Ras S89D mutation induced allosteric changes that promoted its nucleotide exchange and signaling activation.

The small GTPase Ras is among the most frequently mutated genes and its mutations often drive oncogenesis across various cancers. While the role of NRas phosphorylation at S89 in the context of a Q61R mutation in melanoma genesis remains controversial, the impact of S89 phosphorylation on NRas function has not been fully elucidated. In this study, we employed the S89D phosphorylation-mimetic mutation and demonstrated that the S89D mutation alone activated all Ras isoforms by increasing the GTP-bound population, thereby promoting ERK phosphorylation and cell proliferation.

Sesquiterpene Monomers and Dimers from The Flower of Inula japonica Thunb. With Selective Antiproliferation Against Breast Cancer Cells.

A total of 34 sesquiterpene derivates were obtained from the flower of Inula japonica Thunb. Compounds 2, 14-34 were identified as sesquiterpene monomers, while the other 12 isolates (1, 3-13) were characterized as sesquiterpene dimers. Among them, japonicone Z (1), an present undescribed sesquiterpene dimer, and another undescribed monomer, japonicol A (2), were discovered.

A Meta-Analysis of Dietary Inhibitors for Reducing Methane Emissions via Modulating Rumen Microbiota in Ruminants.

Background: Rumen methane emissions (RMEs) significantly contribute to global greenhouse gas emissions, underscoring the essentials to identify effective inhibitors for RME mitigation. Despite various inhibitors shown potential in reducing RME by modulating rumen microbes, their impacts include considerable variations and inconsistency.

Objectives: We aimed to quantitatively assess the impacts of various methane inhibitors on RME, rumen microbial abundance, and fermentation in ruminants.

TLR4 promotes smooth muscle cell-derived foam cells formation by inducing receptor-independent macropinocytosis.

Foam cells are primarily formed through scavenger receptors that mediate the uptake of various modified low-density lipoproteins (LDL) into cells. In addition to the receptor-dependent pathway, macropinocytosis is an essential nonreceptor endocytic pathway for vascular smooth muscle cells (VSMCs) to take up lipids. However, the molecular mechanisms underlying this process remain unclear.

A giant parathyroid carcinoma cause deformation of thorax: Case report.

We present a rare case of a large parathyroid carcinoma (PC) characterized by severe hyperparathyroidism, hypercalcemia, and osteoporosis. Long-standing calcium loss resulted in thoracic and facial deformities, initially misdiagnosed as oral malignancy.

Relationship Between Control of Cardiovascular Risk Factors and Chronic Kidney Disease Progression, Cardiovascular Disease Events, and Mortality in Chinese Adults.

Background: Patients with chronic kidney disease (CKD) are at an elevated risk of cardiovascular disease (CVD) and premature mortality compared to the general population.

Objectives: This study aimed to investigate whether the excess risk of CVD events and death among patients with CKD could be reduced or eliminated through strict control of blood pressure (systolic blood pressure: <130 mm Hg), lipids (low-density lipoprotein cholesterol: <2.6 mmol/L), and glucose (fasting blood glucose: <6.

Molecular classification of geriatric breast cancer displays distinct senescent subgroups of prognostic significance.

Breast cancer in the elderly presents distinct biological characteristics and clinical treatment responses compared with cancer in younger patients. Comprehensive Geriatric Assessment is recommended for evaluating treatment efficacy in elderly cancer patients based on physiological classification. However, research on molecular classification in older cancer patients remains insufficient.

A chemical screen identifies PRMT5 as a therapeutic vulnerability for paclitaxel-resistant triple-negative breast cancer.

Paclitaxel-resistant triple negative breast cancer (TNBC) remains one of the most challenging breast cancers to treat. Here, using an epigenetic chemical probe screen, we uncover an acquired vulnerability of paclitaxel-resistant TNBC cells to protein arginine methyltransferases (PRMTs) inhibition. Analysis of cell lines and in-house clinical samples demonstrates that resistant cells evade paclitaxel killing through stabilizing mitotic chromatin assembly.

Two PNPLA2 heterozygous mutations result in neutral lipid storage disease with myopathy: a case report.

Background: Neutral Lipid Storage Disease with Myopathy (NLSDM) is a rare lipid metabolism disorder caused by PNPLA2 gene mutations. Clinical manifestations are heterogeneous, and diagnosis is often delayed, usually gaining patients' attention due to the increased risk of cardiomyopathy.

Case Presentation: We herein report a 36-year-old Asian male presenting with progressive limb weakness, muscle atrophy of limbs and trunk, dysarthria, and heart failure.

BFNet: a full-encoder skip connect way for medical image segmentation.

In recent years, semantic segmentation in deep learning has been widely applied in medical image segmentation, leading to the development of numerous models. Convolutional Neural Network (CNNs) have achieved milestone achievements in medical image analysis. Particularly, deep neural networks based on U-shaped architectures and skip connections have been extensively employed in various medical image tasks.

Risk factors for necrotizing enterocolitis in small-for-gestational-age infants: a matched case-control study.

Few studies have focused on the risk factors for necrotizing enterocolitis (NEC) in small for gestational age (SGA) infants. The aim of this study was to identify the risk factors for NEC in SGA newborns. This study included consecutive SGA neonates admitted to a tertiary hospital in Jiangxi Province, China from Jan 2008 to Dec 2022.

Sturgeon (Acipenser schrenckii) spinal cord peptides: Antioxidative and acetylcholinesterase inhibitory efficacy and mechanisms.

Providing antioxidants and targeting acetylcholinesterase (AChE) are key strategies in treating neurocognitive dysfunction. In this study, bioactive sturgeon (Acipenser schrenckii) spinal cord peptides (SSCPs) with antioxidant and AChE inhibitory potency were extracted and separated from sturgeon spinal cord by enzymatic hydrolysis and ultrafiltration, and targeted peptide PGGW was screened via computer simulated molecular docking. Further, the molecular dynamic interactions of the PGGW with superoxide dismutase (SOD) and AChE were analyzed, and the protective effect of PGGW on glutamate-induced PC12 cells in vitro was evaluated.

Life's Essential 8 in Relation to Cardiovascular Disease and Mortality in Individuals With Diabetes.

Background: Evidence regarding the potential health effects of Life's Essential 8 (LE8) score among individuals with type 2 diabetes (T2D) is limited.

Objectives: The purpose of this study was to examine the associations of LE8 score with risk of cardiovascular disease (CVD) and mortality among individuals with T2D.

Methods: We prospectively followed 19,915 Chinese participants with T2D at baseline or diagnosed during follow-up (Kailuan Study: 2006-2020), who were free of CVD at diagnosis of diabetes.

Brainstem dominant form of X-linked adrenoleukodystrophy with a novel ABCD1 missense variant: A case report and literature review.

Background: X-linked adrenoleukodystrophy (X-ALD) is the most common peroxisomal disorder attributed to ABCD1 mutations. Case reports with predominant brainstem involvement are rare.

Case Presentation: In this study, we reported a plateau male worker of X-ALD characterized by progressive weakness accompanied by gait instability, mild nystagmus, and constipation.

Formation of NifA-P complex represses ammonium-sensitive nitrogen fixation in diazotrophic proteobacteria lacking NifL.

Biological nitrogen fixation catalyzed by nitrogenase contributes greatly to the global nitrogen cycle. Nitrogenase expression is subject to regulation in response to nitrogen availability. However, the mechanism through which the transcriptional activator NifA regulates nitrogenase expression by interacting with P nitrogen regulatory proteins remains unclear in diazotrophic proteobacteria lacking NifL.

YTHDC1 aggravates high glucose-induced retinal vascular endothelial cell injury via m6A modification of CDK6.

Objective: Retinal vascular endothelial cell (RVECs) injury is a major cause of morbidity and mortality among the patients with diabetes. RVECs dysfunction is the predominant pathological manifestation of vascular complication in diabetic retinopathy. N6-methyladenosine (m6A) serves as the most prevalent modification in eukaryotic mRNAs.

Contingent magnetic variation and beta-band oscillations in sensorimotor temporal decision-making.

The ability to accurately encode the temporal information of sensory events and hence to make prompt action is fundamental to humans' prompt behavioral decision-making. Here we examined the ability of ensemble coding (averaging multiple inter-intervals in a sound sequence) and subsequent immediate reproduction of target duration at half, equal, or double that of the perceived mean interval in a sensorimotor loop. With magnetoencephalography (MEG), we found that the contingent magnetic variation (CMV) in the central scalp varied as a function of the averaging tasks, with a faster rate for buildup amplitudes and shorter peak latencies in the "half" condition as compared to the "double" condition.

Reactive oxygen species-responsive supramolecular deucravacitinib self-assembly polymer micelles alleviate psoriatic skin inflammation by reducing mitochondrial oxidative stress.

Introduction: The new topical formula is urgent needed to meet clinical needs for majority mild patients with psoriasis. Deucravacitinib exerts outstanding anti-psoriatic capacity as an oral TYK2 inhibitor; however, single therapy is insufficient to target the complicated psoriatic skin, including excessive reactive oxygen species (ROS) and persistent inflammation. To address this need, engineered smart nano-therapeutics hold potential for the topical delivery of deucravacitinib.

CYP1A2 Polymorphism and Drug Co-administration Affect the Blood Levels and Adverse Effects of Pirfenidone.

Background: Mutations in metabolic enzymes and co-administration of drugs may affect the blood concentration of pirfenidone effective in pulmonary fibrosis. To provide a basis for the precise clinical use of pirfenidone, the authors analyzed the correlation between steady-state pirfenidone trough concentration and adverse drug reactions (ADRs) and examined the impact of CYP1A2*1C (rs2069514) and *1F (rs762551) variants and co-administration on pirfenidone blood concentrations and ADRs.

Methods: Forty-four patients were enrolled.

Wernicke encephalopathy induced by glucose infusion: A case report and literature review.

Introduction: Wernicke encephalopathy (WE) is a potentially fatal condition caused by thiamine (vitamin B1) deficiency. Chronic alcoholism is the most common cause of WE; however, other conditions responsible for thiamine deficiency should also be considered.

Case Report: We report the case of a 64-year-old woman with a history of diabetes who presented with confusion and apathy.

Hydralazine loaded nanodroplets combined with ultrasound-targeted microbubble destruction to induce pyroptosis for tumor treatment.

Pyroptosis, a novel type of programmed cell death (PCD), which provides a feasible therapeutic option for the treatment of tumors. However, due to the hypermethylation of the promoter, the critical protein Gasdermin E (GSDME) is lacking in the majority of cancer cells, which cannot start the pyroptosis process and leads to dissatisfactory therapeutic effects. Additionally, the quick clearance, systemic side effects, and low concentration at the tumor site of conventional pyroptosis reagents restrict their use in clinical cancer therapy.

Trends in colorectal cancer screening compliance and incidence among 60- to 74-year-olds in China.

Background: Compliance with colonoscopy among elderly individuals participating in colorectal cancer (CRC) screening programs is unsatisfactory, despite a high detection rate of bowel-related diseases. In this study, our aim was to analyze the impact of risk factors on the trends of compliance and detection rates in colonoscopy among high-risk individuals aged 60-74.

Methods: A retrospective study was conducted on the high-risk individuals aged 60-74 participating in the 2021 CRC screening program in Tianjin, China.