Coordinated regulation of two LacI family regulators, GvmR and GvmR2, on guvermectin production in .

Guvermectin, a purine nucleoside natural product produced by the genus S, has recently been registered as a new biopesticide to boost rice yield. Despite its economic and agricultural significance, the regulatory mechanisms of guvermectin biosynthesis remain essentially unknown, hindering industrial production and widespread agricultural application. Here, we examined the roles of two LacI family regulators, and , located within and adjacent to the guvermectin biosynthesis cluster, respectively, in guvermectin production in NEAU6.

miR-217-5p NanomiRs Inhibit Glioblastoma Growth and Enhance Effects of Ionizing Radiation via EZH2 Inhibition and Epigenetic Reprogramming.

: CSCs are critical drivers of the tumor and stem cell phenotypes of glioblastoma (GBM) cells. Chromatin modifications play a fundamental role in driving a GBM CSC phenotype. The goal of this study is to further our understanding of how stem cell-driving events control changes in chromatin architecture that contribute to the tumor-propagating phenotype of GBM.

Tenecteplase Thrombolysis for Stroke up to 24 Hours After Onset With Perfusion Imaging Selection: The CHABLIS-T II Randomized Clinical Trial.

Background: Whether it is effective and safe to extend the time window of intravenous thrombolysis up to 24 hours after the last known well is unknown. We aimed to determine the efficacy and safety of tenecteplase in Chinese patients with acute ischemic stroke due to large/medium vessel occlusion within an extended time window.

Methods: Patients with ischemic stroke presenting 4.

Cardiovascular Events Associated with CDK4/6 Inhibitors: A Safety Meta-Analysis of Randomized Controlled Trials and a Pharmacovigilance Study of the FAERS Database.

Background: CDK4/6 inhibitors are highly valued, but the incidence of cardiovascular adverse events (CVAEs) associated with CDK4/6 inhibitors is not clear.

Objective: Our aim was therefore to assess the risk of developing CVAEs associated with CDK4/6 inhibitors, by conducting a systematic review and meta-analysis of randomized controlled trials (RCTs), along with a pharmacovigilance study of the FDA Adverse Event Reporting System (FAERS) database.

Methods: Eligible CVAEs were extracted from the ClinicalTrials.

METTL4-Mediated Mitochondrial DNA N6-Methyldeoxyadenosine Promoting Macrophage Inflammation and Atherosclerosis.

Background: Mitochondrial dysfunction is a key factor in the development of atherogenesis. METTL4 (methyltransferase-like protein 4) mediates N6- methyldeoxyadenosine (6mA) of mammalian mitochondrial DNA (mtDNA). However, the role of METTL4-mediated mitoepigenetic regulation in atherosclerosis is still unknown.

Co-culture fermentation of Debaryomyces hansenii and Bacillus atrophaeus alleviates quality deterioration of litchi fruit by ameliorating microbial community diversity and composition.

Microbial communities, both on the surface and within fruit, play a crucial role in reducing postharvest diseases and maintaining fruit quality. This study investigated the effects of co-culture fermentation supernatant of Debaryomyces hansenii (Y) and Bacillus atrophaeus (T) on disease control and quality preservation of postharvest litchi fruit, while exploring the underlying mechanisms through microbiome profiling. The results indicated that Y + T treatment not only reduced decay percentage, weight loss, and pH increase but also preserved the pericarp cell integrity and reduced the lignin accumulation.

Pulsed Field Ablation of Paroxysmal Supraventricular Tachycardia: A Prospective Multicenter Single-Arm Study in China.

Background: Pulsed field ablation (PFA) has gained attention in cardiac electrophysiology, but data on its application to paroxysmal supraventricular tachycardia are limited. This study aimed to assess the feasibility and safety of PFA and its combination with radiofrequency ablation for treating paroxysmal supraventricular tachycardia.

Methods: A prospective, multicenter, single-arm study was conducted across 8 centers in China.

Caregiving and Hypertension in Younger Black Women: The Jackson Heart Study.

Background: Caregiving has been associated with high blood pressure in middle-aged and older women, but this relationship is understudied among younger Black women, a population at high risk for hypertension. We examined the associations of caregiving stress and caregiving for high-needs dependents with incident hypertension among reproductive-age women in the JHS (Jackson Heart Study), a cohort of community-dwelling Black adults.

Methods: We included 453 participants, aged 21 to 44 years, with blood pressure <140/90 mm Hg, and not taking antihypertensive medication at baseline (2000-2004).

Discovery of potent dihydro-oxazinoquinolinone inhibitors of GuaB for the treatment of tuberculosis.

Tuberculosis is the leading cause of death from an infectious disease, and is caused by Mycobacterium tuberculosis (M.tb). More than 1 billion people worldwide are thought to harbor an M.

Coupling Habitat Radiomic Analysis with the Diversification of the Tumor ecosystem: Illuminating New Strategy in the Assessment of Postoperative Recurrence of Non-Muscle Invasive Bladder Cancer.

Rationale And Objectives: Non-muscle-invasive bladder cancer (NMIBC) is highly recurrent, with each recurrence potentially progressing to muscle-invasive cancer, affecting patient prognosis. Intratumoral heterogeneity plays a crucial role in NMIBC recurrence. This study investigated a novel habitat-based radiomic analysis for stratifying NMIBC recurrence risk.

[Characteristics of soybean climate potential productivity in frigid region and its response to climate change].

A comprehensive understanding of the evolution of soybean climate potential productivity and its response to climate change in Heilongjiang Province can offer reference and basis for further tapping soybean production potential and realizing stable and high yield of soybean in the frigid region. Based on meteorological data from 80 meteorological stations in Heilongjiang Province from 1961 to 2020, we estimated photosynthesis, light temperature, and climate potential productivity of soybean by the stepwise correction method, examined the spatiotemporal variations by spatial interpolation and statistical analysis methods, and analyzed the impact of changes in climate factors such as radiation, temperature, and precipitation on climate potential productivity. The results showed that during the study period, the average values of photosynthesis potential productivity (), light-temperature potential productivity (), and climate potential productivity () of soybean in Heilongjiang Province were 7533, 6444, and 3515 kg·hm, respectively.

Supramolecular assembly of polycation/mRNA nanoparticles and in vivo monocyte programming.

Size-dependent phagocytosis is a well-characterized phenomenon in monocytes and macrophages. However, this size effect for preferential gene delivery to these important cell targets has not been fully exploited because commonly adopted stabilization methods for electrostatically complexed nucleic acid nanoparticles, such as PEGylation and charge repulsion, typically arrest the vehicle size below 200 nm. Here, we bridge the technical gap in scalable synthesis of larger submicron gene delivery vehicles by electrostatic self-assembly of charged nanoparticles, facilitated by a polymer structurally designed to modulate internanoparticle Coulombic and van der Waals forces.

Immature dendritic cell-targeting mRNA vaccine expressing PfCSP enhances protective immune responses against liver infection.

Resurgence in malaria has been noted in 2022 with 249 million clinical cases resulting in 608,000 deaths, mostly in children under five. Two vaccines, RTS, S, and more recently R21, targeting the circumsporozoite protein (CSP) are recommended by the WHO but are not yet widely available. Strong humoral responses to neutralize sporozoites before they can infect the hepatocytes are important for vaccine-mediated protection.

Efficacy and Safety of Oral Administration of Wine Lees Extract (WLE)-Derived Ceramides and Glucosylceramides in Enhancing Skin Barrier Function: A Randomized, Double-Blind, Placebo-Controlled Study.

Background: Our search for plant-derived ceramides from sustainable sources led to the discovery of ceramides and glucosylceramides in wine lees.

Objective: This study evaluated the efficacy and safety of wine lees extract (WLE)-derived ceramides and glucosylceramides in enhancing skin barrier function.

Methods: A randomized, double-blind, placebo-controlled study was conducted with 30 healthy Japanese subjects aged 20-64.

Affinity-Resolved Size Exclusion Chromatography Coupled to Mass Spectrometry: A Novel Tool to Study the Attribute-and-Function Relationship in Therapeutic Monoclonal Antibodies.

Assessment of critical quality attributes (CQAs) is an important aspect during the development of therapeutic monoclonal antibodies (mAbs). Attributes that affect either the target binding or Fc receptor engagement may have direct impacts on the drug safety and efficacy and thus are considered as CQAs. Native size exclusion chromatography (SEC)-based competitive binding assay has recently been reported and demonstrated significant benefits compared to conventional approaches for CQA identification, owing to its faster turn-around and higher multiplexity.

Arthroscopic Transtibial Pullout Repair and Tibial Condylar Valgus Osteotomy for Medial Meniscus Posterior Root Tear With Varus Knee.

As an important structure for maintaining the hoop tension of the medial meniscus of the knee joint, the posterior root is receiving increasing attention. Medial meniscus posterior root tear is an important reason for the occurrence, development, and kinematics changes of knee osteoarthritis. It is necessary to repair the posterior root of meniscus for restoring joint kinematics and improving clinical efficacy.

Adjuvant treatment strategy evolution and risk stratification for hormone receptor-positive, human epidermal growth factor receptor-2 negative early breast cancer in China.

Background: Patients with hormone receptor-positive (HR+), human epidermal growth factor receptor-2 negative (HER2-) early breast cancer (EBC) with high-risk clinicopathological features face an increased risk of recurrence. This study explored the evolving treatment landscape and clinical outcomes in patients with EBC using a nationwide database.

Patients And Methods: The study cohort comprised HR+/HER2-, stages 1-3, patients with EBC who underwent surgery and received adjuvant endocrine therapy (AET) from January 2013 to March 2021.

Intensive Ambulance-Delivered Blood-Pressure Reduction in Hyperacute Stroke.

Background: Treatment of acute stroke, before a distinction can be made between ischemic and hemorrhagic types, is challenging. Whether very early blood-pressure control in the ambulance improves outcomes among patients with undifferentiated acute stroke is uncertain.

Methods: We randomly assigned patients with suspected acute stroke that caused a motor deficit and with elevated systolic blood pressure (≥150 mm Hg), who were assessed in the ambulance within 2 hours after the onset of symptoms, to receive immediate treatment to lower the systolic blood pressure (target range, 130 to 140 mm Hg) (intervention group) or usual blood-pressure management (usual-care group).

Artificial Intelligence-Assisted Prescription Determination for Orthokeratology Lens Fitting: From Algorithm to Clinical Practice.

Objectives: To explore the potential of artificial intelligence (AI) to assist prescription determination for orthokeratology (OK) lenses.

Methods: Artificial intelligence algorithm development followed by a real-world trial. A total of 11,502 OK lenses fitting records collected from seven clinical environments covering major brands.

Spatiotemporal ATF3 Expression Determines VSMC Fate in Abdominal Aortic Aneurysm.

Background: Abdominal aortic aneurysm (AAA) is a catastrophic disease with little effective therapy, likely due to the limited understanding of the mechanisms underlying AAA development and progression. ATF3 (activating transcription factor 3) has been increasingly recognized as a key regulator of cardiovascular diseases. However, the role of ATF3 in AAA development and progression remains elusive.