Targeted FTO knockout in endothelial cells Boosts adhesion and lowers inflammatory infiltration to alleviate pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a syndrome characterized by increased pulmonary vascular resistance and elevated pulmonary artery pressure, ultimately leading to right heart failure and even death. Increasing evidence implicates the fat mass and obesity-associated protein (FTO) in various metabolic and inflammatory pathways; however, its role in pulmonary endothelial function and PAH remains largely unexplored. In this study, we examined the effects of endothelial cell-specific FTO knockout on PAH development.

Polylactic Acid Micro/Nanoplastic Exposure Induces Male Reproductive Toxicity by Disrupting Spermatogenesis and Mitochondrial Dysfunction in Mice.

Although considered an "eco-friendly" biodegradable plastic, polylactic acid (PLA) microplastic (PLA-MP) poses a growing concern for human health, yet its effects on male reproductive function remain underexplored. This study investigated the reproductive toxicity of PLA in male mice and its potential mechanisms. To this end, our in vivo and in vitro experiments demonstrated that after degradation in the digestive system, a significant number of PLA-MP-derived nanoparticles could penetrate the blood-testis barrier (BTB) and localize within the spermatogenic microenvironment.

Gold(I)-Catalyzed 2-Deoxy-β-glycosylation via 1,2-Alkyl/Arylthio Migration: Synthesis of Velutinoside A Pentasaccharide.

2-Deoxy-β-glycosides are essential components of natural products and pharmaceuticals; however, the corresponding 2-deoxy-β-glycosidic bonds are challenging to chemically construct. Herein, we describe an efficient catalytic protocol for synthesizing 2-deoxy-β-glycosides via either IPrAuNTf-catalyzed activation of a unique 1,2--positioned C2--propargyl xanthate (OSPX) leaving group or (PhO)PAuNTf-catalyzed activation of a 1,2--C2--alkynylbenzoate (OABz) substituent of the corresponding thioglycosides. These activation processes trigger 1,2-alkyl/arylthio-migration glycosylation, enabling the synthesis of structurally diverse 2-deoxy-β-glycosides under mild reaction conditions.

Surface-Sensitive Waveguide Imaging for In Situ Analysis of Membrane Protein Binding Kinetics.

Ligand binding to membrane proteins initiates numerous therapeutic processes. Surface plasmon resonance (SPR), a popular method for analyzing molecular interactions, has emerged as a promising tool for in situ determination of membrane protein binding kinetics owing to its label-free detection, high surface sensitivity, and resistance to intracellular interference. However, the excitation of SPR relies on noble metal films, typically gold, which are biologically incompatible and can cause fluorescence quenching.

Advances in RNA editing in hematopoiesis and associated malignancies.

Adenosine-to-inosine (A-to-I) RNA editing is a prevalent RNA modification essential for cell survival. The process is catalyzed by the Adenosine Deaminase Acting on RNA (ADAR) enzyme family that converts adenosines in double-stranded RNAs (dsRNAs) into inosines, which are read as guanosines during translation. Deep sequencing has helped to reveal that A-to-I editing occurs across various types of RNAs to affect their functions.

Discovery of Metabolic Reprogramming 2-Quinolones as Effective Antimicrobials for MRSA-Infected Wound Therapy.

To date, the abuse of antibiotics and a gradual decline in novel antibiotic discovery enlarge the threat of drug-resistant bacterial infections, especially methicillin-resistant (MRSA). Herein, inspired by the unique structures and antibacterial activities of 2-quinolones, a class of novel 2-quinolones with substituted pyridines was synthesized. Notably, compound , the derivative with a methylpyridine fragment, showed potent antibacterial and antibiofilm activities, especially for MRSA strains (MIC = 0.

Supraspinal facilitation of painful stimuli by glutamatergic innervation from the retrosplenial to the anterior cingulate cortex.

The anterior cingulate cortex (ACC) is recognized as a pivotal cortical region involved in the perception of pain. The retrosplenial cortex (RSC), located posterior to the ACC, is known to play a significant role in navigation and memory processes. Although the projections from the RSC to the ACC have been found, the specifics of the synaptic connections and the functional implications of the RSC-ACC projections remain less understood.

Green Manufacture of Hydrated Polymers Coatings with On-Demand Mechanics and Lubricity Based on Novel Biobased Polymerizable Deep Eutectic Solvents.

The aging population necessitates a critical need for medical devices, where polymers-based surface lubrication coating is essential for optimal functionality. In fact, lubrication and mechanical requirements vary depending on the service environment of different medical devices. Until now, key mean is still blank for general preparation of hydrophilic polymers-based lubrication coatings with on-demand mechanics and lubricity.

METTL3 Potentiates M2 Macrophage-Driven MMT to Aggravate Renal Allograft Fibrosis via the TGF-β1/Smad3 Pathway.

METTL3, a key enzyme in N6-methyladenosine (m6A) modification, plays a crucial role in the progression of renal fibrosis, particularly in chronic active renal allograft rejection (CAR). This study explored the mechanisms by which METTL3 promotes renal allograft fibrosis, focusing on its role in the macrophage-to-myofibroblast transition (MMT). Using a comprehensive experimental approach, including TGF-β1-induced MMT cell models, METTL3 conditional knockout (METTL3 KO) mice, and renal biopsy samples from patients with CAR, the study investigates the involvement of METTL3/Smad3 axis in driving MMT and renal fibrosis during the episodes of CAR.

The Ubiquitin Ligase CHIP Accelerates Papillary Thyroid Carcinoma Metastasis via the Transgelin-Matrix Metalloproteinase-9 Axis.

The carboxyl-terminus of Hsp70-interacting protein (CHIP) plays crucial roles in tumorigenesis and immunity, with previous studies suggesting a double-edged sword in thyroid cancer. However, its precise functions and underlying molecular mechanisms in thyroid cancer remained unclear. Here, we demonstrate through immunohistochemistry (IHC) that CHIP expression progressively increases from normal thyroid tissue to primary papillary thyroid carcinoma (PTC) and lymph node metastases, with CHIP levels positively correlating with lymph node metastasis ( = 0.

Multimodal assessment predicts cognitive impairment after aneurysmal subarachnoid hemorrhage: a prospective cohort study.

Background: Risk factors and mechanisms of cognitive impairment (CI) after aneurysmal subarachnoid hemorrhage (aSAH) are unclear. This study used a neuropsychological battery, MRI, ERP and CSF and plasma biomarkers to predict long-term cognitive impairment after aSAH.

Materials And Methods: 214 patients hospitalized with aSAH (n = 125) or unruptured intracranial aneurysms (UIA) (n = 89) were included in this prospective cohort study.

Developing predictive nomogram models using quantitative electroencephalography for brain function in type a aortic dissection: a prospective observational study.

Background: Type A aortic dissection (TAAD) remains a significant challenge in cardiac surgery, presenting high risks of adverse outcomes such as permanent neurological dysfunction and mortality despite advances in medical technology and surgical techniques. This study investigates the use of quantitative electroencephalography (QEEG) to monitor and predict neurological outcomes during the perioperative period in TAAD patients.

Methods: This prospective observational study was conducted at the hospital, involving patients undergoing TAAD surgery from February 2022 to January 2023.

Design of ROS-Triggered Sesquiterpene Lactone SC Prodrugs as TrxR1 Covalent Inhibitors for the Treatment of Non-Small Cell Lung Cancer.

Thioredoxin reductase 1 (TrxR1) is an important therapeutic target for nonsmall cell lung cancer (NSCLC) treatment due to its overexpression in NSCLC cells. In this work, to address the deficiency that sesquiterpene lactone containing α-methylene-γ-lactone moiety was rapidly metabolized by endogenous nucleophiles, series of novel thioether derivatives were designed and synthesized based on a reactive oxygen species (ROS)-triggered prodrug strategy. Among them, prodrug exhibited potent cytotoxicity against NSCLC cells and better release rates in response to ROS.

Dynamic Force Sensing for Continuous Scraping Towards Endometrium Repair Surgery.

Background: A surgical robot with force feedback can guarantee precise and gentle manipulation for endometrial repair, ensuring the effectiveness and safety of the manipulation. However, the design of force sensors for surgical robots is challenging due to the limited anatomical space and the requirement for continuous rotation.

Methods: This paper presents a novel force-sensing surgical instrument for endometrial repair, including an inner scraping instrument and an outer force sensing sheath.

Nanoencapsulated Optical Fiber-Based PEC Microelectrode: Highly Sensitive and Specific Detection of NT-proBNP and Its Implantable Performance.

Microelectrodes offer exceptional sensitivity, rapid response, and versatility, making them ideal for real-time detection and monitoring applications. Photoelectrochemical (PEC) sensors have shown great value in many fields due to their high sensitivity, fast response, and ease of operation. Nevertheless, conventional PEC sensing relies on cumbersome external light sources and bulky electrodes, hindering its miniaturization and implantation, thereby limiting its application in real-time disease monitoring.

HIV-1 and BLV are insensitive to SERINC5 restriction under the cell-cell infection.

ine orporator 5 (INC5, SER5) suppresses viral cell-free infection. However, its antiviral potency under viral cell-cell infection is not examined yet. Here, we established the cell-cell infection systems to assess SER5's antiviral activity on HIV-1 and bovine leukemia virus (BLV).

High-Viability Circulating Tumor Cells Sorting From Whole Blood at Single Cell Level Using Laser-Induced Forward Transfer-Assisted Microfiltration.

The efficient isolation and molecular analysis of circulating tumor cells (CTCs) from whole blood at single-cell level are crucial for understanding tumor metastasis and developing personalized treatments. The viability of isolated cells is the key prerequisite for the downstream molecular analysis, especially for RNA sequencing. This study develops a laser-induced forward transfer -assisted microfiltration system (LIFT-AMFS) for high-viability CTC enrichment and retrieval from whole blood.

Continuous Blood Gas Control Based on Active Disturbance Rejection Control During Ex Vivo Porcine Liver Perfusion.

Background: Membrane oxygenators facilitate extracorporeal gas exchange, necessitating the monitoring of blood gas. Recent advances in normothermic machine perfusion (NMP) for ex vivo liver offer solutions to the shortage of donor liver. However, maintaining physiological blood gas levels during prolonged NMP is complex and costly.

A locally administered single-cycle influenza vaccine expressing a non-fusogenic stabilized hemagglutinin stimulates strong T-cell and neutralizing antibody immunity.

Unlabelled: Current influenza vaccination approaches protect against specific viral strains, but do not consistently induce broad and long-lasting protection to the diversity of circulating influenza viruses. Single-cycle viruses delivered to the respiratory tract may offer a promising solution as they safely express a diverse array of viral antigens by undergoing just one round of cell infection in their host and stimulate broadly protective resident memory T-cell responses in the lung. We have previously developed a vaccine candidate called S-FLU, which is limited to a single cycle of infection by inactivation of the hemagglutinin signal sequence and induces a broadly cross-reactive T-cell response and antibodies to neuraminidase, but fails to induce neutralizing antibodies to hemagglutinin after intranasal administration.

Low Neutralization of SARS-CoV-2 Omicron BA5248, XBB15 and JN1 by Homologous Booster and Breakthrough Infection.

Immunity against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) can be induced through either infection with the virus or vaccination, providing protection against reinfection or reducing the risk of severe clinical outcomes. In this study, we recruited 172 volunteers who received different vaccination regimens, including 124 individuals who had recovered from breakthrough infections caused by the Omicron variant (27 with 2 doses, 49 with 3 doses, and 48 with 4 doses) and 48 healthy donors who did not experience breakthrough infections (all of whom received a fourth dose during the infection wave). We measured neutralizing antibody levels against Omicron BA.

MYRF Variants in Patients With 46,XY Differences/Disorders of Sex Development and Literature Review.

46,XY differences/disorders of sex development (DSD) are genetically heterogeneous conditions characterized by atypical development of the reproductive system. MYRF, a gene encoding a transcription factor, has been identified as a potential causative gene for DSD and cardiac urogenital syndrome (CUGS). This study aims to delineate the clinical manifestations of patients with 46,XY DSD and MYRF mutations, encompassing both from our cohort and cases reported in the literature.

Family Functioning, Life Satisfaction, and Depressive Symptoms in Chinese Adults With Diabetes and Hypertension: A Cross-Lagged Model.

This study aims to evaluate the bidirectional relationship between family functioning and depressive symptoms, considering life satisfaction as a potential mediator and gender, age and income as a moderator of these associations. A longitudinal study was conducted with 708 Chinese adults with diabetes and hypertension (51.6% women; mean age: 64.

Deciphering the biosynthetic pathway of triterpene saponins in Prunella vulgaris.

The traditional Chinese medicinal plant Prunella vulgaris contains numerous triterpene saponin metabolites, notably ursolic and oleanolic acid saponins, which have significant pharmacological values. Despite their importance, the genes responsible for synthesizing these triterpene saponins in P. vulgaris remain unidentified.

Association of Obstructive Sleep Apnea and Nocturnal Hypoxemia With the Circadian Rhythm of Myocardial Infarction.

Background: The circadian rhythm of myocardial infarction (MI) in patients with obstructive sleep apnea (OSA) remains disputable and no studies have directly evaluated the relationship between nocturnal hypoxemia and the circadian rhythm of MI. The aim of the current study was to evaluate the association of OSA and nocturnal hypoxemia with MI onset during the night.

Methods: Patients with MI in the OSA-acute coronary syndrome (ACS) project (NCT03362385) were recruited.

Structure-Guided Optimization and Preclinical Evaluation of 6--Benzylguanine-Based Pin1 Inhibitor for Hepatocellular Carcinoma Treatment.

Hepatocellular carcinoma (HCC) is a major cause of cancer-related deaths globally, and the need for effective systemic therapies for HCC is urgent. Our previous work reveals that Pin1 is a potential anti-HCC target, which regulates miRNA biogenesis and identifies as a novel Pin1 inhibitor to suppresses HCC. However, a great demand in HCC therapy as well as the limited chemical stability and pharmacokinetic feature of motivated us to find improved Pin1 inhibitors.