Exploring Integrin α5β1 as a Potential Therapeutic Target for Pulmonary Arterial Hypertension: Insights From Comprehensive Multicenter Preclinical Studies.

Background: Pulmonary arterial hypertension (PAH) is characterized by obliterative vascular remodeling of the small pulmonary arteries (PAs) and progressive increase in pulmonary vascular resistance leading to right ventricular failure. Although several drugs are approved for the treatment of PAH, mortality rates remain high. Accumulating evidence supports a pathological function of integrins in vessel remodeling, which are gaining renewed interest as drug targets.

A new class of penicillin-binding protein inhibitors to address drug-resistant .

β-Lactams are the most widely used antibiotics for the treatment of bacterial infections because of their proven track record of safety and efficacy. However, susceptibility to β-lactam antibiotics is continually eroded by resistance mechanisms. Emerging multidrug-resistant (MDR) strains possessing altered alleles (encoding PBP2) pose a global health emergency as they threaten the utility of ceftriaxone, the last remaining outpatient antibiotic.

Effects of surfactin stress on gene expression and pathological changes in Spodoptera litura.

Spodoptera litura (S. litura) is a polyphagous pest of the family Lepidoptera, which causes damage and yields losses to many crops. The long-term use of chemical pesticides for control not only seriously threatens environmental health, but also causes S.

Antigen-specific T cell immunotherapy by in vivo mRNA delivery.

Immunotherapy has shown promise for treating patients with autoimmune diseases or cancer, yet treatment is associated with adverse effects associated with global activation or suppression of T cell immunity. Here, we developed antigen-presenting nanoparticles (APNs) to selectively engineer disease antigen (Ag)-specific T cells by mRNA delivery. APNs consist of a lipid nanoparticle core functionalized with peptide-major histocompatibility complexes (pMHCs), facilitating antigen-specific T cell transfection through cognate T cell receptor-mediated endocytosis.

Prospective prediction of childhood body mass index trajectories using multi-task Gaussian processes.

Background: Body mass index (BMI) trajectories have been used to assess the growth of children with respect to their peers, and to anticipate future obesity and disease risk. While retrospective BMI trajectories have been actively studied, models to prospectively predict continuous BMI trajectories have not been investigated.

Materials And Methods: Using longitudinal BMI measurements between birth and age 10 y from a mother-offspring cohort, we leveraged a multi-task Gaussian process approach to develop and evaluate a unified framework for modeling, clustering, and prospective prediction of BMI trajectories.

Predicting non-small cell lung cancer lymph node metastasis: integrating ctDNA mutation/methylation profiling with positron emission tomography-computed tomography (PET-CT) scan: protocol for a prospective clinical trial (LUNon-invasive Study).

Background: Non-small cell lung cancer (NSCLC) accounts for approximately 85% of lung cancer cases and remains a leading cause of cancer-related death. Lymph node metastasis (LNM) significantly affects recurrence, survival rates, and treatment options. While lymph node sampling is standard for surgically removing operable NSCLC, it can lead to complications.

Selection, Design and Immunogenicity Studies of ASFV Antigens for Subunit mRNA Cocktail Vaccines with Specific Immune Response Profiles.

Development of safe and effective subunit vaccines for controlling African Swine Fever Virus (ASFV) infection has been hampered by a lack of protective viral antigens, complex virion structures, and multiple mechanisms of infection. Here, we selected ASFV antigens based on their localization on the virion, known functions, and homologies to the subunits of the protective vaccinia virus vaccine. We also engineered viral capsid proteins for inducing optimal antibody responses and designed T cell-directed antigen for inducing broad and robust cellular immunity.

Oxysterol Sensing Through GPR183 Triggers Endothelial Senescence in Hypertension.

Background: Despite endothelial dysfunction being an initial step in the development of hypertension and associated cardiovascular/renal injuries, effective therapeutic strategies to prevent endothelial dysfunction are still lacking. GPR183 (G protein-coupled receptor 183), a recently identified G protein-coupled receptor for oxysterols and hydroxylated metabolites of cholesterol, has pleiotropic roles in lipid metabolism and immune responses. However, the role of GPR183 in the regulation of endothelial function remains unknown.

Sacrificial Additive C-Assisted Catholyte Buffer Layer for LiAlTi(PO)-Based All-Solid-State High-Voltage Batteries.

All-solid-state batteries with oxide electrolytes and high-nickel layered oxide cathodes (LiNiCoMnO and LiNiCoAlO, + + = 1, ≥ 60%) have received widespread attention owing to their high energy density and high safety. However, they generally suffer from interfacial structural instability when coupled with solid-state electrolytes, which strongly diminishes the longevity of the battery. In this work, we propose adding a sacrificial additive C to the catholyte buffer layer between LiAlTi(PO) (LATP) and LiNiCoMnO (NCM811) to enhance the electrochemical stability under high-voltage operating conditions.

A randomized phase 2 study of HLX22 plus trastuzumab biosimilar HLX02 and XELOX as first-line therapy for HER2-positive advanced gastric cancer.

Background: Gastric cancer is the fifth most common cancer and the fourth most common cause of cancer death worldwide, yet the prognosis of advanced disease remains poor.

Methods: This was a randomized, double-blinded, phase 2 trial (ClinicalTrials.gov: NCT04908813).

AIDA-1/ANKS1B Binds to the SynGAP Family RasGAPs with High Affinity and Specificity.

AIDA-1, encoded by ANKS1B, is an abundant postsynaptic scaffold protein essential for brain development. Mutations of ANKS1B are closely associated with various psychiatric disorders. However, very little is known regarding the molecular mechanisms underlying AIDA-1's involvements under physiological and pathophysiological conditions.

Comprehensive proteogenomic characterization of rare kidney tumors.

Non-clear cell renal cell carcinomas (non-ccRCCs) encompass diverse malignant and benign tumors. Refinement of differential diagnosis biomarkers, markers for early prognosis of aggressive disease, and therapeutic targets to complement immunotherapy are current clinical needs. Multi-omics analyses of 48 non-ccRCCs compared with 103 ccRCCs reveal proteogenomic, phosphorylation, glycosylation, and metabolic aberrations in RCC subtypes.

Contrast-enhanced Imaging in Peripheral Pulmonary Lesions: The Role in US-guided Biopsies.

Purpose To compare the tissue adequacy and diagnostic accuracy of US-guided biopsies of peripheral pulmonary lesions (PPLs) with and without contrast agents. Materials and Methods A retrospective study was conducted at four medical centers in patients with PPLs who underwent US-guided percutaneous transthoracic needle biopsy (PTNB) between January 2017 and October 2022. The patients were divided into contrast-enhanced US (CEUS) and US groups based on whether prebiopsy CEUS evaluation was performed.

Hijacked enhancer-promoter and silencer-promoter loops in cancer.

Recent work has shown that besides inducing fusion genes, structural variations (SVs) can also contribute to oncogenesis by disrupting the three-dimensional genome organization and dysregulating gene expression. At the chromatin-loop level, SVs can relocate enhancers or silencers from their original genomic loci to activate oncogenes or repress tumor suppressor genes. On a larger scale, different types of alterations in topologically associating domains (TADs) have been reported in cancer, such as TAD expansion, shuffling, and SV-induced neo-TADs.

ZNF397 Deficiency Triggers TET2-Driven Lineage Plasticity and AR-Targeted Therapy Resistance in Prostate Cancer.

Cancer cells exhibit phenotypical plasticity and epigenetic reprogramming that allows them to evade lineage-dependent targeted treatments by adopting lineage plasticity. The underlying mechanisms by which cancer cells exploit the epigenetic regulatory machinery to acquire lineage plasticity and therapy resistance remain poorly understood. We identified zinc finger protein 397 (ZNF397) as a bona fide coactivator of the androgen receptor (AR), essential for the transcriptional program governing AR-driven luminal lineage.

Fast and flexible profiling of chromatin accessibility and total RNA expression in single nuclei using Microwell-seq3.

Single cell chromatin accessibility profiling and transcriptome sequencing are the most widely used technologies for single-cell genomics. Here, we present Microwell-seq3, a high-throughput and facile platform for high-sensitivity single-nucleus chromatin accessibility or full-length transcriptome profiling. The method combines a preindexing strategy and a penetrable chip-in-a-tube for single nucleus loading and DNA amplification and therefore does not require specialized equipment.

Construction of single-cell cross-species chromatin accessibility landscapes with combinatorial-hybridization-based ATAC-seq.

Despite recent advances in single-cell genomics, the lack of maps for single-cell candidate cis-regulatory elements (cCREs) in non-mammal species has limited our exploration of conserved regulatory programs across vertebrates and invertebrates. Here, we developed a combinatorial-hybridization-based method for single-cell assay for transposase-accessible chromatin using sequencing (scATAC-seq) named CH-ATAC-seq, enabling the construction of single-cell accessible chromatin landscapes for zebrafish, Drosophila, and earthworms (Eisenia andrei). By integrating scATAC censuses of humans, monkeys, and mice, we systematically identified 152 distinct main cell types and around 0.

Editorial Commentary: Arthroscopy With Labral Preservation or Reconstruction Plus Capsular Closure Shows Excellent Outcome in Patients With Borderline Hip Dysplasia and is Less Invasive Than Periacetabular Osteotomy.

Borderline developmental dysplasia of the hip (BDDH), or borderline hip dysplasia (BHD), traditionally characterized by a relatively low lateral center-edge angle (LCEA), presents a complex challenge in treatment due to its multifaceted etiology involving instability, femoroacetabular impingement (FAI), or a combination thereof. The optimal approach to managing adult BDDH remains a subject of significant debate. Periacetabular osteotomy (PAO) is considered the preferred treatment for addressing severe acetabular under-coverage, as it rectifies the underlying bony deficiency and promotes stability.

Realization of a crosstalk-avoided quantum network node using dual-type qubits of the same ion species.

Generating ion-photon entanglement is a crucial step for scalable trapped-ion quantum networks. To avoid the crosstalk on memory qubits carrying quantum information, it is common to use a different ion species for ion-photon entanglement generation such that the scattered photons are far off-resonant for the memory qubits. However, such a dual-species scheme can be subject to inefficient sympathetic cooling due to the mass mismatch of the ions.

Genome-wide analysis of the TIFY family and function of and under cold stress in pepper ( L.).

TIFY [TIF(F/Y)XG] proteins are a plant particular transcription factor family that regulates plant stress responses. Therefore, to fill this gap, we investigated genes in pepper. Gene structure and conserved motifs of the pepper TIFY gene family were systematically analyzed using sequence alignment analysis, -acting element analysis, transcriptomic data, and RT-qPCR analysis, and their expression patterns were further analyzed using Virus-Induced Gene Silencing (VIGS) and cold stress reactive oxygen species (ROS) response.