetes during health examinations in a large general population. [ABSTRACT FROM AUTHOR]

In order to solve the problem of large eddy current losses and high temperature rises caused by a large number of permanent magnets, a new type of combined-magnetic-pole permanent magnet motor is proposed in this paper. The sinusoidally distributed subdomain model of a non-uniform-air-gap rotor was established using the Laplace equation, and the analytical expression of eddy current losses in the rotor in a uniform air gap and non-uniform air gap was derived. The effect of the rotor's eccentricity on eddy current losses was obtained. According to the characteristics of the distributed winding of the non-uniform-air-gap combined-pole permanent magnet motor, an equivalent treatment was performed to obtain the equivalent thermal conductivity value; to establish an equivalent thermal network model of the motor; determine the temperature of each component of the motor; and verify the correctness of the thermal network model through magnetothermal bidirectional coupling. Finally, an experimental platform was set up to carry out temperature rise experiments on the two prototypes. The experimental results show that a non-uniform-air-gap rotor structure can effectively reduce a rotor's eddy current losses and motor temperature rise, as well as verify the accuracy of the analytical model's calculation results. [ABSTRACT FROM AUTHOR]

Aerogels, as kinetic energy absorbing materials, can find crucial applications for safeguarding in transportation, sports, buildings, construction, and aerospace. However, the highly porous structure makes it extremely fragile for endurance usage. In this study, a half‐full filled structure has been proposed, and the concept has been demonstrated based on shear thickening fluid (STF) and chemically vapor deposited carbon nanotube aerogels (CNTAs), in which the outer part of CNTA is filled with STF while the inner core keeping unfilled. Chemical vapor deposition significantly enhances the elasticity and electromagnetic shielding performance of the native CNTA. The half‐full filled aerogels (HFFA) show a 348% increase in energy absorption compared to the CNTA. At the same time, the density, electronic conductivity, and electromagnetic interference shielding effectiveness (EMI SE) of the HFFAs are 0.117 g cm−3, 1213 S m−1, and 69.52 dB (which is a neglectable reduction of 0.63% compared to native CNTA), respectively. The HFFA strategy provides an alternative route to fabricate robust aerogels with a remarkable increase of target properties while maintaining other properties, such as low density, high pore volume, and conductivity, with limited changes. [ABSTRACT FROM AUTHOR]

Base editors have substantial promise in basic research and as therapeutic agents for the correction of pathogenic mutations. The development of adenine transversion editors has posed a particular challenge. Here we report a class of base editors that enable efficient adenine transversion, including precise A•T-to-C•G editing. We found that a fusion of mouse alkyladenine DNA glycosylase (mAAG) with nickase Cas9 and deaminase TadA-8e catalyzed adenosine transversion in specific sequence contexts. Laboratory evolution of mAAG significantly increased A-to-C/T conversion efficiency up to 73% and expanded the targeting scope. Further engineering yielded adenine-to-cytosine base editors (ACBEs), including a high-accuracy ACBE-Q variant, that precisely install A-to-C transversions with minimal Cas9-independent off-targeting effects. ACBEs mediated high-efficiency installation or correction of five pathogenic mutations in mouse embryos and human cell lines. Founder mice showed 44–56% average A-to-C edits and allelic frequencies of up to 100%. Adenosine transversion editors substantially expand the capabilities and possible applications of base editing technology. A base editor for precise adenine transversions is demonstrated in mouse embryos. [ABSTRACT FROM AUTHOR]

Main conclusion: Foliar NAA increases photosynthate supplied by enhancing photosynthesis, to strengthen root activity and provide a large sink for root carbohydrate accumulation, which is beneficial to acquire more nitrogen. The improvement of grain yield is an effective component in the food security. Auxin acts as a well-known plant hormone, plays an important role in maize growth and nutrient uptake. In this study, with maize variety Zhengdan 958 (ZD958) as material, the effects of auxin on nitrogen (N) uptake and assimilation of seedling maize were studied by hydroponic experiments. With water as the control, naphthalene acetic acid (NAA, 0.1 mmol/L) and aminoethoxyvinylglycine (AVG, 0.1 mmol/L, an auxin synthesis inhibitor) were used for foliar spraying. The results showed that NAA significantly improved photosynthetic rate and plant biomass by 58.6% and 91.7%, respectively, while the effect of AVG was opposite to that of NAA. At the same time, key enzymes activities related N assimilation in NAA leaves were significantly increased, and the activities of nitrate reductase (NR), glutamine synthetase (GS) and glutamate synthase (GOGAT) were increased by 32.3%, 22.9%, and 16.2% in new leaves. Furthermore, NAA treatment promoted underground growth. When compared with control, total root length, root surface area, root tip number, branch number and root activity were significantly increased by 37.8%, 22.2%, 35.1%, 28.8% and 21.2%. Root growth is beneficial to N capture in maize. Ultimately, the total N accumulation of NAA treatment was significantly increased by 74.5%, as compared to the control. In conclusion, NAA foliar spraying increased endogenous IAA content, and enhanced the activity of N assimilation-related enzymes and photosynthesis rate, in order to build a large sink for carbohydrate accumulation. In addition, NAA strengthened root activity and regulated root morphology and architecture, which facilitated further N uptake and plant growth. [ABSTRACT FROM AUTHOR]

A fundamental understanding of inflammation and tissue healing suggests that the precise regulation of the inflammatory phase, both in terms of location and timing, is crucial for bone regeneration. However, achieving the activation of early inflammation without causing chronic inflammation while facilitating quick inflammation regression to promote bone regeneration continues to pose challenges. This study reveals that black phosphorus (BP) accelerates bone regeneration by building an osteogenic immunological microenvironment. BP amplifies the acute pro‐inflammatory response and promotes the secretion of anti‐inflammatory factors to accelerate inflammation regression and tissue regeneration. Mechanistically, BP creates an osteoimmune‐friendly microenvironment by stimulating macrophages to express interleukin 33 (IL‐33), amplifying the inflammatory response at an early stage, and promoting the regression of inflammation. In addition, BP‐mediated IL‐33 expression directly promotes osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), which further facilitates bone repair. To the knowledge, this is the first study to reveal the immunomodulatory potential of BP in bone regeneration through the regulation of both early‐stage inflammatory responses and later‐stage inflammation resolution, along with the associated molecular mechanisms. This discovery serves as a foundation for the clinical use of BP and is an efficient approach for managing the immune microenvironment during bone regeneration. [ABSTRACT FROM AUTHOR]

Background: Genomic study of cognition decline while considering baseline cognition and lifestyle behaviors is scarce. We aimed to evaluate the impact of a polygenic score for general cognition on cognition decline rate, while considering baseline cognition and lifestyle behaviors, among the general population and people with diabetes, a patient group commonly affected by cognition impairment. Methods: We tested associations of the polygenic score for general cognition with annual changing rates of cognition measures in 8 years of follow-up among 12,090 White and 3100 Black participants of the Health and Retirement Study (HRS), a nationally representative sample of adults aged 50 years and older in the USA. Cognition measures including word recall, mental status, and total cognitive score were measured biannually. To maximize sample size and length of follow-up, we treated the 2010 wave of survey as baseline, and follow-up data until 2018 were analyzed. Baseline lifestyle behaviors, APOE status, and measured cognition were sequentially adjusted. Given racial differences in polygenic score, all analyses were conducted by race. Results: The polygenic score was significantly associated with annual changing rates of all cognition measures independent of lifestyle behaviors and APOE status. Together with age and sex, the polygenic score explained 29.9%, 15.9%, and 26.5% variances of annual changing rates of word recall, mental status, and total cognitive scores among Whites and explained 17.2%, 13.9%, and 18.7% variance of the three traits among Blacks. Among both White and Black participants, those in the top quartile of polygenic score had the three cognition measures increased annually, while those in the bottom quartile had the three cognition measures decreased annually. After further adjusting for the average cognition assessed in 3 visits around baseline, the polygenic score was still positively associated with annual changing rates of all cognition measures for White (P ≤ 2.89E − 19) but not for Black (P ≥ 0.07) participants. In addition, among participants with diabetes, physical activity offset the genetic susceptibility to decline of mental status (interaction P ≤ 0.01) and total cognitive scores (interaction P = 0.03). Conclusions: Polygenic score predicted cognition changes in addition to measured cognition. Physical activity offset genetic risk for cognition decline among diabetes patients. [ABSTRACT FROM AUTHOR]

The quasi‐static tensile properties of carbon nanotube (CNT) composites have already been extensively studied, while their impact tensile properties under high rates have rarely been investigated. In this work, CNT film/PVA composites were prepared by impregnation and hot press curing, whereas CNT films were prepared by floating catalyst chemical vapor deposition (FCCVD). Instron 3365 and the miniaturized split Hopkinson tensile bar (SHTB) were used for tensile tests at various strain rates. The results show that the tensile properties of PVA‐impregnated CNT film are significantly improved, and the strain rate effect is remarkable. The tensile properties are best when the mass fraction of PVA is 1.5%. At a low strain rate of 0.001 s−1, the maximum stress and energy absorption (EA) of CNT composites are 502.5 MPa and 63.6 MJ/m3, respectively. And at the high strain rate of 3100 s−1, the maximum stress and EA of CNT composites are 969.0 MPa and 166.4 MJ/m3, respectively. Scanning electron microscopy (SEM) was used to observe the failure morphologies at tensile fracture of composites under different strain rates. At low strain rate, the failure mode is the pulling fracture of tube bundles and the crushing of polymers, while at high strain rate is the folding and spring back of tube bundles, as well as the debonding of polymers. [ABSTRACT FROM AUTHOR]

Biofloc technology (BFT) as an efficient aquaculture alternative is attracting attention for boosting biosecurity with minimal water exchange and reduced feed intake. BFT relies on applying organic carbon to maintain a high C/N ratio above 10, which allows heterotrophs to assimilate toxic nitrogen. A high percentage of carbon loss is thus generated from BFT. For this review, a thorough search of the relevant literature was conducted to gather valuable information on the optimization of carbon utilization. The keywords searched included 'BFT', 'carbon use efficiency', 'carbon conversion', 'carbon retention', 'carbon emission', 'carbon loss', and 'carbon release'. The current review discusses the possible effects of various C/N ratios, carbon types, addition strategies, and technology integration with respect to the optimized carbon utilization in BFT. Given the extreme lack of accessible research, it was concluded that the carbon utilization in BFT is still in its initial research stage. Anyhow, this review sheds light on plausible approaches for boosted carbon utilization by adopting slow-release carbon, reducing carbon input, integrating with other technologies, and enhancing interactions between functional microbes within BFT, thereby contributing to sustainable aquaculture. [ABSTRACT FROM AUTHOR]

This work explores a simple way to regulate the morphology and structure of biomass-based carbon and effectively utilize its internal functional groups as the substrate for the next energy materials. The unique randomly oriented and highly interconnected cordyceps-like 3D structure of rice husk is formed by direct high-temperature carbonization, and the main component is SiC. The well-arranged cordyceps-like structure of SiC demonstrates a remarkable structural/chemical stability and a high rate of electron migration, and further could be used as a stable substrate for metal deposition and find application in the field of electrocatalysis. The oxygen evolution reaction catalyst (SiC-C@Fe3O4) prepared by chemical deposition exhibits a low overpotential (260 mV), low Tafel slope (56.93 mV dec−1), high electrochemical active surface area (54.92 mF cm−2), and low Rct value (0.15 Ω) at a current density of 10 mA cm−2 in 1 M KOH electrolyte. The produced natural Si-C composite materials overcome the limitations imposed by the intricate internal structure of silicon-rich biomass. The existence of this stable substrate offers a novel avenue for maximizing the utilization of rice-husk-based carbon, and broadens its application field. At the same time, it also provides a theoretical basis for the use of rice husks in the field of hydrogen production by electrolysis of water, thus promoting their high-value utilization. [ABSTRACT FROM AUTHOR]

The formation of a calcified cartilaginous callus (CACC) is crucial during bone repair. CACC can stimulate the invasion of type H vessels into the callus to couple angiogenesis and osteogenesis, induce osteoclastogenesis to resorb the calcified matrix, and promote osteoclast secretion of factors to enhance osteogenesis, ultimately achieving the replacement of cartilage with bone. In this study, a porous polycaprolactone/hydroxyapatite‐iminodiacetic acid‐deferoxamine (PCL/HA‐SF‐DFO) 3D biomimetic CACC is developed using 3D printing. The porous structure can mimic the pores formed by the matrix metalloproteinase degradation of the cartilaginous matrix, HA‐containing PCL can mimic the calcified cartilaginous matrix, and SF anchors DFO onto HA for the slow release of DFO. The in vitro results show that the scaffold significantly enhances angiogenesis, promotes osteoclastogenesis and resorption by osteoclasts, and enhances the osteogenic differentiation of bone marrow stromal stem cells by promoting collagen triple helix repeat‐containing 1 expression by osteoclasts. The in vivo results show that the scaffold significantly promotes type H vessels formation and the expression of coupling factors to promote osteogenesis, ultimately enhancing the regeneration of large‐segment bone defects in rats and preventing dislodging of the internal fixation screw. In conclusion, the scaffold inspired by biological bone repair processes effectively promotes bone regeneration. [ABSTRACT FROM AUTHOR]

Background: Previous studies have reported cross-sectional associations between measures of epigenetic age acceleration (EAA) and kidney function phenotypes. However, the temporal and potentially causal relationships between these variables remain unclear. We conducted a bidirectional two-sample Mendelian randomization study of EAA and kidney function. Genetic instruments for EAA and estimate glomerular filtration rate (eGFR) were identified from previous genome-wide association study (GWAS) meta-analyses of European-ancestry participants. Causal effects of EAA on kidney function and kidney function on EAA were assessed through summary-based Mendelian randomization utilizing data from the CKDGen GWAS meta-analysis of log-transformed estimated glomerular filtration rate (log-eGFR; n = 5,67,460) and GWAS meta-analyses of EAA (n = 34,710). An allele score-based Mendelian randomization leveraging individual-level data from UK Biobank participants (n = 4,33,462) further examined the effects of EAA on kidney function. Results: Using summary-based Mendelian randomization, we found that each 5 year increase in intrinsic EAA (IEAA) and GrimAge acceleration (GrimAA) was associated with − 0.01 and − 0.02 unit decreases in log-eGFR, respectively (P = 0.02 and P = 0.09, respectively), findings which were strongly supported by allele-based Mendelian randomization study (both P < 0.001). Summary-based Mendelian randomization identified 24% increased odds of CKD with each 5-unit increase in IEAA (P = 0.05), with consistent findings observed in allele score-based analysis (P = 0.07). Reverse-direction Mendelian randomization identified potentially causal effects of decreased kidney function on HannumAge acceleration (HannumAA), GrimAA, and PhenoAge acceleration (PhenoAA), conferring 3.14, 1.99, and 2.88 year decreases in HanumAA, GrimAA, and PhenoAA, respectively (P = 0.003, 0.05, and 0.002, respectively) with each 1-unit increase in log-eGFR. Conclusion: This study supports bidirectional causal relationships between EAA and kidney function, pointing to potential prevention and therapeutic strategies. [ABSTRACT FROM AUTHOR]

Falls are the leading cause of fatal and non-fatal injuries among older adults. Evidence-based fall prevention programs are delivered nationwide, largely supported by funding from the Administration for Community Living (ACL), to mitigate fall-related risk. This study utilizes data from 39 ACL grantees in 22 states from 2014 to 2017. The large amount of missing values for falls efficacy in this national database may lead to potentially biased statistical results and make it challenging to implement reliable variable selection. Multiple imputation is used to deal with missing values. To obtain a consistent result of variable selection in multiply-imputed datasets, multiple imputation-stepwise regression (MI-stepwise) and multiple imputation-least absolute shrinkage and selection operator (MI-LASSO) methods are used. To compare the performances of MI-stepwise and MI-LASSO, simulation studies were conducted. In particular, we extended prior work by considering several circumstances not covered in previous studies, including an extensive investigation of data with different signal-to-noise ratios and various missing data patterns across predictors, as well as a data structure that allowed the missingness mechanism to be missing not at random (MNAR). In addition, we evaluated the performance of MI-LASSO method with varying tuning parameters to address the overselection issue in cross-validation (CV)-based LASSO. [ABSTRACT FROM AUTHOR]

Osteogenesis imperfecta (OI) is a genetic disorder caused by mutations of type I collagen‐related genes, and excessive transforming growth factor‐beta (TGF‐β) signaling is a common mechanism. TGF‐β/Smad signaling has inhibitory effects on osteoblast differentiation and maturation and is mainly transduced and regulated by the internalization of a tetrameric receptor complex comprising types I and II TGF‐β receptors (TβRI and TβRII). During internalization, clathrin‐mediated endocytosis enhances TGF‐β/Smad signaling via Smad2/3 phosphorylation and receptors recycling, while caveolae‐mediated endocytosis turns off TGF‐β/Smad signaling by promoting receptor ubiquitination and degradation. In this study, using an animal model of OI (Colla2oim, osteogenesis imperfecta murine [oim]/oim mouse), we found that osteoblastic cells of oim/oim mice were more sensitive to the inhibitory effects of TGF‐β on osteoblast differentiation and maturation and had much higher cell membrane protein levels of TGF‐β receptors than those of wild‐type (wt)/wt mice. Further results showed that clathrin‐mediated endocytosis of TβRI was enhanced, whereas caveolae‐mediated TβRI endocytic degradation was reduced in oim/oim mice, combined with reduced caveolin‐1 (Cav‐1) phosphorylation. In addition, type I collagen downregulated TβRI via focal adhesion kinase (FAK) and Src activation‐dependent Cav‐1 phosphorylation. To further examine this mechanism, 4‐week‐old oim/oim and wt/wt mice were treated with either TβRI kinase inhibitor (SD‐208) or vehicle for 8 weeks. SD‐208 treatment significantly reduced the fracture incidence in oim/oim mice. Micro–computed tomography and biomechanical testing showed that femoral bone mass and strength were significantly improved with SD‐208 treatment in both genotypes. Additionally, SD‐208 significantly promoted osteoblast differentiation and bone formation and inhibited bone resorption. In conclusion, dysfunction of caveolae‐mediated endocytic TβRI degradation is a possible mechanism for the enhanced TGF‐β/Smad signaling in OI. Targeting this mechanism using a TβRI kinase inhibitor effectively reduced fractures and improved bone mass and strength in OI model and, thus, may offer a new strategy for the treatment of OI. © 2022 American Society for Bone and Mineral Research (ASBMR). [ABSTRACT FROM AUTHOR]

SARS-CoV-2 rapidly spreads among humans via social networks, with social mixing and network characteristics potentially facilitating transmission. However, limited data on topological structural features has hindered in-depth studies. Existing research is based on snapshot analyses, preventing temporal investigations of network changes. Comparing network characteristics over time offers additional insights into transmission dynamics. We examined confirmed COVID-19 patients from an eastern Chinese province, analyzing social mixing and network characteristics using transmission network topology before and after widespread interventions. Between the two time periods, the percentage of singleton networks increased from 38.9 $ \% $ to 62.8 $ \% $ $ (p<0.001) $ ; the average shortest path length decreased from 1.53 to 1.14 $ (p<0.001) $ ; the average betweenness reduced from 0.65 to 0.11 $ (p<0.001) $ ; the average cluster size dropped from 4.05 to 2.72 $ (p=0.004) $ ; and the out-degree had a slight but nonsignificant decline from 0.75 to 0.63 $ (p=0.099). $ Results show that nonpharmaceutical interventions effectively disrupted transmission networks, preventing further disease spread. Additionally, we found that the networks' dynamic structure provided more information than solely examining infection curves after applying descriptive and agent-based modeling approaches. In summary, we investigated social mixing and network characteristics of COVID-19 patients during different pandemic stages, revealing transmission network heterogeneities. [ABSTRACT FROM AUTHOR]

Cables are the most common combustibles in nuclear power plants (NPPs) and cable fires are the one of main threaten to the safety of NPPs. Fire characteristics and fire hazards for two typical cables used in NPPs were comparatively studied based on cone calorimeter and cable tray fire tests. The heat release rate (HRR) curves show different patterns, two-peaks and three-peaks for NPP and conventional flame retardant cables, respectively. This difference is attributed to the fire barrier, which distinguishes the burning of sheath and insulation. Moreover, the maximum value of HRR for conventional flame retardant cable is much higher than NPP flame-retardant cable, and the difference is 108 kW m−2. The time from first peak to second peak for NPP flame-retardant cable is approximately four times as conventional flame retardant cable. Based on cable tray fire, the burning time after burner off is much longer for conventional flame retardant cable and its total mass loss is 0.52 kg, which are three times and five times as much as NPP flame-retardant cable, respectively, and it has a self-sustaining stage during cable burning. The above indicates that the NPP flame-retardant cable has less sustained damage, fire development rate and overall fire hazard. In addition, spacing has little effect on the burning time of sheath, but the burning of insulation layer is promoted, the time from first peak to second peak decreases with the increase in spacing. However, the influence of spacing is non-monotonous in cable tray fire, and the burning of cables with 10 mm spacing has higher fire hazard with a maximum mass loss rate. [ABSTRACT FROM AUTHOR]

Background: Cell death and inflammation are the two important triggers of wear particle-induced osteolysis. Particles, including cobalt-chromium-molybdenum and tricalcium phosphate, have been reported to induce pyroptosis in macrophages and osteocytes. Although macrophage pyroptosis facilitates osteoclastic bone resorption and osteolysis, whether osteocyte pyroptosis is involved in osteoclastic osteolysis still needs further investigation. Desferrioxamine (DFO), an FDA-approved medication and a powerful iron chelator, has been proven to reduce ultrahigh-molecular-weight polyethylene (UHMWPE) particle-induced osteolysis. However, whether DFO can ameliorate UHMWPE particle-induced osteolysis by decreasing pyroptosis in osteocytes is unknown. Results: A mouse calvarial osteolysis model and the mouse osteocyte cell line MLO-Y4 was used, and we found that pyroptosis in osteocytes was significantly induced by UHMWPE particles. Furthermore, our findings uncovered a role of caspase-1-dependent pyroptosis in osteocytes in facilitating osteoclastic osteolysis induced by UHMWPE particles. In addition, we found that DFO could alleviate UHMWPE particle-induced pyroptosis in osteocytes in vivo and in vitro. Conclusions: We uncovered a role of caspase-1-dependent pyroptosis in osteocytes in facilitating osteoclastic osteolysis induced by UHMWPE particles. Furthermore, we found that DFO alleviated UHMWPE particle-induced osteoclastic osteolysis partly by inhibiting pyroptosis in osteocytes. Schematic of DFO reducing UHMWPE particle-induced osteolysis by inhibiting osteocytic pyroptosis. Wear particles, such as polymers, generated from prosthetic implant materials activate canonical inflammasomes and promote the cleavage and activation of caspase-1. This is followed by caspase-1-dependent IL-β maturation and GSDMD cleavage. The N-terminal fragment of GSDMD binds to phospholipids on the cell membrane and forms holes in the membrane, resulting in the release of mature IL-β and inflammatory intracellular contents. This further facilitates osteoclastic differentiation of BMMs, resulting in excessive bone resorption and ultimately leading to prosthetic osteolysis. DFO reduces UHMWPE particle-induced osteolysis by inhibiting osteocytic pyroptosis. [ABSTRACT FROM AUTHOR]

The rs6265 in the brain-derived neurotrophic factor (BDNF) is associated with depression in people with diabetes. Both physical activity (PA) and grip strength are negatively associated with depression. We conducted cross-sectional analyses of the wave 10 survey data for a nationally representative sample of 1,051 diabetes participants of the Health and Retirement Study. Both greater PA (β = −.15) and stronger grip strength (β = −.02) were independently associated with depression. Although the interaction between BDNF rs6265 and PA on depressive symptoms was not significant, the negative PA-depression association was stronger among female non-Met carriers (β = −.19) and male Met carriers (β = −.14). Meanwhile, grip strength was associated with depression only in Met carriers (β = −.04), and similar association was observed in both males and females. In conclusion, female non-Met carriers and male Met carriers may benefit from PA. [ABSTRACT FROM AUTHOR]

With the fast consumption of traditional fossil fuels and the urgent requirement for a low-carbon economy and sustainable development, supercapacitors are gaining more and more attention as a clean energy storage and conversion device. The research on electrode materials for supercapacitors has become a hot topic nowadays. An electrode material for a supercapacitor, comprising the ZIF-67 in-built carbon-based material, was prepared from a biomass pre-hydrolysate via a hydrothermal process. As a by-product of dissolving slurry, the pre-hydrolysate is rich in carbon, which is an excellent biomass resource. The utilization of pre-hydrolysate to prepare carbon energy materials could realize the high value utilization of pre-hydrolysate and the efficient energy conversion of biomass. Meanwhile, the cobalt-based MOF (such as ZIF-67), as a porous crystalline material, has the advantages of having a regular order, high specific surface area and controllable pore size, as well as good thermal and chemical stability. The addition of ZIF-67 modified the morphology and pore structure of the carbon, and the obtained samples showed outstanding electrochemical performance. One- and two-step synthetic processes generated specimens with a coral-like cross-linked structure and a new type of rough, hollow, dandelion-like structure, respectively, and the pore size was in the range of 2.0–5.0 nm, which is conducive to ion transport and charge transfer. In C2-ZIF-67, the hollow structures could effectively prevent the accumulation of the electrochemical active center, which could provide enough space for the shrinkage and expansion of particles to protect them from the interference of electrolytes and the formation of solid electrolyte interphase film layers. Additionally, the plush tentacle structure with low density and a large specific surface area could expose more active sites and a large electrolyte electrode contact area, and short electron and charge transport paths. Importantly, active, free electrons of small amounts of Co-MOF (1 wt%) could be stored and released through the redox reaction, further improving the electrical conductivity of Carbon-ZIF-67 materials in this work. Consequently, C2-ZIF-67 exhibited superior specific capacitance (400 F g−1, at 0.5 A g−1) and stability (90%, after 10,000 cycles). [ABSTRACT FROM AUTHOR]

Genetic information may help to identify individuals at increased risk for hypertension in early life, prior to the manifestation of elevated blood pressure (BP) values. We examined 369 Black and 832 White Bogalusa Heart Study (BHS) participants recruited in childhood and followed for approximately 37 years. The multi-ancestry genome-wide polygenic risk scores (PRSs) for systolic BP (SBP), diastolic BP (DBP), and hypertension were tested for an association with incident hypertension and stage 2 hypertension using Cox proportional hazards models. Race-stratified analyses were adjusted for baseline age, age2, sex, body mass index, genetic principal components, and BP. In Black participants, each standard deviation increase in SBP and DBP PRS conferred a 38% (p = 0.009) and 22% (p = 0.02) increased risk of hypertension and a 74% (p < 0.001) and 50% (p < 0.001) increased risk of stage 2 hypertension, respectively, while no association was observed with the hypertension PRSs. In Whites, each standard deviation increase in SBP, DBP, and hypertension PRS conferred a 24% (p < 0.05), 29% (p = 0.01), and 25% (p < 0.001) increased risk of hypertension, and a 27% (p = 0.08), 29% (0.01), and 42% (p < 0.001) increased risk of stage 2 hypertension, respectively. The addition of BP PRSs to the covariable-only models generally improved the C-statistics (p < 0.05). Multi-ancestry BP PRSs demonstrate the utility of genomic information in the early life prediction of hypertension. [ABSTRACT FROM AUTHOR]

We conducted the first genome-wide association study of prediabetes status change (to diabetes or normal glycaemia) among 900 White participants of the Atherosclerosis Risk in Communities (ARIC) study. Single nucleotide polymorphism (SNP)-based analysis was performed by logistic regression models, controlling for age, gender, body mass index, and the first 3 genetic principal components. Gene-based analysis was conducted by combining SNP-based p values using effective Chi-square test method. Promising SNPs (p < 1×10-5) and genes (p < 1×10-4) were further evaluated for replication among 514 White participants of the Framingham Heart Study (FHS). To accommodate familial correlations, generalized estimation equation models were applied for SNP-based analyses in the FHS. Analysis results across ARIC and FHS were combined using inverse-variance-weighted meta-analysis method for SNPs and Fisher's method for genes. We robustly identified 5 novel genes that are associated with prediabetes status change using gene-based analyses, including SGCZ (ARIC p = 9.93×10-6, FHS p = 2.00×10-3, Meta p = 3.72×10-7) at 8p22, HPSE2 (ARIC p = 8.26×10-19, FHS p = 5.85×10-3, Meta p < 8.26×10-19) at 10q24.2, ADGRA1 (ARIC p = 1.34×10-5, FHS p = 1.13×10-3, Meta p = 2.88×10-7) at 10q26.3, GLB1L3 (ARIC p = 3.71×10-6, FHS p = 4.51×10-3, Meta p = 3.16×10-7) at 11q25, and PCSK6 (ARIC p = 6.51×10-6, FHS p = 1.10×10-2, Meta p = 1.25×10-6) at 15q26.3. eQTL analysis indicated that these genes were highly expressed in tissues related to diabetes development. However, we were not able to identify any novel locus in single SNP-based analysis. Future large scale genomic studies of prediabetes status change are warranted. [ABSTRACT FROM AUTHOR]

Introduction: Aging is associated with subtle cognitive decline in attention, memory, executive function, processing speed, and reasoning. Although lower brain-derived neurotrophic factor (BDNF) has been linked to cognitive decline among older adults, it is not known if the association differs among individuals with various BDNF Val66Met (rs6265) genotypes. In addition, it is not clear whether these associations vary by hand grip strength or physical activity (PA). Methods: A total of 2904 older adults were included in this study using data from the Health and Retirement Study. Associations between serum BDNF and measures of cognitive function were evaluated using multivariable linear regression models stratified by Met allele status. PA and hand grip strength were added to the model to evaluate whether including these variables altered associations between serum BDNF and cognition. Results: Mean age was 71.4 years old, and mean body mass index was 28.3 kg/m2. Serum BDNF levels were positively associated with higher total cognitive score (beta = 0.34, p =.07), mental status (beta = 0.16, p =.07), and word recall (beta = 0.22, p =.04) among Met carriers, while serum BDNF levels were negatively associated with mental status (beta = −0.09, p =.07) among non-Met carriers. Furthermore, associations changed when hand grip strength was added to the model but not when PA was added to the model. Conclusions: The BDNF Val66Met variant may moderate the association between serum BDNF levels and cognitive function in older adults. Furthermore, such associations differ according to hand grip strength but not PA. [ABSTRACT FROM AUTHOR]

Objective: The authors hypothesize that an untargeted metabolomics study will identify novel mechanisms underlying smoking‐associated weight loss. Methods: This study performed cross‐sectional analyses among 1,252 participants in the Bogalusa Heart Study and assessed 1,202 plasma metabolites for mediation effects on smoking‐BMI associations. Significant metabolites were tested for associations with smoking genetic risk scores among a subset of participants (n = 654) with available genomic data, followed by direction dependence analysis to investigate causal relationships between the metabolites and smoking and BMI. All analyses controlled for age, sex, race, education, alcohol drinking, and physical activity. Results: Compared with never smokers, current and former smokers had a 3.31‐kg/m2 and 1.77‐kg/m2 lower BMI after adjusting for all covariables, respectively. A total of 22 xenobiotics and 94 endogenous metabolites were significantly associated with current smoking. Eight xenobiotics were also associated with former smoking. Forty metabolites mediated the smoking‐BMI associations, and five showed causal relationships with both smoking and BMI. These metabolites, including 1‐oleoyl‐GPE (18:1), 1‐linoleoyl‐GPE (18:2), 1‐stearoyl‐2‐arachidonoyl‐GPE (18:0/20:4), α‐ketobutyrate, and 1‐palmitoyl‐GPE (16:0), mediated 26.0% of the association between current smoking and BMI. Conclusions: This study cataloged plasma metabolites altered by cigarette smoking and identified five metabolites that partially mediated the association between current smoking and BMI. [ABSTRACT FROM AUTHOR]

Three dimension (3D) printed scaffolds have been shown to be superior in promoting tissue repair, but the cell‐level specific regulatory network activated by 3D printing scaffolds with different material components to form a symbiosis niche have not been systematically revealed. Here, three typical 3D printed scaffolds, including natural polymer hydrogel (gelatin‐methacryloyl, GelMA), synthetic polymer material (polycaprolactone, PCL), and bioceramic (β‐tricalcium phosphate, β‐TCP), are fabricated to explore the regulating effect of the symbiotic microenvironment during bone healing. Enrichment analysis show that hydrogel promotes tissue regeneration and reconstruction by improving blood vessel generation by enhancing oxygen transport and red blood cell development. The PCL scaffold regulates cell proliferation and differentiation by promoting cellular senescence, cell cycle and deoxyribonucleic acid (DNA) replication pathways, accelerating the process of endochondral ossification, and the formation of callus. The β‐TCP scaffold can specifically enhance the expression of osteoclast differentiation and extracellular space pathway genes to promote the differentiation of osteoclasts and promote the process of bone remodeling. In these processes, specific biomaterial properties can be used to guide cell behavior and regulate molecular network in the symbiotic microenvironment to reduce the barriers of regeneration and repair. [ABSTRACT FROM AUTHOR]

The coverage rate is the most crucial index in wireless sensor networks (WSNs) design; it involves making the sensors with a reasonable distribution, which closely relates to the quality of service (QoS) and survival period of the entire network. This article proposes to use particle swarm optimization (PSO) and chaos optimization in conjunction for the coverage optimization. All sensor locations are encoded together as a particle position. PSO was used first to make sensors move close to their optimal positions; furthermore, a variable domain chaos optimization algorithm (VDCOA) was employed to reach a higher coverage rate, along with improved evenness and average moving distance. Six versions of VDCOA, taking circle, logistic, Gaussian, Chebyshev, sinusoidal and cubic maps, respectively, were investigated. The simulation experiment tested three cases: square, rectangular and circular regions using nine algorithms: six versions of PSO plus VDCOA, PSO and other two PSO variants. All six versions showed better performance than PSO and CPSO, with coverage all exceeding 90% for the first two cases. Moreover, one version, PSO plus circle map (PSO-Circle), increased the coverage rate by 3.17%, 2.41% and 12.94% compared with PSO in three cases, respectively, and outperformed the other eight algorithms. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to explore the association of lifelong smoking status with risk of major adverse cardiovascular events (MACE) accounting for weight change in a Chinese cohort. Methods: The cohort of the People's Republic of China‐United States of America (PRC‐USA) Collaborative Study of Cardiovascular and Cardiopulmonary Epidemiology was established in 1983 to 1984, resurveyed during 1987 to 1988 and 1993 to 1994, and followed up to 2005. A total of 5,849 participants who survived in 1993 to 1994 were classified into never smokers, long‐term quitters, short‐term quitters, short‐term relapsers and new smokers, long‐term relapsers and new smokers, and persistent smokers according to the information on lifelong smoking status collected in all three surveys. The associations of lifelong smoking status with MACE in the subsequent 10 years were explored with Cox proportional hazards models. Results: During a median follow‐up of 10.2 years, 694 participants had MACE. Compared with persistent smokers, the multivariable‐adjusted hazard ratio of developing MACE was 0.83 (95% CI: 0.61‐1.12) for short‐term quitters, 0.75 (95% CI: 0.54‐1.02) for long‐term quitters, and 0.68 (95% CI: 0.54‐0.85) for never smokers (ptrend = 0.001). In comparison, the hazard ratio was 1.03 (95% CI: 0.77‐1.35) for long‐term relapsers and new smokers and 0.78 (95% CI: 0.46‐1.22) for short‐term relapsers and new smokers (ptrend = 0.018). These associations were not significantly altered by further adjusting for weight change in the past 10 years. Conclusions: Lifelong smoking status is significantly associated with risk of MACE. As time duration increased, health benefit to quitters would become close to that of never smokers, and harms to relapsers and new smokers would become close to that of persistent smokers. [ABSTRACT FROM AUTHOR]

We aimed to evaluate associations of baseline telomere length with overall and annual change in estimated glomerular filtration rate (eGFR) and trajectory of kidney function during an 8-year follow-up. A total of 3 964 participants of the Health and Retirement Study were included. We identified 3 trajectory groups of kidney function: consistently normal (n = 1 163 or 29.3%), normal to impaired (n = 2 306 or 58.2%), and consistently impaired groups (n = 495 or 12.5%). After controlling for age, sex, race, education, smoking, drinking, diabetes, heart disease, blood pressure, body mass index, total cholesterol, and hemoglobin A1c, participants with longer telomere length were 20% less likely (odds ratio = 0.80, 95% confidence interval: 0.69-0.93, p = .003) to have a normal to impaired kidney function trajectory than a consistently normal function trajectory. Telomere length was not associated with changing rate of eGFR over 8 years (p = .45). Participants with longer telomere length were more likely to have consistently normal kidney function. [ABSTRACT FROM AUTHOR]

Mechanical force regulates bone density, modeling, and homeostasis. Substantial periosteal bone formation is generated by external mechanical stimuli, yet its mechanism is poorly understood. Here, it is shown that myeloid‐lineage cells differentiate into subgroups and regulate periosteal bone formation in response to mechanical loading. Mechanical loading on tibiae significantly increases the number of periosteal myeloid‐lineage cells and the levels of active transforming growth factor β (TGF‐β), resulting in cortical bone formation. Knockout of Tgfb1 in myeloid‐lineage cells attenuates mechanical loading‐induced periosteal bone formation in mice. Moreover, CD68+F4/80+ macrophages, a subtype of myeloid‐lineage cells, express and activate TGF‐β1 for recruitment of osteoprogenitors. Particularly, mechanical loading induces the differentiation of periosteal CD68+F4/80− myeloid‐lineage cells to the CD68+F4/80+ macrophages via signaling of piezo‐type mechanosensitive ion channel component 1 (Piezo1) for TGF‐β1 secretion. Importantly, CD68+F4/80+ macrophages activate TGF‐β1 by expression and secretion of thrombospondin‐1 (Thbs1). Administration of Thbs1 inhibitor significantly impairs loading‐induced TGF‐β activation and recruitment of osteoprogenitors in the periosteum. The results suggest that periosteal myeloid‐lineage cells respond to mechanical forces and consequently produce and activate TGF‐β1 for periosteal bone formation. [ABSTRACT FROM AUTHOR]

Sustained and controllable local gene therapy is a potential method for treating osteoarthritis (OA) through the delivery of therapeutic microRNAs (miRNAs) to targeted cells. However, direct injection of crude miRNAs for local gene therapy is limited due to its inadequate transfection efficiency, easy inactivation, and short half-life. Here, a multifunctional gene vector, arginine, histidine, and phenylalanine-modified generation 5 polyamidoamine (named G5-AHP), was employed to form G5-AHP/miR-140 nanoparticles by forming a complex with microRNA-140 (miR-140). Then, the nanoparticles were entrapped in hydrogel microspheres (MSs) to construct a "nano-micron" combined gene hydrogel to alleviate the degradation of articular cartilage. Monodisperse gelatin methacryloyl hydrogel MSs were produced under ultraviolet light using one-step innovative microfluidic technology. Evenly dispersed MSs showed better injectability in sustainable and matrix metalloproteinases (MMPs)-responsive degradation methods for local gene delivery. The G5-AHP/miR-140 nanoparticles released from the MSs exhibited high gene transfection efficacy and long-term bioactivity, facilitated endocytosis, and thus maintained the metabolic balance of cartilage matrix by promoting the expression of type II collagen and inhibiting the expression of a disintegrin and metalloproteinase with thrombospondin motifs-5 and MMP13 in chondrocytes. After injection of the "nano-micron" combined gene hydrogel into the articular cavity of the OA model, the gene hydrogel increased G5-AHP/miR-140 nanoparticle retention, prevented articular cartilage degeneration, and reduced osteophyte formation in a surgically induced mouse model of OA. The present study provides a novel cell-free approach to alleviate the progression of OA that shows potential for locally injected gene delivery systems. Sustained and controllable local gene therapy is a potential method for treating osteoarthritis (OA). Here, monodisperse gelatin methacryloyl microspheres produced under one-step innovative microfluidic technology were applied to construct "nano-micron" combined gene hydrogel by absorbing gene nanoparticles consisting of microRNA-140 and multifunctional gene vectors, arginine, histidine, and phenylalanine-modified generation 5 polyamidoamine (named G5-AHP). The "nano-micron" combined gene hydrogel showed better injectability in sustainable and matrix metalloproteinases-responsive degradation methods and provided a novel cell-free approach to alleviate the progression of OA. [ABSTRACT FROM AUTHOR]

Background: Few studies have focused on the prevalence of abdominal obesity in Chinese middle-aged and older adults with a normal body mass index (BMI). Furthermore, it is still unclear whether abdominal obesity is an independent risk factor for type 2 diabetes mellitus (T2DM). Participants with a normal BMI are usually neglected during assessments of abdominal obesity-associated T2DM risk since the current recommendations for medical interventions are mainly focused on overall body mass index rather than fat deposition patterns. Methods: In this study, 7942 normal-BMI participants aged over 45 years from the China Health and Retirement Longitudinal Study were included to assess the prevalence of abdominal obesity defined by waist circumference (WC) or waist-to-height ratio (WHtR). In addition, 4348 normal-BMI individuals with no diabetes at baseline were included to evaluate the association between abdominal obesity and the risk of T2DM with the Cox proportional hazards model. Results: The prevalence (95% confidence interval, CI) of increased WC and substantially increased WC among adults with a normal BMI was 22.0% (21.1%-22.9%) and 18.1% (17.3%-19.0%), respectively. The adjusted hazard ratios and 95% CIs for T2DM incidence were 1.39 (1.05– 1.85) and 1.89 (1.42– 2.53) for those with increased WC and substantially increased WC, respectively, compared to the individuals with a normal WC. Similar HRs were obtained for the association between WHtR and the risk of T2DM. In prediabetic patients, the HRs (95% CIs) for new-onset T2DM for those with increased WC and substantially increased WC were 1.85 (1.27– 2.69) and 2.46 (1.67– 3.61), respectively, when compared with individuals with normal WC. This positive association was observed in women but not in men or adults with normal glucose tolerance (NGT). Conclusion: Abdominal obesity is highly prevalent among middle-aged and older Chinese adults with a normal BMI, and maintaining a normal waist circumference may be beneficial in the prevention of T2DM. [ABSTRACT FROM AUTHOR]

The oxidation behavior of Ag-20Cu-30Cr alloy prepared by powder metallurgy method was investigated in 0.1 MPa pure O2 at 700 and 800 °C. The alloy oxidation kinetics deviates from the parabolic rate law and consists of several quasi-parabolic stages with different rate constants. The alloy oxidation rate at 800 °C is bigger in the initial 4 h and afterward smaller than that at 700 °C up to 24 h. Ag-20Cu-30Cr alloy produces complex oxide scales. At 700 °C, the outer region consists of CuO layer partly covered by metal Ag, while the inner mixed oxidation region consists of alloys and oxides. With the increase of time, an irregular continuous and protective thin layer of Cr2O3 is produced at the base of oxide scales. At 800 °C, the outer region consists of CuO layer, the middle region consists of a metal Ag layer plus a mixed layer of Cu, Ag and Cr oxides or their double oxides, while the inner region consists of a regular continuous and protective thin layer of Cr2O3, which avoids the further oxidation of the alloy. [ABSTRACT FROM AUTHOR]

While cognitive dysfunction is an important concern in persons with type 2 diabetes mellitus (T2DM), it has received little attention in the T2DM literature. Although it often remains unrecognized, cognitive dysfunction associated with T2DM can lead to severe consequences. Prior research studies have consistently shown that aerobic exercise enhances cognitive function among healthy subjects. However, very few studies have examined the effects of aerobic exercise on cognitive function in persons with T2DM. In addition, one important single‐nucleotide polymorphism that influences cognition in humans is the brain‐derived neurotrophic factor (BDNF) Val66Met variant. Despite strong evidence suggesting aerobic exercise has a beneficial effect on cognitive function, there is significant variability in individual response to exercise programs on cognitive outcomes among Val/Val versus Met carriers. However, the evidence on how the BDNF Val66Met variant influences cognitive outcomes following an aerobic exercise intervention among individuals with T2DM is currently lacking. Therefore, the purpose of this randomized controlled trial is to pilot‐test a 3‐month supervised exercise program to improve plasma BDNF levels and cognition, overall and according to genotypes of the BDNF Val66Met variant. A total of 81 patients with T2DM will be randomly assigned to either aerobic exercise group (n = 54) or attention control group (n = 27) for 3 months. Outcomes of interest include postintervention changes in plasma BDNF levels, fasting blood glucose, hemoglobin A1c, body mass index, executive function, memory, and processing speed. This study will provide further evidence on use of exercise as a non‐pharmaceutical, low‐cost intervention to improve cognition in this population. [ABSTRACT FROM AUTHOR]

BACKGROUND: Carbon‐MIL‐125 can be successfully prepared from pre‐hydrolysate and metal oxide TiO2 (Ti‐MOF) by coupling hydrothermal and carbonization processes. The use of this pre‐hydrolysate to prepare carbon (C)‐based materials could provide a value‐added product and allow the more complete use of bioresources. Combining the photocatalytic bactericidal properties of Ti‐MOF and adsorption capacity of biomass‐based C materials could further improve the antibacterial efficiency of the materials, and C could expand the response range of TiO2 to light and reduce the reorganization rate of photogenerated electrons and holes. This strategy could potentially increase the rate and efficiency of catalytic reactions. RESULTS: The morphologies and structures of samples were controlled via one‐ and two‐step routes. The obtained samples exhibited 1‐2 μm size and different morphologies. C1‐MIL‐125 showed a spherical morophology via ont‐step, C2‐MIL‐125 displayed a new type of rough tablet structure via two‐step. Meanwhile, Ti exists in the form of the mixture of TiO2 in the anatase and rutile phases. The catalytic activity of mixed TiO2 forms is higher than pure anatase or rutile, removal of Escherichia coli could reach 99.00% and 98.67% under a xenon lamp via one‐ and two‐step processes, respectively. CONCLUSION: This work could realize high value‐added utilization of biomass and is expected to provide new prospects for the design of superior photocatalysts for water disinfection. © 2021 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

Background: Some previous studies on different populations have yielded inconsistent findings with respect to the relationship between levels of high-density lipoprotein cholesterol (HDL-C) and future type 2 diabetes mellitus (T2DM) incidence. This study was designed to gain further insight into this relationship through a cohort study with a 25-year follow-up duration. Methods: In total, 1462 individuals that were 55 years of age or older and were free of T2DM at baseline were enrolled in the present study. T2DM incidence among this study population was detected through self-reported diagnoses or the concentration of fasting plasma glucose. The data were derived from nine surveys conducted from 1992 to 2017. The correlation between HDL-C levels and the T2DM risk was assessed through Cox proportional-hazards model and proportional hazards model for the sub-distribution with time-dependent variables. Results: Over the follow-up period, 120 participants were newly diagnosed with new-onset T2DM. When research participants were separated into four groups on the basis for quartiles of their levels of HDL-C measured at baseline, and incidence of diabetes declined with higher baseline HDL-C levels at 12.60, 9.70, 5.38, and 5.22 per 1000 person-years, respectively. Adjusted hazard ratios (HRs) were 0.98 (95% confidence interval [CI]: 0.62–1.55), 0.48 (95% CI: 0.27–0.85) and 0.44 (95% CI: 0.25–0.80) for individuals with HDL-C levels within the 1.15–1.39, 1.40–1.69, and ≥ 1.70 mmol/L ranges relative to participants with HDL-C levels < 1.15 mmol/L. Multiple sensitivity analyses similarly revealed reduced risk of diabetes incidence with increased HDL-C levels. Incorporating the levels of HDL-C into a multivariate model significantly enhanced the overall power of the predictive model (P values were 0.0296, 0.0011, respectively, for 5- and 10-year risk of diabetes). Conclusions: Levels of HDL-C were independently and negatively associated with the risk of the new-onset T2DM among middle-aged and elderly Chinese. [ABSTRACT FROM AUTHOR]

Introduction: Diabetes is associated with cognitive dysfunction that comes with substantial lifetime consequences, such as interference with diabetes self-management and reduced quality of life. Although regular physical activity has been consistently shown to enhance cognitive function among healthy subjects, significant interpersonal differences in exercise-induced cognitive outcomes have been reported among brain-derived neurotrophic factor (BDNF) Val/Val vs. Met carriers. However, the evidence on how the BDNF Val66Met variant influences the relationship between regular physical activity and cognition among individuals with diabetes is currently lacking. Methods: A total of 3,040 individuals with diabetes were included in this analysis using data from the Health and Retirement Study. Associations among moderate and vigorous physical activities (MVPA) and measures of cognitive function were evaluated using multivariable linear regression models within each stratum of the Val66Met genotypes. Results: MVPA was more strongly associated with total cognitive score, mental status, and words recall among Met/Met carriers, compared to Val/Val and Val/Met carriers. Conclusions: This study provided preliminary findings on how BDNF variants may modulate the exercise-induced cognitive benefits among mid-aged and older adults with diabetes. Given the limitations of the current study, it is necessary for randomized controlled trials to stratify by BDNF genotypes to more conclusively determine whether Met carriers benefit more from increased physical activity. In addition, future research is needed to examine how the interplay of BDNF Val66Met variants, DNA methylation, and physical activity may have an impact on cognitive function among adults with diabetes. [ABSTRACT FROM AUTHOR]