Subtyping-based platform guides precision medicine for heavily pretreated metastatic triple-negative breast cancer: The FUTURE phase II umbrella clinical trial.

Triple-negative breast cancer (TNBC) is a heterogeneous disease and lacks effective treatment. Our previous study classified TNBCs into four subtypes with putative therapeutic targets. Here, we report the final results of FUTURE, a phase II umbrella trial designed to explore whether the subtyping-based strategy may improve the outcomes in metastatic TNBC patients.

METTL3 (Methyltransferase Like 3)-Dependent N6-Methyladenosine Modification on mRNA Promotes Macrophage Inflammatory Response and Atherosclerosis in Mice.

Background: Atherosclerosis is a chronic inflammatory disease, in which macrophages determine the progression of atherosclerotic plaques. However, no studies have investigated how METTL3 (methyltransferase like 3) in macrophages affects atherosclerotic plaque formation in vivo. Additionally, whether mRNA is modified by METTL3-dependent N6-methyladenosine (m6A) methylation remains unknown.

A phase I open-label clinical trial to study drug-drug interactions of Dorzagliatin and Sitagliptin in patients with type 2 diabetes and obesity.

This is a phase 1, open-label, single-sequence, multiple-dose, single-center trial conducted in the US (NCT03790839), to evaluate the clinical pharmacokinetics, safety and pharmacodynamics of dorzagliatin co-administered with sitagliptin in patients with T2D and obesity. The trial has completed. 15 patients with T2D and obesity were recruited and treated with sitagliptin 100 mg QD on Day 1-5, followed by a combination of sitagliptin 100 mg QD with dorzagliatin 75 mg BID at second stage on Day 6-10 and the third stage of dorzagliatin 75 mg BID alone on Day 11-15.

Microwave Ablation for Papillary Thyroid Microcarcinoma with and without US-detected Capsule Invasion: A Multicenter Prospective Cohort Study.

Background Microwave ablation (MWA) has achieved favorable results in the treatment of papillary thyroid microcarcinoma (PTMC) confined in glandular parenchyma. However, studies on the outcome of MWA for PTMC with US-detected capsular invasion remain unclarified in the literature. Purpose To compare the feasibility, effectiveness, and safety of MWA in the treatment of PTMC with and without US-detected capsular invasion.

On-Site Computed Tomography-Derived Fractional Flow Reserve to Guide Management of Patients With Stable Coronary Artery Disease: The TARGET Randomized Trial.

Background: Computed tomography-derived fractional flow reserve (CT-FFR) using on-site machine learning enables identification of both the presence of coronary artery disease and vessel-specific ischemia. However, it is unclear whether on-site CT-FFR improves clinical or economic outcomes when compared with the standard of care in patients with stable coronary artery disease.

Methods: In total, 1216 patients with stable coronary artery disease and an intermediate stenosis of 30% to 90% on coronary computed tomographic angiography were randomized to an on-site CT-FFR care pathway using machine learning or to standard care in 6 Chinese medical centers.

Se-Enriched Improves Laying Performance and Regulates Ovarian Antioxidative Function in Aging Laying Hens.

As a selenium-enriched plant, (SEC) has an excellent antioxidant function. The edibility of SEC is expected to develop new sources of organic Se supplementation for human and animal nutrition. This study was conducted to investigate the effects of SEC on laying performance and ovarian antioxidant capacity in aging laying hens.

Endovascular Recanalization of Symptomatic Chronic ICA Occlusion: Procedural Outcomes and Radiologic Predictors.

Background And Purpose: Endovascular recanalization has been attempted in patients with symptomatic chronic ICA occlusion, however, the heterogeneity of recanalization outcomes and the perioperative complications present challenges for the clinical application. Our aim was to evaluate the safety and efficacy of endovascular recanalization for symptomatic chronic ICA occlusion and identify potential predictors for successful recanalization.

Materials And Methods: This study included 47 consecutive patients with symptomatic chronic ICA occlusion who underwent endovascular recanalization at our institution.

Longitudinal Assessment of Chest CT Findings and Pulmonary Function after COVID-19 Infection.

Background Information on pulmonary sequelae and pulmonary function 2 years after recovery from SARS-CoV-2 infection is lacking. Purpose To longitudinally assess changes in chest CT abnormalities and pulmonary function in individuals after SARS-CoV-2 infection. Materials and Methods In this prospective study, participants discharged from the hospital after SARS-CoV-2 infection from January 20 to March 10, 2020, were considered for enrollment.

Deacetylation of Septin4 by SIRT2 (Silent Mating Type Information Regulation 2 Homolog-2) Mitigates Damaging of Hypertensive Nephropathy.

Background: Hypertension can lead to podocyte damage and subsequent apoptosis, eventually resulting in glomerulosclerosis. Although alleviating podocyte apoptosis has clinical significance for the treatment of hypertensive nephropathy, an effective therapeutic target has not yet been identified. The function of septin4, a proapoptotic protein and an important marker of organ damage, is regulated by post-translational modification.

Reaching the initial coulombic efficiency and structural stability limit of P2/O3 biphasic layered cathode for sodium-ion batteries.

The P2/O3 biphasic layered oxide (NaMnMO, M: doping elements) is a cathode family with great promise for sodium-ion batteries (SIBs) because of their tunable electrochemical performance and low cost. However, the ultrahigh initial coulombic efficiency (ICE) and inferior cycling performance of P2/O3-NaMnMO need to be improved for practical application. Herein, Ni/Cu co-doped P2/O3-NaMnNiCuO materials are well-designed.

Inhibition of Fap Promotes Cardiac Repair by Stabilizing BNP.

Background: Myocardial infarction (MI) elicits cardiac fibroblast activation and extracellular matrix (ECM) deposition to maintain the structural integrity of the heart. Recent studies demonstrate that Fap (fibroblast activation protein)-a prolyl-specific serine protease-is an important marker of activated cardiac fibroblasts after MI.

Methods: Left ventricle and plasma samples from patients and healthy donors were used to analyze the expression level of FAP and its prognostic value.

Sex Differences in Associations Between Socioeconomic Status and Incident Hypertension Among Chinese Adults.

Background: With rapid socioeconomic development and transition, associations between socioeconomic status (SES) and hypertension remained uncertain in China. We aimed to examine the health effects of SES on hypertension incidence and explore the sex differences among Chinese adults.

Methods: We included 53 891 participants without hypertension from the China-PAR (Prediction for Atherosclerotic Cardiovascular Disease Risk in China) project.

Softening by charging: how collective modes of ionic association in concentrated redoxmer/electrolyte solutions define the structural and dynamic properties in different states of charge.

Understanding the physical and chemical processes occurring in concentrated electrolyte solutions is required to achieve redox flow batteries with high energy density. Highly concentrated electrolyte solutions are often studied in which collective crowded interactions between molecules and ions become predominant. Herein, experimental and computational methods were used to examine non-aqueous electrolyte solutions in two different states of charge as a function of redoxmer concentration.

Interdependent Nuclear Co-Trafficking of ASPP1 and p53 Aggravates Cardiac Ischemia/Reperfusion Injury.

Objective: ASPP1 (apoptosis stimulating of p53 protein 1) is critical in regulating cell apoptosis as a cofactor of p53 to promote its transcriptional activity in the nucleus. However, whether cytoplasmic ASPP1 affects p53 nuclear trafficking and its role in cardiac diseases remains unknown. This study aims to explore the mechanism by which ASPP1 modulates p53 nuclear trafficking and the subsequent contribution to cardiac ischemia/reperfusion (I/R) injury.

Evolutionarily conserved regulators of tau identify targets for new therapies.

Tauopathies are neurodegenerative diseases that involve the pathological accumulation of tau proteins; in this family are Alzheimer disease, corticobasal degeneration, and chronic traumatic encephalopathy, among others. Hypothesizing that reducing this accumulation could mitigate pathogenesis, we performed a cross-species genetic screen targeting 6,600 potentially druggable genes in human cells and Drosophila. We found and validated 83 hits in cells and further validated 11 hits in the mouse brain.

Blood Pressure Levels, Cardiovascular Events, and Renal Outcomes in Chronic Kidney Disease Without Antihypertensive Therapy: A Nationwide Population-Based Cohort Study.

Background: High blood pressure (BP) is highly prevalent in patients with chronic kidney disease. However, the thresholds to initiate BP-lowering treatment in this population are unclear. We aimed to examine the associations between BP levels and clinical outcomes and provide evidence on potential thresholds to initiate BP-lowering therapy in people with chronic kidney disease.

Impaired Human Cardiac Cell Development due to NOTCH1 Deficiency.

Background: pathogenic variants are implicated in multiple types of congenital heart defects including hypoplastic left heart syndrome, where the left ventricle is underdeveloped. It is unknown how regulates human cardiac cell lineage determination and cardiomyocyte proliferation. In addition, mechanisms by which pathogenic variants lead to ventricular hypoplasia in hypoplastic left heart syndrome remain elusive.

Young Patients With Colorectal Cancer Have Higher Early Mortality but Better Long-Term Survival.

Introduction: To define the prognosis of colorectal cancer (CRC) in young patients and to compare their postoperative treatment with that of older patients.

Methods: This multicenter study enrolled 5,457 patients with primary CRC who underwent surgical resection. The overall survival (OS), clinicopathologic characteristics, and postoperative treatment of 253 young patients aged 18-44 years and 5,204 older patients aged 44-80 years were analyzed.

Disruption of the ATXN1-CIC complex reveals the role of additional nuclear ATXN1 interactors in spinocerebellar ataxia type 1.

Spinocerebellar ataxia type 1 (SCA1) is a paradigmatic neurodegenerative disease in that it is caused by a mutation in a broadly expressed protein, ATXN1; however, only select populations of cells degenerate. The interaction of polyglutamine-expanded ATXN1 with the transcriptional repressor CIC drives cerebellar Purkinje cell pathogenesis; however, the importance of this interaction in other vulnerable cells remains unknown. Here, we mutated the 154Q knockin allele of Atxn1 mice to prevent the ATXN1-CIC interaction globally.

Protects Against Elevated Arterial Stiffness.

Background: Dysbiosis of gut microbiota plays a pivotal role in vascular dysfunction and microbial diversity was reported to be inversely correlated with arterial stiffness. However, the causal role of gut microbiota in the progression of arterial stiffness and the specific species along with the molecular mechanisms underlying this change remain largely unknown.

Methods: Participants with elevated arterial stiffness and normal controls free of medication were matched for age and sex.