Oncogenic mutant KRAS inhibition through oxidation at cysteine 118.

Specific reactive oxygen species activate the GTPase Kirsten rat sarcoma virus (KRAS) by reacting with cysteine 118 (C118), leading to an electron transfer between C118 and nucleoside guanosine diphosphate (GDP), which causes the release of GDP. Here, we have mimicked permanent oxidation of human KRAS at C118 by replacing C118 with aspartic acid (C118D) in KRAS to show that oncogenic mutant KRAS is selectively inhibited via oxidation at C118, both in vitro and in vivo. Moreover, the combined treatment of hydrogen-peroxide-producing pro-oxidant paraquat and nitric-oxide-producing inhibitor N(ω)-nitro-l-arginine methyl ester selectively inhibits human mutant KRAS activity by inducing oxidization at C118.

Capture primed pluripotency in guinea pig.

Guinea pigs are valuable models for human disease research, yet the lack of established pluripotent stem cell lines has limited their utility. In this study, we isolate and characterize guinea pig epiblast stem cells (gpEpiSCs) from post-implantation embryos. These cells differentiate into the three germ layers, maintain normal karyotypes, and rely on FGF2 and ACTIVIN A signaling for self-renewal and pluripotency.

Intratumor heterogeneity of EGFR expression mediates targeted therapy resistance and formation of drug tolerant microenvironment.

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors are commonly used to treat non-small cell lung cancers with EGFR mutations, but drug resistance often emerges. Intratumor heterogeneity is a known cause of targeted therapy resistance and is considered a major factor in treatment failure. This study identifies clones of EGFR-mutant non-small cell lung tumors expressing low levels of both wild-type and mutant EGFR protein.

Knockdown of RUVBL2 improves hnRNPA2/B1-stress granules dynamics to inhibit perioperative neurocognitive disorders in aged mild cognitive impairment rats.

Perioperative neurocognitive disorders (PND) is common in aged mild cognitive impairment (MCI) patients and can accelerate the progression to dementia. This process involves heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2/B1)-mediated aggregates of stress granules (SGs), while RUVBL2 influences the dynamics of these SGs. Our research explored a new target for modulating hnRNAPA2/B1-SGs dynamics to accelerate their disassembly and potentially delay MCI progression due to PND.

Twisted hyperbolic-sine-correlated beams.

In this study, a novel class of spatially non-uniformly correlated beams called twisted hyperbolic-sine-correlated (THSC) beams is introduced. The coherence structure of such beam sources is characterized by a hyperbolic sine function with a high-order twist phase embedded in its argument. The propagation properties of the THSC beams are numerically examined in detail.

scPharm: Identifying Pharmacological Subpopulations of Single Cells for Precision Medicine in Cancers.

Intratumour heterogeneity significantly hinders the efficacy of anticancer therapies. Compared with drug perturbation experiments, which yield pharmacological data at the bulk cell level, single-cell RNA sequencing (scRNA-seq) technology provides a means to capture molecular heterogeneity at single-cell resolution. Here, scPharm is introduced, a computational framework that integrates pharmacological profiles with scRNA-seq data to identify pharmacological subpopulations of cells within a tumour and prioritize tailored drugs.

Analysis of influencing factors of clinical pregnancy rate in second cycle intrauterine insemination.

To explore the factors influencing the clinical pregnancy rate in the Reproductive Center of the Affiliated Hospital of North Sichuan Medical College in the second cycle, a retrospective analysis of the clinical data of 175 patients who underwent the second cycle of intrauterine insemination (175 cycles) from July 2019 to July 2022 was performed. According to whether the patients reached clinical pregnancy, they were divided into the pregnant group (32 cycles) and non-pregnant group (143 cycles). The age, infertility years, infertility factors, infertility type, number of sinus follicles, intimal thickness, intimal type, basal follicle-stimulating hormone, basal luteinizing hormone, basal estradiol, stimulation regimen, season, body mass index, and male semen quality were statistically analyzed between the 2 groups.

Combinatorial lipidomics and proteomics underscore erythrocyte lipid membrane aberrations in the development of adverse cardio-cerebrovascular complications in maintenance hemodialysis patients.

Patients on maintenance hemodialysis exhibit a notably higher risk of cardio-cerebrovascular complications that constitute the major cause of death. Preceding studies have reported conflicting associations between traditional lipid measures and clinical outcome in dialysis patients. In this prospective longitudinal study, we utilized quantitative lipidomics to elucidate, at molecular resolution, changes in lipidome profiles of erythrocyte and plasma samples collected from maintenance hemodialysis patients followed up for 86 months (≈7 years).

Exploring an economic and highly efficient genetic transformation and genome-editing system for radish through developmental regulators and visible reporter.

Radish (Raphanus sativus L.) is one of the most important root vegetable crops worldwide. However, gene function exploration and germplasm innovation still face tremendous challenges due to its extremely low transformation efficiency.

Tensile Deformation Mechanism of an Formed Ti-Based Bulk Metallic Glass Composites.

Ti-based bulk metallic glass composites (BMGMCs) containing an formed metastable β phase normally exhibit enhanced plasticity attributed to induced phase transformation or twinning. However, the underlying deformation micromechanism remains controversial. This study investigates a novel deformation mechanism of Ti-based BMGMCs with a composition of TiZrCuNbNiBe (at%).

scHyper: reconstructing cell-cell communication through hypergraph neural networks.

Cell-cell communications is crucial for the regulation of cellular life and the establishment of cellular relationships. Most approaches of inferring intercellular communications from single-cell RNA sequencing (scRNA-seq) data lack a comprehensive global network view of multilayered communications. In this context, we propose scHyper, a new method that can infer intercellular communications from a global network perspective and identify the potential impact of all cells, ligand, and receptor expression on the communication score.

Voltage abnormity prediction method of lithium-ion energy storage power station using informer based on Bayesian optimization.

Accurately detecting voltage faults is essential for ensuring the safe and stable operation of energy storage power station systems. To swiftly identify operational faults in energy storage batteries, this study introduces a voltage anomaly prediction method based on a Bayesian optimized (BO)-Informer neural network. Firstly, the temporal characteristics and actual data collected by the battery management system (BMS) are considered to establish a long-term operational dataset for the energy storage station.

Type I interferon signaling pathway enhances immune-checkpoint inhibition in KRAS mutant lung tumors.

Lung cancer is the leading cause of cancer mortality worldwide. KRAS oncogenes are responsible for at least a quarter of lung adenocarcinomas, the main subtype of lung cancer. After four decades of intense research, selective inhibitors of KRAS oncoproteins are finally reaching the clinic.

Loss of histone deubiquitinase Bap1 triggers anti-tumor immunity.

Purpose: Immunotherapy using PD-L1 blockade is effective in only a small group of cancer patients, and resistance is common. This emphasizes the importance of understanding the mechanisms of cancer immune evasion and resistance.

Methods: A genome-scale CRISPR-Cas9 screen identified Bap1 as a regulator of PD-L1 expression.

Intermittent fasting alleviates postoperative cognitive dysfunction by reducing neuroinflammation in aged mice.

Elderly individuals undergoing surgical procedures are often confronted with the peril of experiencing postoperative cognitive dysfunction (POCD). Prior research has demonstrated the exacerbating effect of sevoflurane anesthesia on neuroinflammation, which can further deteriorate the condition of POCD in elderly patients. Intermittent fasting (IF) restricts food consumption to a specific time window and has been demonstrated to ameliorate cognitive dysfunction induced by neuropathic inflammation.

Propofol improves sleep deprivation-induced sleep structural and cognitive deficits via upregulating the BMAL1 expression and suppressing microglial M1 polarization.

Background: Sleep deprivation (SD) is a growing global health problem with many deleterious effects, such as cognitive impairment. Microglia activation-induced neuroinflammation may be an essential factor in this. Propofol has been shown to clear sleep debt after SD in rats.

Effects of minimally invasive surgery combined with specialized pain management nursing care on postoperativepain improvement and life quality after spinal injury.

Objective: To determine the impacts to research the impacts of pain's Specialized Pain Management Nursing Care in the perioperative period on pain symptoms and life quality of patients experiencing minimally invasive surgery for spinal injury.

Method: Eighty patients with a spinal injury who underwent minimally invasive surgery in the Department of Orthopedics of Baoding No.1 Hospital from January 2018 to December 2021 were retrospectively analyzed.

Inhibition of PIKfyve Leads to Lysosomal Disorders via Dysregulation of mTOR Signaling.

PIKfyve is an endosomal lipid kinase that synthesizes phosphatidylinositol 3,5-biphosphate from phosphatidylinositol 3-phsphate. Inhibition of PIKfyve activity leads to lysosomal enlargement and cytoplasmic vacuolation, attributed to impaired lysosomal fission processes and homeostasis. However, the precise molecular mechanisms underlying these effects remain a topic of debate.

Measuring the orbital angular momentum of generalized higher-order twisted partially coherent beams.

Recently a new family of partially coherent fields incorporating generalized inseparable cross-coupled phases named generalized higher-order twisted partially coherent beams (GHTPCBs) have been introduced. The twist factor u is a key parameter that not only quantifies the strength of the generalized cross-coupled phase for a given order, but also determines the amount of the concomitant orbital angular momentum (OAM). In this paper, we propose a simple and reliable method to measure the factor u using a two-pinhole mask.

The Effect of Physical Activity on Sleep Quality Among Chinese College Students: The Chain Mediating Role of Stress and Smartphone Addiction During the COVID-19 Pandemic.

Purpose: During the period of COVID-19 pandemic, the social restrictions and isolation exerted a significant impact on the sleep quality of Chinese college students. This study aims to delve into the influence of physical activity on the sleep quality of college students as well as the mediating roles of stress and smartphone addiction.

Materials And Methods: A cohort of 274 eligible college students (146 males and 128 females) were selected for the investigation.

Dissecting Spatiotemporal Structures in Spatial Transcriptomics via Diffusion-Based Adversarial Learning.

Recent advancements in spatial transcriptomics (ST) technologies offer unprecedented opportunities to unveil the spatial heterogeneity of gene expression and cell states within tissues. Despite these capabilities of the ST data, accurately dissecting spatiotemporal structures (e.g.