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High salt (HS) consumption is a risk factor for multiple autoimmune disorders via disturbing immune homeostasis. Nevertheless, the exact mechanisms by which HS exacerbates rheumatoid arthritis (RA) pathogenesis remain poorly defined. Herein, we found that heightened phosphorylation of PDPK1 and SGK1 upon HS exposure attenuated FoxO1 expression to enhance the glycolytic capacity of CD4 T cells, resulting in strengthened Th17 but compromised Treg program. GSK2334470 (GSK), a dual PDPK1/SGK1 inhibitor, effectively mitigated the HS-induced enhancement in glycolytic capacity and the overproduction of IL-17A. Therefore, administration of GSK markedly alleviated HS-exacerbated RA progression in collagen-induced arthritis (CIA) model. Collectively, our data indicate that HS consumption subverts Th17/Treg homeostasis through the PDPK1-SGK1-FoxO1 signaling, while GSK could be a viable drug against RA progression in clinical settings.
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Metal-organic frameworks (MOFs) are metal-organic skeleton compounds composed of self-assembled metal ions or clusters and organic ligands. MOF materials often have porous structures, high specific surface areas, uniform and adjustable pores, high surface activity and easy modification and have a wide range of prospects for application. MOFs have been widely used. In recent years, with the continuous expansion of MOF materials, they have also achieved remarkable results in the field of antimicrobial agents. In this review, the structural composition and synthetic modification of MOF materials are introduced in detail, and the antimicrobial mechanisms and applications of these materials in the healing of infected wounds are described. Moreover, the opportunities and challenges encountered in the development of MOF materials are presented, and we expect that additional MOF materials with high biosafety and efficient antimicrobial capacity will be developed in the future.
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Estruturas Metalorgânicas , Cicatrização , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacologia , Cicatrização/efeitos dos fármacos , Humanos , Animais , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Antibacterianos/farmacologia , Antibacterianos/química , Porosidade , Infecção dos Ferimentos/tratamento farmacológicoRESUMO
Introduction: Respiratory infectious diseases, such as influenza and coronavirus disease 2019 (COVID-19), present significant global public health challenges. The emergence of artificial intelligence (AI) and big data offers opportunities to improve traditional disease surveillance and early warning systems. Methods: The study analyzed data from January 2020 to May 2023, comprising influenza-like illness (ILI) statistics, Baidu index, and clinical data from Weifang. Three methodologies were evaluated: the adaptive dynamic threshold method (ADTM) for dynamic threshold adjustments, the machine learning supervised method (MLSM), and the machine learning unsupervised method (MLUM) utilizing anomaly detection. The comparison focused on sensitivity, specificity, timeliness, and warning consistency. Results: ADTM issued 37 warnings with a sensitivity of 71% and a specificity of 85%. MLSM generated 35 warnings, with a sensitivity of 82% and a specificity of 87%. MLUM produced 63 warnings with a sensitivity of 100% and specificity of 80%. The initial warnings from ADTM and MLUM preceded those from MLSM by five days. The Kappa coefficient indicated moderate agreement between the methods, with values ranging from 0.52 to 0.62 (P<0.05). Discussion: The study explores the comparison between traditional methods and two machine learning approaches for early warning systems. It emphasizes the validation of machine learning's reliability and underscores the unique advantages of each method. Furthermore, it stresses the significance of integrating machine learning models with various data sources to enhance public health preparedness and response, alongside acknowledging limitations and the need for broader validation.
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Increased inflammatory responses and oxidative stress at the wound site following skin trauma impair healing. Furthermore, skin scarring places fibroblasts under severe mechanical stress and aggravates pathological fibrosis. A novel liposomal composite hydrogel is engineered for wound microenvironment remodeling, incorporating dual-loaded liposomes into gelatin methacrylate to create a nanocomposite hydrogel. Notably, tetrahydrocurcumin (THC) and hepatocyte growth factor (HGF) are encapsulated in the hydrophobic and hydrophilic layers of liposomes, respectively. The composite hydrogel maintains porous nanoarchitecture, demonstrating sustainable THC and HGF release and enhanced mechanical properties and biocompatibility. This system effectively promotes cell proliferation and angiogenesis and attenuates apoptosis. It decreases the expression of the inflammatory factors by inhibiting the high-mobility group box /receptor for advanced glycation end product/NF-κB (HMGB1/RAGE/NF-κB)pathway and increases macrophage polarization from M1 to M2 in vitro, effectively controlling inflammatory responses. It exhibits remarkable antioxidant properties by scavenging excess reactive oxygen species and free radicals. Most importantly, it effectively prevents scar formation by restraining the transforming growth factor beta (TGF-ß)/Smads pathway that downregulates associated fibrotic factors. It demonstrates strong therapeutic effects against inflammation and fibrosis in a rat skin wound model with biosafety, advancing the development of innovative hydrogel-based therapeutic delivery strategies for clinical scarless wound therapy.
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We demonstrate the integration of a thin BaTiO3 (BTO) membrane with monolayer MoSe2 in a dual-gate device that enables in situ manipulation of the BTO ferroelectric polarization with a voltage pulse. While two-dimensional (2D) transition metal dichalcogenides (TMDs) offer remarkable adaptability, their hybrid integration with other families of functional materials beyond the realm of 2D materials has been challenging. Released functional oxide membranes offer a solution for 2D/3D integration via stacking. 2D TMD excitons can serve as a local probe of the ferroelectric polarization in BTO at a heterogeneous interface. Using photoluminescence (PL) of MoSe2 excitons to optically read out the doping level, we find that the relative population of charge carriers in MoSe2 depends sensitively on the ferroelectric polarization. This finding points to a promising avenue for future-generation versatile sensing devices with high sensitivity, fast readout, and diverse applicability for advanced signal processing.
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Objective: This study aims to assess the combined predictive value of C-reactive protein (CRP) and albumin (ALB) for major adverse cardiovascular events (MACE) post-percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI). Methods: We analyzed data from continuously enrolled AMI patients who underwent emergency PCI at the First Affiliated Hospital of Xinjiang Medical University over six years, employing logistic regression to derive a predictive equation for in-hospital mortality and out-of-hospital MACE events. Primary endpoints: In-hospital death and out-of-hospital major adverse cardiovascular events. The patients were followed up for 1, 3, 6, and 12 months after discharge. The average follow-up time was 41 months. Results: Among the 601 patients studied, we observed 16 in-hospital deaths and 131 out-of-hospital MACE events. Multivariate logistic regression analysis showed that the independent predictors of out-of-hospital MACE events were age (OR=1.067, 95% CI 1.013-1.124, P = .028), C-reactive protein (OR=1.012, 95% CI 1.000-1.025, P = .045) and albumin (OR=0.874, 95% CI 0.785-0.973, P = .014). Our multivariate logistic regression analysis identified age, CRP, and albumin as independent predictors, with the combined equation yielding an ROC curve area of 0.85, effectively stratifying patients into high-risk and low-risk groups. Subsequent follow-up results validated this risk stratification approach. Conclusion: The study underscores the efficacy of combining CRP and albumin levels as a predictive measure for in-hospital death and out-of-hospital MACE events in AMI patients post-PCI.
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The close relationship between bacteria and tumors has recently attracted increasing attention, and an increasing number of resources are being invested in the research and development of biomedical materials designed for the treatment of both. In this study, prefabricated TiN nanodots (NDs) and Fe(CO)5 nanoparticles are combined into sodium alginate (ALG) hydrogels to create a biomedical material for the topical treatment of breast cancer and subcutaneous abscesses, and a pseudocatalytic hydrogel with intrinsic photothermal and antibacterial activities is synthesized. TiN+Fe(CO)5+ALG hydrogels are used to determine the ability of Fe(CO)5 to promote CO production. Moreover, TiN NDs catalyze the production of reactive oxygen species (ROS) from hydrogen peroxide in tumor microenvironments and exhibit excellent photothermal conversion properties. After local injection of the TiN+Fe(CO)5+ALG hydrogel into subcutaneous tumors and subcutaneous abscesses, and two-zone near-infrared (NIR-II) irradiation, tumor cells and methicillin-resistant Staphylococcus aureus are effectively removed by the hydrogel, the mouse epidermis exhibiting complete recovery within 8 d, indicating that this hydrogel exhibits better antibacterial efficacy than the small-molecule antibiotic penicillin. This study demonstrates the potential of novel hydrogels for antitumor and antimicrobial combination therapy and aims to provide design ideas for the research and development of multifunctional antitumor and antimicrobial drug combinations.
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The study of exciton polarons has offered profound insights into the many-body interactions between bosonic excitations and their immersed Fermi sea within layered heterostructures. However, little is known about the properties of exciton polarons with interlayer interactions. Here, through magneto-optical reflectance contrast measurements, we experimentally investigate interlayer Fermi polarons for 2s excitons in WSe2/graphene heterostructures, where the excited exciton states (2s) in the WSe2 layer are dressed by free charge carriers of the adjacent graphene layer in the Landau quantization regime. First, such a system enables an optical detection of integer and fractional quantum Hall states (e.g., ν = ±1/3, ±2/3) of monolayer graphene. Furthermore, we observe that the 2s state evolves into two distinct branches, denoted as attractive and repulsive polarons, when graphene is doped out of the incompressible quantum Hall gaps. Our work paves the way for the understanding of the excited composite quasiparticles and Bose-Fermi mixtures.
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Dysregulated T cell activation underpins the immunopathology of rheumatoid arthritis (RA), yet the machineries that orchestrate T cell effector program remain incompletely understood. Herein, we leveraged bulk and single-cell RNA sequencing data from RA patients and validated protein disulfide isomerase family A member 3 (PDIA3) as a potential therapeutic target. PDIA3 is remarkably upregulated in pathogenic CD4 T cells derived from RA patients and positively correlates with C-reactive protein level and disease activity score 28. Pharmacological inhibition or genetic ablation of PDIA3 alleviates RA-associated articular pathology and autoimmune responses. Mechanistically, T cell receptor signaling triggers intracellular calcium flux to activate NFAT1, a process that is further potentiated by Wnt5a under RA settings. Activated NFAT1 then directly binds to the Pdia3 promoter to enhance the expression of PDIA3, which complexes with STAT1 or PKM2 to facilitate their nuclear import for transcribing T helper 1 (Th1) and Th17 lineage-related genes, respectively. This non-canonical regulatory mechanism likely occurs under pathological conditions, as PDIA3 could only be highly induced following aberrant external stimuli. Together, our data support that targeting PDIA3 is a vital strategy to mitigate autoimmune diseases, such as RA, in clinical settings.
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Artrite Reumatoide , Isomerases de Dissulfetos de Proteínas , Fator de Transcrição STAT1 , Isomerases de Dissulfetos de Proteínas/metabolismo , Isomerases de Dissulfetos de Proteínas/genética , Humanos , Artrite Reumatoide/metabolismo , Camundongos , Animais , Fator de Transcrição STAT1/metabolismo , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Transporte Ativo do Núcleo Celular , Proteínas de Transporte/metabolismo , Transdução de Sinais , Proteínas de Ligação a Hormônio da Tireoide , Fatores de Transcrição NFATC/metabolismo , Ativação Linfocitária , Hormônios Tireóideos/metabolismo , Regulação da Expressão Gênica , Células Th17/metabolismo , Células Th17/imunologia , Células Th1/imunologia , Células Th1/metabolismo , Modelos Animais de Doenças , Piruvato QuinaseRESUMO
Bacterial infection hampers wound repair by impeding the healing process. Concurrently, inflammation at the wound site triggers the production of reactive oxygen species (ROS), causing oxidative stress and damage to proteins and cells. This can lead to chronic wounds, posing severe risks. Therefore, eliminating bacterial infection and reducing ROS levels are crucial for effective wound healing. Nanozymes, possessing enzyme-like catalytic activity, can convert endogenous substances into highly toxic substances, such as ROS, to combat bacteria and biofilms without inducing drug resistance. However, the current nanozyme model with single enzyme activity falls short of meeting the complex requirements of antimicrobial therapy. Thus, developing nanozymes with multiple enzymatic activities is essential. Herein, we engineered a novel metalloenzyme called Ru-procyanidin nanoparticles (Ru-PC NPs) with diverse enzymatic activities to aid wound healing and combat bacterial infections. Under acidic conditions, due to their glutathione (GSH) depletion and peroxidase (POD)-like activity, Ru-PC NPs combined with H2O2 exhibit excellent antibacterial effects. However, in a neutral environment, the Ru-PC NPs, with catalase (CAT) activity, decompose H2O2 to O2, alleviating hypoxia and ensuring a sufficient oxygen supply. Furthermore, Ru-PC NPs possess exceptional antioxidant capacity through their superior superoxide dismutase (SOD) enzyme activity, effectively scavenging excess ROS and reactive nitrogen species (RNS) in a neutral environment. This maintains the balance of the antioxidant system and prevents inflammation. Ru-PC NPs also promote the polarization of macrophages from M1 to M2, facilitating wound healing. More importantly, Ru-PC NPs show good biosafety with negligible toxicity. In vivo wound infection models have confirmed the efficacy of Ru-PC NPs in inhibiting bacterial infection and promoting wound healing. The focus of this work highlights the quadruple enzymatic activity of Ru-PC NPs and its potential to reduce inflammation and promote bacteria-infected wound healing.
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Inflammatory bowel disease (IBD) may arise due to disruption of mucosal barriers as a result of dysregulation of the intestinal flora and excessive oxidative stress. The creation of nanomaterials with only microbiota-regulating effects often leads to inadequate therapeutic outcomes caused by the disruption of a healthy microbial balance and the emergence of tissue harm caused by excessive oxidative stress. This report describes the multifunctional activity of ultrasmall W-GA nanodots, which can precisely regulate the intestinal microbiome by inhibiting the abnormal expansion of Enterobacteriaceae during colitis and alleviating the damage caused by oxidative stress to the reconstructive microflora, ultimately restoring intestinal barrier function. W-GA nanodots have been synthesized through a simple coordination reaction and can be dispersed in various solvents in vitro, demonstrating favorable safety profiles in cells, significant clearance of reactive oxygen and nitrogen species (RONS), and increased cell survival in models of oxidative stress induced by hydrogen peroxide (H2O2). Through oral or intravenous administration, the W-GA nanodots were shown to be highly safe when tested in vivo, and they effectively reduced colon damage in mice with DSS-induced colitis by restoring the integrity of the intestinal barrier. W-GA nanodots have enabled the integration of microflora reprogramming and RONS clearance, creating a potent therapeutic strategy for treating gut inflammation. Consequently, the development of W-GA nanodots represents a promising strategy for enhancing the formation and preservation of the intestinal barrier to treat IBD by suppressing the growth of Enterobacteriaceae, a type of facultative anaerobic bacterium, and facilitating the effective removal of RONS. Ultimately, this leads to the restoration of the intestinal barrier's functionality. STATEMENT OF SIGNIFICANCE: An increasing number of nanoparticles are under development for treating inflammatory bowel disease. Although they can alleviate inflammation symptoms by regulating reactive oxygen and nitrogen species (RONS) and microbiota, their understanding of the mechanism behind microbiota regulation is limited. This study synthesized W-GA nanodots using a straightforward one-pot synthesis method. Simple synthesis holds significant promise for clinical applications, as it encompasses multiple nanoenzyme functions and also exhibits Enterobacteriaceae inhibitory properties.Thus, it contributes to ameliorating the current medical landscape of inflammatory bowel disease.
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Colite , Microbioma Gastrointestinal , Estresse Oxidativo , Estresse Oxidativo/efeitos dos fármacos , Animais , Colite/tratamento farmacológico , Colite/patologia , Camundongos , Microbioma Gastrointestinal/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Humanos , Camundongos Endogâmicos C57BL , Nanopartículas/química , Masculino , Espécies Reativas de Oxigênio/metabolismo , Função da Barreira IntestinalRESUMO
Acute wounds are converted to chronic wounds due to advanced age and diabetic complications. Nanozymes catalyze ROS production to kill bacteria without causing drug resistance, while microneedles (MNs) can break through the skin barrier to deliver drugs effectively. Nanozymes can be intergrateded into MNs delivery systems to improve painless drug delivery. It can also reduce the effective dose of drug sterilization while increasing delivery efficiency and effectively killing wounded bacteria while preventing drug resistance. This paper describes various types of metal nanozymes from previous studies and compares their mutual enhancement with nanozymes. The pooled results show that the MNs, through material innovation, are able to both penetrate the scab and deliver nanozymes and exert additional anti-inflammatory and bactericidal effects. The catalytic effect of some of the nanozymes can also accelerate the lysis of the MNs or create a cascade reaction against inflammation and infection. However, the issue of increased toxicity associated with skin penetration and clinical translation remains a challenge. This study reviews the latest published results and corresponding challenges associated with the use of MNs combined with nanozymes for the treatment of wounds, providing further information for future research.
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Agulhas , Cicatrização , Humanos , Animais , Cicatrização/efeitos dos fármacos , Sistemas de Liberação de Medicamentos/métodos , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/administração & dosagem , Doença CrônicaRESUMO
Bacterial infections are among the most significant causes of death in humans. Chronic misuse or uncontrolled use of antibiotics promotes the emergence of multidrug-resistant superbugs that threaten public health through the food chain and cause environmental pollution. Based on the above considerations, copper selenide nanosheets (CuSe NSs) with photothermal therapy (PTT)- and photodynamic therapy (PDT)-related properties have been fabricated. These CuSe NSs possess enhanced PDT-related properties and can convert O2 into highly toxic reactive oxygen species (ROS), which can cause significant oxidative stress and damage to bacteria. In addition, CuSe NSs can efficiently consume glutathione (GSH) at bacterial infection sites, thus further enhancing their sterilization efficacy. In vitro antibacterial experiments with near-infrared (NIR) irradiation have shown that CuSe NSs have excellent photothermal bactericidal properties. These experiments also showed that CuSe NSs exerted excellent bactericidal effects on wounds infected with methicillin-resistant Staphylococcus aureus (MRSA) and significantly promoted the healing of infected wounds. Because of their superior biological safety, CuSe NSs are novel copper-based antimicrobial agents that are expected to enter clinical trials, serving as a modern approach to the major problem of treating bacterially infected wounds.
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Antibacterianos , Cobre , Staphylococcus aureus Resistente à Meticilina , Testes de Sensibilidade Microbiana , Nanoestruturas , Terapia Fototérmica , Cobre/química , Cobre/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Animais , Nanoestruturas/química , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Humanos , Propriedades de Superfície , Tamanho da Partícula , Selênio/química , Selênio/farmacologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Infecções Estafilocócicas/tratamento farmacológicoRESUMO
Quantum spin Hall (QSH) insulators are two-dimensional electronic materials that have a bulk band gap similar to an ordinary insulator but have topologically protected pairs of edge modes of opposite chiralities1-6. So far, experimental studies have found only integer QSH insulators with counter-propagating up-spins and down-spins at each edge leading to a quantized conductance G0 = e2/h (with e and h denoting the electron charge and Planck's constant, respectively)7-14. Here we report transport evidence of a fractional QSH insulator in 2.1° twisted bilayer MoTe2, which supports spin-Sz conservation and flat spin-contrasting Chern bands15,16. At filling factor ν = 3 of the moiré valence bands, each edge contributes a conductance 3 2 G 0 with zero anomalous Hall conductivity. The state is probably a time-reversal pair of the even-denominator 3/2-fractional Chern insulators. Furthermore, at ν = 2, 4 and 6, we observe a single, double and triple QSH insulator with each edge contributing a conductance G0, 2G0 and 3G0, respectively. Our results open up the possibility of realizing time-reversal symmetric non-abelian anyons and other unexpected topological phases in highly tunable moiré materials17-19.
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Premature ovarian insufficiency (POI) patients experience a decline in ovarian function and a reduction in serum reproductive hormones, leading to a significant impact on the outcomes of assisted reproductive technology. Despite the absence of an effective clinical treatment to restore fertility in POI patients, recent research has indicated that cord blood plasma (CBP) derived from human umbilical cord blood (hUCB) may offer therapeutic benefits for various degenerative diseases. The primary aim of this study is to explore approaches for enhancing ovarian function and serum reproductive hormones through the administration of CBP in a murine model. Initially, hUCB was utilized to obtain CBP (CBP), which was subsequently analyzed for cytokine and growth factor profiles in comparison to adult blood plasma (ABP) by use of flow cytometry. Subsequently, POI mouse models were established through the induction of 4-vinylcyclohexene diepoxide, followed by the injection of CBP into the tail. At 7, 14, and 21 days posttreatment, mouse ovaries and blood were collected, and their estrus cycle, body weight, and ovarian weights were evaluated using precise electronic balance. Finally, ovarian morphology and follicle number were assessed through HE staining, while serum levels of anti-Müllerian hormone (AMH), estradiol (E2) and follicle-stimulating hormone (FSH) were determined by ELISA. Our study revealed that individuals with CBP exhibited significantly lower concentrations of proinflammatory cytokines, including IL-ß (p < 0.01) and IL-2 (p < 0.05), while displaying elevated levels of anti-inflammatory cytokines and chemokines, such as IL-2, IL-4, IL-6, IL-8, IL-12P70, IL-17A, IP-10, interferon-γ, and tumor necrosis factor-α (p < 0.01). Furthermore, CBP demonstrated remarkably higher levels of growth factors, including transforming growth factor-ß1, vascular endothelial growth factor, and insulin-like growth factor-1 (p < 0.01) than ABP. Notably, our investigation also revealed that CBP restored the content of serum reproductive hormones, such as AMH, E2, and FSH (p < 0.05), and increased the number of primordial and primary follicles (p < 0.01) and decreased the number of luteal and atretic follicles (p < 0.01) in vivo. Our findings suggested that CBP-secreted cytokines and growth factors could be restored POI ovarian function, enhanced serum reproductive hormones and rescued follicular development in vivo. These findings further support the potential of CBP as a promising strategy in clinical applications for POI related infertility.
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Citocinas , Insuficiência Ovariana Primária , Feminino , Adulto , Humanos , Camundongos , Animais , Sangue Fetal , Fator A de Crescimento do Endotélio Vascular , Interleucina-2 , Insuficiência Ovariana Primária/terapia , Insuficiência Ovariana Primária/patologia , Estradiol , Hormônio Foliculoestimulante , Peptídeos e Proteínas de Sinalização Intercelular , PlasmaRESUMO
Endophytic fungi establish mutualistic relationships with host plants and can promote the growth and development of plants. In this study, the endophytic fungus JRF11 was isolated from Carya illinoinensis. Sequence analysis of the internal transcribed spacer (ITS) region and 18S rRNA gene combined with colonial and conidial morphology identified JRF11 as a Paraphaosphaeria strain. Plant-fungus interaction assays revealed that JRF11 showed significant growth-promoting effects on plants. In particular, JRF11 significantly increased the root biomass and soluble sugar content of plants. Furthermore, transcriptome analysis demonstrated that JRF11 treatment reprogrammed a variety of genes involved in plant mitogen-activated protein kinase (MAPK) signaling and starch and sucrose metabolism pathways through Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Our research indicates that beneficial endophytic fungi are able to interact with plants and exhibit outstanding plant growth-promoting activities.
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Two-dimensional moiré materials are formed by overlaying two layered crystals with small differences in orientation or/and lattice constant, where their direct coupling generates moiré potentials. Moiré materials have emerged as a platform for the discovery of new physics and device concepts, but while moiré materials are highly tunable, once formed, moiré lattices cannot be easily altered. Here we demonstrate the electrostatic imprinting of moiré lattices onto a target monolayer semiconductor. The moiré potential-created by a lattice of electrons that is supported by a Mott insulator state in a remote MoSe2/WS2 moiré bilayer-imprints a moiré potential that generates flat bands and correlated insulating states in the target monolayer and can be turned on/off by gate tuning the doping density of the moiré bilayer. Additionally, we studied the interplay between the electrostatic and structural relaxation contributions to moiré imprinting. Our results demonstrate a pathway towards gate control of moiré lattices.
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Objective@#To examine the prospective effect of cesarean section on pubertal development after controlling the polygenic susceptibility for early puberty in boys and girls,and to provide a reference for choosing a delivervary way beneficial to pubertal development.@*Methods@#Cluster sampling method was used to select 997 students of grade 1 to 3 from 2 priwary schools in Bengbu of Anhui in 2016 to establish the puberty development cohort. Delivery mode,birth weight,gestational age,early teeding way,family income and parental educational background were derived from parental questionnaire. Breast Tanner stage and testicular volume of 997 children were annually assessed. The polygenic risk score (PRS) was computed based on 17 SNPs derived from published genome-wide association studies for early pubertal timing. Kaplan-Meier analyses was used to examine associations between cesarean section with pubertal development in boys and girls.@*Results@#The average age of 997 children was 8.01±0.84 years old, and average BMI was (17.96±2.96) kg/m2. The prevalence of cesarean section for boys and girls was 43.30% and 32.47%, respectively. At baseline, the detection of thelarche in girls delivered by cesarean section (39.89%) was higher than that of girls delivered naturally (4.39%) (χ2=118.65, P<0.01). Similar result was observed during the last follow-up, the detection of thelarche in girls born by cesarean section (95.21%) was higher than girls born vaginally (68.48%), respectively (χ2=51.42, P<0.01). After adjusting for confounding factors (age, BMI, birthweight, infancy feeding, gestational age, household monthly income and parental education), girls delivered by cesarean section had maturation at significantly younger than girls who delivered naturally (Hazard Ratio, HR=1.98,95%CI=1.67-2.34,P<0.01).@*Conclusion@#Caesarean section might increase the risk of earlier age at pubertal onset in a sex-specific manner. Whether natural delivery could be one of the protective measures to prevent early pubertal timing in children warrants further investigation.
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<p><b>OBJECTIVE</b>To investigate the relationship among serum reproductive hormone levels, serum homocysteine (Hcy) levels, metabolic syndrome (MS), and the components of MS in middle-aged and elderly males.</p><p><b>METHODS</b>Using the cluster and stratified sampling methods and a unified structured questionnaire, we conducted a survey among 948 men aged 40 - 80 years in the rural community, measured their basic physical parameters, and obtained their reproductive hormone levels, serum Hcy concentrations, and metabolism-related indicators. We collected 868 valid questionnaires along with their serum samples, divided the subjects into an MS and a non-MS control group in a 1:1 ratio, and measured their serum Hcy concentrations.</p><p><b>RESULTS</b>Among the subjects included, 132 were diagnosed with MS. Nonparametric tests showed statistically significant differences between the MS and non-MS groups in the waist circumference (WC), waist-hip ratio (WHR), body mass index (BMI), systolic blood pressure (SBP), and diastolic blood pressure (DBP) (P < 0.05), but not in age (P > 0.05). Significant differences were also observed between the two groups in the levels of serum tT, SHBG, LH, and FTI (P < 0.05) , but not in the concentrations of serum Hcy (P > 0.05). The concentration of serum Hcy exhibited no correlation with BMI, SBP, DBP, FBG, TG, and HDL-C (P > 0.05) and had no influence on MS.</p><p><b>CONCLUSION</b>The concentration of serum Hcy is not significantly correlated with MS, nor with its components. The levels of male serum reproductive hormones are associated both with MS and with its components.</p>