Two-billion-year-old volcanism on the Moon from Chang'e-5 basalts.

The Moon has a magmatic and thermal history that is distinct from that of the terrestrial planets1. Radioisotope dating of lunar samples suggests that most lunar basaltic magmatism ceased by around 2.9-2.8 billion years ago (Ga)2,3, although younger basalts between 3 Ga and 1 Ga have been suggested by crater-counting chronology, which has large uncertainties owing to the lack of returned samples for calibration4,5. Here we report a precise lead-lead age of 2,030 ± 4 million years ago for basalt clasts returned by the Chang'e-5 mission, and a 238U/204Pb ratio (µ value)6 of about 680 for a source that evolved through two stages of differentiation. This is the youngest crystallization age reported so far for lunar basalts by radiometric dating, extending the duration of lunar volcanism by approximately 800-900 million years. The µ value of the Chang'e-5 basalt mantle source is within the range of low-titanium and high-titanium basalts from Apollo sites (µ value of about 300-1,000), but notably lower than those of potassium, rare-earth elements and phosphorus (KREEP) and high-aluminium basalts7 (µ value of about 2,600-3,700), indicating that the Chang'e-5 basalts were produced by melting of a KREEP-poor source. This age provides a pivotal calibration point for crater-counting chronology in the inner Solar System and provides insight on the volcanic and thermal history of the Moon.

Integrative splicing-quantitative-trait-locus analysis reveals risk loci for non-small-cell lung cancer.

Splicing quantitative trait loci (sQTLs) have been demonstrated to contribute to disease etiology by affecting alternative splicing. However, the role of sQTLs in the development of non-small-cell lung cancer (NSCLC) remains unknown. Thus, we performed a genome-wide sQTL study to identify genetic variants that affect alternative splicing in lung tissues from 116 individuals of Chinese ancestry, which resulted in the identification of 1,385 sQTL-harboring genes (sGenes) containing 378,210 significant variant-intron pairs. A comprehensive characterization of these sQTLs showed that they were enriched in actively transcribed regions, genetic regulatory elements, and splicing-factor-binding sites. Moreover, sQTLs were largely distinct from expression quantitative trait loci (eQTLs) and showed significant enrichment in potential risk loci of NSCLC. We also integrated sQTLs into NSCLC GWAS datasets (13,327 affected individuals and 13,328 control individuals) by using splice-transcriptome-wide association study (spTWAS) and identified alternative splicing events in 19 genes that were significantly associated with NSCLC risk. By using functional annotation and experiments, we confirmed an sQTL variant, rs35861926, that reduced the risk of lung adenocarcinoma (rs35861926-T, OR = 0.88, 95% confidence interval [CI]: 0.82-0.93, p = 1.87 × 10-5) by promoting FARP1 exon 20 skipping to downregulate the expression level of the long transcript FARP1-011. Transcript FARP1-011 promoted the migration and proliferation of lung adenocarcinoma cells. Overall, our study provided informative lung sQTL resources and insights into the molecular mechanisms linking sQTL variants to NSCLC risk.

Development and evaluation of a polygenic risk score for lung cancer in never-smoking women: A large-scale prospective Chinese cohort study.

The proportion of lung cancer in never smokers is rising, especially among Asian women, but there is no effective early detection tool. Here, we developed a polygenic risk score (PRS), which may help to identify the population with higher risk of lung cancer in never-smoking women. We first performed a large GWAS meta-analysis (8595 cases and 8275 controls) to systematically identify the susceptibility loci for lung cancer in never-smoking Asian women and then generated a PRS using GWAS datasets. Furthermore, we evaluated the utility and effectiveness of PRS in an independent Chinese prospective cohort comprising 55 266 individuals. The GWAS meta-analysis identified eight known loci and a novel locus (5q11.2) at the genome-wide statistical significance level of P < 5 × 10-8 . Based on the summary statistics of GWAS, we derived a polygenic risk score including 21 variants (PRS-21) for lung cancer in never-smoking women. Furthermore, PRS-21 had a hazard ratio (HR) per SD of 1.29 (95% CI = 1.18-1.41) in the prospective cohort. Compared with participants who had a low genetic risk, those with an intermediate (HR = 1.32, 95% CI: 1.00-1.72) and high (HR = 2.09, 95% CI: 1.56-2.80) genetic risk had a significantly higher risk of incident lung cancer. The addition of PRS-21 to the conventional risk model yielded a modest significant improvement in AUC (0.697 to 0.711) and net reclassification improvement (24.2%). The GWAS-derived PRS-21 significantly improves the risk stratification and prediction accuracy for incident lung cancer in never-smoking Asian women, demonstrating the potential for identification of high-risk individuals and early screening.

Identification of genetically predicted DNA methylation markers associated with non-small cell lung cancer risk among 34,964 cases and 448,579 controls.

BACKGROUND: Although the associations between genetic variations and lung cancer risk have been explored, the epigenetic consequences of DNA methylation in lung cancer development are largely unknown. Here, the genetically predicted DNA methylation markers associated with non-small cell lung cancer (NSCLC) risk by a two-stage case-control design were investigated. METHODS: The genetic prediction models for methylation levels based on genetic and methylation data of 1595 subjects from the Framingham Heart Study were established. The prediction models were applied to a fixed-effect meta-analysis of screening data sets with 27,120 NSCLC cases and 27,355 controls to identify the methylation markers, which were then replicated in independent data sets with 7844 lung cancer cases and 421,224 controls. Also performed was a multi-omics functional annotation for the identified CpGs by integrating genomics, epigenomics, and transcriptomics and investigation of the potential regulation pathways. RESULTS: Of the 29,894 CpG sites passing the quality control, 39 CpGs associated with NSCLC risk (Bonferroni-corrected p ≤ 1.67 × 10-6 ) were originally identified. Of these, 16 CpGs remained significant in the validation stage (Bonferroni-corrected p ≤ 1.28 × 10-3 ), including four novel CpGs. Multi-omics functional annotation showed nine of 16 CpGs were potentially functional biomarkers for NSCLC risk. Thirty-five genes within a 1-Mb window of 12 CpGs that might be involved in regulatory pathways of NSCLC risk were identified. CONCLUSIONS: Sixteen promising DNA methylation markers associated with NSCLC were identified. Changes of the methylation level at these CpGs might influence the development of NSCLC by regulating the expression of genes nearby. PLAIN LANGUAGE SUMMARY: The epigenetic consequences of DNA methylation in lung cancer development are still largely unknown. This study used summary data of large-scale genome-wide association studies to investigate the associations between genetically predicted levels of methylation biomarkers and non-small cell lung cancer risk at the first time. This study looked at how well larotrectinib worked in adult patients with sarcomas caused by TRK fusion proteins. These findings will provide a unique insight into the epigenetic susceptibility mechanisms of lung cancer.

Integrative analyses of N6-methyladenosine-associated single-nucleotide polymorphisms (m6A-SNPs) identify tumor suppressor gene AK9 in lung cancer.

N6 -methyladenosine (m6 A) modification has been identified as one of the most important epigenetic regulation mechanisms in the development of human cancers. However, the association between m6 A-associated single-nucleotide polymorphisms (m6 A-SNPs) and lung cancer risk remains largely unknown. Here, we identified m6 A-SNPs and examined the association of these m6 A-SNPs with lung cancer risk in 13,793 lung cancer cases and 14,027 controls. In silico functional annotation was used to identify causal m6 A-SNPs and target genes. Furthermore, methylated RNA immunoprecipitation and quantitative real-time polymerase chain reaction (MeRIP-qPCR) assay was performed to assess the m6 A modification level of different genotypes of the causal SNP. In vitro assays were performed to validate the potential role of the target gene in lung cancer. A total of 8794 m6 A-SNPs were detected, among which 397 SNPs in nine susceptibility loci were associated with lung cancer risk, including six novel loci. Bioinformatics analyses indicated that rs1321328 in 6q21 was located around the m6 A modification site of AK9 and significantly reduced AK9 expression (ß = -0.15, p = 2.78 × 10-8 ). Moreover, AK9 was significantly downregulated in lung cancer tissues than that in adjacent normal tissues of samples from the Cancer Genome Atlas and Nanjing Lung Cancer Cohort. MeRIP-qPCR assay suggested that C allele of rs1321328 could significantly decrease the m6 A modification level of AK9 compared with G allele. In vitro assays verified the tumor-suppressing role of AK9 in lung cancer. These findings shed light on the pathogenic mechanism of lung cancer susceptibility loci linked with m6 A modification.

Inhibition of porcine origin Klebsiella pneumoniae capsular polysaccharide and immune escape by BY3 compounded traditional Chinese medicine residue fermentation broth.

Klebsiella pneumoniae (K. pneumoniae) is a gram-negative conditionally pathogenic bacterium that causes disease primarily in immunocompromised individuals. Recently, highly virulent K. pneumoniae strains have caused severe disease in healthy individuals, posing significant challenges to global infection control. Capsular polysaccharide (CPS), a major virulence determinant of K. pneumoniae, protects the bacteria from being killed by the host immune system, suggesting an urgent need for the development of drugs to prevent or treat K. pneumoniae infections. In this study, BY3 compounded traditional Chinese medicine residue (TCMR) was carried out using Lactobacillus rhamnosus as a fermentation strain, and BY3 compounded TCMR fermentation broth (BY3 fermentation broth) was obtained. The transcription of K. pneumoniae CPS-related biosynthesis genes after treatment with BY3 fermentation broth was detected using quantitative real-time polymerase chain reaction. The effects of BY3 fermentation broth on K. pneumoniae serum killing, macrophage phagocytosis, complement deposition and human ß-defensin transcription were investigated. The therapeutic effect of BY3 fermentation broth on K. pneumoniae-infected mice was also observed, and the major active components of BY3 fermentation broth were analysed via LC‒MS analysis, network pharmacology, and molecular docking. The results showed that BY3 fermentation broth inhibited K. pneumoniae CPS production and downregulated transcription of CPS-related biosynthesis genes, which weakened bacterial resistance to serum killing and phagocytosis, while promoting bacterial surface complement C3 deposition and human ß-defensin expression. BY3 fermentation broth demonstrated safety and therapeutic effects in vivo and in vitro, restoring body weight and visceral indices, significantly reducing the organ bacterial load and serum cytokine levels, and alleviating pathological organ damage in mice. In addition, three natural compounds-oleanolic acid, quercetin, and palmitoleic acid-were identified as the major active components in the BY3 fermentation broth. Therefore, BY3 fermentation broth may be a promising strategy for the prevention or treatment of K. pneumoniae infections.

Maternal Dietary Cholesterol and Egg Intake during Pregnancy and Large-for-Gestational-Age Infants: A Prospective Cohort Study.

BACKGROUND: Cholesterol plays a vital role in fetal growth and development during pregnancy. There remains controversy over whether pregnant females should limit their cholesterol intake. OBJECTIVES: The objective of this study was to investigate the association between maternal dietary cholesterol intake during pregnancy and infant birth weight in a Chinese prospective cohort study. METHODS: A total of 4146 mother-child pairs were included based on the Jiangsu Birth Cohort study. Maternal dietary information was assessed with a semiquantitative food-frequency questionnaire. Birth weight z-scores and large-for-gestational-age (LGA) infants were converted by the INTERGROWTH-21st neonatal weight-for-gestational-age standard. Poisson regression and generalized estimating equations were employed to examine the relationships between LGA and maternal dietary cholesterol across the entire pregnancy and trimester-specific cholesterol intake, respectively. RESULTS: The median intake of maternal total dietary cholesterol during the entire pregnancy was 671.06 mg/d, with eggs being the main source. Maternal total dietary cholesterol and egg-sourced cholesterol were associated with an increase in birth weight z-score, with per standard deviation increase in maternal total and egg-sourced dietary cholesterol being associated with an increase of 0.16 [95% confidence interval (CI): 0.07, 0.25] and 0.06 (95% CI: 0.03, 0.09) in birth weight z-score, respectively. Egg-derived cholesterol intake in the first and third trimesters was positively linked to LGA, with an adjusted relative risk of 1.11 (95% CI: 1.04, 1.18) and 1.09 (95% CI: 1.00, 1.18). Compared with mothers consuming ≤7 eggs/wk in the third trimester, the adjusted relative risk for having an LGA newborn was 1.37 (95% CI: 1.09, 1.72) for consuming 8-10 eggs/wk and 1.45 (95% CI: 1.12, 1.86) for consuming >10 eggs/wk (P-trend = 0.015). CONCLUSIONS: Maternal total dietary cholesterol intake, as well as consuming over 7 eggs/wk during pregnancy, displayed significant positive relationships with the incidence of LGA, suggesting that mothers should avoid excessive cholesterol intake during pregnancy to prevent adverse birth outcomes.

Lymphoma-associated hemophagocytic syndrome: a retrospective, single-center study of 86 patients.

To explore the clinical features, treatment, and prognosis of patients with lymphoma-associated hemophagocytic syndrome (LAHS) in a real-world clinical setting. We retrospectively examined LAHS patients diagnosed at our center between January 2016 and August 2023, focusing primarily on their clinical features, therapeutic approaches, overall response rate (ORR), and overall survival (OS). A combination of univariate and multivariate analyses was conducted to identify potential prognostic factors. A total of 86 patients diagnosed with LAHS were included to evaluate clinical characteristics and prognostic factors. Patients with T/NK cell lymphoma had a higher probability of developing hemophagocytic syndrome (HPS) during the clinical process than those with B cell lymphoma. The median survival time was 55 days for all patients, and 47 and 81 days for the T/NK cell LAHS and B cell LAHS cohorts, respectively (P = 0.025). Among the patients evaluated, the ORR was 42.2%. Patients starting with anti-lymphoma treatment had a better, albeit not significant, ORR than those beginning with anti-HPS treatment. In the univariate analysis, T/NK cell LAHS (P = 0.027), HPS onset at relapse (P = 0.036), higher baseline plasma EBV-DNA levels (> 4,000 copies/mL, P = 0.034), and treatments including cytokine adsorption and ruxolitinib (P < 0.001 and P = 0.017, respectively) were potentially associated with worse OS, while corticosteroid therapy benefited OS. In the multivariate analysis, T/NK cell LAHS (adjusted hazard ratio (aHR) = 2.007), cytokine adsorption therapy (aHR = 4.547), and corticosteroid therapy (aHR = 0.118) were independently associated with mortality. T/NK cell lymphoma was the main cause of LAHS and carried a worse prognosis. Whether anti-lymphoma or anti-HPS treatment should start first still requires prospective studies with larger sample sizes. The key point in controlling HPS is to block the cytokine storm promptly. Corticosteroid therapy is both effective and accessible and should be used early and in sufficient quantities.

Assisted reproductive technology and neurodevelopment in children at 1 year of age: a longitudinal birth cohort study.

BACKGROUND: With remarkable advancements in assisted reproductive technology (ART), the number of ART-conceived children continues to increase. Despite increased research investigating the outcomes of ART children, evidence on neurodevelopment remains controversial. OBJECTIVE: The aim of this study was to investigate the association between ART use and neurodevelopment in children at 1 year of age and to determine whether the characteristics of parental infertility and specific ART procedures affect neurodevelopment in children. STUDY DESIGN: The Jiangsu Birth Cohort enrolled couples who received ART treatment and who conceived spontaneously (2014-2020) in Jiangsu Province, China. In this study, we included 3531 pregnancies with 3840 cohort children who completed neurodevelopment assessment at 1 year of age, including 1906 infants conceived by ART (including 621 twins). Poisson regressions were fitted to estimate unadjusted and adjusted risk ratios (RRs) and 95% confidence intervals (CIs) for ART use with neurodevelopmental outcomes (cognition, receptive communication, expressive communication, fine motor, and gross motor) in children. RESULTS: Among singletons, ART use was associated with a 24% to 34% decrease in the risk for noncompetent development in 3 domains (cognition, adjusted RR, 0.66; 95% CI, 0.53-0.82; receptive communication, 0.76; 0.64-0.91; expressive communication, 0.69; 0.51-0.93) after adjustment for conventional covariates. However, an inverse association was observed in the gross motor domain, with ART singletons having a greater risk of being noncompetent in gross motor development than their non-ART counterparts (adjusted RR, 1.41; 95% CI, 1.11-1.79). Compared with singletons, twins resulting from ART treatment demonstrated compromised neurodevelopment in several domains. Furthermore, we continued to observe that the transfer of 'poor' quality embryos was associated with greater risks for noncompetent development in receptive communication (adjusted RR, 1.50; 95% CI, 1.05-2.14) and gross motor domains (1.55; 1.02-2.36) among ART singletons. CONCLUSION: These results generally provide reassuring evidence among singletons born after ART in the cognition, communication, and fine motor domains, but drawn attention to their gross motor development. The quality of transferred embryos in ART treatment might be associated with offspring neurodevelopment; however, the potential associations warrant further validation in independent studies, and the clinical significance needs careful interpretation.

Association of lifestyle with reduced stroke risk in 41 314 individuals with diabetes: Two prospective cohort studies in China.

AIM: To investigate the associations of individual and combined healthy lifestyle factors (HLS) with the risk of stroke in individuals with diabetes in China. METHODS: This prospective analysis included 41 314 individuals with diabetes [15 191 from the Comprehensive Research on the Prevention and Control of the Diabetes (CRPCD) project and 26 123 from the China Kadoorie Biobank (CKB) study]. Associations of lifestyle factors, including cigarette smoking, alcohol consumption, physical activity, diet, body shape and sleep duration, with the risk of stroke, intracerebral haemorrhage (ICH) and ischaemic stroke (IS) were assessed using Cox proportional hazard models. RESULTS: During median follow-up periods of 8.02 and 9.05 years, 2499 and 4578 cases of stroke, 2147 and 4024 of IS, and 160 and 728 of ICH were documented in individuals with diabetes in the CRPCD and CKB cohorts, respectively. In the CRPCD cohort, patients with ≥5 HLS had a 14% lower risk of stroke (hazard ratio (HR): 0.86, 95% confidence interval (CI): 0.75-0.98) than those with ≤2 HLS. In the CKB cohort, the adjusted HR (95% CI) for patients with ≥5 HLS were 0.74 (0.66-0.83) for stroke, 0.74 (0.66-0.83) for IS, and 0.57 (0.42-0.78) for ICH compared with those with ≤2 HLS. The pooled adjusted HR (95% CI) comparing patients with ≥5 HLS versus ≤2 HLS was 0.79 (0.69-0.92) for stroke, 0.80 (0.68-0.93) for IS, and 0.60 (0.46-0.78) for ICH. CONCLUSIONS: Maintaining a healthy lifestyle was associated with a lower risk of stroke, IS and ICH among individuals with diabetes.

Prenatal Parental Exposure to Metals and Birth Defects: A Prospective Birth Cohort Study.

While maternal exposure to high metal levels during pregnancy is an established risk factor for birth defects, the role of paternal exposure remains largely unknown. We aimed to assess the associations of prenatal paternal and maternal metal exposure and parental coexposure with birth defects in singletons. This study conducted within the Jiangsu Birth Cohort recruited couples in early pregnancy. We measured their urinary concentrations for 25 metals. A total of 1675 parent-offspring trios were included. The prevalence of any birth defects among infants by one year of age was 7.82%. Paternal-specific gravity-corrected urinary concentrations of titanium, vanadium, chromium, manganese, cobalt, nickel, copper, and selenium and maternal vanadium, chromium, nickel, copper, selenium, and antimony were associated with a 21-91% increased risk of birth defects after adjusting for covariates. These effects persisted after mutual adjustment for the spouse's exposure. Notably, when assessing the parental mixture effect by Bayesian kernel machine regression, paternal and maternal chromium exposure ranked the highest in relative importance. Parental coexposure to metal mixture showed a pronounced joint effect on the risk of overall birth defects, as well as for some specific subtypes. Our findings suggested a couple-based prevention strategy for metal exposure to reduce birth defects in offspring.

Bioinformatics-based analysis of potential therapeutic target genes for polycystic ovary syndrome.

The purpose of this study was to screen differentially expressed genes in PCOS using gene chip data and investigate the biological functions of these DEGs in PCOS. Additionally, the study aimed to analyze the potential clinical significance of these genes using clinical data. In this study, we first screened the DEGs related to PCOS by using the gene chip data (GSE5090) from GEO database. Target gene prediction software was used to predict the target genes for these DEGs, and their functional enrichment was analysed. Subsequently, the STRING online tool and Cytoscape software were utilized to identify key genes by constructing protein-protein interaction networks (PPI). In the analysis of the GSE5090 dataset, seventeen differentially expressed genes (DEGs) were identified. Functional enrichment analysis revealed that these DEGs are predominantly associated with biological functions related to polycystic ovary syndrome (PCOS). Moreover, the tissue-specific expression analysis highlighted immune system markers, with a notable difference observed in 18 of these markers, accounting for 20.5% of the total. By constructing PPI networks and key gene regulatory networks, a total of three genes (RPL13, LEP, and ANXA1) were identified as key genes. In addition, the column-line graphical model performed well in predicting the risk of PCOS. Using ROC curves, the model proved to be effective in diagnosis. This study represents the first application of a bioinformatics approach to identify and confirm high expression levels of RPL13, LEP, and ANXA1 in patients with Polycystic Ovary Syndrome (PCOS). These key genes-RPL13, LEP, and ANXA1-may present viable targets for therapeutic interventions in PCOS, underscoring their potential clinical importance.

Associations of inflammation related prenatal adversities with neurodevelopment of offspring in one year: a longitudinal prospective birth cohort study.

BACKGROUND: The recent Maternal Immune Activation (MIA) theory suggests maternal systemic inflammation may serve as a mediator in associations between prenatal maternal adversities and neurodevelopmental diseases in offspring. Given the co-exposure to multiple adversities may be experienced by pregnant person, it is unclear whether a quantitative index can be developed to characterize the inflammation related exposure level, and whether this index is associated with neurodevelopmental delays in offspring. METHODS: Based on Jiangsu Birth Cohort (JBC), a total of 3051 infants were included in the analysis. Inflammation related Prenatal Adversity Index (IPAI) was constructed using maternal data. Neurodevelopmental outcomes were assessed using the Bayley Scales of Infant and Toddler Development, third edition, screening test in one year. Multivariate linear regression and Poisson regression model were performed to analyze the associations between IPAI and neurodevelopment in offspring. RESULTS: Compared with "low IPAI" group, offspring with "high IPAI" have lower scores of cognition, receptive communication, expressive communication, and fine motor. The adjusted ß were - 0.23 (95%CI: -0.42, -0.04), -0.47 (95%CI: -0.66, -0.28), -0.30 (95%CI: -0.49, -0.11), and - 0.20 (95%CI: -0.33, -0.06). Additionally, the elevated risk for noncompetent development of cognition and receptive communication among "high IPAI" group was observed. The relative risk [RR] and 95% confidence interval [CI] were 1.35 (1.01, 1.69) and 1.37 (1.09, 1.72). CONCLUSIONS: Our results revealed a significant association between higher IPAI and lower scores across cognition, receptive communication, expressive communication, and fine motor domains, and an increased risk of noncompetent development in the cognition and receptive communication domains.

Enhanced glycolysis in the myometrium with ectopic endometrium of patients with adenomyosis: a preliminary study.

OBJECTIVES: The objective of this study was to investigate the glycolytic activity of adenomyosis, which is characterized by malignant biological behaviors including abnormal cell proliferation, migration, invasion, cell regulation, and epithelial-mesenchymal transition. METHODS: From January 2021 to August 2022, a total of 15 patients who underwent total hysterectomy for adenomyosis and 14 patients who had non-endometrial diseases, specifically with cervical squamous intraepithelial neoplasia and uterine myoma, were included in this study. Myometrium with ectopic endometrium from patients with adenomyosis while normal myometrium from patients in the control group were collected. All samples were confirmed by a histopathological examination. The samples were analyzed by liquid chromatography-mass spectrometry (LC-MS), real-time quantitative PCR, NAD+/NADH assay kit as well as the glucose and lactate assay kits. RESULTS: Endometrial stroma and glands could be observed within the myometrium of patients in the adenomyosis group. We found that the mRNA expressions of HK1, PFKFB3, glyceraldehyde-3-phospate dehydrogenase (GAPDH), PKM2, and PDHA as well as the protein expressions of PFKFB3 were elevated in ectopic endometrial tissues of the adenomyosis group as compared to normal myometrium of the control group. The level of fructose 1,6-diphosphate was increased while NAD + and NAD+/NADH ratio were decreased compared with the control group. Besides, increased glucose consumption and lactate production were observed in myometrium with ectopic endometrium. CONCLUSIONS: We concluded that altered glycolytic phenotype of the myometrium with ectopic endometrium in women with adenomyosis may contribute the development of adenomyosis.

The association between METS-IR, an indirect index for insulin resistance, and lung cancer risk.

BACKGROUND: Insulin resistance has been reported to increase the risk of breast, prostate and colorectal cancer. However, the role of insulin resistance and its interaction with genetic risk in the development of lung cancer remains controversial. Therefore, we aimed to explore the association between a novel metabolic score for insulin resistance (METS-IR) and lung cancer risk. METHODS: A total of 395 304 participants without previous cancer at baseline were included. The Cox proportional hazards regression model was performed to investigate the association between METS-IR and lung cancer risk. In addition, a Mendelian randomization analysis was also performed to explore the causal relationship. The joint effects and additive interactions between METS-IR and polygenetic risk score (PRS) of lung cancer were also investigated. RESULTS: During a median follow-up of 11.03 years (Inter-quartile range (IQR): 10.30-11.73), a total of 3161 incident lung cancer cases were diagnosed in 395 304 participants. There was a significant association between METS-IR and lung cancer risk, with an HR of 1.28 (95% CI: 1.17-1.41). Based on the Mendelian randomization analysis, however, no causal associations were observed. We observed a joint effect but no interaction between METS-IR and genetic risk. The lung cancer incidence was estimated to be 100.42 (95% CI: 91.45-109.38) per 100 000 person-year for participants with a high METS-IR and PRS, while only 42.76 (95% CI: 36.94-48.59) with low METS-IR and PRS. CONCLUSIONS: High METS-IR was significantly associated with an increased risk of lung cancer. Keeping a low level of METS-IR might help reduce the long-term incident risk of lung cancer.

The Relationship Between Ureaplasma Species and Male Infertility: Pathogenicity, Biology, Diagnosis, and Treatment.

Objective: Ureaplasma spp. comprise a group of mycoplasmas containing two human-associated species, namely, Ureaplasma urealyticum (UUR) and Ureaplasma parvum (UPA). The characterization of Ureaplasma species as pathogens contributing to male infertility remains a subject of considerable controversy. While numerous authors have proposed a relationship between UUR and changes in fertility, there is limited evidence supporting the involvement of UPA in this context. There has been an increased focus on Ureaplasma spp. and its potential role in the development of male infertility, especially over the past few years. The review aims to clarify the relationship between Ureaplasma species and male infertility. Methods: Firstly, we introduce a background of the appropriate biology including growth characteristics, the divided biovars, and the transmission pathways. Secondly, we examine the studies that support a causal role for Ureaplasma spp. in the development of infertility in the last 30 years. Finally, the diagnosed method, antimicrobial susceptibility, and potential therapeutic considerations are evaluated. Results: UPA and UUR can impair semen motility. The species of Ureaplasma spp., the sexual history of the patient, the number of sexual partners, the load of Ureaplasma, and antimicrobial resistance are expected to constitute key risk factors in the development of male infertility. In terms of treatment, Doxycycline remains the drug of first choice for ureaplasmal infections. Conclusion: Ureaplasma spp. are not simply "innocent bystanders" in infertility and may indeed be an "underestimated enemy of human reproduction". Ureaplasma spp. can be considered an etiological agent in unexplained infertility and a useful marker.

Effects of Respiratory Function Exercise and Psychological Nursing on COPD Patients: A Comprehensive Study.

Background: Chronic Obstructive Pulmonary Disease (COPD) is a prevalent and impactful respiratory condition, necessitating effective interventions for improved patient outcomes. This retrospective analysis aimed to explore the efficacy of respiratory function exercise combined with psychological nursing on cardiopulmonary function index, exercise tolerance, and quality of life in patients with stable COPD. Methods: The data of 100 patients with stable COPD admitted to Cangzhou Central Hospital from June 2019 to June 2021 were retrospectively analyzed. Patients were assigned to the experimental group (n=50) and the control group (n=50) alphabetically by their initials. Patients in both groups were treated with conventional care combined with respiratory function exercise, and the experimental group additionally received psychological care intervention. Pulmonary function indicators, including forced vital capacity (FVC), forced expiratory volume in one second (FEV1), one-second rate (FEV1/FVC), 6-min walking test (6MWT) results, quality of life (physical health and role emotional), anxiety and depression self-rating scale scores, nursing satisfaction, and clinical efficacy were compared between the two groups before and after treatment. Results: The two groups presented no significant differences in baseline data (P > .05). The experimental group outperformed the control group in terms of pulmonary function index, quality of life, and nursing satisfaction (P < .001). The observation group obtained lower negative emotion scores than the control group after nursing intervention (P < .001). After nursing, the FEV1/FVC in the experimental group was significantly higher than that in the control group [(58.63 ± 5.64) vs (46.36 ± 5.23)]. The 6MWT results in the experimental group were significantly better than those in the control group [(398.35 ± 28.65) m vs (348.97 ± 26.98) m] (all P < .001). Conclusion: The results revealed that this combined approach effectively improves lung function, mitigates negative emotions, enhances nursing satisfaction, and significantly boosts the quality of life in patients with stable COPD. These findings underscore the potential clinical relevance of implementing such interventions for better COPD management and patient well-being.

Association of serum metal levels with type 2 diabetes: A prospective cohort and mediating effects of metabolites analysis in Chinese population.

Several studies have suggested an association between exposure to various metals and the onset of type 2 diabetes (T2D). However, the results vary across different studies. We aimed to investigate the associations between serum metal concentrations and the risk of developing T2D among 8734 participants using a prospective cohort study design. We utilized inductively coupled plasmamass spectrometry (ICP-MS) to assess the serum concentrations of 27 metals. Cox regression was applied to calculate the hazard ratios (HRs) for the associations between serum metal concentrations on the risk of developing T2D. Additionally, 196 incident T2D cases and 208 healthy control participants were randomly selected for serum metabolite measurement using an untargeted metabolomics approach to evaluate the mediating role of serum metabolite in the relationship between serum metal concentrations and the risk of developing T2D with a nested casecontrol study design. In the cohort study, after Bonferroni correction, the serum concentrations of zinc (Zn), mercury (Hg), and thallium (Tl) were positively associated with the risk of developing T2D, whereas the serum concentrations of manganese (Mn), molybdenum (Mo), barium (Ba), lutetium (Lu), and lead (Pb) were negatively associated with the risk of developing T2D. After adding these eight metals, the predictive ability increased significantly compared with that of the traditional clinical model (AUC: 0.791 vs. 0.772, P=8.85×10-5). In the nested casecontrol study, a machine learning analysis revealed that the serum concentrations of 14 out of 1579 detected metabolites were associated with the risk of developing T2D. According to generalized linear regression models, 7 of these metabolites were significantly associated with the serum concentrations of the identified metals. The mediation analysis showed that two metabolites (2-methyl-1,2-dihydrophthalazin-1-one and mestranol) mediated 46.81% and 58.70%, respectively, of the association between the serum Pb concentration and the risk of developing T2D. Our study suggested that serum Mn, Zn, Mo, Ba, Lu, Hg, Tl, and Pb were associated with T2D risk. Two metabolites mediated the associations between the serum Pb concentration and the risk of developing T2D.

The Long-Acting Serine Protease Inhibitor mPEG-SPA-MDSPI16 Alleviates LPS-Induced Acute Lung Injury.

Anti-inflammatory drugs have become the second-largest class of common drugs after anti-infective drugs in animal clinical care worldwide and are often combined with other drugs to treat fever and viral diseases caused by various factors. In our previous study, a novel serine protease inhibitor-encoding gene (MDSPI16) with improved anti-inflammatory activity was selected from a constructed suppressive subducted hybridization library of housefly larvae. This protein could easily induce an immune response in animals and had a short half-life, which limited its wide application in the clinic. Thus, in this study, mPEG-succinimidyl propionate (mPEG-SPA, Mw = 5 kDa) was used to molecularly modify the MDSPI16 protein, and the modified product mPEG-SPA-MDSPI16, which strongly inhibited elastase production, was purified. It had good stability and safety, low immunogenicity, and a long half-life, and the IC50 for elastase was 86 nM. mPEG-SPA-MDSPI16 effectively inhibited the expression of neutrophil elastase and decreased ROS levels. Moreover, mPEG-SPA-MDSPI16 exerted anti-inflammatory effects by inhibiting activation of the NF-κB signaling pathway and the MAPK signaling pathway in neutrophils. It also exerted therapeutic effects on a lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model. In summary, mPEG-SPA-MDSPI16 is a novel anti-inflammatory protein modified with PEG that has the advantages of safety, nontoxicity, improved stability, and strong anti-inflammatory activity in vivo and in vitro and is expected to become an effective anti-inflammatory drug.

Hydrogel Wound Dressings Accelerating Healing Process of Wounds in Movable Parts.

Skin is the largest organ in the human body and requires proper dressing to facilitate healing after an injury. Wounds on movable parts, such as the elbow, knee, wrist, and neck, usually undergo delayed and inefficient healing due to frequent movements. To better accommodate movable wounds, a variety of functional hydrogels have been successfully developed and used as flexible wound dressings. On the one hand, the mechanical properties, such as adhesion, stretchability, and self-healing, make these hydrogels suitable for mobile wounds and promote the healing process; on the other hand, the bioactivities, such as antibacterial and antioxidant performance, could further accelerate the wound healing process. In this review, we focus on the recent advances in hydrogel-based movable wound dressings and propose the challenges and perspectives of such dressings.