Multivariate stochastic modeling for transcriptional dynamics with cell-specific latent time using SDEvelo.

Recently, RNA velocity has driven a paradigmatic change in single-cell RNA sequencing (scRNA-seq) studies, allowing the reconstruction and prediction of directed trajectories in cell differentiation and state transitions. Most existing methods of dynamic modeling use ordinary differential equations (ODE) for individual genes without applying multivariate approaches. However, this modeling strategy inadequately captures the intrinsically stochastic nature of transcriptional dynamics governed by a cell-specific latent time across multiple genes, potentially leading to erroneous results.

Repair of Retrorsine-Induced DNA Damage in Rat Livers: Insights Gained from Transcriptomic and Proteomic Studies.

Pyrrolizidine alkaloids (PAs) are common phytotoxins that are found worldwide. Upon hepatic metabolic activation, the reactive PA metabolites covalently bind to DNAs and form DNA adducts, causing mutagenicity and tumorigenicity in the liver. However, the molecular basis of the formation and removal of PA-derived DNA adducts remains largely unexplored.

One-Step Process for the Regiodivergent Double Hydrocyanation of 1,3-Butadiene.

In industry, the two important nitrile starting materials, adiponitrile and 2-methylglutaronitrile, are primarily manufactured through the well-known DuPont process, which consists of a tandem sequence including first hydrocyanation, isomerization and second hydrocyanation. However, this mature process has the intrinsic defects of step efficiency and regioselectivity. Herein, we report a nickel-catalyzed divergent, one-step double hydrocyanation of 1,3-butadiene to produce either adiponitrile or 2-methylglutaronitrile in high regioselectivity.

MiR-378 exaggerates angiogenesis and bone erosion in collagen-induced arthritis mice by regulating endoplasmic reticulum stress.

Rheumatoid arthritis (RA) is a chronic autoimmune disorder marked by pain, inflammation, and discomfort in the synovial joints. It is critical to understand the pathological mechanisms of RA progression. MicroRNA-378 (miR-378) is highly expressed in the synovium of RA patients and positively correlated with disease severity, but its function and underlying mechanisms remain poorly understood.

Facet-engineered NaNbO cubes with exposed (101) plane for enhanced lithium-ion storage.

Density functional theory (DFT) predicts superior lithium-ion diffusion the (101) plane of NaNbO. Experimental results confirm that despite a reduction in surface area, 6 μm NaNbO cubes with more (101) plane exposure exhibit enhanced Li storage, underscoring the significance of crystal facet engineering.

Electrical Spin State Manipulation in All-Magnet Heterojunctions Using a Ferromagnetic Spin Source.

The ability to electrically manipulate spin states in magnetic materials is essential for the advancement of energy-efficient spintronic device, which is typically achieved in systems composed of a spin source and a magnetic target, where the magnetic state of the target is altered by a charge current. While theories suggest that ferromagnets could function as more versatile spin sources, direct experimental studies involving only the spin source and target layers have been lacking. Here electrical manipulation of spin states in noncolinear antiferromagnet MnSn using ferromagnets (Ni, Fe, NiFe, CoFeB) as the spin sources is reported.

The concept of cone opponency may extend beyond accommodation, to myopiagenesis and emmetropization, for a better peripheral defocus lens.

Myopia has ever-rising prevalence in the past few decades globally. Its pathogenesis is still not adequately elucidated especially at the signal transduction level. For the environmental risk factors, there is a large body of fragmented knowledge about the visual inputs for accommodation, myopiagenesis and emmetropization, with the latter two being essentially local processes.

Cascade Reaction of Enyne-Amides with Sulfur-Ylides for the Synthesis of Indole-Tethered 5-Oxaspiro[2.4]hept-6-ene Derivatives.

An unexpected cascade reaction of enyne-amides with sulfur-ylides has been developed. This cascade reaction involves cycloisomerization, dearomatic cyclopropanation, ring-opening rearomatization, and subsequent cyclopropanation, differing from the common [2 + n] cyclization of enyne-amides. A variety of (spirocyclopropane)dihydrofuran derivatives have been efficiently and conveniently synthesized in a single vessel, exhibiting excellent diastereoselectivity and good functional group tolerance.

Spatially ordered immobilization of cascade enzymes for the construction of a robust colorimetric hydrogel sensor.

The development of a suitable mimetic scaffolds for maintaining high activity and stability of co-immobilized multi-enzymes is a key challenge in biotechnology. Herein, we achieved the regular distribution of cascade enzymes through spatially controlled hierarchical loading into protein-inorganic hybrid nanoflowers using a mild biomineralization technique. The comprehensive understanding of sequential regulation in constructing controlled nanoarchitecture enables to combine a continuous reaction and achieve tailoring catalysis for biomimetic application.

How mortality awareness regulates intertemporal Choice: A joint effect of endpoint reminder and retrospective episodic thinking.

Although life is lived forward, it can only be understood backward. From the perspective of life-history theory, we propose that mortality reminders may induce backward thinking from the endpoint of life and regulate intertemporal choice between smaller-and-sooner (SS) and large-and-later rewards (LL), thereby helping individuals with time management. Experiment 1 compared the effects of mortality (endpoint) imagination with the imagination of being at age 70 and found that only mortality imagination significantly reduced delay discounting, the extent to which a delayed reward is discounted.

DeepForest-HTP: A novel deep forest approach for predicting antihypertensive peptides.

Hypertension is a major preventable risk factor for cardiovascular disease, affecting over 1.5 billion adults worldwide. Antihypertensive peptides (AHTPs) have gained attention as a natural therapeutic option with minimal side effects.

Mapping the 9-year sleep trajectory and its implications for chronic disease risks among middle-aged and older adults.

Objective: To identify the 9-year trajectories of sleep duration and to assess the relationship between time-dependent sleep duration and sleep trajectories with 14 chronic diseases in adults.

Methods: This study used five waves of data of the China Health and Retirement Longitudinal Survey. Participants with complete sleep duration data and at least one record of 14 chronic diseases were included.

Association between pyrrolizidine alkaloids exposure and risk of abnormal serum indices-Insights from a descriptive cross-sectional study in Yunnan Province.

The hazard of pyrrolizidine alkaloids (PAs) has been widely reported in animal studies but rarely in population-based research, especially reports about daily exposure. A single-centre descriptive cross-sectional study was conducted on 552 Lahu Autonomous County residents recruited in 2021. Blood PAs exposure biomarker (pyrrole- protein adduct, PPA) and serum biochemical indices were measured.

PlmCas12e Utilizes Glu662 to Prevent Cleavage Site Occupation by Positively Charged Residues Before Target Strand Cleavage.

CRISPR-Cas12e is a recently identified gene-editing tool mainly known because its relatively small size benefits cell delivery. Drastically different from Cas9, it creates a blunt-end double-strand breakage of the DNA via two cleavage sites; Cas12e produces a sticky-end double-strand breakage of the DNA through only one cleavage site in its RuvC domain, meaning two consecutive cleavage events first on the non-target strand (ntsDNA) and then the target strand (tsDNA). Though crucial for Cas12e's cleavage efficiency, the mechanism by which Cas12e loads tsDNA for the second cleavage remains elusive.

Discovering a novel dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A) inhibitor and its impact on tau phosphorylation and amyloid-β formation.

Dual-specificity tyrosine-regulated kinase 1 A (DYRK1A) is crucial in neurogenesis, synaptogenesis, and neuronal functions. Its dysregulation is linked to neurodegenerative disorders like Down syndrome and Alzheimer's disease. Although the development of DYRK1A inhibitors has significantly advanced in recent years, the selectivity of these drugs remains a critical challenge, potentially impeding further progress.

Identification, biological evaluation, and crystallographic analysis of coumestrol as a novel dual-specificity tyrosine-phosphorylation-regulated kinase 1A inhibitor.

Alzheimer's disease (AD) is an irreversible neurodegenerative disease, with tau pathology caused by abnormally activated dual-specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A) being one of the culprits. Coumestrol, a phytoestrogen and natural antioxidant found in various plants, has been reported to alleviate AD, but the underlying mechanism remains unclear. We confirmed coumestrol as a novel DYRK1A inhibitor through enzyme-based assays, X-ray crystallography, and cell line experiments.

Intravitreal indocyanine green is toxic to the retinal cells.

Background: Indocyanine green (ICG) is widely used to stain the epiretinal membranes and internal limiting membranes during the pars plana vitrectomy (PPV). This study aims to evaluate the effect of ICG on rat retinas and various retinal cell lines, including ARPE-19 cells, rMC-1 cells, BV2 cells, HRMECs and R28 cells.

Methods: ICG solutions were prepared and diluted with glucose solution (GS) according to the standard clinical protocols.

Non-invasively predicting euploidy in human blastocysts via quantitative 3D morphology measurement: a retrospective cohort study.

Background: Blastocyst morphology has been demonstrated to be associated with ploidy status. Existing artificial intelligence models use manual grading or 2D images as the input for euploidy prediction, which suffer from subjectivity from observers and information loss due to incomplete features from 2D images. Here we aim to predict euploidy in human blastocysts using quantitative morphological parameters obtained by 3D morphology measurement.

Robotic manipulation of cardiomyocytes to identify gap junction modifiers for arrhythmogenic cardiomyopathy.

Arrhythmogenic cardiomyopathy (ACM) is a leading cause of sudden cardiac death among young adults. Aberrant gap junction remodeling has been linked to disease-causative mutations in plakophilin-2 (). Although gap junctions are a key therapeutic target, measurement of gap junction function in preclinical disease models is technically challenging.

Noise Exposure in the Workplace, Genetic Susceptibility, and Incidence of Atrial Fibrillation: A Prospective Cohort Study.

Background: No study explored the association of noise exposure in the workplace and genetic susceptibility with incidence of atrial fibrillation (AF). We aimed to assess the separate and joint relationship of noise exposure in the workplace and genetic susceptibility with the risk of AF.

Methods And Results: We included 167 577 participants without AF at baseline in UK Biobank.