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.

Health Expenditures of Patients With Diabetes After Bariatric Surgery: Comparing Gastric Bypass and Sleeve Gastrectomy.

Background: Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) differ in their effects on body weight and risk for reoperation. However, it is unclear whether long-term health expenditures differ by procedure type in patients with diabetes.

Objective: To compare health expenditures 3 years before and 5.

Guidelines International Network: Principles for Use of Artificial Intelligence in the Health Guideline Enterprise.

Description: Artificial intelligence (AI) has been defined by the High-Level Expert Group on AI of the European Commission as "systems that display intelligent behaviour by analysing their environment and taking actions-with some degree of autonomy-to achieve specific goals." Artificial intelligence has the potential to support guideline planning, development and adaptation, reporting, implementation, impact evaluation, certification, and appraisal of recommendations, which we will refer to as "guideline enterprise." Considering this potential, as well as the lack of guidance for the use of AI in guidelines, the Guidelines International Network (GIN) proposes a set of principles for the development and use of AI tools or processes to support the health guideline enterprise.

Exploring the Feasibility of a 5-Week mHealth Intervention to Enhance Physical Activity and an Active, Healthy Lifestyle in Community-Dwelling Older Adults: Mixed Methods Study.

Background: Advancements in mobile technology have paved the way for innovative interventions aimed at promoting physical activity (PA).

Objective: The main objective of this feasibility study was to assess the feasibility, usability, and acceptability of the More In Action (MIA) app, designed to promote PA among older adults. MIA offers 7 features: personalized tips, PA literacy, guided peer workouts, a community calendar, a personal activity diary, a progression monitor, and a chatbot.

Mass Casualty Incident Training in Immersive Virtual Reality: Quasi-Experimental Evaluation of Multimethod Performance Indicators.

Background: Immersive virtual reality (iVR) has emerged as a training method to prepare medical first responders (MFRs) for mass casualty incidents (MCIs) and disasters in a resource-efficient, flexible, and safe manner. However, systematic evaluations and validations of potential performance indicators for virtual MCI training are still lacking.

Objective: This study aimed to investigate whether different performance indicators based on visual attention, triage performance, and information transmission can be effectively extended to MCI training in iVR by testing if they can discriminate between different levels of expertise.

Effects of daylong exposure to indoor overheating on enterocyte damage and inflammatory responses in older adults: A randomized crossover trial.

We evaluated enterocyte damage (IFABP), microbial translocation (sCD14), and inflammatory responses (TNF-α, IL-6, CRP) in 16 older adults (66-78 years) during 8 hours rest in conditions simulating homes maintained at 22°C (control), the 26°C indoor temperature upper limit proposed by health agencies, and homes without air-conditioning during heatwaves (31°C, 36°C). Relative to 22°C, IFABP was elevated ~181 pg/mL after exposure to 31°C (P=0.07), and by ~378 pg/mL (P<0.

Clinical Activity of Mitogen-Activated Protein Kinase Inhibitors in Patients With MAP2K1 (MEK1)-Mutated Metastatic Cancers.

Purpose: MAP2K1/MEK1 mutations are potentially actionable drivers in cancer. MAP2K1 mutations have been functionally classified into three groups according to their dependency on upstream RAS/RAF signaling. However, the clinical efficacy of mitogen-activated protein kinase (MAPK) pathway inhibitors (MAPKi) for MAP2K1-mutant tumors is not well defined.

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.

Botensilimab (Fc-enhanced anti-cytotoxic lymphocyte-association protein-4 antibody) Plus Balstilimab (anti-PD-1 antibody) in Patients With Relapsed/Refractory Metastatic Sarcomas.

Purpose: Outcomes for patients with advanced sarcomas are poor and there is a high unmet need to develop novel therapies. The purpose of this phase I study was to define the safety and efficacy of botensilimab (BOT), an Fc-enhanced anti-cytotoxic lymphocyte-association protein-4 antibody, plus balstilimab (BAL), an anti-PD-1 antibody, in advanced sarcomas.

Methods: BOT was administered intravenously (IV) at 1 mg/kg or 2 mg/kg once every 6 weeks in combination with BAL IV at 3 mg/kg once every 2 weeks for up to 2 years.

How can we make sound replication decisions?

Replication and the reported crises impacting many fields of research have become a focal point for the sciences. This has led to reforms in publishing, methodological design and reporting, and increased numbers of experimental replications coordinated across many laboratories. While replication is rightly considered an indispensable tool of science, financial resources and researchers' time are quite limited.

Automating the practice of science: Opportunities, challenges, and implications.

Automation transformed various aspects of our human civilization, revolutionizing industries and streamlining processes. In the domain of scientific inquiry, automated approaches emerged as powerful tools, holding promise for accelerating discovery, enhancing reproducibility, and overcoming the traditional impediments to scientific progress. This article evaluates the scope of automation within scientific practice and assesses recent approaches.

The present and future of peer review: Ideas, interventions, and evidence.

What is wrong with the peer review system? Is peer review sustainable? Useful? What other models exist? These are central yet contentious questions in today's academic discourse. This perspective critically discusses alternative models and revisions to the peer review system. The authors highlight possible changes to the peer review system, with the goal of fostering further dialog among the main stakeholders, including producers and consumers of scientific research.

Is Ockham's razor losing its edge? New perspectives on the principle of model parsimony.

The preference for simple explanations, known as the parsimony principle, has long guided the development of scientific theories, hypotheses, and models. Yet recent years have seen a number of successes in employing highly complex models for scientific inquiry (e.g.

The misalignment of incentives in academic publishing and implications for journal reform.

For most researchers, academic publishing serves two goals that are often misaligned-knowledge dissemination and establishing scientific credentials. While both goals can encourage research with significant depth and scope, the latter can also pressure scholars to maximize publication metrics. Commercial publishing companies have capitalized on the centrality of publishing to the scientific enterprises of knowledge dissemination and academic recognition to extract large profits from academia by leveraging unpaid services from reviewers, creating financial barriers to research dissemination, and imposing substantial fees for open access.

Discourse on measurement.

Measurement literacy is required for strong scientific reasoning, effective experimental design, conceptual and empirical validation of measurement quantities, and the intelligible interpretation of error in theory construction. This discourse examines how issues in measurement are posed and resolved and addresses potential misunderstandings. Examples drawn from across the sciences are used to show that measurement literacy promotes the goals of scientific discourse and provides the necessary foundation for carving out perspectives and carrying out interventions in science.

Fatty acid metabolism and the oxidative stress response support bacterial predation.

Despite growing awareness of their importance in soil ecology, the genetic and physiological traits of bacterial predators are still relatively poorly understood. In the course of a predator evolution experiment, we identified a class of genotypes leading to enhanced predation against diverse species. RNA-seq analysis demonstrated that this phenotype is linked to the constitutive activation of a predation-specific program.

Carbonate fluorapatite coatings on phillipsite represent a significant sink of phosphorus in abyssal plains of the western Pacific Ocean.

As an essential micronutrient, phosphorus plays a key role in oceanic biogeochemistry, with its cycling intimately connected to the global carbon cycle and climate change. Authigenic carbonate fluorapatite (CFA) has been suggested to represent a significant phosphorus sink in the deep ocean, but its formation mechanisms in oceanic low-productivity settings remain poorly constrained. Applying X-ray absorption near edge structure, transmission electron microscopy, and laser ablation inductively coupled plasma mass spectrometer analyses, we report a unique mineral assemblage where CFA crystals coat phillipsite in abyssal sediments of the East Mariana Basin and the Philippine Sea.

Rational Design of Nanozymes for Engineered Cascade Catalytic Cancer Therapy.

Nanozymes have shown significant potential in cancer catalytic therapy by strategically catalyzing tumor-associated substances and metabolites into toxic reactive oxygen species (ROS) , thereby inducing oxidative stress and promoting cancer cell death. However, within the complex tumor microenvironment (TME), the rational design of nanozymes and factors like activity, reaction substrates, and the TME itself significantly influence the efficiency of ROS generation. To address these limitations, recent research has focused on exploring the factors that affect activity and developing nanozyme-based cascade catalytic systems, which can trigger two or more cascade catalytic processes within tumors, thereby producing more therapeutic substances and achieving efficient and stable cancer therapy with minimal side effects.

Protozoa-enhanced conjugation frequency alters the dissemination of soil antibiotic resistance.

Protozoa, as primary predators of soil bacteria, represent an overlooked natural driver in the dissemination of antibiotic resistance genes. However, the effects of protozoan predation on antibiotic resistance genes dissemination at the community level, along with the underlying mechanisms, remain unclear. Here we used fluorescence-activated cell sorting, qPCR, combined with metagenomics and reverse transcription quantitative PCR, to unveil how protozoa (Colpoda steinii and Acanthamoeba castellanii) influence the plasmid-mediated transfer of antibiotic resistance genes to soil microbial communities.

Strigolactones regulate Bambusa multiplex sheath senescence by promoting chlorophyll degradation.

Culm sheaths are capable of photosynthesis and are an important class of non-leaf organs in bamboo plants. The source-sink interaction mechanism has been found to play an important role in the interaction between culm sheaths and internodes in Bambusa multiplex. Research on the regulatory mechanisms of culm sheath senescence is important for the study of internode growth, but reports in this regard are limited.

Metabolomic and proteomic changes in leaves of rubber seedlings infected by Phytophthora palmivora.

Phytophthora palmivora, an oomycete pathogen, induces leaf fall disease in rubber trees (Hevea brasiliensis), causing significant economic losses. Effective disease management requires an understanding metabolic dynamics during infection. This study employed untargeted metabolomic and proteomic analyses to investigate the response of rubber seedling leaves to P.

Microbial competition for iron determines its availability to the ferrous wheel.

Iron plays a pivotal role in regulating ocean primary productivity. Iron is supplied from diverse sources such as the atmosphere and the geosphere, and hence iron biogeochemical research has focused on identifying and quantifying such sources of "new" iron. However, the recycling of this new iron fuels up to 90% of the productivity in vast oceanic regions.

Highly Optimized CNS Penetrant Inhibitors of EGFR Exon20 Insertion Mutations.

Despite recent advances in the inhibition of EGFR (epidermal growth factor receptor), there remains a clinical need for new EGFR Exon20 insertion (Ex20Ins) inhibitors that spare EGFR WT. Herein, we report the discovery and optimization of two chemical series leading to ether and biaryl as potent, selective, and brain-penetrant inhibitors of Ex20Ins mutants. Building on our earlier discovery of alkyne which allowed access to CNS property space for an Ex20Ins inhibitor, we utilized structure-based design to move to lower lipophilicity and lower CL compounds while maintaining a WT selectivity margin.

Poor Olfaction and Risk of Stroke in Older Adults: The Atherosclerosis Risk in Communities Study.

Background: Poor olfaction may be associated with adverse cerebrovascular events, but empirical evidence is limited. We aimed to investigate the association of olfaction with the risk of stroke in the Atherosclerosis Risk in Communities Study.

Methods: We included 5799 older adults with no history of stroke at baseline from 2011 to 2013 (75.