Identification of hub lncRNAs correlated with tetralogy of fallot based on weighted gene co-expression network analysis.

The most prevalent cyanotic congenital heart disease, Tetralogy of Fallot (TOF), has an unknown etiology. Long-stranded non-coding RNAs (lncRNAs) have been linked to cardiac development and congenital heart disease, as evidenced by an increasing number of studies; nevertheless, additional research is necessary to fully understand the function that TOF-related lncRNAs play in the condition. This study constructed lncRNA-mRNA co-expression networks, performed functional enrichment analysis, and screened hub lncRNAs using Weighted Gene Co-expression Network Analysis (WGCNA) using the Gene Expression Omnibus dataset GSE36761. Ten hub lncRNAs, including IRF1-AS1, AC012360.6, HLA-F-AS1, RP1-253P7.4, NPTN-IT1, RP11-166P13.4, RP5-1183I21.2, SNHG14, CH17-98J9.1, and RP11-894P9.1, were identified by WGCNA analysis as potentially significant contributors to the development of TOF. Based on functional enrichment analysis, lncRNA mainly contributes to TOF by altering gene splicing patterns. New insights on the mechanism underlying TOF occurrence are provided by identifying hub lncRNAs associated with the disease and analyzing their regulatory networks.

Single-cell RNA-seq analysis hearts in patients with fetal tetralogy of Fallot.

INTRODUCTION: To explore the cytological characteristics of tetralogy of Fallot (TOF), we collected samples and studied the differences in cytological classification between normal fetal hearts and fetuses with TOF, and then we searched for possible differential genes of disease markers through single-cell sequencing analysis. METHODS: In this study, we analyzed the right ventricle of a TOF and a healthy human fetal heart sample by single-cell sequencing. Utilizing Cellranger to perform data quality control filtering, comparison, quantification, and identification of recovered cells on the raw data, ultimately obtaining gene expression matrices for each cell. Subsequently, Seurat was used for further cell filtration, standardization, cell subgroup classification, differential expression gene analysis of each subgroup, and Marker gene screening. RESULTS: Bioinformatic analysis identified 9979 and 15224 cells derived from the healthy and disease samples, respectively, with an average read depth of 25000/cell. The cardiomyocyte cell populations derived from the abnormal samples identified by the first-level graph-based analysis were separated into six distinct cell clusters. CONCLUSIONS: Our study reveals some information on TOF in a fetus, which can provide a new reference for early detection and treatment of TOF by comparing it with normal heart cells.

Influential factors of adherence to inhalation drug therapy in patients with stable chronic obstructive pulmonary disease.

OBJECTIVE: This study aimed to investigate the influential factors of adherence to inhalation drug therapy (IDT) in patients with stable chronic obstructive pulmonary disease (COPD). METHODS: A total of 243 patients with stable COPD who visited the chronic disease clinic of the respiratory department of our hospital between April 2022 and October 2022 were selected as participants using the convenience sampling method. Relevant information about all participants was collected by questionnaire for investigation, including basic information, clinical characteristics, inhaled drug names, situational awareness, dose and frequency. RESULTS: Univariate analysis revealed positive correlations between the following factors: (1) the total score of drug adherence and the total scores of the COPD knowledge questionnaire (COPD-Q), social support, subjective support, objective support and support utilisation, (2) the total score of dosage adherence and the total scores of COPD-Q, objective support and support utilisation and (3) the total score of technical standardisation and the total scores of social support, subjective support and objective support (p < 0.05). Multifactorial analysis showed that COPD health literacy, number of acute exacerbations in the past year and social support factors collectively accounted for 37.4% of the variable of patient adherence to IDT, as did COPD health literacy, modified Medical Research Council (mMRC) grading, duration of COPD, utilisation of support and marital status collectively account for 47.4% of the variable of patient dosage adherence. The goodness-of-fit of age, mMRC grading, social support, mode of residence, number of acute exacerbations in the past year and literacy to the patients' inhalation technical standardisation in the model was 47.4%. CONCLUSION: Dose adherence was predominantly influenced by COPD health literacy, mMRC grading, duration of COPD, utilisation of support and marital status. Inhalation technical standardisation was substantially limited by age, mMRC grading, social support, mode of residence, number of acute exacerbations in the past year and literacy.

Association of Iron Therapy with Mortality in Patients with Acute Myocardial Infarction and Iron Deficiency.

Iron deficiency (ID) is common in patients with acute myocardial infarction (AMI). It is unknown whether patients with AMI combined with ID will benefit from iron supplementation therapy. This study aimed to assess the relationship between iron therapy and mortality in AMI patients. Retrospective analysis was performed in subjects screened from the Medical Information Mart in Intensive Care-IV database. The data were obtained from ICU patients admitted to Beth Israel Deaconess Medical Center between 2008 and 2019. The patients were divided into two groups according to iron treatment exposure. Propensity score matching (PSM) was performed in the original cohort at a 1:1 ratio. Univariate and multivariate analyses were performed to adjust for confounding factors. The primary outcome was 28-day mortality. A total of 426 patients were included in this study. After 1:1 PSM, 208 patients were analyzed. Iron treatment was associated with a lower risk of 28-day mortality (9 deaths (8.65%) in the iron treatment group vs. 21 deaths (20.19%) in the non-iron treatment group; HR = 0.39; 95% CI = 0.17-0.89; p = 0.025) and in-hospital mortality (4 deaths (3.85%) in the iron treatment group vs. 12 deaths (11.54%) in the non-iron treatment group; OR, 0.15; 95% CI, 0.03-0.74; p = 0.029). Iron treatment was associated with reduced 28-day mortality in patients with AMI combined with ID. Iron treatment had no significant effect on the length of hospitalization or the length of ICU stay. Prospective studies are needed to verify this conclusion.

The effect of BMI on survival outcome of breast cancer patients: a systematic review and meta-analysis.

OBJECTIVE: The main goal of the present research is to explore the potential link of body mass index (BMI) with different survival metrics in breast cancer patients. Our aim is to offer the latest and most thorough meta-analysis, assessing the strength and reliability of the connection that BMI has with prognostic indicators in this disease. PATIENTS AND METHODS: As of January 2024, we conducted a systematic literature search across PubMed, Embase, Web of Science, and the Cochrane Library databases. Our search aimed to identify studies examining BMI as an exposure factor, with breast cancer patients constituting the study population, and utilizing adjusted hazard ratio (HR) as the data type of interest. RESULTS: The evidence synthesis incorporated a total of 61 eligible articles involving 201,006 patients. Being underweight posed a risk factor for overall survival (OS) in breast cancer patients compared to normal weight (HR 1.15, 95% CI 0.98-1.35; P = 0.08). Overweight or obesity, in comparison to normal weight, was a risk factor for OS (HR 1.18, 95% CI 1.14-1.23; P < 0.00001), disease-free survival (DFS) (HR 1.11, 95% CI 1.08-1.13; P < 0.00001), relapse-free survival (RFS) (HR 1.14, 95% CI 1.06-1.22; P = 0.03), and breast cancer-specific survival (BCSS) (HR 1.18, 95% CI 1.11-1.26; P < 0.00001), but not for progression-free survival (PFS) (HR 0.91, 95% CI 0.76-1.10; P = 0.33). Notably, in subgroup analyses, overweight patients achieved prolonged PFS (HR 0.80, 95% CI 0.64-0.99; P = 0.04), and compared to the obese population, the overweight cohort exhibited a significant difference in OS (HR 1.11, 95% CI 1.05-1.16; P < 0.00001) and DFS (HR 1.06, 95% CI 1.03-1.10; P = 0.0004), with a considerably stronger association. Furthermore, compared to HER- patients, HER + patients exhibited a greater predictive value for OS (HR 1.23, 95% CI 1.10-1.37; P = 0.0004), RFS (HR 1.30, 95% CI 1.03-1.64; P < 0.00001), and DFS (HR 1.10, 95% CI 1.03-1.17; P = 0.003). CONCLUSIONS: The results of our meta-analysis reveal a notable association between BMI and various survival measures in breast cancer prognosis. These findings provide a solid basis for predicting breast cancer outcomes and implementing more effective therapeutic approaches.

Ultra-low-field magnetic resonance angiography at 0.05 T: A preliminary study.

We aim to explore the feasibility of head and neck time-of-flight (TOF) magnetic resonance angiography (MRA) at ultra-low-field (ULF). TOF MRA was conducted on a highly simplified 0.05 T MRI scanner with no radiofrequency (RF) and magnetic shielding. A flow-compensated three-dimensional (3D) gradient echo (GRE) sequence with a tilt-optimized nonsaturated excitation RF pulse, and a flow-compensated multislice two-dimensional (2D) GRE sequence, were implemented for cerebral artery and vein imaging, respectively. For carotid artery and jugular vein imaging, flow-compensated 2D GRE sequences were utilized with venous and arterial blood presaturation, respectively. MRA was performed on young healthy subjects. Vessel-to-background contrast was experimentally observed with strong blood inflow effect and background tissue suppression. The large primary cerebral arteries and veins, carotid arteries, jugular veins, and artery bifurcations could be identified in both raw GRE images and maximum intensity projections. The primary brain and neck arteries were found to be reproducible among multiple examination sessions. These preliminary experimental results demonstrated the possibility of artery TOF MRA on low-cost 0.05 T scanners for the first time, despite the extremely low MR signal. We expect to improve the quality of ULF TOF MRA in the near future through sequence development and optimization, ongoing advances in ULF hardware and image formation, and the use of vascular T1 contrast agents.

Effects of catechin on the malignant biological behavior of gastric cancer cells through the PI3K/Akt signaling pathway.

Catechin is a kind of flavonoids, mainly derived from the plant Camellia sinensis. It has a strong antioxidant effect, and it also has significant therapeutic effects on anti-cancer, anti-diabetes, and anti-infection. This study was intended to look at how catechin affected the malignant biological activity of gastric cancer cells. We used databases to predict the targets of catechin and the pathogenic targets of gastric cancer. Venn diagram was used to find the intersection genes, the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses were performed on intersection genes. Using the STRING database, the Protein-Protein Interaction (PPI) network was built. The top 8 genes were screened by Cytoscape 3.9.1, then their binding was verified by molecular docking. The proliferation ability, cell cycle, apoptosis and migration of gastric cancer cells were detected, as well as the protein expression levels of PI3K, p-AKT, and AKT and the mRNA expression levels of AKT1, VEGFA, EGFR, HRAS, and HSP90AA1 in gastric cancer cells. Our research revealed that different concentrations of catechin could effectively inhibit the proliferation and migration of gastric cancer cells, regulate the cell cycle, and promote the death of these cells, and it's possible that the PI3K/Akt pathway was crucial in mediating this impact. Moreover, adding the PI3K/Akt pathway agonist significantly reduced the promoting effect of catechin on the apoptosis of gastric cancer cells. This study suggested that catechin was a potential drug for the treatment of gastric cancer.

Assessment of Water Intake among Chinese Toddlers: The Report of a Survey.

Toddlerhood (aged 13~36 months) is a period of dietary transition, with water intake being significantly influenced by parental feeding patterns, cultural traditions, and the availability of beverages and food. Nevertheless, given the lack of applicable data, it is challenging to guide and evaluate the water intake of toddlers in China. In this study, our objectives were to assess the daily total water intake (TWI), evaluate the consumption patterns of various beverages and food sources contributing to the TWI, determine the conformity of participants to the adequate intake (AI) recommendation of water released by the Chinese Nutrition Society, and analyze the various contributors to the daily total energy intake (TEI). The data for the assessment of water and dietary intake were obtained from the cross-sectional dietary intake survey of infants and young children (DSIYC, 2018-2019). A total of 1360 eligible toddlers were recruited in the analysis. The differences in related variables between two age groups were compared by Mann-Whitney U test and Chi-Square test. The potential correlation between water and energy intake was examined utilizing age-adjusted partial correlation. Toddlers consumed a median daily TWI of 1079 mL, with 670 mL (62.3%, r = 0.752) derived from beverages and 393 mL (37.7%, r = 0.716) from foods. Plain water was the primary beverage source, contributing 300 mL (52.2%, r = 0.823), followed by milk and milk derivatives (MMDs) at 291 mL (45.6%, r = 0.595). Notably, only 28.4% of toddlers managed to reach the recommended AI value. Among these, toddlers obtain more water from beverages than from foods. The median daily TEI of toddlers was 762 kcal, including 272 kcal from beverages (36.4%, r = 0.534) and 492 kcal from foods (63.6%, r = 0.894). Among these, the median daily energy intake from MMDs was 260 kcal, making up 94.6% of the energy intake from beverages (r = 0.959). As the pioneer survey on TWI of toddlers in China based on nationally representative data, attention to the quality and quantity of water intake and actions to better guide parents by both individuals and authorities are eagerly anticipated. Additionally, the revision of the reference value of TWI for Chinese toddlers is urgently required.

Ultra-low-field magnetization transfer imaging at 0.055T with low specific absorption rate.

PURPOSE: To demonstrate magnetization transfer (MT) effects with low specific absorption rate (SAR) on ultra-low-field (ULF) MRI. METHODS: MT imaging was implemented by using sinc-modulated RF pulse train (SPT) modules to provide bilateral off-resonance irradiation. They were incorporated into 3D gradient echo (GRE) and fast spin echo (FSE) protocols on a shielding-free 0.055T head scanner. MT effects were first verified using phantoms. Brain MT imaging was conducted in both healthy subjects and patients. RESULTS: MT effects were clearly observed in phantoms using six SPT modules with total flip angle 3600° at central primary saturation bands of approximate offset ±786 Hz, even in the presence of large relative B0 inhomogeneity. For brain, strong MT effects were observed in gray matter, white matter, and muscle in 3D GRE and FSE imaging using six and sixteen SPT modules with total flip angle 3600° and 9600°, respectively. Fat, cerebrospinal fluid, and blood exhibited relatively weak MT effects. MT preparation enhanced tissue contrasts in T2-weighted and FLAIR-like images, and improved brain lesion delineation. The estimated MT SAR was 0.0024 and 0.0008 W/kg for two protocols, respectively, which is far below the US Food and Drug Administration (FDA) limit of 3.0 W/kg. CONCLUSION: Robust MT effects can be readily obtained at ULF with extremely low SAR, despite poor relative B0 homogeneity in ppm. This unique advantage enables flexible MT pulse design and implementation on low-cost ULF MRI platforms to achieve strong MT effects in brain and beyond, potentially augmenting their clinical utility in the future.

Interaction between antiretroviral therapy regimens and body mass index on triglyceride levels in people living with HIV: a cross-sectional and longitudinal study.

OBJECTIVE: To investigate how antiretroviral therapy (ART) regimens and body mass index (BMI) interact to affect triglyceride (TG) levels in people living with HIV (PLWH). METHODS: This research involved 451 men living with HIV for cross-sectional analysis, and 132 underwent follow-up assessments in 2021 and 2023. Multivariate logistic regression identified key factors, while covariance regression models assessed interactions between ART regimens and BMI on TG levels. RESULTS: The result of this cross-sectional study indicated that advanced AIDS (acquired immune deficiency syndrome) stage (OR = 2.756, P = 0.003), higher BMI (OR = 1.131, P = 0.003), and waist-hip ratio (WHR, OR = 44.684, P = 0.019) are closely associated with high triglyceride levels. Additionally, regimens containing zidovudine (AZT) (OR = 3.927, P < 0.001) or protease inhibitors/integrase strand transfer inhibitors (PI/INSTI) (OR = 5.167, P < 0.001) were significantly linked to hypertriglyceridemia. Cross-sectional and longitudinal analyses from 2021 to 2023 emphasized that changes in BMI interact with antiretroviral treatment regimens to affect TG levels in PLWH (Pinteraction < 0.05). Especially in the AZT-based drug regimen, the correlation between BMI and TG is more prominent. CONCLUSION: The interaction between ART regimens and BMI influences TG levels in PLWH, indicating that weight management is crucial for reducing the risk of hypertriglyceridemia in this population.

Transcriptome profiling of fast/glycolytic and slow/oxidative muscle fibers in aging and obesity.

Aging and obesity pose significant threats to public health and are major contributors to muscle atrophy. The trends in muscle fiber types under these conditions and the transcriptional differences between different muscle fiber types remain unclear. Here, we demonstrate distinct responses of fast/glycolytic fibers and slow/oxidative fibers to aging and obesity. We found that in muscles dominated by oxidative fibers, the proportion of oxidative fibers remains unchanged during aging and obesity. However, in muscles dominated by glycolytic fibers, despite the low content of oxidative fibers, a significant decrease in proportion of oxidative fibers was observed. Consistently, our study uncovered that during aging and obesity, fast/glycolytic fibers specifically increased the expression of genes associated with muscle atrophy and inflammation, including Dkk3, Ccl8, Cxcl10, Cxcl13, Fbxo32, Depp1, and Chac1, while slow/oxidative fibers exhibit elevated expression of antioxidant protein Nqo-1 and downregulation of Tfrc. Additionally, we noted substantial differences in the expression of calcium-related signaling pathways between fast/glycolytic fibers and slow/oxidative fibers in response to aging and obesity. Treatment with a calcium channel inhibitor thapsigargin significantly increased the abundance of oxidative fibers. Our study provides additional evidence to support the transcriptomic differences in muscle fiber types under pathophysiological conditions, thereby establishing a theoretical basis for modulating muscle fiber types in disease treatment.

Phase Transformation on Multilayer 2M-WS2 for Improved Surface-enhanced Raman Scattering.

In recent years, two-dimensional (2D) transition metal dichalcogenides (TMDCs) have been widely recognized as an ideal platform for surface-enhanced Raman scattering (SERS). Given their rich structural phases, phase transformation in 2D TMDCs is an efficient strategy to tailor their SERS performance. In this paper, we present the great SERS performance of multilayer 2M-WS2 and then investigate the effect of its phase transformation on SERS performance. It is observed that multilayer 2M-WS2 nanosheets undergo a thermally induced single-crystal phase transition from 2M-WS2 to 2H-WS2 upon thermal annealing or laser treatment. Distinguishing from the commercially available pure 2H-WS2 (P-2H-WS2), 2H-WS2 obtained by annealing and laser treatment still retain SERS properties comparable to those of 2M-WS2, among which the detection limits for CV molecules (10-8 M) are 3 orders of magnitude lower than that of P-2H-WS2 and the Raman intensity enhancements are ∼10-37 times higher. In contrast to the charge transfer (CT) mechanism governed by the Fermi level in metallic-phase 2M-WS2, 2H-WS2 obtained by phase transition exhibits accelerated CT facilitated by the bandgap reduction and reorganization resulting from the abundance of vacancies. This study introduces an interesting perspective and potential avenue for enhancing SERS through metal-to-semiconductor phase transitions in 2D TMDCs materials.

Metagenome next-generation sequencing plays a key role in the diagnosis and selection of effective antibiotics on the treatment of Nocardia pneumonia: a case report.

Nocardia disease is an opportunistic infection, the occurrence is rare and mostly occurs in patients with immune deficiency. Even if the patient is immunocompetent, it can still be life-threatening. This case report describes a previously healthy 78-year-old male farmer with lung lesions discovered on a computerized tomography scan. Combined with the patient's history of fever and the results of elevated laboratory markers associated with inflammation, the patient was diagnosed with a lung infection. After escalating empirical broad-spectrum antibiotics, antiviral and antifungal therapy, the patient continued to deteriorate to septic shock. In the meanwhile, the patient's sputum was cultured repeatedly, and no obvious positive pathogenic bacteria were found. Considering the patient was elderly and that these lesions were solid with burr signs, as well as the progression after antimicrobial therapy cancer was considered in the differential diagnosis. Artificial intelligence (YITU, Hangzhou Yitu Medical Technology Limited Company) was also applied, and it also calculated that these lesions were cancerous. The patient received a puncture biopsy of the largest lung lesion. During the puncture pus was withdrawn from largest lung lesion. Culture and metagenome next-generation sequencing (mNGS) detection performed on pus indicated Nocardia otitidiscaviarum. The test report of the mNGS is also attached with a susceptibility report of commonly used clinical antibiotics to this Nocardia spp. Using this result, the patient's disease was quickly controlled after selecting the targeted drug compound sulfamethoxazole and intravenous meropenem for treatment. In view of the high misdiagnosis rate and poor sensitivity of culture for Nocardia spp., this case emphasized mNGS playing a key role in the diagnosis and selection of effective antibiotics for the treatment of Nocardia spp. lung infections.

Protective effect of melatonin on imidacloprid-induced pyroptosis and ferroptosis by mediating peptidoglycan in the gut of the common carp (Cyprinus carpio).

Imidacloprid (IMI) is a contaminant widespread in surface water, causing serious intestinal damage in the common carp. Melatonin (MT), an endogenous indoleamine hormone, plays a crucial role in mitigating pesticide-induced toxicity. Our previous research has demonstrated that MT effectively reduces the production of intestinal microbial-derived signal peptidoglycan (PGN) induced by IMI, thereby alleviating intestinal tight junction injuries in the common carp. In this study, we performed a transcriptomic analysis to explore the effect of MT on the IMI exposure-induced gut damage of the common carp. The results elucidated that the ferroptosis, mitogen-activated protein kinases (MAPKs), and nucleotide oligomerization domain (NOD)-like signaling pathways were significantly associated with IMI exposure and MT treatment. Meanwhile, the exposure to IMI resulted in the formation of pyroptotic bodies and distinct morphological features of ferroptosis, both mitigated with the addition of MT. Immunofluorescence double staining demonstrated that MT abolished the elevated expression of NOD-like receptor thermal protein domain associated protein 3 (NLRP3) and Gasdermin D (GSDMD) induced by IMI, as well as reduced expression of ferritin heavy chains (FTH) and glutathione peroxidase 4 (GPX4) in gut tissues. Subsequently, we found that the exposure to IMI or PGN enhanced the expression of toll-like receptors (TLR) 2 (a direct recognition receptor of PGN) triggering the P38MAPK signaling pathway, thereby aggravating the process of pyroptosis and ferroptosis of cell models. The addition of MT or SB203580 (a P38MAPK inhibitor) significantly reduced pyroptotic cells, and also decreased iron accumulation. Consequently, these results indicate that MT alleviates IMI-induced pyroptosis and ferroptosis in the gut of the common carp through the PGN/TLR2/P38MAPK pathway.

Whole-body magnetic resonance imaging at 0.05 Tesla.

Despite a half-century of advancements, global magnetic resonance imaging (MRI) accessibility remains limited and uneven, hindering its full potential in health care. Initially, MRI development focused on low fields around 0.05 Tesla, but progress halted after the introduction of the 1.5 Tesla whole-body superconducting scanner in 1983. Using a permanent 0.05 Tesla magnet and deep learning for electromagnetic interference elimination, we developed a whole-body scanner that operates using a standard wall power outlet and without radiofrequency and magnetic shielding. We demonstrated its wide-ranging applicability for imaging various anatomical structures. Furthermore, we developed three-dimensional deep learning reconstruction to boost image quality by harnessing extensive high-field MRI data. These advances pave the way for affordable deep learning-powered ultra-low-field MRI scanners, addressing unmet clinical needs in diverse health care settings worldwide.

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.

RBM3 enhances the stability of MEF2C mRNA and modulates blood-brain barrier permeability in AD microenvironment.

Blood-brain barrier (BBB) changes are acknowledged as early indicators of Alzheimer's disease (AD). The permeability and integrity of the BBB rely significantly on the essential role played by the tight junction proteins (TJPs) connecting endothelial cells. This study found the reduced RNA binding motif protein 3 (RBM3) expression in brain microvascular endothelial cells (BMECs) incubated with Aß1-42. This downregulation of RBM3 caused a decrease in the levels of ZO-1 and occludin and increased the permeability of BBB cell model in AD microenvironment. Myocyte enhancer factor 2C (MEF2C) expression was also inhibited in BMECs incubated with Aß1-42. A decrease in MEF2C expression led to increased permeability of BBB cell model in AD microenvironment and reductions in the levels of ZO-1 and occludin. Further analysis of the underlying mechanism revealed that RBM3 binds to and stabilizes MEF2C mRNA. MEF2C binds to the promoters of ZO-1 and occludin, enhancing their transcriptional activities and modulating BBB permeability. RBM3 increases the stability of MEF2C mRNA and subsequently modulates BBB permeability through the paracellular pathway of TJPs. This may provide new insights for AD research.

Transformer fault diagnosis method based on SMOTE and NGO-GBDT.

In order to improve the accuracy of transformer fault diagnosis and improve the influence of unbalanced samples on the low accuracy of model identification caused by insufficient model training, this paper proposes a transformer fault diagnosis method based on SMOTE and NGO-GBDT. Firstly, the Synthetic Minority Over-sampling Technique (SMOTE) was used to expand the minority samples. Secondly, the non-coding ratio method was used to construct multi-dimensional feature parameters, and the Light Gradient Boosting Machine (LightGBM) feature optimization strategy was introduced to screen the optimal feature subset. Finally, Northern Goshawk Optimization (NGO) algorithm was used to optimize the parameters of Gradient Boosting Decision Tree (GBDT), and then the transformer fault diagnosis was realized. The results show that the proposed method can reduce the misjudgment of minority samples. Compared with other integrated models, the proposed method has high fault identification accuracy, low misjudgment rate and stable performance.

Selective deletion of E3 ubiquitin ligase FBW7 in VE-cadherin-positive cells instigates diffuse large B-cell lymphoma in mice in vivo.

During the maturation of hematopoietic stem/progenitor cells (HSPCs) to fully differentiated mature B lymphocytes, developing lymphocytes may undergo malignant transformation and produce B-cell lymphomas. Emerging evidence shows that through the endothelial-hematopoietic transition, specialized endothelial cells called the hemogenic endothelium can differentiate into HSPCs. However, the contribution of genetic defects in hemogenic endothelial cells to B-cell lymphomagenesis has not yet been investigated. Here, we report that mice with endothelial cell-specific deletion of Fbw7 spontaneously developed diffuse large B-cell lymphoma (DLBCL) following Bcl6 accumulation. Using lineage tracing, we showed that B-cell lymphomas in Fbw7 knockout mice were hemogenic endothelium-derived. Mechanistically, we found that FBW7 directly interacted with Bcl6 and promoted its proteasomal degradation. FBW7 expression levels are inversely correlated with BCL6 expression. Additionally, pharmacological disruption of Bcl6 abolished Fbw7 deletion-induced B-cell lymphomagenesis. We conclude that selective deletion of E3 ubiquitin ligase FBW7 in VE-cadherin positive endothelial cells instigates diffuse large B-cell lymphoma via upregulation of BCL6 stability. In addition, the mice with endothelial cell-specific deletion of Fbw7 provide a valuable preclinical platform for in vivo development and evaluation of novel therapeutic interventions for the treatment of DLBCL.

Implementation and Validation of an OpenMM Plugin for the Deep Potential Representation of Potential Energy.

Machine learning potentials, particularly the deep potential (DP) model, have revolutionized molecular dynamics (MD) simulations, striking a balance between accuracy and computational efficiency. To facilitate the DP model's integration with the popular MD engine OpenMM, we have developed a versatile OpenMM plugin. This plugin supports a range of applications, from conventional MD simulations to alchemical free energy calculations and hybrid DP/MM simulations. Our extensive validation tests encompassed energy conservation in microcanonical ensemble simulations, fidelity in canonical ensemble generation, and the evaluation of the structural, transport, and thermodynamic properties of bulk water. The introduction of this plugin is expected to significantly expand the application scope of DP models within the MD simulation community, representing a major advancement in the field.