Identification of Novel 2‑(Azetidin-3-ylamino)-nicotinamide Derivatives as Potent KRAS::SOS1 Inhibitors.

Son of Sevenless 1 (SOS1), the principal guanine nucleotide exchange factor for KRAS activation, has emerged as a promising therapeutic target for KRAS-driven cancers. Utilizing structure-based drug design, we discovered a novel class of nicotinamide derivatives incorporating strategically positioned basic groups that engage with an acidic region in the SOS1 protein. The representative compound showed potent biochemical activity and 3D cellular antiproliferative activity and minimal hERG inhibition.

Comparison of complications between total hip arthroplasty following failed internal fixation and primary total hip arthroplasty for femoral neck fractures: A meta-analysis.

Objectives: In this meta-analysis, we discuss the complication rates of conversion to total hip arthroplasty (cTHA) following failed internal fixation (IF) of femoral neck fractures (FNFs) versus primary total hip arthroplasty (pTHA).

Materials And Methods: The Cochrane Library, Web of Science, PubMed, Embase, and Science Direct databases were searched for eligible publications published prior to December 2024. The search terms included "femoral neck fracture", "internal fixation failure", and "total hip arthroplasty".

Effects of Intracellular Polysaccharides and Proteins of on Water Quality, Floc Formation, and Microbial Composition in a Biofloc System.

The use of (formerly ) and its intracellular substances (ISs) to promote biofloc development has been extensively studied. To identify the key components of the ISs of that drive biofloc formation, algal-extracted polysaccharides (AEPSs) and algal-extracted proteins (AEPTs) were isolated from the ISs. In this study, we established four groups: ISs, AEPSs, AEPTs, and tap water (TW, control), to investigate the effects of AEPSs and AEPTs on biofloc formation dynamics, water quality parameters, and microbial community composition.

The Cardiorenal Protective Effects of Finerenone in Patients with Diabetes and Heart Failure: A Meta-Analysis.

Introduction: To evaluate the cardiorenal protective effects of finerenone in patients with diabetes and heart failure through a meta-analysis of randomized controlled trials (RCTs).

Methods: This meta-analysis included 12 RCTs (total  = 65,226) assessing finerenone versus placebo. Primary outcomes included cardiovascular composite endpoints (major adverse cardiovascular events [MACE]) and kidney composite outcomes (sustained eGFR decline, end-stage kidney disease, or renal mortality).

A rare, evolutionarily conserved venom protein benefits endoparasitism across parasitoids.

Although many venom proteins and other parasitic effectors have been identified in various specific systems of parasitoids, key elements that contribute to parasitic success across a broad range of taxa remain largely unexplored. Here, we focus on Leptopilina and conduct a large-scale, multi-omics study to explore common venom proteins for these drosophilid parasitoids. We find that this genus has undergone extensive chromosome rearrangements and a rapid turnover of venom gene repertoires between species.

PI3K-dependent GAB1/Erk phosphorylation renders head and neck squamous cell carcinoma sensitive to PI3Kα inhibitors.

The hyperactivation of the PI3K pathway in head and neck squamous cell carcinoma (HNSCC) suggests that targeting PI3K is a potential therapeutic strategy. CYH33 is a novel PI3Kα-selective inhibitor discovered by our group, which is currently undergoing a phase I clinical trial (NCT03544905) for the treatment of advanced solid tumors including HNSCC. However, there is an urgent need to elucidate its mechanism of action and improve its efficacy against HNSCC.

Anode-free Zn-I batteries without fear of Zn loss: Hybrid energy-storage mechanism and dynamic capacity compensation.

Anode-free zinc (Zn) batteries (AFZBs) are promising in delivering high energy density at high Zn utilization. However, the limited availability and inevitable loss of Zn pose challenges such as reduced lifespan and inadequate stability to AFZBs. Herein, copper iodide (CuI) is introduced as a conversion-electrode material on the Cu current collector of an AFZB, composing a hybrid energy storage mechanism and forming an anode-free Zn-I battery (AFZIB).

Case Report: FAP fibroblasts and SPP1 macrophages in SMARCA2-deficient while SMARCA4-preserved poorly differentiated lung adenocarcinoma: two case reports and multi-omics analysis.

Two ATPase subunits, SMARCA4 (which encodes BRG1) and SMARCA2 (which encodes BRM), facilitate this process by hydrolyzing ATP to energize the activity of the mammalian switch/sucrose-non-fermenting (mSWI/SNF) complexes. Clinically, SMARCA4-deficient non-small cell lung carcinoma (SMARCA4-dNSCLC) were associated with the poorly differentiated histologic manifestations and poor prognosis. However, NSCLC exhibited the similar poorly differentiated features but loss of SMARCA2 and retained SMARCA4 have so far been underrecognized.

A Generative Artificial Intelligence Copilot for Biomedical Nanoengineering.

The recent success of large language models (LLMs) in performing natural language processing tasks has increased interest in applying generative artificial intelligence (AI) to scientific research. However, a common problem of LLMs is their tendency to produce inaccurate and sometimes "hallucinated" outputs. Here, we established a generative AI tool, NanoSafari, to automatically extract knowledge from the biomedical nanoscience literature and address scientific queries.

From simulation to clinic: Assessing the required channel count for effective clinical use of OPM-MEG systems.

The channel count in an Optically Pumped Magnetometer Magnetoencephalography (OPM-MEG) system plays a pivotal role in determining its overall performance. While existing research consistently highlights that a greater number of channels enhances system capabilities, practical constraints such as sensor placement on the head, inter-channel interference, and cost-efficiency impose limitations on channel scalability. Additionally, the optimal channel count required for clinical applications of OPM-MEG remains unclear.

Formation and structural dynamics of Lotus seed starch-linolenic acid complexes under high pressure microfluidization and their evolution during simulated gastrointestinal digestion.

Linolenic acid (ALA) can promote the production of intestinal short-chain fatty acids and the growth of beneficial bacteria. However, its polyunsaturated nature makes it prone to oxidation. To address this, lotus seed starch (LS) was used as a carrier to form LS-ALA complexes via dynamic high-pressure microfluidization (DHPM) at 180 MPa.

The efficacy of laparoscopic cholecystectomy vs. non-invasive gallstone dissolution to manage cholelithiasis: clinical outcomes and quality of life.

Background: This retrospective study aims to compare the clinical efficacy and impact on the quality of life of laparoscopic cholecystectomy with medication dissolution of gallstones.

Methods: Clinical data of 86 cholelithiasis patients admitted to our hospital from January 2021 to December 2022 were retrospectively analyzed. The patients were divided into a conservative group of 40 cases and a surgical group of 46 cases based on different treatment methods.

Prediction models for sleep quality among frontline medical personnel during the COVID-19 pandemic: cross-sectional study based on internet new media.

Background: The factors associated with sleep quality among medical personnel providing support on the frontline during the height of the COVID-19 pandemic remain unclear, and appropriate predictive and screening tools are lacking. This study was designed and conducted to investigate whether factors such as weight change, job title, and tea consumption influence the sleep quality of these workers. Additionally, the study aims to develop predictive models to analyze the sleep problems experienced by healthcare workers during periods of epidemic instability, and to provide relevant data and tools to support effective intervention and prevention strategies.

Corrigendum: Red cell distribution width to albumin ratio is associated with asthma risk: a population-based study.

[This corrects the article DOI: 10.3389/fmed.2024.

Dynamic simulation imaging for complex atmospheric turbulence scenes based on atmospheric coherence length and associated with phase structure function.

Atmospheric turbulence disturbance degrades the quality of long-range image transmission in applications such as marine monitoring and satellite imaging. Simulating an atmospheric turbulence image dataset facilitates the correction of turbulence-distorted images. However, the current simulation algorithms suffer from long computation times, undersampling of frequency, and unrealistic turbulence image simulation.

Predicting sleep quality among college students during COVID-19 lockdown using a LASSO-based neural network model.

Background: In March 2022, a new outbreak of COVID-19 emerged in Quanzhou, leading to the implementation of strict lockdown management measures in colleges. While existing research has indicated that the pandemic has had a significant impact on sleep quality, the specific effects of containment measures on college students' sleep patterns remain understudied.

Objective: This study aimed to understand the sleep quality of college students in Fujian Province during the epidemic and determine sensitive variables, in order to develop an efficient prediction model for the early screening of sleep problems in college students.

Association between SOX gene family expression, DNA methylation, and miRNA regulation in lung adenocarcinoma progression.

Objective: To analyze the expression of the SOX gene family in lung adenocarcinoma and its impact on the prognosis of lung adenocarcinoma patients using tumor databases.

Methods: The cBioPortal database was used to retrieve and analyze the mutation frequencies and variants of 10 genes in the SOX gene family in lung adenocarcinoma tissues. Using clinical information from the Kaplan-Meier plotter database, the potential prognostic values of 10 genes in the SOX gene family in lung adenocarcinoma patients were further explored.

A multi-classification deep neural network for cancer type identification from high-dimension, small-sample and imbalanced gene microarray data.

Gene microarray technology provides an efficient way to diagnose cancer. However, microarray gene expression data face the challenges of high-dimension, small-sample, and multi-class imbalance. The coupling of these challenges leads to inaccurate results when using traditional feature selection and classification algorithms.

Effect of artificial fish nest placement on spawning site preference and reproductive efficiency in reservoir fish with adhesive and demersal eggs.

Artificial fish nests are common tools in fisheries management, providing spawning grounds to enhance the size and diversity of fish populations. This study aimed to explore the effects of deployment locations on the reproductive efficiency and preferences of fish with adhesive and demersal eggs using artificial nests. Floating artificial nests were deployed in three regions (upstream, midstream, and downstream) of a reservoir in Zhejiang, China, at locations with three topographical types: steep slope (reservoir shore, slopes > 60°), gentle slope (reservoir shore, slopes < 30°), and confluence (middle thread of channel).

Evaluating the impact of ESICM 2023 guidelines and the new global definition of ARDS on clinical outcomes: insights from MIMIC-IV cohort data.

Background: In 2023, the European Society of Intensive Care Medicine (ESICM) recommended updated criteria for acute respiratory distress syndrome (ARDS). In 2024, Matthay et al. updated the global ARDS definition in AJRCCM, titled "A New Global Definition of Acute Respiratory Distress Syndrome.

Drug-phospholipid conjugate nano-assembly for drug delivery.

Phospholipid-based liposomes are among the most successful nanodrug delivery systems in clinical use. However, these conventional liposomes present significant challenges including low drug-loading capacity and issues with drug leakage. Drug-phospholipid conjugates (DPCs) and their assemblies offer a promising strategy for addressing these limitations.

Red cell distribution width to albumin ratio is associated with asthma risk: a population-based study.

Background: The red cell distribution width to albumin ratio (RAR), a newly identified biomarker of inflammation, has been linked to a variety of inflammatory diseases. Asthma, a major burden on global health, is an inflammatory airway disease that is profoundly affected by inflammation. This study primarily sought to examine the influence of RAR on the risk of developing asthma.

EZH2 directly methylates PARP1 and regulates its activity in cancer.

DNA repair dysregulation is a key driver of cancer development. Understanding the molecular mechanisms underlying DNA repair dysregulation in cancer cells is crucial for cancer development and therapies. Here, we report that enhancer of zeste homolog 2 (EZH2) directly methylates poly(adenosine diphosphate-ribose) polymerase-1 (PARP-1), an essential enzyme involved in DNA repair, and regulates its activity.

Ixochymostatin, a trypsin inhibitor-like (TIL) protein from Ixodes scapularis, inhibits chymase and impairs vascular permeability.

Ticks obtain a blood meal by lacerating small blood vessels and ingesting the blood that flows to the feeding site, which triggers various host responses. However, ticks face the challenge of wound healing, a process involving hemostasis, inflammation, cell proliferation and migration, and remodeling, hindering blood acquisition. To overcome these obstacles, tick salivary glands produce an array of bioactive molecules.