High-dose estrogen impairs demethylation of H3K27me3 by decreasing Kdm6b expression during ovarian hyperstimulation in mice.

Given that ovarian stimulation is vital for assisted reproductive technology (ART) and results in elevated serum estrogen levels, exploring the impact of elevated estrogen exposure on oocytes and embryos is necessary. We investigated the effects of various ovarian stimulation treatments on oocyte and embryo morphology and gene expression using a mouse model and estrogen-treated mouse embryonic stem cells (mESCs). Female C57BL/6J mice were subjected to two types of conventional ovarian stimulation and ovarian hyperstimulation; mice treated with only normal saline served as controls.

Unveiling the Complete Spectrum of SARS-CoV-2 Fusion Stages by In Situ Cryo-ET.

SARS-CoV-2 entry into host cells is mediated by the spike protein, which drives membrane fusion. While cryo-EM has revealed stable prefusion and postfusion conformations of the spike, the transient intermediate states during the fusion process have remained poorly understood. Here, we designed a near-native viral fusion system that recapitulates SARS-CoV-2 entry and used cryo-electron tomography (cryo-ET) to capture fusion intermediates leading to complete fusion.

Cellular polarity pilots breast cancer progression and immunosuppression.

Disrupted cellular polarity (DCP) is a hallmark of solid cancer, the malignant disease of epithelial tissues, which occupies ~90% of all human cancers. DCP has been identified to affect not only the cancer cell's aggressive behavior but also the migration and infiltration of immune cells, although the precise mechanism of DCP-affected tumor-immune cell interaction remains unclear. This review discusses immunosuppressive tumor microenvironments (TME) caused by DCP-driven tumor cell proliferation with DCP-impaired immune cell functions.

[An atrial fibrillation prediction model based on quantitative features of electrocardiogram during sinus rhythm in the Chinese population].

Objectives: To develop an early atrial fibrillation (AF) risk prediction model based on large-scale electrocardiogram (ECG) data from the Chinese population.

Methods: The data of multiple ECG records of 30 383 patients admitted in the Chinese PLA General Hospital between 2009 and 2023 were randomly divided into the training set and the internal testing set in a 7:3 ratio. The predictive factors were selected based on the training set using univariate analysis, LASSO regression, and the Boruta algorithm.

Cross-tissue multi-omics analyses reveal the gut microbiota's absence impacts organ morphology, immune homeostasis, bile acid and lipid metabolism.

The gut microbiota influences host immunity and metabolism, and changes in its composition and function have been implicated in several non-communicable diseases. Here, comparing germ-free (GF) and specific pathogen-free (SPF) mice using spatial transcriptomics, single-cell RNA sequencing, and targeted bile acid metabolomics across multiple organs, we systematically assessed how the gut microbiota's absence affected organ morphology, immune homeostasis, bile acid, and lipid metabolism. Through integrated analysis, we detect marked aberration in B, myeloid, and T/natural killer cells, altered mucosal zonation and nutrient uptake, and significant shifts in bile acid profiles in feces, liver, and circulation, with the alternate synthesis pathway predominant in GF mice and pronounced changes in bile acid enterohepatic circulation.

The synergistic effect of c-Myb hyperactivation and Pu.1 deficiency induces Pelger-Huët anomaly and promotes sAML.

Approximately 30% of patients with myelodysplastic syndrome (MDS) progress to secondary acute myeloid leukemia (sAML) via accumulating gene mutations. Genomic analyses reveal a complex interplay among mutant genes, with co-occurring and mutually exclusive patterns. Hyperactivation of c-MYB and deficiency of PU.

Integrative single-cell and spatial transcriptome analysis reveals heterogeneity of human liver progenitor cells.

Background: Liver progenitor cells (LPCs) with bipotential differentiation capacities are essential for restoring liver homeostasis and hepatocyte population after damage. However, the low proportion and shared markers with epithelial cells make studying LPC heterogeneity difficult, especially in humans. To address this gap, we explored over 259,400 human liver single cells across 4 conditions (fetal, healthy, cirrhotic, and HCC-affected livers).

Coordination Competition Strategy for Constructing High-Energy Photosensitive Complexes.

High-dimensional energetic coordination compounds (ECCs) exhibit high stability and low sensitivity owing to their complex network structure, making them valuable in functional energetic materials such as combustion catalysis and insensitive detonating explosives. Four ECCs, [Co(DNBT)(HO)] (ECC-1), [Ni(DNBT)(HO)] (ECC-2), [Cu(DNBT)(HO)MeOH] (ECC-3), and [Zn(DNBT)(HO)] (ECC-4), were synthesized by modifying the metal centers and using 5,5'-dinitro-4,4'-3,3'-bi(1,2,4-triazole) (DNBT) as ligands. After changing the solution environment and adding the auxiliary ligand 4-1,2,4-triazol-4-amine (4-ATr), we obtained three ECCs with similar coordination structures once again: [Co(DNBT)(4-ATr)(HO)] (ECC-5), [Ni(DNBT)(4-ATr)(HO)] (ECC-6), and [Cu(DNBT)(4-ATr)] (ECC-7).

Exploring resistance mechanisms and identifying QTLs for brown planthopper in tropical and subtropical rice (Oryza sativa L.) germplasm.

A total of 4006 tropical and subtropical rice germplasms were screened for brown planthopper resistance, and the resistance mechanisms of 63 highly resistant accessions were characterized. This led to the designation of three novel resistance QTLs: Bph47, Bph48, and Bph49. The brown planthopper (BPH) is a significant piercing-sucking pest of rice plants that causes widespread destruction globally.

Structural basis for HIV-1 capsid adaption to rescue IP6-packaging deficiency.

Inositol hexakisphosphate (IP6) promotes HIV-1 assembly via its interaction with the immature Gag lattice, effectively enriching IP6 within virions. During particle maturation, the HIV-1 protease cleaves the Gag polyproteins comprising the immature Gag lattice, releasing IP6 from its original binding site and liberating the capsid (CA) domain of Gag. IP6 then promotes the assembly of mature CA protein into the capsid shell of the viral core, which is required for infection of new target cells.

The Interplay Between Endoplasmic Reticulum Stress and Ferroptosis in Neurological Diseases.

Many studies in the open literature have highlighted the critical roles of endoplasmic reticulum stress and ferroptosis in neurological diseases such as neurodegenerative diseases, brain injuries, and depression, indicating that they are involved in the onset and progression of these diseases. Therefore, it is essential to explore the regulatory mechanisms and potential interventions targeting endoplasmic reticulum stress and ferroptosis in neurological diseases. However, most existing research has primarily focused on the unidirectional mechanisms of endoplasmic reticulum stress and ferroptosis within the nervous system, with a lack of in-depth investigations into their interactions.

Spatiotemporal transcriptomics elucidates the pathogenesis of fulminant viral myocarditis.

Fulminant myocarditis (FM) is a severe inflammatory condition of the myocardium that often results in sudden death, particularly in young individuals. In this study, we employed single-nucleus and spatial transcriptomics to perform a comprehensive analysis of coxsackievirus B3 (CVB3)-induced FM in A/J mice, spanning seven distinct time points pre- and post-treatment. Our findings reveal that mesothelial cells play a critical role in the early stage of myocarditis by acting as primary targets for CVB3 infection.

Brassica rapa receptor-like cytoplasmic kinase BrRLCK1 negatively regulates freezing tolerance in transgenic Arabidopsis via the CBF pathway.

Some winter rapeseed (Brassica rapa) varieties can endure extremely low temperatures (-20°C to -32°C). However, because of a lack of mutant resources, the molecular mechanisms underlying cold tolerance in B. rapa remain unclear.

Systematic free energy insights into the enhanced dispersibility of myofibrillar protein in low-salt solutions through ultrasound-assisted enzymatic deamidation.

This work aimed to investigate the effects of ultrasound assisted enzymatic deamidation by protein-glutaminase (PG) on the dispersion of myofibrillar protein (MP) in low-salt solutions. The solubility, structural characteristics, transmission electron microscopy, asymmetric-flow field-flow fractionation, steady shear rheological property and multiple light scattering of MP deamidated by PG (MP-PG) and MP pretreated with ultrasound followed by PG deamidation (MP-U-PG) were determined. Molecular docking and molecular dynamics (MD) simulations were used to estimate the interaction between PG and MP.

Exome Sequencing Identified Susceptible Genes for High Residual Risks in Early-Onset Coronary Atherosclerotic Disease.

Aims: Despite the tremendous improvement in therapeutic medication and intervention for coronary atherosclerotic disease (CAD), residual risks remain. Exome sequencing enables identification of rare variants and susceptibility genes for residual risks of early-onset coronary atherosclerotic disease (EOCAD) with well-controlled conventional risk factors.

Methods: We performed whole-exome sequencing of subjects who had no conventional risk factors, defined as higher body mass index, smoking, hypertension and dyslipidemia, screened from 1950 patients with EOCAD (age ≤ 45 years, at least 50% stenosis of coronary artery by angiography), and selected control subjects from 1006 elder (age ≥ 65 years) with < 30% coronary stenosis.

Enzymatic degradation of mycotoxin patulin by a short-chain dehydrogenase/reductase from Bacillus subtilis and its application in apple juice.

Patulin (PAT), a notorious mycotoxin widely found in fruits and their derived products, poses serious health risks to humans and animals due to its high toxicity. Biodegradation based on microbial enzymes has shown broad application prospects in controlling PAT contamination due to its environmental friendliness, high efficiency, strong specificity, and mild conditions of action. Bacillus subtilis is a cosmopolitan probiotic bacterium with an extensive enzymatic profile, which could serve as a valuable resource for the effective production of a range of enzymes utilized in various industrial processes and production applications.

Identifying cell types by lasso-constraint regularized Gaussian graphical model based on weighted distance penalty.

Single-cell RNA sequencing (scRNA-seq) technology is one of the most cost-effective and efficacious methods for revealing cellular heterogeneity and diversity. Precise identification of cell types is essential for establishing a robust foundation for downstream analyses and is a prerequisite for understanding heterogeneous mechanisms. However, the accuracy of existing methods warrants improvement, and highly accurate methods often impose stringent equipment requirements.

Injectable pH-responsive polypeptide hydrogels for local delivery of doxorubicin.

Cancer, as a global health threat, is often treated with chemotherapy, but its effect is limited, especially the drugs such as doxorubicin (DOX) are limited by their non-specificity and side effects. This study focuses on developing a new drug delivery system to overcome these challenges. Based on the self-assembling peptide hemopressin (HP), we designed and screened FOK peptide, which serves as a pH-responsive carrier with excellent pH sensitivity and mechanical stability.

Identification and Application of Novel Patulin-Degrading Enzymes from 168.

Patulin (PAT), a toxic secondary metabolite produced mainly by species that frequently contaminates fruit and fruit-derived products, poses serious health risks to humans and animals. In the present study, three short-chain dehydrogenases/reductases (SDRs) with PAT-degrading ability, designated SDR1, SDR2, and SDR3, were identified from the genome of 168. SDR1 and SDR2 showed powerful PAT elimination abilities, which can completely convert PAT to nontoxic E-ascladiol.

Three RLKs integrate SHR-SCR and gibberellins to regulate root ground tissue patterning in Arabidopsis thaliana.

Precise regulation of cell division is essential for proper tissue patterning in multicellular organisms. In Arabidopsis, the ground tissue (GT) comprises cortex and endodermis in the early stages of root development. During GT maturation, additional periclinal cell divisions (PCDs) occasionally occur of the endodermis, generating a middle cortex (MC) layer between the cortex and endodermis.

Adaptive multi-epitope targeting and avidity-enhanced nanobody platform for ultrapotent, durable antiviral therapy.

Pathogens constantly evolve and can develop mutations that evade host immunity and treatment. Addressing these escape mechanisms requires targeting evolutionarily conserved vulnerabilities, as mutations in these regions often impose fitness costs. We introduce adaptive multi-epitope targeting with enhanced avidity (AMETA), a modular and multivalent nanobody platform that conjugates potent bispecific nanobodies to a human immunoglobulin M (IgM) scaffold.

HAPLN3 p.T34A contributes to incomplete penetrance of moyamoya disease in Chinese carrying RNF213 p.R4810K.

Background And Purpose: The penetrance of the RNF213 p.R4810K, a founder mutation of moyamoya disease (MMD), is estimated to be only 1/150-1/300. However, the factors affecting its penetrance remain unclear.