Causal Association of Rheumatoid Arthritis With Adverse Pregnancy Outcomes: Genetic Evidence From Mendelian Randomization.

OBJECTIVE: Although the association of rheumatoid arthritis (RA) to multiple adverse pregnancy outcomes has been well-studied, the association between serum antibody levels in patients with RA and multiple adverse pregnancy outcomes has not been conclusively demonstrated. Here, we comprehensively assessed the causal impact of RA, serologic antibody-positive RA (pRA), and serologic antibody-negative RA (nRA) on the risk of 14 adverse pregnancy outcomes. METHODS: The causal impact of RA, pRA, and nRA on 14 adverse pregnancy outcomes was comprehensively assessed using two-sample Mendelian randomization (MR). Evidence maps based on the results of these two-sample MR analyses were developed. Data from the UK Biobank and FinnGen databases were utilized for this analysis. The inverse variance weighted (IVW) test was employed as the primary method to estimate causality. "TwoSampleMR" and "MR-PRESSO" packages were used for data analysis in this study. RESULTS: Using two-sample MR analysis, we found a significant positive causal association between RA and increased risk of cesarean section (p = 0.003), gestational hypertension (p < 0.001), number of spontaneous miscarriages (p = 0.041), preeclampsia (p = 0.008), premature rupture of membranes (p = 0.030), and preterm (p = 0.010). pRA had a significant positive causal association with an increased risk of cesarean section (p = 0.012), gestational hypertension (p < 0.001), preeclampsia (p = 0.002), and preterm (p = 0.007). A significant positive causal association was also established between nRA and gestational hypertension (p = 0.010), the number of spontaneous miscarriages (p = 0.024), and placental abruption (p = 0.027). In addition, we found a causal association between nRA and birth weight (p = 0.007), but not between RA and pRA and birth weight. CONCLUSION: The results of this study have important implications for the individualized treatment of RA patients, especially those with positive serum antibody levels.

Anti-Toxoplasma gondii effects of XYP1-derived peptides and regulatory mechanisms of XYP1.

BACKGROUND: Toxoplasmosis, caused by Toxoplasma gondii , poses serious health issues for humans and animals. Individuals with impaired immune systems are more susceptible to severe toxoplasmosis. Pregnant women infected by T. gondii can face the possibility of birth defects and miscarriages. While pyrimethamine and sulfadiazine are commonly used drugs in clinical practice, concerns over their side effects and resistance are on the rise. A spider peptide XYP1 isolated from Lycosa coelestis had potent anti-T. gondii effects, but it had a high synthesis cost and strong cytotoxicity. METHODS: This study intended to modify XYP1 for producing derived peptides via amino acid truncation and substitution. The anti-T. gondii effect was evaluated by trypan blue staining assay and killing experiment of RH strain tachyzoites. The CCK8 and hemolysis assays were used to compare their safeties. The morphological changes of T. gondii were observed by scanning electron microscope and transmission electron microscope. In addition, the mechanism of XYP1 against T. gondii through RNA-sequencing was further explored. RESULTS: In vivo and in vitro experiments revealed that XYP1-18 and XYP1-18-1 had excellent anti-T. gondii activity with lower cytotoxicity and hemolysis activity than XYP1. XYP1, XYP1-18, and XYP1-18-1 were able to disrupt the surface membrane integrity of T. gondii tachyzoites, forming pores and causing the disruption of organelles. Furthermore, RNA-sequencing analysis indicated that XYP1 could stimulate the host immune response to effectively eliminate T. gondii and lessen the host's inflammatory reaction. CONCLUSIONS: XYP1-18 had lower cytotoxicity and hemolysis activity than XYP1, as well as significantly extending the survival time of the mice. XYP1 played a role in host inflammation and immune responses, revealing its potential mechanism. Our research provided valuable insights into the development and application of peptide-based drugs, offering novel strategies and directions for treating toxoplasmosis.

Can formal home and community-based care substitute informal care? Evidence from Chinese Longitudinal Healthy Longevity Survey.

BACKGROUND: Formal home and community-based care are often considered as the preferable option to institutional care, offering older individuals the convenience of receiving care in their homes. Although research has found that these services may alleviate the burden on informal caregivers, there is a lack of research on which specific types of formal home and community-based care influence informal care provision. METHODS: Employing fixed-effects and quantile regression models, this study seeks to explore the effects that various formal home and community-based care services have on reducing the burden of informal care. This study draws data from the Chinese Longitudinal Healthy Longevity Survey 2005, 2008, 2011, 2014, and 2018. RESULTS: Our findings indicate that two types of formal care substantially influence the provision of informal care. The availability of daily living assistance services correlates with reduced informal caregiving hours, especially for those with extensive care needs. The availability of community-based health care services is linked to a reduction in the direct expenses incurred from informal caregiving, especially for those incurring greater direct caregiving costs. These effects are more prominent among urban residents. Other services, such as mental health support and legal advice services, do not demonstrate significant effects on reducing informal care hours and costs. CONCLUSIONS: Daily living assistance and community-based health care services play a crucial role in benefiting informal caregivers. It is important to prioritize the expansion of these services, especially among those with greater care needs.

Rapid spread, slow evaporation: a long-lasting water film on hydrogel nanowire arrays for continuous wearables.

A successful flexible wearable not only has to fulfill its function, but also has to ensure long-term wettability and comfort during wearing. In biological systems, tears spread rapidly across the cornea to ensure clear imaging while slowly evaporating to maintain moisture in the eyes. This dynamic behavior of 'rapid spread, slow evaporation' ensures durative humidity and comfort, which can provide design guidelines for continuous wearable devices. However, realizing this dynamic process in vitro remains a challenge. Herein, inspired by a healthy ocular surface, we biomimetically construct a hybrid surface featuring mucin-like hydrophilic layer@hydrogel nanowire arrays (HL@HNWs). A droplet (2 µL) rapidly spreads into a thin film, stabilizing for ∼10 minutes, whereas the contrast sample rapidly ruptures and dewets within 1 minute. We demonstrate that enhancing the proportion of hydrated water (HW), which includes intermediate water (IW) and bound water (BW), and introducing the capillary resistance of the nanowire arrays could synergistically stabilize the water film and improve the wettability. Hydrogel-based nanowire array contact lenses can ensure wettability during continuous wear, and a stable water film can substantially improve comfort and provide superior visual quality.

Genome-wide association study of Verticillium longisporum resistance in Brassica genotypes.

Verticillium stripe, caused by Verticillium longisporum, presents an emerging threat to Canadian canola (Brassica napus). Initially detected in Manitoba in 2014, the presence of this pathogen has since been confirmed across western Canada. Infections by V. longisporum can result in yield losses of up to 50%, which is a cause for concern given the susceptibility of most commercial Canadian canola cultivars. The objective of this study was to screen a collection of 211 Brassica genotypes for their reactions to V. longisporum, and to use genome-wide association study (GWAS) to identify single nucleotide polymorphism (SNP) markers for resistance. The plant material consisted of 110 rutabaga (B. napus ssp. napobrassica), 35 canola, 40 Brassica rapa, and 15 Brassica oleracea accessions or cultivars, alongside 11 hosts of the European Clubroot Differential (ECD) set. These materials were screened for resistance under greenhouse conditions and were genotyped using a 19K Brassica SNP array. Three general linear models (GLM), four mixed linear models (MLM), and three GWAS methods were employed to evaluate the markers. Eleven non-commercial Brassica accessions and 9 out of 35 commercial canola cultivars displayed a low normalized area under the disease progress curve (AUDPCnorm.). The non-commercial accessions could prove valuable as potential sources of resistance against V. longisporum. Forty-five SNP markers were identified to be significantly associated with V. longisporum resistance using single-SNP based GWAS analysis. In comparison, haplotype-based GWAS analyses identified 10 to 25 haplotype blocks to be significantly associated with V. longisporum resistance. Between 20% and 56% of QTLs identified by the more conventional single-SNP based GWAS analysis were also detected by the haplotype-based GWAS analysis. The overlapping genomic regions identified by the two GWAS methods present promising hotspots for marker-assisted selection in the future development of Verticillium stripe-resistant canola.

Prediction of early remission after infliximab in Crohn's disease using baseline microbiome and metabolomics.

To characterize the microbiome and metabolic profile in Crohn's disease (CD) patients with different outcome after infliximab (IFX) treatment. The clinical data of a cohort of 35 patients with moderate-to-severe CD admitted at Jinling hospital between Oct 2022 and Dec 2023 were collected. Stool samples at baseline were collected to perform 16SrRNA and ITS2 sequencing and LC-MS untargeted metabolomics. Of these, seven discontinued IFX and underwent surgery during the induction period, and 28 received IFX at weeks 0, 2, and 6, each administered intravenously. Clinical remission was assessed based on the clinical symptoms and HBI at baseline and week 14. Baseline microbial richness and evenness was not significantly different between remission and non-remission group. The taxonomic community analysis identified decrease of Ruminococcus, Lachnoclostridium, Akkermansia in bacterial community and decrease of Asterotremella and Wallemia in fungal community in the non-remission group. LC-MS analysis showed that histamine, creatinine and L-proline significantly increased in remission group, while androsterone, berberine and episterol significantly decreased. The combined prediction model of histamine, androsterone, and episterol demonstrated a high predictive value of remission in patients after IFX treatment (AUC=0.898, p<0.001). Together, these data might facilitate a priori determination of optimal therapeutics for CD patients.

The Serum NLRP1 Level and Coronary Artery Calcification: From Association to Development of a Risk-Prediction Nomogram.

Background: To investigate the correlation between inflammasomes and coronary artery calcification (CAC), and develop and validating a nomogram for predicting the risk of CAC in patients with coronary artery disease (CAD). Methods: A total of 626 patients with CAD at the Affiliated Hospital of Xuzhou Medical University were enrolled in this study. The patients were divided into the calcification group and the non-calcification group based on the assessment of coronary calcification. We constructed a training set and a validation set through random assignment. The least absolute shrinkage and selection operator (LASSO) regression and multivariate analysis were performed to identify independent risk factors of CAC in patients with CAD. Based on these independent predictors, we developed a web-based dynamic nomogram prediction model. The area under the receiver operating characteristic curve (AUC-ROC), calibration curves, and decision curve analysis (DCA) were used to evaluate this nomogram. Results: Age, smoking, diabetes mellitus (DM), hyperlipidemia, the serum level of nucleotide-binding oligomerization domain (NOD)-like receptor protein 1 (NLRP1), alkaline phosphatase (ALP) and triglycerides (TG) were identified as independent risk factors of CAC. The AUC-ROC of the nomogram is 0.881 (95% confidence interval (CI): 0.850-0.912) in the training set and 0.825 (95% CI: 0.760-0.876) in the validation set, implying high discriminative ability. Satisfactory performance of this model was confirmed using calibration curves and DCA. Conclusions: The serum NLRP1 level is an independent predictor of CAC. We established a web-based dynamic nomogram, providing a more accurate estimation and comprehensive perspective for predicting the risk of CAC in patients with CAD.

Acyl-CoA synthetase 6 controls rod photoreceptor function and survival by shaping the phospholipid composition of retinal membranes.

The retina is light-sensitive neuronal tissue in the back of the eye. The phospholipid composition of the retina is unique and highly enriched in polyunsaturated fatty acids, including docosahexaenoic fatty acid (DHA). While it is generally accepted that a high DHA content is important for vision, surprisingly little is known about the mechanisms of DHA enrichment in the retina. Furthermore, the biological processes controlled by DHA in the eye remain poorly defined as well. Here, we combined genetic manipulations with lipidomic analysis in mice to demonstrate that acyl-CoA synthetase 6 (Acsl6) serves as a regulator of the unique composition of retinal membranes. Inactivation of Acsl6 reduced the levels of DHA-containing phospholipids, led to progressive loss of light-sensitive rod photoreceptor neurons, attenuated the light responses of these cells, and evoked distinct transcriptional response in the retina involving the Srebf1/2 (sterol regulatory element binding transcription factors 1/2) pathway. This study identifies one of the major enzymes responsible for DHA enrichment in the retinal membranes and introduces a model allowing an evaluation of rod functioning and pathology caused by impaired DHA incorporation/retention in the retina.

RNA-binding proteins potentially regulate alternative splicing of immune/inflammatory-associated genes during the progression of generalized pustular psoriasis.

Generalized pustular psoriasis (GPP) is a rare but severe form of psoriasis. However, the pathogenesis of GPP has not been fully elucidated. Although RNA-binding proteins (RBPs) and the alternative splicing (AS) process are essential for regulating post-transcriptional gene expression, their roles in GPP are still unclear. We aimed to elucidate the regulatory mechanisms to identify potential new therapeutic targets. Here, We analyzed an RNA sequencing (RNA-seq) dataset (GSE200977) of peripheral blood mononuclear cells (PBMCs) of 24 patients with GPP, psoriasis vulgaris (PV), and healthy controls (HCs) from the Gene Expression Omnibus (GEO) database. We found that the abnormal alternative splicing (AS) events associated with GPP were mainly "alt3p/alt5p", and 15 AS genes were differentially expressed. Notably, the proportions of different immune cell types were correlated with the expression levels of regulatory alternatively spliced genes (RASGs): significant differences were observed in expression levels of DTD2, NDUFAF3, NBPF15, and FBLN7 in B cells and ARFIP1, IPO11, and RP11-326L24.9 in neutrophils in the GPP samples. Furthermore, We identified 32 differentially expressed RNA-binding proteins (RBPs) (18 up-regulated and 14 down-regulated). Co-expression networks between 14 pairs of differentially expressed RBPs and RASGs were subsequently constructed, demonstrating that these differentially expressed RBPs may affect the progression of GPP by regulating the AS of downstream immune/inflammatory-related genes such as LINC00989, ENC1 and MMP25-AS1. Our results were innovative in revealing the involvement of inflammation-related RBPs and RASGs in the development of GPP from the perspective of RBP-regulated AS.

AtCIPK20 regulates microtubule stability to mediate stomatal closure under drought stress in Arabidopsis.

Drought stress is a common abiotic challenge that profoundly impacts plant growth and development. As sessile organisms, plants rely on various physiological and morphological adaptations to cope with drought conditions. The CIPK (calcineurin B-like protein-interacting protein kinase) family proteins play a pivotal role in mediating plant responses to abiotic stress through modulation of cellular membrane events via the CBL-CIPK complex. However, reports documenting the CIPKs' regulation of non-membrane events are scant. In this study, we discovered a novel subcellular localisation pattern of the AtCIPK20 protein of Arabidopsis, specifically to cortical microtubules (cMT), which is distinct from previously reported localisation patterns of plant CIPKs. AtCIPK20 regulates ABA-induced loss of cMT organisation in guard cells, thereby facilitating stomatal closure, mitigating leaf water loss, and protecting plants from drought stress in Arabidopsis. The C-terminal regulatory domain of AtCIPK20 governs its cMT targeting, whereas the interaction of AtCIPK20 with its CBL partners disrupts this localisation. Notably, the cMT targeting characteristic of AtCIPK20 is not exclusive, as several other CIPK members in Arabidopsis, maize, and rice exhibit similar localisation patterns. These findings broaden our current understanding of the role of plant CIPK members in abiotic stress resistance and suggest that future exploration of CIPK molecular functions should adopt a more comprehensive perspective.

A Review of Fluoride Removal from Phosphorous Gypsum: A Quantitative Analysis via a Machine Learning Approach.

This review comprehensively explores fluoride removal from phosphogypsum, focusing on its composition, fluorine-containing compounds, characterization methods, and defluorination techniques. It initially outlines the elemental composition of phosphogypsum prevalent in major production regions and infers the presence of fluorine compounds based on these constituents. The study highlights X-ray photoelectron spectroscopy (XPS) as a pivotal method for characterizing fluorine compounds, emphasizing its capability to determine precise binding energies essential for identifying various fluorine species. Additionally, the first-principle density functional theory (DFT) is employed to estimate binding energies of different fluorine-containing compounds. Significant correlations are observed between the total atomic energy of binary fluorides (e.g., of alkali metals, earth metals, and boron group metals) and XPS binding energies. However, for complex compounds like calcium fluorophosphate, correlations with the calculated average atomic total energy are less direct. The review categorizes defluorination methods applied to phosphogypsum as physical, chemical, thermal, and thermal-combined processes, respectively. It introduces neural network machine learning (ML) technology to quantitatively analyze and optimize reported defluorination strategies. Simulation results indicate potential optimizations based on quantitative analyses of process conditions reported in the literature. This review provides a systematic approach to understanding the phosphogypsum composition, fluorine speciation, analytical methodologies, and effective defluorination strategies. The attempts of adopting DFT simulation and quantitative analysis using ML in optimization underscore its potential and feasibility in advancing the industrial phosphogypsum defluorination process.

The Relationship Between the Serum NLRP3 and Adiponectin Levels and Coronary Lesions in Patients with Unstable Angina with Type 2 Diabetes.

Objective: To investigate the Levels of Nucleotide-binding, leucine-rich repeat and pyrin domain-containing protein 3 (NLRP3) and Adiponectin (APN) and their relationship with the severity of coronary artery disease in patients with Unstable Angina (UA) and Type 2 Diabetes (T2D). Methods: Two hundred and thirty-one patients with UA were diagnosed by CAG in the Department of Cardiology of the Affiliated Hospital of Xuzhou Medical University from July 2022 to May 2023 were included, and 74 healthy subjects were included as the control group. The levels of NLRP3 and APN in each group were detected by ELISA and the Gensini score in each patient according to the results of CAG. The correlations between NLRP3, APN, and Gensini score were analyzed. According to whether complicated with T2D or not, we further analyze the effect of NLRP3 and APN levels of patients with UA and T2D on the severity of coronary artery stenosis. Results: The levels of NLRP3 in UA with T2D group were the highest, followed by simple UA group, and the lowest in the control group, and the level of APN was the opposite. Spearman Correlation analysis showed that the level of NLRP3 was positively correlated with Gensini score (ρ1=0.688, P<0.05) and the level of APN was negatively associated with Gensini score (ρ2= -0.515, P<0.05). There was a negative correlation between NLRP3 and the level of APN (ρ3= -0.366, P<0.05). High NLRP3 and low APN levels are the risk factors for atherosclerosis. Conclusion: The NLRP3 and APN were abnormally expressed in patients with UA complicated with T2D. With the aggravation of atherosclerosis, the level of NLRP3 increased and the level of APN decreased.

Risk Factors for Postpartum Hemorrhage in Severe Pre-Eclampsia: A Retrospective Single-Centre Study of 1953 Cases.

BACKGROUND Severe pre-eclampsia (sPE) and postpartum hemorrhage (PPH) in pregnancy have serious impact on maternal and fetal health and life. Co-occurrence of sPE and PPH often leads to poor pregnancy outcomes. We explored risk factors associated with PPH in women with sPE. MATERIAL AND METHODS This retrospective study included 1953 women with sPE who delivered at the Women's Hospital of Nanjing Medical University between April 2015 and April 2023. Risk factors for developing PPH in sPE were analyzed, and subgroups were analyzed by delivery mode (cesarean and vaginal). RESULTS A total of 197 women with PPH and 1756 women without PPH were included. Binary logistic regression results showed twin pregnancy (P<0.001), placenta accreta spectrum disorders (P=0.045), and placenta previa (P<0.001) were independent risk factors for PPH in women with sPE. Subgroup analysis showed risk factors for PPH in cesarean delivery group were the same as in the total population, but vaginal delivery did not reduce risk of PPH. Spinal anesthesia reduced risk of PPH relative to general anesthesia (P=0.034). Vaginal delivery group had no independent risk factors for PPH; however, magnesium sulfate (P=0.041) reduced PPH incidence. CONCLUSIONS Women with twin pregnancy, placenta accreta spectrum disorders, placenta previa, and assisted reproduction with sPE should be alerted to the risk of PPH, and spinal anesthesia should be preferred in cesarean delivery. Magnesium sulfate should be used aggressively in women with sPE; however, the relationship between magnesium sulfate and PPH risk needs further investigation.

Association between triglyceride-glucose index and risk of endometriosis in US population: results from the national health and nutrition examination survey (1999-2006).

Background and Aims: The association of the triglyceride-glucose (TyG) index, a promising novel biomarker for insulin resistance, with the risk of endometriosis has not been investigated to date. This nationwide study aimed to explore the association between the TyG index and the endometriosis risk. Methods: Data were obtained from the National Health and Nutrition Examination Survey (1999-2006). Female participants who provided complete data on the TyG index and endometriosis were enrolled in the analysis. Multivariate logistic regression analyses were utilized to assess the association of the TyG index with endometriosis, adjusted by multiple potential confounders. Meanwhile, in-depth subgroup analyses were conducted. Results: A total of 1,590 eligible participants were included, among whom 135 (8.5%) women were diagnosed with endometriosis. The fully adjusted multivariate logistic model showed TyG index was significantly associated with the endometriosis risk (odds ratio [OR]Q4 versus Q1 2.04, 95% confidence interval [CI]: 1.15-3.62; P for trend=0.013). In subgroup analyses, the significantly positive association between TyG index and the risk of endometriosis was also found in parous women (ORQ4 versus Q1 2.18, 95% CI: 1.20-3.96), women without diabetes (OR Q4 versus Q1 2.12, 95% CI: 1.19-3.79), women who smoke currently (OR Q4 versus Q1 3.93, 95% CI: 1.33-11.58), women who drink currently (OR Q4 versus Q1 2.54, 95% CI: 1.27-5.07), and in women who use oral contraceptives (OR Q4 versus Q1 1.91, 95% CI: 1.04-3.51). Additionally, significantly increasing trends in the odds of endometriosis across the quartiles of the TyG index were observed in the above-mentioned subgroups (all P for trend<0.05). Conclusions: This population-based study found that a higher TyG index, representing an increased level of insulin resistance, was associated with a higher risk of endometriosis among the US population. Our findings suggested TyG index might be a promising tool for the risk assessment of endometriosis. Prospective studies are warranted to further verify these findings.

Tumor suppressor function of RBMS3 overexpression in EOC associated with immune cell infiltration.

Objectives: Epithelial ovarian cancer (EOC) is considered to be a prevalent female malignancy with both high incidence and mortality. It is reported that RNA-binding protein 3 (RBMS3) executives a tumor suppressor function in different cancers. This investigation was designed to examine the expression of RBMS3 in epithelial ovarian cancer, the effects on EOC cells, and its connection to immune cells that infiltrate tumors in the EOC microenvironment. Methods: The expression levels of RBMS3 in EOC tissues as well as their correlations with immune cell infiltration and clinical outcome were examined using bioinformatics approaches. Western blotting as well as immunohistochemistry were carried out to determine the protein levels in EOC tissues. In addition, qRT-PCR was employed to look at the expression of the mRNA. The role of RBMS3 in EOC cells was investigated, and an RBMS3 lentiviral vector was developed. The effects of RBMS3 on subcutaneous tumor development, the proliferation protein Ki-67, the tumor angiogenesis indicator CD31, and its function in controlling the tumor immune microenvironment were evaluated by in vivo tests. Results: There was a considerable decrease in RBMS3 expression in EOC tissues, which was linked to a poor prognosis for patients and the infiltration of multiple immune cell. Given immunohistochemical studies, tissues with increased RBMS3 expression had decreased markers of myeloid-derived suppressor cells, regulatory T cells, and M2 macrophages, whereas M1 macrophage markers were elevated. RBMS3 appears to suppress the capabilities of proliferating, invading, and migrating in EOC cells according to in vitro tests, whereas tumors overexpressing RBMS3 developed more slowly in syngeneic mouse models. The overexpression of RBMS3 led to a decline in the levels of Ki-67 protein and CD31. Additionally, it showed a negatively correlation with markers of regulatory T cell, myeloid-derived suppressor cell, and M2 macrophage but a positive correlation with markers of M1 macrophage. Conclusions: The findings revealed that elevated RBMS3 expression plays a tumor suppressor role in EOC and was connected to patient survival in EOC. The studies conducted in vitro and in vivo demonstrated a link between RBMS3 expression and the infiltration of certain immune cells, indicating a function for RBMS3 in the immunosuppressive tumor microenvironment and its promising efficiency as a novel target for immunotherapy against EOC.

Liquiritigenin Induces Cell Cycle Arrest and Apoptosis in Lung Squamous Cell Carcinoma.

Liquiritigenin (LQ), as a dihydroflavone monomer compound extracted from Glycyrrhiza uralensis Fisch, has been demonstrated to show anti-tumor effects in multiple human cancers, including lung adenocarcinoma. Our study aimed to explore its role in lung squamous cell carcinoma (LSCC) development and the related mechanism. The effects of LQ on SK-MES-1 and NCI-H520 cell proliferation, cell cycle, and apoptosis were investigated. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and colony formation assays revealed that LQ inhibited LSCC cell viability and proliferation in a dose- and time-dependent manner. Flow cytometry analysis demonstrated that LQ promoted G2/M cell cycle arrest, cell apoptosis, and loss of mitochondrial membrane potential. In vivo assays showed that LQ administration suppressed tumor growth in nude mice. Additionally, LQ treatment reduced the levels of phosphorylated PI3K, AKT, and mTOR levels in LSCC cells. Pretreatment with the PI3K inhibitor LY294002 antagonized the LQ-mediated effects on cell proliferation, cell cycle arrest, and apoptosis in LSCC cells. Collectively, LQ induces cell cycle arrest and apoptosis in LSCC by inactivating the PI3K/AKT/mTOR pathway.

SARS-CoV-2 Antibodies in Human Milk After mRNA and Adenovector-Based Vaccination: A Systematic Review and Meta-Analysis.

BACKGROUND: SARS-CoV-2 specific antibodies exist in human milk expressed by lactating parents after vaccination. In the existing research, the effects of vaccine types on human milk are inconsistent. RESEARCH AIM: This study aims to perform a systematic review and meta-analysis of the existing observational studies to compare the positive rates of SARS-CoV-2 specific antibodies in human milk according to mRNA and adenovector-based vaccination. METHODS: PubMed, Web of Science, Elsevier Science Direct and Cochrane Library databases were systematically searched for relevant articles published from December 30, 2019 to February 15, 2023. Observational studies were considered eligible provided they reported data on SARS-CoV-2 specific antibodies in human milk. The risk of bias in non-randomized studies of interventions (ROBINS-I) tool, the Newcastle-Ottawa Scale (NOS), and the Agency for Healthcare Research and Quality (AHRQ) were used to assess risk of bias. Seven studies, including 511 lactating participants, were included in this review and meta-analysis. RESULTS: The positive rate of SARS-CoV-2 IgA is higher in mRNA vaccine groups than in adenovector-based vaccine groups (OR = 4.80, 95% CI [3.04, 7.58], p < 0.001). The positive rate of SARS-CoV-2 IgG was higher in mRNA vaccines than in adenovector-based vaccines. CONCLUSIONS: Compared to adenovector-based vaccines, mRNA vaccines present a higher positivity rate of IgA and IgG in human milk after vaccination. In other words, mRNA vaccinations may offer breastfed children a higher level of protection than adenovector-based vaccinations. Further high-quality data is still required to substantiate these findings.

Association between cognitive function and body composition in older adults: data from NHANES (1999-2002).

Aim: To investigate the association between cognitive function and body composition in older adults. Methods: We collected data on 2080 older adults (>60 years of age) from the National Health and Nutrition Examination Survey (NHANES) for the years 1999-2000 and 2001-2002. Candidate variables included: demographic data (sex, age, race, education level, marital status, poverty-to-income ratio), alcohol consumption, cardiovascular disease, diabetes, osteoporosis, total bone mineral density, and total fat mass. A logistic regression model was established to analyze the association between cognitive function and body composition in older adults. In addition, stratified logics regression analysis was performed by sex and age. Results: Bone mineral density significantly affects cognitive function in older adults (p<0.01). When examining the data according to sex, this correlation is present for women (p < 0.01). For men, though, it is not significant (p = 0.081). Stratified by age, total bone mineral density was significantly correlated with cognitive function in 60-70 and 70-80 years old people, but not in older adults older than 80 years(for 60-70 years old, p = 0.019; for 70-80 years old, p = 0.022). There was no significant correlation between total bone mineral density and cognitive function (p = 0.575). Conclusion: The decrease of total bone mineral density was significantly correlated with cognitive decline in the older adults, especially among women and older people in the 60 to 80 age group. There was no connection between total fat mass, total percent fat, total lean mass, appendicular lean mass, appendicular lean mass /BMI and cognitive function in the older adults.

Identification of Intersite Distance Effects in Au-Ag Single-Atom Alloy Catalysts Using Single Nanoparticle Collision Electrochemistry.

Regulating the atomic density of single-atom alloys (SAAs) promotes the potential to significantly enhance the electrocatalytic activity. However, conventional methods for study on the electrocatalytic performance of SAAs versus the intersite distance demand exhaustive experiments and characterization. Herein, we present a combinatorial synthesis and analysis method to investigate the intersite distance effect of SAA electrocatalysts. We employ single-nanoparticle collision electrochemistry to realize in situ electrodeposition of a precisely tunable Au atomic density onto individual parent Ag nanoparticles, followed by instantaneous electrocatalytic measurement of the newborn Au-Ag SAAs. In this work, the utility of our method is confirmed by the identification of intersite distance effects of Au-Ag SAAs toward the oxygen reduction reaction. When the site distance between two neighboring Au atoms is 1.9 nm, Au-Ag SAAs exhibit optimal activity. This work provides a simple and efficient method for screening other SAA electrocatalysts with ideal intersite distance at the single-nanoparticle level.

Antimicrobial peptide cecropin B functions in pathogen resistance of Mythimna separata.

Mythimna separata (Lepidoptera: Noctuidae) is an omnivorous pest that poses a great threat to food security. Insect antimicrobial peptides (AMPs) are small peptides that are important effector molecules of innate immunity. Here, we investigated the role of the AMP cecropin B in the growth, development, and immunity of M. separata. The gene encoding M. separata cecropin B (MscecropinB) was cloned. The expression of MscecropinB was determined in different developmental stages and tissues of M. separata. It was highest in the prepupal stage, followed by the pupal stage. Among larval stages, the highest expression was observed in the fourth instar. Tissue expression analysis of fourth instar larvae showed that MscecropinB was highly expressed in the fat body and haemolymph. An increase in population density led to upregulation of MscecropinB expression. MscecropinB expression was also upregulated by the infection of third and fourth instar M. separata with Beauveria bassiana or Bacillus thuringiensis (Bt). RNA interference (RNAi) targeting MscecropinB inhibited the emergence rate and fecundity of M. separata, and resulted in an increased sensitivity to B. bassiana and Bt. The mortality of M. separata larvae was significantly higher in pathogen plus RNAi-treated M. separata than in controls treated with pathogens only. Our findings indicate that MscecropinB functions in the eclosion and fecundity of M. separata and plays an important role in resistance to infection by B. bassiana and Bt.