Angiogenesis, a key point in the association of gut microbiota and its metabolites with disease.

The gut microbiota is a complex and dynamic ecosystem that plays a crucial role in human health and disease, including obesity, diabetes, cardiovascular diseases, neurodegenerative diseases, inflammatory bowel disease, and cancer. Chronic inflammation is a common feature of these diseases and is closely related to angiogenesis (the process of forming new blood vessels), which is often dysregulated in pathological conditions. Inflammation potentially acts as a central mediator.

Differences in brain spindle density during sleep between patients with and without type 2 diabetes.

Background: Sleep spindles may be implicated in sensing and regulation of peripheral glucose. Whether spindle density in patients with type 2 diabetes mellitus (T2DM) differs from that of healthy subjects is unknown.

Methods: Our retrospective analysis of polysomnography (PSG) studies identified 952 patients with T2DM and 952 sex-, age- and BMI-matched control subjects.

Discovery of Pyrazolo[1,5,4-de]quinoxalin-2(3)-one Derivatives as Highly Potent and Selective PARP1 Inhibitors.

Poly-ADP-ribose-polymerase 1/2 (PARP1/2) inhibitors have been approved for cancers with homologous recombination deficiency (HRD). However, their narrow therapeutic indexes largely due to hematologic toxicities have limited their clinical usefulness. Developing selective PARP1 inhibitors has emerged as an attractive strategy to achieve equivalent antitumor activity while alleviating the hematological toxicity caused by PARP2 inhibition.

Statistical Shape Modeling to Determine Poromechanics of the Human Knee Joint.

Subject-specific knee joint models are widely used to predict joint contact mechanics for individuals but may not capture the variance in knee joint geometry across a population. Statistical shape modeling uses the dataset of a cohort to encapsulate population-wide variability. The present study aimed to develop a shape modeling procedure for poromechanical finite element models of knee joint to account for population diversity in the creep response of knees.

p53 mutation biases squamocolumnar junction progenitor cells towards dysplasia rather than metaplasia in Barrett's oesophagus.

Background: While p53 mutations occur early in Barrett's oesophagus (BE) progression to oesophageal adenocarcinoma (EAC), their role in gastric cardia stem cells remains unclear.

Objective: This study investigates the impact of p53 mutation on the fate and function of cardia progenitor cells in BE to EAC progression, particularly under the duress of chronic injury.

Design: We used a BE mouse model (L2-IL1β) harbouring a mutation (R172H) to study the effects of p53 on Cck2r cardia progenitor cells.

Combined pretreatment of malic acid and kraft pulping for the production of fermentable sugars and highly active lignin.

The separation and utilization of cellulose, hemicellulose, and lignin in lignocellulosic biorefineries present significant challenges. This study proposes a pretreatment method for biomass refining by combining acid and kraft pulping. Firstly, the biomass was pretreated by malic acid, resulting in the isolation of xylo-oligosaccharides (XOS) with a yield of 86.

Effect of amino acid supplementation on short-term complications after gastrointestinal tumor surgery: the AMIGITS randomized clinical trial.

Background: There is a scarcity of large randomized clinical trials on the efficacy and safety of high-dose amino acid supplementation (AAS) in patients with gastrointestinal tumors undergoing surgical treatment.

Methods: This pragmatic, randomized, controlled, single-center, open-label, parallel-group AMIGITS trial was performed in a tertiary care teaching hospital. Patients with gastrointestinal tumors were randomly assigned to receive either AAS or standard care (SC).

Molecular characterization and clinical relevance of metabolic signature subtypes in gastric cancer.

Metabolic reprogramming dictates tumor molecular attributes and therapeutic potentials. However, the comprehensive metabolic characteristics in gastric cancer (GC) remain obscure. Here, metabolic signature-based clustering analysis identifies three subtypes with distinct molecular and clinical features: MSC1 showed better prognosis and upregulation of the tricarboxylic acid (TCA) cycle and lipid metabolism, combined with frequent TP53 and RHOA mutation; MSC2 had moderate prognosis and elevated nucleotide and amino acid metabolism, enriched by intestinal histology and mismatch repair deficient (dMMR); and MSC3 exhibited poor prognosis and enhanced glycan and energy metabolism, accompanied by diffuse histology and frequent CDH1 mutation.

Tumor microenvironment characteristics association with clinical outcome in patients with resected intestinal-type gastric cancer.

Background: Tumor microenvironment (TME) characteristics including tumor stroma ratio (TSR), tumor budding (TB), and tumor-infiltrating lymphocytes (TILs) were examined in resected gastric cancer. These TME features have been shown to indicate metastatic potential in colon cancer, and intestinal-type gastric cancer (IGC) has pathological similarities with that malignancy.

Methods: TSR, TB, and TILs were quantified in routine histological sections from 493 patients with IGC who underwent radical resection at 2 university hospitals in China from 2010 to 2016.

OSApredictor: A tool for prediction of moderate to severe obstructive sleep apnea-hypopnea using readily available patient characteristics.

Sleep apnea is a common sleep disorder. The availability of an easy-to-use sleep apnea predictor would provide a public health benefit by promoting early diagnosis and treatment. Our goal was to develop a prediction tool that used commonly available variables and was accessible to the public through a web site.

Clinical features and molecular landscape of cuproptosis signature-related molecular subtype in gastric cancer.

Recent studies have highlighted the biological significance of cuproptosis in disease occurrence and development. However, it remains unclear whether cuproptosis signaling also has potential impacts on tumor initiation and prognosis of gastric cancer (GC). In this study, 16 cuproptosis-related genes (CRGs) transcriptional profiles were harnessed to perform the regularized latent variable model-based clustering in GC.

Lead Identification of Novel Naphthyridine Derivatives as Potent SOS1 Inhibitors.

SOS1, a guanine nucleotide exchange factor (GEF), plays a critical role in catalyzing the conversion of KRAS from its GDP- to GTP-bound form, regardless of mutation status, and represents a promising new drug target to treat all KRAS-driven tumors. Herein, we employed a scaffold hopping strategy to design, synthesize, and optimize a series of novel binary ring derivatives as SOS1 inhibitors. Among them, compound (HH0043) displayed potent activities in both biochemical and cellular assays and favorable pharmacokinetic profiles.

Efficacy and regulatory strategies of gut microbiota in immunotherapy: a narrative review.

Background And Objective: With advances in gut microbiome research, it has been recognized that the gut microbiome has an important and far-reaching impact on many human diseases, including cancer. Therefore, more and more researchers are focusing on the treatment of gut flora in tumors. In this article, we present a review of the mechanisms of gut microbes in tumor immunotherapy and related studies to provide reference for further research and insights into the clinical application of gut microbes.

Differences in sleep spindle wave density between patients with diabetes mellitus and matched controls: implications for sensing and regulation of peripheral blood glucose.

Background: Brain waves during sleep are involved in sensing and regulating peripheral glucose level. Whether brain waves in patients with diabetes differ from those of healthy subjects is unknown. We examined the hypothesis that patients with diabetes have reduced sleep spindle waves, a form of brain wave implicated in periphery glucose regulation during sleep.

Effect of norepinephrine reuptake inhibitors combined with antimuscarinic agents vs monotherapy for OSA: a systematic review and meta-analysis.

Study Objectives: Randomized controlled trials have shown that combining norepinephrine reuptake inhibitors and antimuscarinics can ameliorate the severity of obstructive sleep apnea. This article explores whether the effectiveness and safety of combining norepinephrine reuptake inhibitors with antimuscarinic agents surpass monotherapy for treating obstructive sleep apnea.

Methods: We searched randomized controlled trials including adult patients with obstructive sleep apnea who received combination therapy and monotherapy in 8 databases from inception until April 5, 2023 and evaluated the studies' quality and conducted a meta-analysis and systematic review.

Comparison of power spectra from overnight electroencephalography between patients with Down syndrome and matched control subjects.

Electroencephalograms can capture brain oscillatory activities during sleep as a form of electrophysiological signals. We analysed electroencephalogram recordings from full-night in-laboratory polysomnography from 100 patients with Down syndrome, and 100 age- and sex-matched controls. The ages of patients with Down syndrome spanned 1 month to 31 years (median 4.

Phospholysine phosphohistidine inorganic pyrophosphate phosphatase suppresses insulin-like growth factor 1 receptor expression to inhibit cell adhesion and proliferation in gastric cancer.

Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) has recently emerged as a novel tumor suppressor. Researchers have observed that LHPP plays a crucial role in inhibiting proliferation, growth, migration, invasion, and cell metabolism across various cancers. Nevertheless, the specific functions and underlying mechanisms of LHPP as a tumor suppressor in gastric cancer (GC) require further exploration.

Tumor mutation load better predicts the prognosis of patients treated with immune checkpoint inhibitors in upper gastrointestinal cancers: A systematic review and meta-analysis.

Background: Tumor mutational load (TML) has emerged as a potential biomarker for multiple solid tumors. However, data on its prognostic impact on upper gastrointestinal (UGI) cancer are limited. Therefore, the aim of this systematic review and meta-analysis was to assess the prognostic value of TML for the survival of patients with UGI cancer.

Pan-cancer analysis of the tumorigenic role of Fanconi anemia complementation group D2 (FANCD2) in human tumors.

Monoubiquitination of FANCD2 is a central step in the activation of the Fanconi anemia (FA) pathway after DNA damage. Defects in the FA pathway centered around FANCD2 not only lead to genomic instability but also induce tumorigenesis. At present, few studies have investigated FANCD2 in tumors, and no pan-cancer research on FANCD2 has been conducted.

Safety and effectiveness of totally laparoscopic total gastrectomy vs laparoscopic-assisted total gastrectomy: a meta-analysis.

Background: For gastric cancer with total gastrectomy, the usual laparoscopic surgical approaches are totally laparoscopic total gastrectomy (TLTG) and laparoscopic-assisted total gastrectomy (LATG). Due to its difficult anastomotic technique, the adoption of TLTG is limited. Therefore, surgeons prefer using LATG, which also led to TLTG being somewhat overlooked, so there is no clear conclusion today as to which surgical procedure is more favorable to the patient's recovery.