Sensing ceramides by CYSLTR2 and P2RY6 to aggravate atherosclerosis.

Recent evidence shows elevated circulating long-chain ceramide levels predict atherosclerotic cardiovascular disease (ASCVD) independently of cholesterol. Although targeting ceramide signaling may provide therapeutic benefits beyond the treatment of hypercholesterolemia, the underlying mechanism by which circulating ceramides aggravate ASCVD remains elusive. We examined whether circulating long-chain ceramides activate membrane G protein-coupled receptors (GPCRs) to exacerbate atherosclerosis.

MMP19 in vascular smooth muscle cells protects against thoracic aortic aneurysm and dissection via the MMP19/Aggrecan/Wnt/β-catenin axis.

Background: Thoracic aortic aneurysm and dissection (TAAD) is a life-threatening cardiovascular event characterized by high mortality rates. Previous studies have shown that matrix metalloproteinases 19 (MMP19) was involved in TAAD formation, while the detailed role of MMP19 in TAAD pathogenesis and underlying mechanism remain unclear.

Methods: To investigate the role of MMP19 in the progression of TAAD, we generated global Mmp19 knockout mice, as well as VSMCs (vascular smooth muscle cells)-specific Mmp19 knockdown mice, and established a BAPN-induced TAAD model.

Peritoneal dialysis-associated peritonitis caused by Coxiella Burnetii: A case report.

Rationale: Peritoneal dialysis (PD)-associated peritonitis (PDAP) is the leading cause of PD failure and discontinuation of PD. Several zoonotic pathogens could lead to the development of PDAP. Coxiella burnetii (C.

Safe Production of Rice ( L.) in Arsenic-Contaminated Soil: a Remedial Strategy using Micro-Nanostructured Bone Biochar.

This study investigated the effects of fine-sized pork bone biochar particles on remediating As-contaminated soil and alleviating associated phytotoxicity to rice in 50-day short-term and 120-day full-life-cycle pot experiments. The addition of micro-nanostructured pork bone biochar (BC) pyrolyzed at 400 and 600 °C (BC400 and BC600) significantly increased the As-treated shoot and root fresh weight by 24.4-77.

Comprehensive Analysis of Physicochemical Properties and Sensory Attributes of Original-Cut Potato Chips in the Chinese Market.

This study investigates the Chinese market's physicochemical properties and sensory attributes of 14 original-cut potato chip brands. Color characteristics, compositional analysis, sugar content, acrylamide levels, and textural properties were examined alongside sensory evaluations. Significant variations were observed across all the parameters.

Nanoscale‑boron nitride positively alters rhizosphere microbial communities and subsequent cucumber (Cucumis sativa) growth: A metagenomic analysis.

Boron (B) deficiency affects over 132 crop species globally, making effective B supplement crucial for enhancing agricultural yield and health. This study explores an innovative application of nanoscale boron nitride (nano-BN) as a sustainable solution for addressing B deficiency in crops. Cucumber seedlings were treated with different contents of nano-BN under greenhouse conditions and both B and N ionic treatments were set as comparisons.

Molecular Evidence of CeO Nanoparticle Modulation of ABA and Genes Containing ABA-Responsive Cis-Elements to Promote Rice Drought Resistance.

Cerium dioxide nanoparticles (CeO NPs) have enzyme-like properties and scavenge excess ROS induced by stressors such as drought. However, the underlying molecular mechanisms by which CeO NPs enhance drought resistance are unknown. In this work, both foliar application and soil injection of CeO NPs were used to rice seedlings under a 30 day moderate drought (40% soil relative moisture).

Alkaline ceramidase 1-mediated platelet ceramide catabolism mitigates vascular inflammation and abdominal aortic aneurysm formation.

Abdominal aortic aneurysm (AAA) is a highly lethal vascular disease. The role of platelets in AAA remains incompletely understood. Here we show that platelet ceramides, rather than other phospholipids, were elevated in an angiotensin II (AngII)-induced AAA murine model and in patients with AAA by using targeted lipidomic analysis.

In-Situ Grown Nanocrystal TiO on 2D TiC Nanosheets with Anti-Tumor Activity from Photo-Sonodynamic Treatment and Immunology.

Introduction: Traditional cancer treatment strategies often have severe toxic side effects and poor therapeutic efficacy. To address the long-standing problems related to overcoming the complexity of tumors, we develop a novel nanozyme based on the in situ oxidation of 2D TiC structure to perform simultaneous phototherapy and sonodynamic therapy on tumors. TiC nanozymes exhibit multi-enzyme activity, including intrinsic peroxidase (POD) activities, which can react with HO in the tumor microenvironment.

Biosynthesized Selenium Nanoparticles as an Effective Tool to Combat Soil Metal Stresses in Rice ( L.).

Nanotechnology has demonstrated significant potential to improve agricultural production and increase crop tolerance to abiotic stress including exposure to heavy metals. The present study investigated the mechanisms by which aloe vera extract gel-biosynthesized (AVGE) selenium nanoparticles (Se NPs) alleviated cadmium (Cd)-induced toxicity to rice ( L.).

Design, Synthesis, and Biological Evaluation of Novel EGFR PROTACs Targeting C797S Mutation.

The epidermal growth factor receptor (EGFR) tertiary C797S mutation is an important cause of resistance to Osimertinib, which seriously hinders the clinical application of Osimertinib. Developing proteolysis-targeting chimeras (PROTACs) targeting EGFR mutants can offer a promising strategy to overcome drug resistance. In this study, some novel PROTACs targeting C797S mutation were designed and synthesized based on a new EGFR inhibitor and displayed a potent degradation effect in H1975-TM cells harboring EGFR.

Tumor Microenvironment-Sensitive Ca Nanomodulator Combined with the Sonodynamic Process for Enhanced Cancer Therapy.

Tumor therapy presents significant challenges, and conventional treatments exhibit limited therapeutic effectiveness. Imbalance of calcium homeostasis as a key cause of tumor cell death has been extensively studied in tumor therapy. Calcium overload therapy has garnered significant interest as a new cancer treatment strategy.

Agathis dammara Extract and its Monomer Araucarone Attenuate Abdominal Aortic Aneurysm in Mice.

Background: Abdominal aortic aneurysm (AAA) is a chronic vascular disease wherein the inflammation of vascular smooth muscle cells (VSMCs) plays a pivotal role in its development. Effectively mitigating AAA involves inhibiting VSMC inflammation. Agathis dammara (Lamb.

Visible-Light-Induced Defluorinative α-C(sp)-H Alkylation for the Synthesis of -Difluoroallylated α-Trifluoromethylamines.

Herein, we describe a novel and efficient photoredox catalytic C radical addition/defluoroalkylation coupling reaction between α-trifluoromethyl alkenes and -trifluoroethyl hydroxylamine. A series of -difluoroallylated α-trifluoromethylamines were synthesized by the C radical addition enabled by a 1,2-H shift of the in situ-generated trifluoroethyl radical. Notably, this protocol is distinguished by its mild conditions, easy operation, and excellent functional group tolerability.

Discovery of Novel Fourth-Generation EGFR Inhibitors to Overcome C797S-Mediated Resistance.

Epidermal growth factor receptor (EGFR)-activating mutation is an important oncogenic driver of nonsmall cell lung cancer (NSCLC) patients. Osimertinib has been the first-line treatment for EGFR-mutated NSCLC. However, the tertiary C797S mutation leads to Osimertinib resistance by blocking the covalent binding of Cys797 to Osimertinib.

Root Exposure of Graphitic Carbon Nitride (g-CN) Modulates Metabolite Profile and Endophytic Bacterial Community to Alleviate Cadmium- and Arsenate-Induced Phytotoxicity to Rice ( L.).

To investigate the mechanisms by which g-CN alleviates metal(loid)-induced phytotoxicity, rice seedlings were exposed to 100 and 250 mg/kg graphitic carbon nitride (g-CN) with or without coexposure to 10 mg/kg Cd and 50 mg/kg As for 30 days. Treatment with 250 mg/kg g-CN significantly increased shoot and root fresh weight by 22.4-29.

Nanoscale ZnO Improves the Amino Acids and Lipids in Tomato Fruits and the Subsequent Assimilation in a Simulated Human Gastrointestinal Tract Model.

With the widespread use of nanoenabled agrochemicals, it is essential to evaluate the food safety of nanomaterials (NMs)-treated vegetable crops in full life cycle studies as well as their potential impacts on human health. Tomato seedlings were foliarly sprayed with 50 mg/L ZnO NMs, including ZnO quantum dots (QDs) and ZnO nanoparticles once per week over 11 weeks. The foliar sprayed ZnO QDs increased fruit dry weight and yield per plant by 39.

[Genetic analysis and in vitro validation of a case of Alport syndrome due to a splicing variant of COL4A5 gene].

Objective: To explore the genetic basis for a patient with Alport syndrome (AS) and confirm the existence of a splicing variant.

Methods: An AS patient diagnosed at the Affiliated Hospital of Inner Mongolia Medical University on January 8, 2021 for significant proteinuria and occult hematuria was selected as the study subject. Clinical data was collected.

Genetic and molecular dynamics analysis of two variants of the COL4A5 gene causing Alport syndrome.

Background: Alport syndrome (AS; OMIM#308,940) is a hereditary kidney disease that progresses over time and is distinguished by hearing loss and ocular irregularities. The syndrome has three subtypes, namely X-linked (XL; OMIM#301,050), autosomal recessive (AR; OMIM#203,780), and autosomal dominant (AD; OMIM#104,200), which are categorized based on their respective modes of inheritance. XLAS is attributed to a pathogenic variant in the COL4A5 (OMIM*303,630) gene, which encodes the α5(IV) chain of type IV collagen (Col-IV).

Aloe Vera Extract Gel-Biosynthesized Selenium Nanoparticles Enhance Disease Resistance in Lettuce by Modulating the Metabolite Profile and Bacterial Endophytes Composition.

The use of nanotechnology to suppress crop diseases has attracted significant attention in agriculture. The present study investigated the antifungal mechanism by which aloe vera extract gel-biosynthesized (AVGE) selenium nanoparticles (Se NPs) suppressed -induced wilt disease in lettuce (). AVGE Se NPs were synthesized by utilizing sodium selenite as a Se source and AVGE as a biocompatible capping and reducing agent.

Discovery of Potent and Wild-Type-Sparing Fourth-Generation EGFR Inhibitors for Treatment of Osimertinib-Resistance NSCLC.

Osimertinib resistance is an unmet clinical need for the treatment of non-small cell lung cancer (NSCLC), and the main mechanism is tertiary C797S mutation of epidermal growth factor receptor (EGFR). To date, there is no inhibitor approved for the treatment of Osimertinib-resistant NSCLC. Herein, we reported a series of Osimertinib derivatives as fourth-generation inhibitors which were rationally designed.

Urate-Lowering Therapy Inhibits Thoracic Aortic Aneurysm and Dissection Formation in Mice.

Background: Thoracic aortic aneurysm and dissection (TAAD) is a highly lethal vascular disease without effective drug therapy. Whether elevated serum concentrations of uric acid are involved in TAAD development remains unclear.

Methods: Serum uric acid levels were detected in different TAAD mouse models and patients.

Activin Receptor-Like Kinase 3 Directly Couples Gαq (Guanine Nucleotide-Binding Protein Subunit αq)/ Gαq (Guanine Nucleotide-Binding Protein Subunit α11) to Regulate Vascular Contractility.

Background: Vascular smooth muscle cell (VSMC) contractility is critical for blood pressure regulation and vascular homeostasis. Identifying the key molecule that maintains VSMC contractility may provide a novel therapeutic target for vascular remodeling. ALK3 (activin receptor-like kinase 3) is a serine/threonine kinase receptor, and deletion of ALK3 causes embryonic lethality.

Molecular dynamics and minigene assay of new splicing variant c.4298-20T>A of gene that cause Alport syndrome.

Alport syndrome (AS; OMIM#308940) is a progressive hereditary kidney disease characterized by hearing loss and ocular abnormalities. According to the mode of inheritance, AS has three subtypes: X-linked (XL; OMIM#301050), autosomal recessive (AR; OMIM#203780), and autosomal dominant (AD; OMIM#104200). XLAS is caused by a pathogenic variant in (OMIM*303630) gene encoding type IV collagen (Col-IV) α5 chain, while ADAS and ARAS are consequences of a variant in (OMIM*120070) and (OMIM*120131) genes that encode Col-IV α3 and α4 chains, respectively.