An antidepressant mechanism underlying the allosteric inhibition of GluN2D-incorporated NMDA receptors at GABAergic interneurons.

-methyl-d-aspartate receptors (NMDARs), key excitatory ion channels, have gained attention as anti-depression targets. NMDARs consist of two GluN1 and two GluN2 subunits (2A-2D), which determine their pharmacological properties. Few compounds selectively targeting GluN2 subunits with antidepressant effects have been identified.

The Percentage of Neutrophils is Independently Associated with Blood-Brain Barrier(BBB) Disruption in Myelin Oligodendrocyte Glycoprotein Antibody Associated Disease (MOGAD).

Purpose: This study aims to investigate the risk factors associated with blood-brain barrier(BBB) disruption in patients with myelin oligodendrocyte glycoprotein antibody associated disease(MOGAD).

Patients And Methods: We collected clinical data from 95 patients diagnosed with MOGAD at the Department of Neurology, the First Affiliated Hospital of Zhengzhou University from October 2018 to May 2024. Patients were classified into normal or damaged BBB groups based on cerebrospinal fluid (CSF) albumin/serum albumin (QAlb).

Stromal architecture and fibroblast subpopulations with opposing effects on outcomes in hepatocellular carcinoma.

Dissecting the spatial heterogeneity of cancer-associated fibroblasts (CAFs) is vital for understanding tumor biology and therapeutic design. By combining pathological image analysis with spatial proteomics, we revealed two stromal archetypes in hepatocellular carcinoma (HCC) with different biological functions and extracellular matrix compositions. Using paired single-cell RNA and epigenomic sequencing with Stereo-seq, we revealed two fibroblast subsets CAF-FAP and CAF-C7, whose spatial enrichment strongly correlated with the two stromal archetypes and opposing patient prognosis.

Comparative proteomic landscapes elucidate human preimplantation development and failure.

Understanding mammalian preimplantation development, particularly in humans, at the proteomic level remains limited. Here, we applied our comprehensive solution of ultrasensitive proteomic technology to measure the proteomic profiles of oocytes and early embryos and identified nearly 8,000 proteins in humans and over 6,300 proteins in mice. We observed distinct proteomic dynamics before and around zygotic genome activation (ZGA) between the two species.

Assembly and architecture of endogenous NMDA receptors in adult cerebral cortex and hippocampus.

The cerebral cortex and hippocampus are crucial brain regions for learning and memory, which depend on activity-induced synaptic plasticity involving N-methyl-ᴅ-aspartate receptors (NMDARs). However, subunit assembly and molecular architecture of endogenous NMDARs (eNMDARs) in the brain remain elusive. Using conformation- and subunit-dependent antibodies, we purified eNMDARs from adult rat cerebral cortex and hippocampus.

Adenine base editors induce off-target structure variations in mouse embryos and primary human T cells.

Background: The safety of CRISPR-based gene editing methods is of the utmost priority in clinical applications. Previous studies have reported that Cas9 cleavage induced frequent aneuploidy in primary human T cells, but whether cleavage-mediated editing of base editors would generate off-target structure variations remains unknown. Here, we investigate the potential off-target structural variations associated with CRISPR/Cas9, ABE, and CBE editing in mouse embryos and primary human T cells by whole-genome sequencing and single-cell RNA-seq analyses.

Polarized exocytosis and anionic phospholipid species implicated in the initiation of clathrin-mediated endocytosis.

Understanding of the mechanisms that initiate clathrin-mediated endocytosis (CME) is incomplete. Recent studies in budding yeast identified the endocytic adaptor protein Yap1801/Yap1802 (budding yeast AP180) as a key CME factor that promotes CME initiation in daughter cells during polarized growth, but how Yap1801/2 is recruited preferentially to the plasma membrane of daughter cells is not clear. The only known cargos for Yap1801/2 in yeast are the synaptobrevins Snc1 and Snc2, which act as v-SNARES for exocytic vesicles arriving at the plasma membrane and are essential for polarized cell growth.

Single-cell transcriptome analysis reveals immune microenvironment changes and insights into the transition from DCIS to IDC with associated prognostic genes.

Background: Ductal carcinoma in situ (DCIS) of the breast is an early stage of breast cancer, and preventing its progression to invasive ductal carcinoma (IDC) is crucial for the early detection and treatment of breast cancer. Although single-cell transcriptome analysis technology has been widely used in breast cancer research, the biological mechanisms underlying the transition from DCIS to IDC remain poorly understood.

Results: We identified eight cell types through cell annotation, finding significant differences in T cell proportions between DCIS and IDC.

Use of rice straw nano-biochar to slow down water infiltration and reduce nitrogen leaching in a clayey soil.

Biochar exhibits numerous advantages in enhancing the soil environment despite a few limitations due to its lower surface energy. Nanomodified biochar combines the advantages of biochar and nanoscale materials. However, its effects on water infiltration and N leaching in a clayey soil remain unclear.

A comprehensive survey of dimensionality reduction and clustering methods for single-cell and spatial transcriptomics data.

In recent years, the application of single-cell transcriptomics and spatial transcriptomics analysis techniques has become increasingly widespread. Whether dealing with single-cell transcriptomic or spatial transcriptomic data, dimensionality reduction and clustering are indispensable. Both single-cell and spatial transcriptomic data are often high-dimensional, making the analysis and visualization of such data challenging.

Synthesis of struvite-enriched slow-release fertilizer using magnesium-modified biochar: Desorption and leaching mechanisms.

To improve the retention and slow-release abilities of nitrogen (N) and phosphorus (P), an 82 %-purity struvite fertilizer (MAP-BC) was synthesized using magnesium-modified biochar and a solution with a 2:1 concentration ratio of NH to PO at a pH of 8. Batch microscopic characterizations and soil column leaching experiments were conducted to study the retention and slow-release mechanisms and desorption kinetics of MAP-BC. The slow-release mechanism revealed that the dissolution rate of high-purity struvite was the dominant factor of NP slow release.

Deep learning models incorporating endogenous factors beyond DNA sequences improve the prediction accuracy of base editing outcomes.

Adenine base editors (ABEs) and cytosine base editors (CBEs) enable the single nucleotide editing of targeted DNA sites avoiding generation of double strand breaks, however, the genomic features that influence the outcomes of base editing in vivo still remain to be characterized. High-throughput datasets from lentiviral integrated libraries were used to investigate the sequence features affecting base editing outcomes, but the effects of endogenous factors beyond the DNA sequences are still largely unknown. Here the base editing outcomes of ABE and CBE were evaluated in mammalian cells for 5012 endogenous genomic sites and 11,868 genome-integrated target sequences, with 4654 genomic sites sharing the same target sequences.

Integrated proteomic and phosphoproteomic data-independent acquisition data evaluate the personalized drug responses of primary and metastatic tumors in colorectal cancer.

Mass spectrometry (MS)-based proteomics and phosphoproteomics are powerful methods to study the biological mechanisms, diagnostic biomarkers, prognostic analysis, and drug therapy of tumors. Data-independent acquisition (DIA) mode is considered to perform better than data-dependent acquisition (DDA) mode in terms of quantitative reproducibility, specificity, accuracy, and identification of low-abundance proteins. Mini patient derived xenograft (MiniPDX) model is an effective model to assess the response to antineoplastic drugs and is helpful for the precise treatment of cancer patients.

Effects of acid modified biochar on potassium uptake, leaching and balance in an alternate wetting and drying paddy ecosystem.

Straw biochar amended soils reduce fertilizer losses and alleviate soil K-exhaustion, while decrease grain yield due to its high pH. HSO-modified biochar has been studied as a means to enhance the advantages of biochar and address yield decrease. However, little information is available on its effects on aboveground K uptake, soil K fixation, K leaching, and utilization in paddy rice systems, especially under water stress.

Effects of five-year field aged zeolite on grain yield and reactive gaseous N losses in alternate wetting and drying paddy system.

Clinoptilolite zeolite has been widely used in agricultural production systems for enhancing water and fertilizer savings, mitigating greenhouse gas emissions, and increasing yield. However, there is little information on field-aged effects of zeolite on reactive gaseous N losses under alternate wetting and drying irrigation (AWD). We conducted a five-year field experiment to investigate field-aged effect of natural zeolite addition at 0 (Z), 5 (Z), and 10 (Z) t ha on reactive gaseous N losses (NH, NO), N-related global warming potential (GWP), soil properties and grain yield under two irrigation regimes (CF: continuous flooding irrigation; AWD) in the 4 (2020) and 5 (2021) years since its initial application in 2017.

Pharmaco-proteogenomic characterization of liver cancer organoids for precision oncology.

Organoid models have the potential to recapitulate the biological and pharmacotypic features of parental tumors. Nevertheless, integrative pharmaco-proteogenomics analysis for drug response features and biomarker investigation for precision therapy of patients with liver cancer are still lacking. We established a patient-derived liver cancer organoid biobank (LICOB) that comprehensively represents the histological and molecular characteristics of various liver cancer types as determined by multiomics profiling, including genomic, epigenomic, transcriptomic, and proteomic analysis.

Single-cell spatial transcriptome reveals cell-type organization in the macaque cortex.

Elucidating the cellular organization of the cerebral cortex is critical for understanding brain structure and function. Using large-scale single-nucleus RNA sequencing and spatial transcriptomic analysis of 143 macaque cortical regions, we obtained a comprehensive atlas of 264 transcriptome-defined cortical cell types and mapped their spatial distribution across the entire cortex. We characterized the cortical layer and region preferences of glutamatergic, GABAergic, and non-neuronal cell types, as well as regional differences in cell-type composition and neighborhood complexity.