A primate-specific endogenous retroviral envelope protein sequesters SFRP2 to regulate human cardiomyocyte development.

Endogenous retroviruses (ERVs) occupy a significant part of the human genome, with some encoding proteins that influence the immune system or regulate cell-cell fusion in early extra-embryonic development. However, whether ERV-derived proteins regulate somatic development is unknown. Here, we report a somatic developmental function for the primate-specific ERVH48-1 (SUPYN/Suppressyn). ERVH48-1 encodes a fragment of a viral envelope that is expressed during early embryonic development. Loss of ERVH48-1 led to impaired mesoderm and cardiomyocyte commitment and diverted cells to an ectoderm-like fate. Mechanistically, ERVH48-1 is localized to sub-cellular membrane compartments through a functional N-terminal signal peptide and binds to the WNT antagonist SFRP2 to promote its polyubiquitination and degradation, thus limiting SFRP2 secretion and blocking repression of WNT/ß-catenin signaling. Knockdown of SFRP2 or expression of a chimeric SFRP2 with the ERVH48-1 signal peptide rescued cardiomyocyte differentiation. This study demonstrates how ERVH48-1 modulates WNT/ß-catenin signaling and cell type commitment in somatic development.

"Why wouldn't we want to do this?" The challenge for oncology hospital nurses to engage in serious illness conversation and advance care planning.

BACKGROUND: The viability of advance care planning (ACP) in cultures where discussing future desires is taboo is unclear, it is essential to examine the challenges faced by Chinese nurses lacking legal protection for ACP. AIMS: To comprehend Chinese oncology nurses' perceptions of serious illness conversation and ACP, and identify barriers to engagement. METHODS: A qualitative descriptive exploratory study involving semi-structured interviews with 13 experienced oncology nurses, analyzed using thematic analysis and critical incident technique, following the Consolidated Criteria for Reporting Qualitative Research (COREQ) guidelines. FINDINGS: Four themes emerged: Inadequate Competence Causes Patient Harm, Cultural Influences to Patient Autonomy, Psychological Tolerance Neglects Best Interests, and Systemic and Legal Uncertainties Impact Patient Rights. CONCLUSION: Policy changes supporting nurses in ACP implementation, a 'whole-system strategic approach' involving legislative changes, organizational support, and public awareness are crucial for optimizing ACP and meeting diverse patient needs.

Gabapentinoids-Related Delirium Adverse Events: A Real-World Study from 2004 to 2022 Based on FAERS.

Purpose: This study comprehensively describes and evaluates the correlation between gabapentinoids and all types of delirium. Methods: We used AERSMine to select all adverse reaction data from 2004 Q1 to the 2022 Q4 in the FDA Adverse Event Reporting System (FAERS) database, and delirium events reported by gabapentinoids drugs were included in this study. Collected and analyzed the clinical details of these reports. We have developed four models. Among the four models, reporting odds ratio (ROR) and proportional reporting ratio (PRR) were used to evaluate the potential association between and delirium. We undertook a subgroup analysis for the age and sex cohorts. Results: A total of 2950 reports of gabapentinoids-related delirium was collected. Excluding cases with a history of delirium (Model 2), opioid drugs (Model 3), and other adverse events related to gabapentinoids drugs (Model 4), pain cases with gabapentin drugs as the main suspected drug were selected. In model 1, the reporting rates of delirium at the delirium and delirium tremens levels were higher in the gabapentinoids group than in the non-gabapentinoids group (ROR 1.09(1.05,1.13); ROR 1.54(1.16,2.04)). In model 2.3 the delira and the delirium level were higher in the gabapentinoids group (ROR 1.42(1.29,1.56), ROR 1.44(1.31,1.59); ROR 1.43(1.30,1.58), ROR 1.46(1.33,1.61)). There is no difference in delirium levels in Model 4. Delirium levels were higher in the gabapentinoids group than in the non-gabapentinoids group in ≥65 years old. The delirium and deliria levels were higher in the male group than in the female group. Conclusion: The delirium adverse reactions of the gabapentinoids group were significantly higher than those of non-gabapentinoids group in the first three models. However, with the removal of confounding factors, there was no significant difference in this type of adverse reaction in Model 4. In elderly and male patients, the incidence of delirium with gabapentinoids was significantly increased.

Isolating Immune Cells from Mouse Brain and Skull.

Mounting evidence indicates that the immune response triggered by brain disorders (e.g., brain ischemia and autoimmune encephalomyelitis) occurs not only in the brain, but also in the skull. A key step toward analyzing changes in immune cell populations in both the brain and skull bone marrow after brain damage (e.g., stroke) is to obtain sufficient numbers of high-quality immune cells for downstream analyses. Here, two optimized protocols are provided for isolating immune cells from the brain and skull bone marrow. The advantages of both protocols are reflected in their simplicity, speed, and efficacy in yielding a large quantity of viable immune cells. These cells may be suitable for a range of downstream applications, such as cell sorting, flow cytometry, and transcriptomic analysis. To demonstrate the effectiveness of the protocols, immunophenotyping experiments were performed on stroke brains and normal brain skull bone marrow using flow cytometry analysis, and the results aligned with findings from published studies.

Case report: Durable response of ensartinib targeting EML4-ALK fusion in osimertinib-resistant non-small cell lung cancer.

Background: Despite significant benefits from targeted therapy in patients with driver mutations, inevitable drug resistance usually occurred in non-small cell lung cancer, highlighting the necessity for sequential treatments to prolong overall survival. Unfortunately, durable drug response has not been reported in posterior-line therapy of cases with acquired EML4-ALK fusion after resistance to osimertinib, urging the need of referable decision-making in clinical management. Case presentation: We present a case of a 71-year-old Chinese female, never smoker, diagnosed with invasive adenocarcinoma in the left inferior lobe of her lung, with metastases in regional lymph nodes. She received erlotinib treatment after the detection of coexistent EGFR L858R/G719S and BRAF V600E via next-generation sequencing of resected tumor tissue. Routine imaging revealed disease progression approximately 14 months after starting erlotinib treatment, followed by the detection of EGFR L858R through non-invasive liquid biopsy. Subsequently, osimertinib was administered, showing clinical activities for nearly 19 months until the emergence of an EML4-ALK fusion. Given the EML4-ALK fusion, a relatively rare resistance mechanism to osimertinib, she received third-line ensartinib treatment. One month later, alleviated tumor lesions plus normal serum marker levels demonstrated the effectiveness of ensartinib in overcoming resistance to osimertinib. Of note, the clinical response to ensartinib persisted for more than 14 months, superior to the previously reported efficacy of aletinib and crizotinib in osimertinib-failure cases. As of the last follow-up in July 2022, the patient showed no signs of recurrence and maintained a good life quality. Conclusion: We reported a third-line ensartinib therapy in a patient with lung adenocarcinoma who developed an acquired EML4-ALK fusion after sequential treatment with erlotinib and osimertinib. Given the rarity of the EML4-ALK fusion as a resistance mechanism to osimertinib, ensartinib emerges as a promising treatment option for this specific clinical challenge, offering superior efficacy and good safety.

Gal-1-mediated cytochrome p450 activation promotes fibroblast into myofibroblast differentiation in pulmonary fibrosis.

Pulmonary fibrosis (PF) results from excessive extracellular matrix (ECM) deposition and tissue remodeling after activation of fibroblasts into myofibroblasts. Abnormally deposited fibrotic ECM, in turn, promotes fibroblast activation and accelerates loss of lung structure and function. However, the molecular mediators and exact mechanisms by which fibrotic ECM promotes fibroblast activation are unclear. In a bleomycin-induced PF mouse model, we found Galectin-1 (Gal-1) expression was significantly increased in lung tissue, and overexpression of Gal-1 plasmid-transfected fibroblasts were activated into myofibroblasts. Using the decellularization technique to prepare decellularized fibrotic ECM and constructing a 3D in vitro co-culture system with fibroblasts, we found that decellularized fibrotic ECM induced a high expression of Gal-1 and promoted the activation of fibroblasts into myofibroblasts. Therefore, Gal-1 has been identified as a pivotal mediator in PF. Further, we found that decellularized fibrotic ECM delivered mechanical signals to cells through the Gal-1-mediated FAK-Src-P130Cas mechanical signalling pathway, while the CYP450 enzymes (mainly involved in CYP1A1, CYP24A1, CYP3A4, and CYP2D6 isoforms) acted as a chemical signalling pathway to receive mechanical signals transmitted from upstream Gal-1, thereby promoting fibroblast activation. The Gal-1 inhibitor OTX008 or the CYP1A1 inhibitor 7-Hydroxyflavone prevented PF in mice and inhibited the role of fibrotic ECM in promoting fibroblast activation into myofibroblasts, preventing PF. These results reveal novel molecular mechanisms of lung fibrosis formation and identify Gal-1 and its downstream CYP1A1 as potential therapeutic targets for PF disease treatmnts.

Lymphedema in Turner syndrome: correlations with phenotype and karyotype.

OBJECTIVES: Lymphedema (LD) in Turner syndrome (TS) is a commonly reported comorbidity, though its associations with karyotype and other comorbidities are poorly understood. Characteristics of patients with TS and LD, including correlation with phenotype and karyotype, are described. METHODS: Medical records of patients with TS seen in two pediatric institutions from 2002 to 2020 were retrospectively reviewed. Demographic data (age, presentation onset, clinical features, genetics, LD presence, investigations, treatments) were collected. RESULTS: 393 girls with TS with mean age of 12.5 years (SD: 5.7) were identified. LD was noted in 37 % of patients (n=146). Among the 112 patients with TS and documentation of onset of LD, LD was noted within the first year of life in 78.6 % (n=88). 67.6 % (n=96) of total patients with TS and LD had non-mosaic 45, X karyotype. Frequency of webbed neck was significantly greater in girls with TS and LD compared with girls without LD (58 vs. 7 %, p<0.001). Congenital heart anomalies, hypertension, and renal anomalies were also more common in girls with LD. Nail abnormalities with presence of hypoplastic or dysplastic nails were significantly associated with LD (OR: 6.784, 95 % CI 4.235-11.046). The number of girls reporting presence of LD decreased with age. CONCLUSIONS: LD in TS often occurs within the first year of life, is less prevalent in older children and adolescents, and is significantly associated with 45, X karyotype, presence of webbed neck, nail changes, congenital heart anomalies, and renal anomalies.

Variation in a Poaceae-conserved fatty acid metabolic gene cluster controls rice yield by regulating male fertility.

A wide variety of metabolic gene clusters exist in eukaryotic genomes, but fatty acid metabolic gene clusters have not been discovered. Here, combining with metabolic and phenotypic genome-wide association studies, we identify a major locus containing a six-gene fatty acid metabolic gene cluster on chromosome 3 (FGC3) that controls the cutin monomer hydroxymonoacylglycerols (HMGs) contents and rice yield, possibly through variation in the transcription of FGC3 members. We show that HMGs are sequentially synthesized in the endoplasmic reticulum by OsFAR2, OsKCS11, OsGPAT6, OsCYP704B2 and subsequently transported to the apoplast by OsABCG22 and OsLTPL82. Mutation of FGC3 members reduces HMGs, leading to defective male reproductive development and a significant decrease in yield. OsMADS6 and OsMADS17 directly regulate FGC3 and thus influence male reproduction and yield. FGC3 is conserved in Poaceae and likely formed prior to the divergence of Pharus latifolius. The eukaryotic fatty acid and plant primary metabolic gene cluster we identified show a significant impact on the origin and evolution of Poaceae and has potential for application in hybrid crop breeding.

Prediction of non-dipper blood pressure pattern in Chinese patients with hypertension using a nomogram model.

Non-dipper blood pressure has been shown to affect cardiovascular outcomes and cognitive function in patients with hypertension. Although some studies have explored the influencing factors of non-dipper blood pressure, there is still relatively little research on constructing a prediction model. This study aimed to develop and validate a simple and practical nomogram prediction model and explore relevant elements that could affect the dipper blood pressure relationship in patients with hypertension. A convenient sampling method was used to select 356 inpatients with hypertension who visited the Affiliated Hospital of Jining Medical College from January 2022 to September 2022. All patients were randomly assigned to the training cohort (75%, n = 267) and the validation cohort (25%, n = 89). Univariate and multivariate logistic regression were utilized to identify influencing factors. The nomogram was developed and evaluated based on the receiver operating characteristic (ROC) curve, the area under the ROC curve (AUC), and decision curve analyses. The optimal cutoff values for the prevalence of dipper blood pressure were estimated. The nomogram was established using six variables, including age, sex, hemoglobin (Hb), estimated glomerular filtration rate (eGFR), ejection fraction (EF), and heart rate. The AUC was 0.860 in the training cohort. The cutoff values for optimally predicting the prevalence of dipper blood pressure were 41.50 years, 151.00 g/L, 117.53 mL/min/1.73 m2, 64.50%, and 75 beats per minute for age, Hb, eGFR, ejection fraction, and heart rate, respectively. In summary, our nomogram can be used as a simple, plausible, affordable, and widely implementable tool to predict the blood pressure pattern of Chinese patients with hypertension.

Microglial heterogeneity in the ischemic stroke mouse brain of both sexes.

BACKGROUND: Ischemic stroke elicits a complex and sustained immune response in the brain. Immunomodulatory treatments have long held promise for improving stroke outcomes, yet none have succeeded in the clinical setting. This lack of success is largely due to our incomplete understanding of how immune cells respond to stroke. The objective of the current study was to dissect the effect of permanent stroke on microglia, the resident immune cells within the brain parenchyma. METHODS: A permanent middle cerebral artery occlusion (pMCAO) model was used to induce ischemic stroke in young male and female mice. Microglia were sorted from fluorescence reporter mice after pMCAO or sham surgery and then subjected to single-cell RNA sequencing analysis. Various methods, including flow cytometry, RNA in situ hybridization, immunohistochemistry, whole-brain imaging, and bone marrow transplantation, were also employed to dissect the microglial response to stroke. Stroke outcomes were evaluated by infarct size and behavioral tests. RESULTS: First, we showed the morphologic and spatial changes in microglia after stroke. We then performed single-cell RNA sequencing analysis on microglia isolated from sham and stroke mice of both sexes. The data indicate no major sexual dimorphism in the microglial response to permanent stroke. Notably, we identified seven potential stroke-associated microglial clusters, including four major clusters characterized by a disease-associated microglia-like signature, a highly proliferative state, a macrophage-like profile, and an interferon (IFN) response signature, respectively. Importantly, we provided evidence that the macrophage-like cluster may represent the long-sought stroke-induced microglia subpopulation with increased CD45 expression. Lastly, given that the IFN-responsive subset constitutes the most prominent microglial population in the stroke brain, we used fludarabine to pharmacologically target STAT1 signaling and found that fludarabine treatment improved long-term stroke outcome. CONCLUSIONS: Our findings shed new light on microglia heterogeneity in stroke pathology and underscore the potential of targeting specific microglial populations for effective stroke therapies.

Effects of dexmedetomidine on depression-like behaviour in chronic restraint stress mice: Involvement of specific brain regions.

It is crucial to develop novel antidepressants. Dexmedetomidine (DEX) can exert antidepressant effects, but its underlying mechanism remains unclear. We used chronic restraint stress (CRS) to induce depression-like behaviour in mice and administered low-dose DEX (2 µg/kg per day) during CRS modelling or one injection of high-dose DEX (20 µg/kg) after CRS. The results of the behavioural tests revealed that both methods ameliorated CRS-induced depression. The brain slices of the mice were subjected to immunohistochemical staining for c-fos and phosphorylated ERK (pERK). Results showed that the continuous low-dose DEX-treated group, but not the single high-dose DEX-treated group expressed less c-fos in the nucleus locus coeruleus (LC) with a mean optical density (MOD) of 0.06. Other brain regions, including the dentate gyrus (DG), pyriform cortex (Pir), anterior part of paraventricular thalamic nucleus (PVA), arcuate nucleus (Arc), and core or shell of accumbens nucleus (Acbc or Acbs), presented differences in c-fos expression. In contrast, the low-dose DEX-treated group exhibited three-fold greater pERK expression in the LC of the CRS mice, with a MOD of 0.15. Pir, cingulate cortex (Cg) and, anterior and posterior part of paraventricular thalamic nucleus (PVA and PVP) exhibited pERK expression differences due to distinct reagent treatments. These changes indicate that the responses of brain regions to different DEX administration methods and doses vary. This study confirmed the ability of DEX to ameliorate CRS-induced depression and identified candidate target brain regions, thus providing new information for the antidepressant mechanism of DEX.

[Cluster Analysis and Ablation Success Rate in Atrial Fibrillation Patients Undergoing Catheter Ablation]. / æˆ¿é¢¤å°„é¢‘æ¶ˆèžæ‚£è€ çš„èšç±»åˆ†æžåŠæ¶ˆèžæˆåŠŸçŽ‡è¯„ä»·.

Objective: Atrial fibrillation (AF) is a disease of high heterogeneity, and the association between AF phenotypes and the outcome of different catheter ablation strategies remains unclear. Conventional classification of AF (e.g. according to duration, atrial size, and thromboembolism risk) fails to provide reference for the optimal stratification of the prognostic risks or to guide individualized treatment plan. In recent years, research on machine learning has found that cluster analysis, an unsupervised data-driven approach, can uncover the intrinsic structure of data and identify clusters of patients with pathophysiological similarity. It has been demonstrated that cluster analysis helps improve the characterization of AF phenotypes and provide valuable prognostic information. In our cohort of AF inpatients undergoing radiofrequency catheter ablation, we used unsupervised cluster analysis to identify patient subgroups, to compare them with previous studies, and to evaluate their association with different suitable ablation patterns and outcomes. Methods: The participants were AF patients undergoing radiofrequency catheter ablation at West China Hospital between October 2015 and December 2017. All participants were aged 18 years or older. They underwent radiofrequency catheter ablation during their hospitalization. They completed the follow-up process under explicit informed consent. Patients with AF of a reversible cause, severe mitral stenosis or prosthetic heart valve, congenital heart disease, new-onset acute coronary syndrome within three months prior to the surgery, or a life expectancy less than 12 months were excluded according to the exclusion criteria. The cohort consisted of 1102 participants with paroxysmal or persistent/long-standing persistent AF. Data on 59 variables representing demographics, AF type, comorbidities, therapeutic history, vital signs, electrocardiographic and echocardiographic findings, and laboratory findings were collected. Overall, data for the variables were rarely missing (<5%), and multiple imputation was used for correction of missing data. Follow-up surveys were conducted through outpatient clinic visits or by telephone. Patients were scheduled for follow-up with 12-lead resting electrocardiography and 24-hours Holter monitoring at 3 months and 6 months after the ablation procedure. Early ablation success was defined as the absence of documented AF, atrial flutter, or atrial tachycardia >30 seconds at 6-month follow-up. Hierarchical clustering was performed on the 59 baseline variables. All characteristic variables were standardized to have a mean of zero and a standard deviation of one. Initially, each patient was regarded as a separate cluster, and the distance between these clusters was calculated. Then, the Ward minimum variance method of clustering was used to merge the pair of clusters with the minimum total variance. This process continued until all patients formed one whole cluster. The "NbClust" package in R software, capable of calculating various statistical indices, including pseudo t2 index, cubic clustering criterion, silhouette index etc, was applied to determine the optimal number of clusters. The most frequently chosen number of clusters by these indices was selected. A heatmap was generated to illustrate the clinical features of clusters, while a tree diagram was used to depict the clustering process and the heterogeneity among clusters. Ablation strategies were compared within each cluster regarding ablation efficacy. Results: Five statistically driven clusters were identified: 1) the younger age cluster (n=404), characterized by the lowest prevalence of cardiovascular and cerebrovascular comorbidities but the highest prevalence of obstructive sleep apnea syndrome (14.4%); 2) a cluster of elderly adults with chronic diseases (n=438), the largest cluster, showing relatively higher rates of hypertension, diabetes, stroke, and chronic obstructive pulmonary disease; 3) a cluster with high prevalence of sinus node dysfunction (n=160), with patients showing the highest prevalence of sick sinus syndrome and pacemaker implantation; 4) the heart failure cluster (n=80), with the highest prevalence of heart failure (58.8%) and persistent/long-standing persistent AF (73.7%); 5) prior coronary artery revascularization cluster (n=20), with patients of the most advanced age (median: 69.0 years old) and predominantly male patients, all of whom had prior myocardial infarction and coronary artery revascularization. Patients in cluster 2 achieved higher early ablation success with pulmonary veins isolation alone compared to extensive ablation strategies (79.6% vs. 66.5%; odds ratio [OR]=1.97, 95% confidence interval [CI]: 1.28-3.03). Although extensive ablation strategies had a slightly higher success rate in the heart failure group, the difference was not statistically significant. Conclusions: This study provided a unique classification of AF patients undergoing catheter ablation by cluster analysis. Age, chronic disease, sinus node dysfunction, heart failure and history of coronary artery revascularization contributed to the formation of the five clinically relevant subtypes. These subtypes showed differences in ablation success rates, highlighting the potential of cluster analysis in guiding individualized risk stratification and treatment decisions for AF patients.

Effectiveness of decision aids on critically ill patients' outcomes and family members' knowledge, anxiety, depression and decisional conflict: A systematic review and meta-analysis.

BACKGROUND: Decision aids (DAs) have been proposed to support patients and families with disease information processing and decision-making, but their effectiveness for critically ill patients and their families is incompletely understood. AIM: To systematically synthesize evidence on the effectiveness of the DAs on the prognosis of critically ill patients and knowledge, anxiety, depression and decisional conflict of their family members. STUDY DESIGN: Systematic review and meta-analysis. We conducted a systematic search of literature using PubMed, Embase, Cochrane Library, Web of Science, Cumulative Index to Nursing and Allied Health Literature database, Scopus, PsycNet, CNKI and Wanfang Database from the inception of the databases until May 2023 to identify randomized clinical trials (RCTs) describing DAs interventions targeted at adult intensive care unit (ICU) patients or their families. We also searched grey literature in four databases: Chinese Clinical Trials Registry, Chinese Cochrane Center, Open Grey and GreyNet International. RESULTS: Seven RCTs were included in the review. Meta-analysis identified longer hospital length of stay (LOS) among all patients compared with usual care (mean difference [MD] = 5.64 days, 95% confidence interval, CI [0.29, 10.98], p = .04), but not in surviving patients (MD = 2.09 days, 95% CI [-3.70, 7.89], p = .48). However, there was no evidence of an effect of DAs on hospital mortality (RR = 1.25, 95% CI [0.92, 1.70], p = .15), ICU LOS (MD = 3.77 days, 95% CI [-0.17, 7.70], p = .06) and length of mechanical ventilation (MD = 0.88 days, 95% CI [-2.22, 3.97], p = .58). DAs led to a statistically significant improvement in family members' knowledge (standard mean difference = 0.84, 95% CI [0.12, 1.56], p = .02). We found no significant effect of DAs on anxiety, depression, post-traumatic stress disorder, decisional conflict and quality of communication of family members. CONCLUSIONS: This review provides effective evidence that DAs can potentially improve the knowledge level of family members while prolonging the hospital LOS among critically ill patients. RELEVANCE TO CLINICAL PRACTICE: Well-designed large-scale studies with DAs tailored to the individuals' preferences and existing cultural values are warranted.

Analysis of risk factors and construction of a predictive model for macrosomia in deliveries with gestational diabetes.

BACKGROUND: Gestational diabetes, a frequent pregnancy complication marked by elevated maternal blood glucose, can cause serious adverse effects for both mother and fetus, including increased amniotic fluid and risks of fetal asphyxia, hypoxia, and premature birth. OBJECTIVE: To construct a predictive model to analyze the risk factors for macrosomia in deliveries with gestational diabetes. METHODS: From January 2021 to February 2023, 362 pregnant women with gestational diabetes were selected for the study. They were followed up until delivery. Based on newborn birth weight, the participants were divided into the macrosomia group (birth weight ⩾ 4000 g) and the non-macrosomia group (birth weight < 4000 g). The data of the two groups of pregnant women were compared. ROC curves were plotted to analyze the predictive value of multiple factors for the delivery of macrosomic infants among pregnant women with gestational diabetes. A logistic regression model was constructed to identify the risk factors for delivering macrosomic infants and the model was tested. RESULTS: A total of 362 pregnant women with gestational diabetes were included, of which 58 (16.02%) had babies with macrosomia. The macrosomia group exhibited higher metrics in several areas compared to those without: pre-pregnancy BMI, fasting glucose, 1 h and 2 h OGTT sugar levels, weight gain during pregnancy, and levels of triglycerides, LDL-C, and HDL-C, all with significant differences (P< 0.05). ROC analysis revealed predictive value for macrosomia with AUCs of 0.761 (pre-pregnancy BMI), 0.710 (fasting glucose), 0.671 (1 h OGTT), 0.634 (2 h OGTT), 0.850 (weight gain), 0.837 (triglycerides), 0.742 (LDL-C), and 0.776 (HDL-C), indicating statistical significance (P< 0.05). Logistic regression identified high pre-pregnancy BMI, fasting glucose, weight gain, triglycerides, and LDL-C levels as independent risk factors for macrosomia, with odds ratios of 2.448, 2.730, 1.884, 16.919, and 5.667, respectively, and all were statistically significant (P< 0.05). The model's AUC of 0.980 (P< 0.05) attests to its reliability and stability. CONCLUSION: The delivery of macrosomic infants in gestational diabetes may be related to factors such as body mass index before pregnancy, blood-glucose levels, gain weight during pregnancy, and lipid levels. Clinical interventions targeting these factors should be implemented to reduce the incidence of macrosomia.

Perfluorinated Amines: Accelerating Lithium Electrodeposition by Tailoring Interfacial Structure and Modulated Solvation for High-Performance Batteries.

Modulating interfacial electrochemistry represents a prevalent approach for mitigating lithium dendrite growth and enhancing battery performance. Nevertheless, while most additives exhibit inhibitory characteristics, the accelerating effects on interfacial electrochemistry have garnered limited attention. In this work, perfluoromorpholine (PFM) with facilitated kinetics is utilized to preferentially adsorb on the lithium metal interface. The PFM molecules disrupt the solvation structure of Li+ and enhance the migration of Li+. Combined with the benzotrifluoride, a synergistic acceleration-inhibition system is formed. The ab initio molecular dynamics (AIMD) and density functional theory (DFT) calculation of the loose outer solvation clusters and the key adsorption-deposition step supports the fast diffusion and stable interface electrochemistry with an accelerated filling mode with C─F and C─H groups. The approach induces the uniform lithium deposition. Excellent cycling performance is achieved in Li||Li symmetric cells, and even after 200 cycles in Li||NCM811 full cells, 80% of the capacity is retained. This work elucidates the accelerated electrochemical processes at the interface and expands the design strategies of acceleration fluorinated additives for lithium metal batteries.

FOXQ1, deubiquitinated by USP10, alleviates sepsis-induced acute kidney injury by targeting the CREB5/NF-κB signaling axis.

Sepsis-induced acute kidney injury (S-AKI) is a severe and frequent complication that occurs during sepsis. This study aimed to understand the role of FOXQ1 in S-AKI and its potential upstream and downstream regulatory mechanisms. A cecal ligation and puncture induced S-AKI mouse model in vivo and an LPS-induced HK-2 cell model in vitro were used. FOXQ1 was significantly upregulated in CLP mice and downregulated in the LPS-induced HK-2 cells. Upregulation of FOXQ1 improved kidney injury and dysfunction in CLP mice. Overexpression of FOXQ1 remarkably suppressed the apoptosis and inflammatory response via down-regulating oxidative stress indicators and pro-inflammatory factors (IL-1ß, IL-6, and TNF-α), both in vivo and in vitro. From online analysis, the CREB5/NF-κB axis was identified as the downstream target of FOXQ1. FOXQ1 transcriptionally activated CREB5, upregulating its expression. Overexpression of FOXQ1 suppressed the phosphorylation level and nucleus transport of p65. Rescue experiments showed that CREB5 mediates the protective role of FOXQ1 on S-AKI. Furthermore, FOXQ1 was identified as a substrate of USP10, a deubiquitinating enzyme. Ectopic expression of USP10 reduced the ubiquitination of FOXQ1, promoting its protein stability. USP10 upregulation alleviated LPS-induced cell apoptosis and inflammatory response, while suppression of FOXQ1 augmented these trends. Collectively, our results suggest that FOXQ1, deubiquitinated by USP10, plays a protective role in S-AKI induced inflammation and apoptosis by targeting CREB5/NF-κB axis.

Synergistic Enhancement of the Friction and Wear Performance for UHMWPE Composites under Different Aging Times.

With the rapid development of the pipeline transportation and exploitation of mineral resources, there is an urgent requirement for high-performance polymer matrix composites with low friction and wear, especially under oxidative and prolonged working conditions. In this work, ultra-high-molecular-weight polyethylene (UHMWPE) matrix composites with the addition of carbon fibers (CFs), TiC, and MoS2 were prepared by the hot press sintering method. The influence of thermal oxygen aging time (90 °C, 0 h-64 h) on their mechanical and frictional performance was investigated. The results showed that TiC ceramic particles can increase wear resistance, especially by aging times up to 32 and 64 h. The wear mechanisms were analyzed based on the results of SEM images, EDS, and Raman spectra. The knowledge obtained herein will facilitate the design of long-service-life polymer matrix composites with promising low friction and wear performances.

Mtnr1b deletion disrupts placental angiogenesis through the VEGF signaling pathway leading to fetal growth restriction.

The placenta, as a "transit station" between mother and fetus, has functions delivering nutrients, excreting metabolic wastes and secreting hormones. A healthy placenta is essential for fetal growth and development while the melatonergic system seems to play a critical physiological role in this organ since melatonin, its synthetic enzymes and receptors are present in the placenta. In current study, Mtnr1a and Mtnr1b knockout mice were constructed to explore the potential roles of melatonergic system played on the placental function and intrauterine growth retardation (IUGR). The result showed that Mtnr1a knockout had little effect on placental function while Mtnr1b knockout reduced placental efficiency and increased IUGR. Considering the extremely high incidence of IURG in sows, the pregnant sows were treated with melatonin. This treatment reduced the incidence of IUGR. All the evidence suggests that the intact melatonergic system in placenta is required for its function. Mechanistical studies uncovered that Mtnr1b knockout increased placental oxidative stress and apoptosis but reduced the angiogenesis. The RNA sequencing combined with histochemistry study identified the reduced angiogenesis and placental vascular density in Mtnr1b knockout mice. These alterations were mediated by the disrupted STAT3/VEGFR2/PI3K/AKT pathway, i.e., Mtnr1b knockout reduced the phosphorylation of STAT3 which is the promotor of VEGFR2. The downregulated VEGFR2 and its downstream elements of PI3K and AKT expressions, then, jeopardizes the angiogenesis and placental development.

Altered executive control network and default model network topology are linked to acute electronic cigarette use: A resting-state fNIRS study.

In recent years, electronic cigarettes (e-cigs) have gained popularity as stylish, safe, and effective smoking cessation aids, leading to widespread consumer acceptance. Although previous research has explored the acute effects of combustible cigarettes or nicotine replacement therapy on brain functional activities, studies on e-cigs have been limited. Using fNIRS, we conducted graph theory analysis on the resting-state functional connectivity of 61 male abstinent smokers both before and after vaping e-cigs. And we performed Pearson correlation analysis to investigate the relationship between alterations in network metrics and changes in craving. E-cig use resulted in increased degree centrality, nodal efficiency, and local efficiency within the executive control network (ECN), while causing a decrease in these properties within the default model network (DMN). These alterations were found to be correlated with reductions in craving, indicating a relationship between differing network topologies in the ECN and DMN and decreased craving. These findings suggest that the impact of e-cig usage on network topologies observed in male smokers resembles the effects observed with traditional cigarettes and other forms of nicotine delivery, providing valuable insights into their addictive potential and effectiveness as aids for smoking cessation.