Long-Term Prognostic Implications of Non-Culprit Lesions in Patients Presenting With an Acute Myocardial Infarction: Is It the Angiographic Stenosis Severity or the Underlying High-Risk Morphology?

Background: Patients with acute myocardial infarction and angiographically obstructive non-culprit lesions are at high risk for recurrent major adverse cardiac events (MACEs). However, it remains largely unknown whether events are due to stenosis severity or due to the underlying high-risk lesion morphology.

Methods: Between January 2017 and December 2021, 1312 patients with acute myocardial infarction underwent optical coherence tomography of all the 3 main epicardial arteries after successful percutaneous coronary intervention.

Remote Ischemic Conditioning Attenuates Transneuronal Degeneration and Promotes Stroke Recovery via CD36-Mediated Efferocytosis.

Background: Remote ischemic conditioning (RIC) has been implicated in cross-organ protection in cerebrovascular disease, including stroke. However, the lack of a consensus protocol and controversy over the clinical therapeutic outcomes of RIC suggest an inadequate mechanistic understanding of RIC. The current study identifies RIC-induced molecular and cellular events in the blood, which enhance long-term functional recovery in experimental cerebral ischemia.

Assessment of cardiac iron deposition and genotypic classification in pediatric beta-thalassemia major: the role of cardiac MRI.

Background: Beta thalassemia major (β-TM) is a severe genetic anemia with considerable phenotypic heterogeneity. This study investigated whether genotype correlates with distinct myocardial iron overload patterns, assessed by cardiovascular magnetic resonance (CMR) T2* values.

Methods: CMR data for cardiac iron deposition evaluation, which recruited pediatric participants between January 2021 and December 2024, were analyzed with CVI42.

Peripheral nerve regeneration using a bioresorbable silk fibroin-based artificial nerve conduit fabricated via a novel freeze-thaw process.

While silk fibroin (SF) obtained from silkworm cocoons is expected to become a next-generation natural polymer, a fabrication method for SF-based artificial nerve conduits (SFCs) has not yet been established. Here, we report a bioresorbable SFC, fabricated using a novel freeze-thaw process, which ensures biosafety by avoiding any harmful chemical additives. The SFC demonstrated favorable biocompatibility (high hydrophilicity and porosity with a water content of > 90%), structural stability (stiffness, toughness, and elasticity), and biodegradability, making it an ideal candidate for nerve regeneration.

Muscarinic acetylcholine receptor 3 localized to primary endothelial cilia regulates blood pressure and cognition.

We previously demonstrated that the inability of primary endothelial cilia to sense fluid shear stress can lead to nitric oxide (NO) deficiency and cause hypertension (HTN). Decreased biosynthesis of NO contributes to cerebral amyloid angiopathy in Alzheimer's disease (AD) patients through increased deposition of amyloid beta (Aβ). However, the molecular mechanisms underlying the pathogenesis of HTN and AD are incompletely understood.

Optimizing Extraction Solvents for Plant Chemical Analysis Using H NMR and Principal Component Analysis.

Natural products, particularly plants, remain a vital source of bioactive compounds owing to their unparalleled metabolic diversity across pharmaceuticals, cosmetics, foods, and agriculture. However, this diversity, encompassing not only a multitude of compounds but also their varying chemical and physical properties, presents a challenge in their effective utilization. Targeted analysis of specific metabolites, as well as untargeted approaches covering a wide metabolite range, necessitate optimal extraction solvents tailored to meet diverse requirements.

Strategies for Implementing Integrated Behavioral Health into Health Centers.

Background: Integrated behavioral health (IBH) is a promising approach which embeds behavioral health services into primary care. Yet, IBH has had limited implementation. Our objective was to identify strategies to successfully implement the "Cherokee" IBH model by examining a 2013 to 2019 IBH demonstration project in New Jersey that included Federally Qualified Health Centers (FQHCs) and Community Health Centers (CHCs).

Historical biogeography of the Mugil cephalus species complex and its rapid global colonization.

Our understanding of speciation processes in marine environments remains very limited and the role of different reproductive barriers are still debated. While physical barriers were considered important drivers causing reproductive isolation, recent studies highlight the importance of climatic and hydrological changes creating unsuitable habitat conditions as factors promoting population isolation. Although speciation in marine fish has been investigated from different perspectives, these studies often have a limited geographical extant.

Histological and genetic features and therapeutic responses of lung cancers explored via the global analysis of their metabolome profile.

Background: Lung cancer is the deadliest disease globally, with more than 120,000 diagnosed cases and more than 75,000 deaths annually in Japan. Several treatment options for advanced lung cancer are available, and the discovery of biomarkers will be useful for personalized medicine. Using metabolome analysis, we aimed to identify biomarkers for diagnosis and treatment response by examining the changes in metabolites associated with lung cancer progression.

Prospective trial of the Oncobox platform RNA sequencing bioinformatic analysis for personalized prescription of targeted drugs.

Interrogating gene expression in tumor can identify up- and downregulated molecular targets of cancer drugs. Here we report the results of prospective clinical investigation of using RNA sequencing analysis for personalized cancer therapy. Transcriptomic profiles were analyzed using Oncobox platform that identifies altered expression of drug target genes and molecular pathways and builds a personalized rating of targeted therapeutics.

Small-molecule activators of NRF1 transcriptional activity prevent protein aggregation.

Intracellular protein aggregation causes proteotoxic stress, underlying highly debilitating neurodegenerative disorders in parallel with decreased proteasome activity. Nevertheless, under such stress conditions, the expression of proteasome subunits is upregulated by Nuclear Factor Erythroid 2-related factor 1 (NRF1), a transcription factor that is encoded by NFE2L1. Activating the NRF1 pathway could accordingly delay the onset of neurodegenerative and other disorders with impaired cell proteostasis.

Rational design and modular synthesis of biodegradable ionizable lipids via the Passerini reaction for mRNA delivery.

The ionizable lipid component of lipid nanoparticle (LNP) formulations is essential for mRNA delivery by facilitating endosomal escape. Conventionally, these lipids are synthesized through complex, multistep chemical processes that are both time-consuming and require significant engineering. Furthermore, the development of new ionizable lipids is hindered by a limited understanding of the structure-activity relationships essential for effective mRNA delivery.

Bone Marrow Niche in Cardiometabolic Disease: Mechanisms and Therapeutic Potential.

Cardiovascular and cardiometabolic diseases are leading causes of morbidity and mortality worldwide, driven in part by chronic inflammation. Emerging research suggests that the bone marrow microenvironment, or marrow niche, plays a critical role in both immune system regulation and disease progression. The bone marrow niche is essential for maintaining hematopoietic stem cells (HSCs) and orchestrating hematopoiesis.

Mechanisms underlying the interactions and adaptability of nitrogen removal microorganisms in freshwater sediments.

Microorganisms in eutrophic water play a vital role in nitrogen (N) removal, which contributes significantly to the nutrient cycling and sustainability of eutrophic ecosystems. However, the mechanisms underlying the interactions and adaptation strategies of the N removal microorganisms in eutrophic ecosystems remain unclear. We thus analyzed field sediments collected from a eutrophic freshwater ecosystem, enriched the N removal microorganisms, examined their function and adaptability through amplicon, metagenome and metatranscriptome sequencing.

Effects of water ammonia nitrogen on hemolymph and intestinal microbiota of Litopenaeus vannamei.

Ammonia stress was detrimental to shrimp, but how water ammonia nitrogen (ammonia-N) influences the shrimp's health remains unclear. Thus, this study was designed to investigate the effects of water ammonia-N on hemolymph ammonia-N concentration, hepatopancreas structure, and the intestinal microbiota of Litopenaeus vannamei with four experiments. We found that the concentration of ammonia-N in shrimp hemolymph was significantly higher than that in pond water, indicating that water ammonia-N stimulates the accumulation of hemolymph ammonia-N.

Evaluation of LMG S-31876 for immunomodulation and stress: a double-blind, placebo-controlled clinical trial.

Objective: The study aimed to analyze the safety and effectiveness of the ProBC Plus ( LMG S-31876) supplement across various health parameters, including stress levels, immunoglobulin levels, biochemical parameters, and vital signs.

Methods: A randomized, double-blind, placebo-controlled clinical trial study was conducted involving 50 subjects diagnosed with ailments related to immune system dysfunction and stress related disorders. Patients were treated with ProBC Plus (2 billion colony-forming units [CFU]) along with a placebo capsule administered once daily for a period of 8 weeks.

Adult phenotypes of genetic developmental and epileptic encephalopathies.

Developmental and epileptic encephalopathies constitute a group of severe epilepsies, with seizure onset typically occurring in infancy or childhood, and diverse clinical manifestations, including neurodevelopmental deficits and multimorbidities. Many have genetic aetiologies, identified in up to 50% of individuals. Whilst classically considered paediatric disorders, most are compatible with survival into adulthood, but their adult phenotypes remain inadequately understood.

Performance of algorithms using wrist temperature for retrospective ovulation day estimate and next menses start day prediction: a prospective cohort study.

Study Question: Can algorithms using wrist temperature, available on compatible models of iPhone and Apple Watch, retrospectively estimate the day of ovulation and predict the next menses start day?

Summary Answer: Algorithms using wrist temperature can provide retrospective ovulation estimates and next menses start day predictions for individuals with typical or atypical cycle lengths.

What Is Known Already: Wrist skin temperature is affected by hormonal changes associated with the menstrual cycle and can be used to estimate the timing of cycle events.

Study Design, Size, Duration: We conducted a prospective cohort study of 262 menstruating females (899 menstrual cycles) aged 14 and older who logged their menses, performed urine LH testing to define day of ovulation, recorded daily basal body temperature (BBT), and collected overnight wrist temperature.

Thermostable terahertz metasurface enabled by graphene assembly film for plasmon-induced transparency.

With the increasing demand on high-density integration and better performance of micro-nano optoelectronic devices, the operation temperatures are expected to significantly increase under some extreme conditions, posing a risk of degradation to metal-based micro-/nano-structured metasurfaces due to their low tolerance to high temperature. Therefore, it is urgent to find new materials with high-conductivity and excellent high-temperature resistance to replace traditional micro-nano metal structures. Herein, we have proposed and fabricated a thermally stable graphene assembly film (GAF), which is calcined at ultra-high temperature (~ 3000 ℃) during the reduction of graphite oxide (GO).

Mechanical properties and piecewise constitutive model of fine sandstone in mining area of western China.

Owing to the differences in sedimentary environments in the mining areas of western China, the mechanical properties of rocks in this region are significantly different from those in the central and eastern regions. Therefore, uniaxial cyclic loading-unloading tests were conducted on fine sandstone found in many roof rocks to study the evolution laws of mechanical properties, deformation characteristics, acoustic emission (AE) parameters, and energy under cyclic loading and unloading conditions. The accumulated residual strain, dissipative energy, acoustic emission cumulative ringing counts, and cumulative energy were introduced to characterize the degree of rock damage.

Assessment of Hsp90β-selective inhibitor safety and on-target effects.

The heat shock protein 90 (Hsp90) family of molecular chaperones mediates the folding and activation of ~ 400 client proteins, many of which contribute to oncogenesis. As a result, Hsp90 pan-inhibitors, which inhibit all four Hsp90 isoforms, have been investigated in the clinic for the treatment of cancer. Unfortunately, detrimental side effects were observed and hindered the clinical development of pan-Hsp90 inhibitors.

Effects of psilocybin on mouse brain microstructure.

Background And Purpose: There is surging interest in the therapeutic potential of psychedelic compounds like psilocybin in the treatment of psychiatric illnesses like major depressive disorder (MDD). Recent studies point to the rapid antidepressant effect of psilocybin; however, the biological mechanisms underlying these differences remain unknown. This study determines the feasibility of using diffusion MRI to characterize and define the potential spatiotemporal microstructural differences in the brain following psilocybin treatment in C57BL/6J male mice.

Oral Regimens for Rifampin-Resistant, Fluoroquinolone-Susceptible Tuberculosis.

Background: For decades, poor treatment options and low-quality evidence plagued care for patients with rifampin-resistant tuberculosis. The advent of new drugs to treat tuberculosis and enhanced funding now permit randomized, controlled trials of shortened-duration, all-oral treatments for rifampin-resistant tuberculosis.

Methods: We conducted a phase 3, multinational, open-label, randomized, controlled noninferiority trial to compare standard therapy for treatment of fluoroquinolone-susceptible, rifampin-resistant tuberculosis with five 9-month oral regimens that included various combinations of bedaquiline (B), delamanid (D), linezolid (L), levofloxacin (Lfx) or moxifloxacin (M), clofazimine (C), and pyrazinamide (Z).

Trajectory of the arterial-alveolar oxygen gradient in COPD for a decade.

Background: Chronic respiratory failure (CRF) is a critical complication in patients with chronic obstructive pulmonary disease (COPD) and is characterized by an increase in the arterial-alveolar oxygen gradient (A-aDO2). The long-term trajectory and prognostic significance remain unclear. This study aimed to assess the prognostic impact of A-aDO2 and elucidate its trajectory over ten years.