Nanomedicines harnessing cGAS-STING pathway: sparking immune revitalization to transform 'cold' tumors into 'hot' tumors.

cGAS-STING pathway stands at the forefront of innate immunity and plays a critical role in regulating adaptive immune responses, making it as a key orchestrator of anti-tumor immunity. Despite the great potential, clinical outcomes with cGAS-STING activators have been disappointing due to their unfavorable in vivo fate, signaling an urgent need for innovative solutions to bridge the gap in clinical translation. Recent advancements in nanotechnology have propelled cGAS-STING-targeting nanomedicines to the cutting-edge of cancer therapy, leveraging precise drug delivery systems and multifunctional platforms to achieve remarkable region-specific biodistribution and potent therapeutic efficacy.

[Significance of disorders of brain-gut interaction in the diagnosis and management of refractory constipation].

Chronic constipation is a common digestive disease that affects people's quality of life, with complex causes and difficult treatment. Nearly half of the patients with chronic constipation do not achieve satisfactory treatment results, which is referred to as refractory constipation.Current clinical strategies for addressing refractory constipation have predominantly focused on the mitigation of intestinal symptoms.

A novel conditioning regimen with pre-transplantation immunosuppression reduces the complication rates in hematopoietic stem cell transplantation in transfusion-dependent β-thalassemia.

Background: Allo-HSCT is a curative therapy for patients with transfusion-dependent thalassemia (TDT). The high incidence of transplant-related complications is becoming an obstacle to safe and effective unrelated donor (URD) transplantation.

Methods: In this retrospective study, we reported the survival outcomes and complications of transplantation in thalassemia patients using a novel regimen consisting of pre-transplantation immunosuppression (PTIS) and modified myeloablative conditioning based on intravenous busulfan, cyclophosphamide, fludarabine, and rabbit anti-human thymocyte immunoglobulin.

Exploring the molecular mechanisms by which secretory phospholipase a2 regulates lymphatic endothelial cell dysfunction by activating macrophages.

This study offers new insights into the dual role of secretory phospholipase A2 (sPLA2) in lymphedema, highlighting its impact on lymphatic endothelial cell (LEC) functionality. Through transcriptomic analyses and co-culture experiments, we observed that sPLA2 has both protective and detrimental effects on human LECs (HLECs), mediated by macrophage activation. Our findings reveal that while low levels of sPLA2 promote LEC health, excessive sPLA2 leads to dysfunction, emphasizing the significance of the sPLA2/PLA2R axis and arachidonic acid metabolism (AA) in lymphedema pathology.

Impact of Lysine to Methionine Ratios on Antioxidant Capacity and Immune Function in the Rumen of Tibetan Sheep: An RNA-Seq Analysis.

With global protein prices on the rise, lowering protein levels in animal feed, together with balancing diet composition and reducing nitrogen emissions, can both reduce the environmental impact of agriculture and save on feed costs. However, the formulation of an ideal amino acid (AA) composition is crucial for better protein utilization by livestock. This study aimed to investigate the effects of different lysine to methionine ratios on the antioxidant capacity and immune function of the rumen in Tibetan sheep.

The Efficacy of Cecropin Against Multidrug-Resistant Bacteria Is Linked to the Destabilization of Outer Membrane Structure LPS of Gram-Negative Bacteria.

The escalating prevalence of antibiotic-resistant bacteria has emerged as a formidable threat to global health, and the quest for alternative antimicrobial agents is imperative. Cecropins, a class of antimicrobial peptides (AMPs), have garnered attention due to their potent bactericidal properties. This investigation delves into the antibacterial prowess of Cecropin A (CA) and Cecropin AD (CAD), showcasing their robust activity against Gram-negative bacteria, inclusive of multidrug-resistant bacteria.

Clinical and Proteomic Risk Profiles of New-Onset Heart Failure in Men and Women.

Background: Previous studies have examined clinical predictors of incident heart failure (HF) in men and women. However, potential mechanisms through which these clinical predictors relate to the onset of HF remain to be established.

Objectives: The authors studied the association between clinical and proteomic risk profiles of new-onset HF in men and women.

The Long-Term Risk of Metachronous Advanced Adenoma Recurrence After Endoscopic Submucosal Dissection for Colorectal Neoplasia: A Propensity-Score Matched Longitudinal Cohort With 5-Year Follow-Up.

Introduction: Long-term data on metachronous advanced adenoma (AA) recurrence after endoscopic submucosal dissection (ESD) remain scarce, leading to a lack of a standardized surveillance strategy. This study aims to evaluate the long-term risk of recurrent AA after ESD.

Materials And Methods: A longitudinal retrospective cohort study with propensity-score matching was conducted in a tertiary hospital in Hong Kong.

EGCG inhibits the oxidative damage induced by TiO2-NPs in human colon cell lines.

To assess the protective effects of (-)-Epigallocatechin-3-gallate (EGCG), a natural antioxidant, against cellular oxidative damage induced by titanium dioxide nanoparticles (TiO2-NPs), Human Colon cells NCM460 and Colon Cancer cells SW620 were selected for this study. The cells were divided into three groups: control group, TiO2-NPs (80 μg/mL) exposure group, and EGCG (20 μmol/L)+TiO2-NPs (80 μg/mL) co-exposure group. The study evaluated the precipitation rate of TiO2-NPs influenced by EGCG in a cell-free system.

Aconitine promotes ROS-activated P38/MAPK/Nrf2 pathway to inhibit autophagy and promote myocardial injury.

Background: Aconitine has cardiotoxicity, but the mechanism of cardiotoxicity induced by aconitine is limited. The aim of this study was to investigate the mechanism of myocardial injury induced by aconitine.

Methods: Using aconitine, ROS inhibitor N-acetylcysteine(NAC), the autophagy activitor Rapamycin (Rap) or the P38/MAPK pathway activitor Dehydrocorydaline treats H9C2 cells.

METTL3, m6A modification, and EGR1: interplay affecting myocardial I/R injury outcomes.

The occurrence of severe myocardial ischemia/reperfusion (I/R) injury is associated with the clinical application of reestablishment technique for heart disease, and understanding its underlying mechanisms is currently an urgent issue. Prior investigations have demonstrated the potential enhancement of MIRI through EGR1 suppression, although the precise underlying regulatory pathways require further elucidation. The core focus of this investigation is to examine the molecular pathways through EGR1 regulates mitophagy-mediated myocardial cell pyroptosis and its impact on MIRI.

M6A modification-mediated LIMA1 promotes the progression of hepatocellular carcinoma through the wnt-βcatenin/Hippo pathway.

Background: Hepatocellular carcinoma (HCC), considered as one of the most common and lethal cancers worldwide, has drawn significant attention from researchers.Extensively studied diverse cancers, the function of LIMA1 in tumorigenesis and cancer progression remains ambiguous..

A bacterial methyltransferase that initiates biotin synthesis, an attractive anti-ESKAPE druggable pathway.

The covalently attached cofactor biotin plays pivotal roles in central metabolism. The top-priority ESKAPE-type pathogens, and , constitute a public health challenge of global concern. Despite the fact that the late step of biotin synthesis is a validated anti-ESKAPE drug target, the primary stage remains fragmentarily understood.

"The COVID-19 pandemic in BRICS: Milestones, interventions, and molecular epidemiology".

Brazil, Russia, India, China, and South Africa (BRICS) are a group of developing countries with shared economic, healthcare, and scientific interests. These countries navigate multiple syndemics, and the COVID-19 pandemic placed severe strain on already burdened BRICS' healthcare systems, hampering effective pandemic interventions. Genomic surveillance and molecular epidemiology remain indispensable tools for facilitating informed pandemic intervention.

Vitamin D binding protein genetic isoforms, serum vitamin D, and cancer risk in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial.

Associations between vitamin D biochemical status and cancer may be modified by vitamin D binding protein isoforms which are encoded by GC (group-specific component). We examined interactions between serum 25-hydroxyvitamin D [25(OH)D], the Gc isoforms Gc1-1, Gc1-2, and Gc2-2, and cancer risk within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial cohort based on 3,795 cases and 3,856 controls. Multivariable-adjusted logistic regression models estimated odds ratios (ORs) and 95% confidence intervals (CIs) of cancer risk according to 25(OH)D quantiles, stratified by Gc isoform.

Supplementation with probiotics co-cultivation improves the reproductive performance in a sow-piglet model by mother-infant microbiota transmission and placental mTOR signaling.

Maternal nutritional supplementation has a profound effect on the growth and development of offspring. FAM is produced by co-cultivation of Lactobacillus acidophilus and Bacillus subtilis and has been demonstrated to potentially alleviate diarrhea, improve growth performance and the intestinal barrier integrity of weaned piglets. This study aimed to explore how maternal FAM improves the reproductive performance through mother-infant microbiota, colostrum and placenta.

Diagnostic and predictive values of m5C‑associated genes in idiopathic pulmonary fibrosis.

In patients with idiopathic pulmonary fibrosis (IPF), the role of 5‑methylcytosine (m5C)‑associated genes in the pathogenesis and development of the disease remains unclear. The present study aimed to identify reliable diagnostic markers based on the expression of m5C‑associated genes for the early detection of IPF. Count data were obtained by screening the IPF genome‑wide assay in the Gene Expression Omnibus database, followed by a comparison of m5C gene expression in patients with IPF and controls.

Hierarchical Targeting Nanodrug with Holistic DNA Protection for Effective Treatment of Acute Kidney Injury.

Acute kidney injury (AKI) manifests a hallmark pathological feature of extensive and severe DNA damage in renal tubules, primarily induced by the excessive of toxic reactive oxygen species (ROS) from the mitochondrial electron transport chain. The kidney's complex intricate physiological architecture and the heterogeneous intracellular environment pose significant challenges for effective sequential and high-resolution drug delivery-an urgent issue that remains unresolved. To address this, a hierarchical-targeting antioxidant nanodrug has been developed with a folic acid moiety (HAND) designed for high-resolution drug delivery in AKI treatment.

Causal Relationships Between Epilepsy, Anti-Epileptic Drugs, and Serum Vitamin D and Vitamin D Binding Protein: A Bidirectional and Drug Target Mendelian Randomization Study.

Aims: Previous studies suggest potential associations between epilepsy, anti-epileptic drugs (AEDs), and levels of vitamin D and vitamin D-binding protein (VDBP). This study aims to investigate the causal relationships among these variables using Mendelian Randomization (MR) methods.

Methods: Using summary data from genome-wide association studies on serum 25-hydroxyvitamin D [25(OH)D] levels (N = 417,580), VDBP concentrations (N = 65,589), and various types of epilepsy (Ncases = 27,559), MR analyses were conducted to determine bidirectional causal relationships among these variables.

Association of maternal folic acid supplementation and offspring MTRR gene polymorphism with congenital heart disease: a hospital-based case-control study in Han population.

Background: Although many studies shown that the risk of congenital heart disease (CHD) was closely related to genetic and environmental factors, the exact mechanism was still unclear. This study was to assess the association of maternal folic acid supplementation (FAS), the 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR) gene polymorphisms in offspring and their interaction effects with the risk of CHD and its subtypes.

Methods: A case-control study was conducted on 595 children with CHD and 605 healthy child controls.

Compression force promotes the osteogenic differentiation of periodontal ligament stem cells by regulating NAT10-mediated ac4C modification of BMP2.

Background: Orthodontic treatment applies specific corrective forces to teeth, transmitting stress to periodontal tissue, thereby regulating the growth and development of periodontal ligament stem cells (PDLSCs). Recently, N-acetyltransferase 10 (NAT10) mediated N4-acetylcytidine (ac4C) modification is demonstrated to play a key role in the osteogenic differentiation of stem cells. Therefore, this study aimed explore the effects of Orthodontic treatment on the NAT10 mediated ac4C modification and osteogenic differentiation of PDLSCs.

Metabolic engineering strategies for L-Homoserine production in Escherichia coli.

L-Homoserine, serves as a non-essential precursor for the essential amino acids derived from L-aspartate in both animals and humans. It finds widespread applications across the food, cosmetics, pharmaceutical, and animal feed industries. Microbial fermentation, primarily utilizing Escherichia coli, is the dominant approach for L-Homoserine production.

Acute kidney injury and in-hospital outcomes after transcatheter aortic valve replacement in patients without chronic kidney disease: insights from the national inpatient sample.

Background: Acute kidney injury (AKI) complicates transcatheter aortic valve replacement (TAVR), leading to higher mortality. The incidence and effects of AKI on clinical outcomes in patients undergoing TAVR without chronic kidney disease (CKD) are unclear. We aimed to determine the association between AKI and in-hospital outcomes in patients with TAVR using propensity score matching (PSM).

[One new galloyl derivative from Isodon henryi].

Seven compounds(1-7) were isolated from Isodon henryi through silica gel, Sephadex LH-20, ODS, MCI column chromatography and semi-preparative HPLC. Their structures were identified as isogallicacid(1), caffeic acid(2), syringic acid(3), protocatechuic acid(4), oresbiusin A(5), lophanthoside A(6), and 8-hydroxypinoresinol(7), by spectroscopic techniques including HR-MS, IR, UV, NMR, and ECD. Compound 1 was a new galloyl derivative.