Milk Exosome-Based Delivery System for Probiotic Encapsulation That Enhances the Gastrointestinal Resistance and Adhesion of Probiotics.

The oral administration of probiotics is a promising strategy to regulate the host-intestinal flora balance and improve health. Nevertheless, adverse gastrointestinal (GI) conditions affect the activity of free native probiotics. In this study, a novel probiotic encapsulation system based on milk exosomes (mExos) and DSPE-PEG-PBA was developed.

Dual-function regulator MexL as a target to control phenazines production and pathogenesis of Pseudomonas aeruginosa.

Antibiotic resistance or tolerance of pathogens has become one of the global public crises. Finding new drug targets may open up a way of infection control. Phenazine pyocyanin (PYO) is an important virulence factor produced by the pathogen Pseudomonas aeruginosa.

A Silk Fibroin Nanoparticle Hydrogel Loaded With NK1R Antagonist Has Synergistic Anti-Inflammatory and Reparative Effects on Dry Eye Disease.

Dry eye disease (DED) is a multifactorial illness affecting tears and the ocular surface. The neurokinin 1 receptor (NK1R) is a target for controlling T helper 17 (Th17) and regulatory T cell (Treg) imbalances. This work creates a silk fibroin (SF) nanoparticle hydrogel that targets NK1R with CP-99,994 (CP).

Restoring Vascular Smooth Muscle Cell Mitochondrial Function Attenuates Abdominal Aortic Aneurysm in Mice.

Background: Abdominal aortic aneurysm (AAA) is a complex vascular pathology without pharmaceutical interventions. This study aimed to evaluate whether restoring vascular smooth muscle cell (VSMC) mitochondrial function could prevent AAA development.

Methods: Ang II (angiotensin II)-induced AAA was established in -deficient mice, and the gene expression profiles in abdominal aortic tissues exhibiting varying degrees of severity were analyzed.

Penfluridol targets septin7 to suppress endometrial cancer by septin7-Orai/IP3R-Ca-PIK3CA pathway.

Phenotypic screening of existing drugs is a good strategy to discover new drugs. Herein, 33 psychotherapeutic drugs in our drug library were screened by phenotypic screening and penfluridol (PFD) was found to exhibit excellent anti-endometrial cancer (EC) activity both and . Furthermore, the molecular target of PFD was identified as septin7, a tumor suppressor in EC.

Nonclinical and clinical characterization of the absorption, metabolism, and excretion of islatravir.

The development of new and improved antiretroviral therapies that allow for alternative dosing schedules is needed for people living with HIV-1. Islatravir is a deoxyadenosine analog in development for the treatment of HIV-1 that suppresses HIV-1 replication via multiple mechanisms of action, including reverse transcriptase translocation inhibition and delayed chain termination. Islatravir is differentiated from other HIV-1 antiretrovirals by its high potency, long , broad tissue distribution, and favorable drug resistance profile.

Multimodal cell-free DNA whole-genome TAPS is sensitive and reveals specific cancer signals.

The analysis of circulating tumour DNA (ctDNA) through minimally invasive liquid biopsies is promising for early multi-cancer detection and monitoring minimal residual disease. Most existing methods focus on targeted deep sequencing, but few integrate multiple data modalities. Here, we develop a methodology for ctDNA detection using deep (80x) whole-genome TET-Assisted Pyridine Borane Sequencing (TAPS), a less destructive approach than bisulphite sequencing, which permits the simultaneous analysis of genomic and methylomic data.

BRISC-Mediated PPM1B-K63 Deubiquitination and Subsequent TGF-β Pathway Activation Promote High-Fat/High-Sucrose Diet-Induced Arterial Stiffness.

Background: Metabolic syndrome heightens cardiovascular disease risk primarily through increased arterial stiffness. We previously demonstrated the involvement of YAP (Yes-associated protein) in high-fat/high-sucrose diet (HFHSD)-induced arterial stiffness via modulation of PPM1B (protein phosphatase Mg/Mn-dependent 1B)-lysine 63(K63) deubiquitination. In this study, we aimed to elucidate the role and mechanisms underlying PPM1B deubiquitination in HFHSD-induced arterial stiffness.

[Explanation and interpretation of the compilation of neonatal blood transfusion in the national health standard "Guideline for pediatric transfusion"].

In order to guide clinical blood transfusion practices for pediatric patients, the National Health Commission has released the health standard "Guideline for pediatric transfusion" (WS/T 795-2022). Considering the physiological particularities of the neonatal period, blood transfusion practices for neonates are more complex than those for other children, the guidelines include a separate chapter dedicated to neonatal blood transfusion. This paper interprets the background and evidence for the compilation of the neonatal blood transfusion provisions, hoping to aid in the understanding and implementation of the neonatal blood transfusion section of the guidelines.

Activation of Imprinted Gene Promotes Cardiac Fibrosis After Ischemic Injury.

Background: Cardiac fibrosis, characterized by excessive extracellular matrix (ECM) deposition in the myocardium, is an important target for heart disease treatments. (paternally expressed gene 3) is an imprinted gene expressed from the paternal allele, and de novo purine biosynthesis (DNPB) is a crucial pathway for nucleotide synthesis. However, the roles of PW1 and DNPB in ECM production by cardiac fibroblasts during myocardial ischemia are not yet understood.

The Impact of MAFLD on Coronary Plaque Characteristics and Physiologic Status: A Coronary CT Angiography Study.

Rationale And Objectives: Metabolic dysfunction-associated fatty liver disease (MAFLD) is linked to an increased risk of cardiovascular events. Our study sought to determine the impact of MAFLD on both the anatomy and function of coronary plaques.

Materials And Methods: A total of 203 participants (including 728 plaques) with suspected coronary artery disease (CAD) who underwent coronary CT angiography (CCTA) and abdominal ultrasound were prospectively enrolled.

Prediction for children with autism spectrum disorder based on digital behavioral features during free play.

Background: Play is an indispensable and meaningful activity in children's daily life. Research has shown that autistic children often exhibit differences in play development. The core traits of autism, such as distinct patterns in social interaction and communication, focused interests, and repetitive behaviors, frequently manifest in their play.

High beam quality and high peak power 1.6 µm deuterium Raman laser.

In this work, a 1.67 µm laser was generated in the pressurized deuterium pumped by a pulsed 1064 nm laser via the stimulated vibration + rotation Raman scattering (SV-RRS). By the optimization of the deuterium pressure, focal length, and polarization of the pump laser, a 66.

Tumor-Specific Antigen Delivery for T-cell Therapy via a pH-Sensitive Peptide Conjugate.

Identifying an optimal antigen for targeted cancer therapy is challenging as the antigen landscape on cancerous tissues mimics that of healthy tissues, with few unique tumor-specific antigens identified in individual patients. pH low insertion peptide (pHLIP) acts as a unique delivery platform that can specifically target the acidic microenvironment of tumors, sparing healthy tissue in the process. We developed a pHLIP-peptide conjugate to deliver the SIINFEKL peptide, an immunogenic fragment of ovalbumin (OVA), to tumor cells in vivo.

Tuning collective anion motion enables superionic conductivity in solid-state halide electrolytes.

Halides of the family LiMX (M = Y, In, Sc and so on, X = halogen) are emerging solid electrolyte materials for all-solid-state Li-ion batteries. They show greater chemical stability and wider electrochemical stability windows than existing sulfide solid electrolytes, but have lower room-temperature ionic conductivities. Here we report the discovery that the superionic transition in LiYCl is triggered by the collective motion of anions, as evidenced by synchrotron X-ray and neutron scattering characterizations and ab initio molecular dynamics simulations.

ctDNA-based molecular residual disease and survival in resectable colorectal cancer.

The interim analysis of the CIRCULATE-Japan GALAXY observational study demonstrated the association of circulating tumor DNA (ctDNA)-based molecular residual disease (MRD) detection with recurrence risk and benefit from adjuvant chemotherapy (ACT) in resectable colorectal cancer (CRC). This updated analysis with a 23-month median follow-up, including 2,240 patients with stage II-III colon cancer or stage IV CRC, reinforces the prognostic value of ctDNA positivity during the MRD window with significantly inferior disease-free survival (DFS; hazard ratio (HR): 11.99, P < 0.

Targeting stress induction of GRP78 by cardiac glycoside oleandrin dually suppresses cancer and COVID-19.

Background: Despite recent therapeutic advances, combating cancer resistance remains a formidable challenge. The 78-kilodalton glucose-regulated protein (GRP78), a key stress-inducible endoplasmic reticulum (ER) chaperone, plays a crucial role in both cancer cell survival and stress adaptation. GRP78 is also upregulated during SARS-CoV-2 infection and acts as a critical host factor.

Crotonylation of NAE1 Modulates Cardiac Hypertrophy via Gelsolin Neddylation.

Background: Cardiac hypertrophy and its associated remodeling are among the leading causes of heart failure. Lysine crotonylation is a recently discovered posttranslational modification whose role in cardiac hypertrophy remains largely unknown. NAE1 (NEDD8 [neural precursor cell expressed developmentally downregulated protein 8]-activating enzyme E1 regulatory subunit) is mainly involved in the neddylation modification of protein targets.

The Impact of Intraocular Pressure Changes on Corneal Biomechanics in Primary Open-angle Glaucoma.

Purpose: To investigate the relationship between intraocular pressure (IOP) changes and corneal biomechanical properties, determine the quantitative relationship between IOP changes and corneal biomechanical properties in patients with glaucoma and observe the differences among different types of glaucoma when the effects of high-level IOP were excluded.

Design: Prospective clinical cohort study.

Methods: Setting: Institutional.

Effect of Colchicine on Coronary Plaque Stability in Acute Coronary Syndrome as Assessed by Optical Coherence Tomography: The COLOCT Randomized Clinical Trial.

Background: Colchicine has been approved to reduce cardiovascular risk in patients with coronary heart disease on the basis of its potential benefits demonstrated in the COLCOT (Colchicine Cardiovascular Outcomes Trial) and LoDoCo2 (Low-Dose Colchicine 2) studies. Nevertheless, there are limited data available about the specific impact of colchicine on coronary plaques.

Methods: This was a prospective, single-center, randomized, double-blind clinical trial.