PTEN restricts IL-21R signaling in GC B cells and suppresses their differentiation to plasma cells.

The germinal center (GC) reaction is essential for generating high-quality humoral memory. Positively selected GC B cells must decide whether to remain in the GC for further affinity maturation or differentiate into memory or plasma cells (PCs). Previously, we identified IL-21R and CD40 signaling as critical promoters of GC B cell effector differentiation.

Chronic stress in mice: how gut bacteria influence gene activity in key brain neurons.

Major depressive disorder (MDD) is a serious mental disorder. Increasing evidence suggests that changes of gut microbiota are involved in pathogenesis of depression, yet the underlying mechanisms remains unknown. Here, chronic unpredictable mild stress (CUMS) mice model was constructed to mimic depression.

The Combined Inhibition of SREBP and mTORC1 Signaling Synergistically Inhibits B-Cell Lymphoma.

Background: The sterol regulatory element-binding protein (SREBP) pathway is essential for maintaining sterol homeostasis during B cell activation and germinal center B cell proliferation. However, its potential as a therapeutic target to treat B-cell lymphoma remains unclear.

Methods: We examined SREBP protein expression in human B-cell lymphoma samples using immunohistochemistry.

Ipsilateral immunization after a prior SARS-CoV-2 mRNA vaccination elicits superior B cell responses compared to contralateral immunization.

mRNA vaccines have proven to be pivotal in the fight against COVID-19. A recommended booster, given 3 to 4 weeks post the initial vaccination, can substantially amplify protective antibody levels. Here, we show that, compared to contralateral boost, ipsilateral boost of the SARS-CoV-2 mRNA vaccine induces more germinal center B cells (GCBCs) specific to the receptor binding domain (RBD) and generates more bone marrow plasma cells.

ATM/ATR Phosphorylation of CtIP on Its Conserved Sae2-like Domain Is Required for Genotoxin-Induced DNA Resection but Dispensable for Animal Development.

Homology-directed repair (HDR) of double-strand DNA breaks (DSBs) is dependent on enzymatic resection of DNA ends by the Mre11/Rad50/Nbs1 complex. DNA resection is triggered by the CtIP/Sae2 protein, which allosterically promotes Mre11-mediated endonuclease DNA cleavage at a position internal to the DSB. Although the mechanics of resection, including the initial endonucleolytic step, are largely conserved in eucaryotes, CtIP and its functional counterpart in (Sae2) share only a modest stretch of amino acid homology.

Screening of Immune-related lncRNAs in Lung Adenocarcinoma and Establishing a Survival Prognostic Risk Prediction Model.

Objective: This study aimed to improve lung adenocarcinoma (LUAD) prognosis prediction based on a signature of immune-related long non-coding RNAs (lncRNAs).

Methods: LUAD samples from the TCGA database were divided into the immunity_H group and the immunity_L group. Differentially expressed RNAs (DERs) between the two groups were identified.

B-cell-derived IL-10 promotes allergic sensitization in asthma regulated by Bcl-3.

Aeroallergen sensitization, mainly mediated by lung epithelium and dendritic cells (DCs), is integral to allergic asthma pathogenesis and progression. IL-10 has a dual role in immune responses, as it inhibits myeloid cell activation but promotes B-cell responses and epithelial cell proliferation. Here, we report a proinflammatory function of B-cell-derived IL-10 modulated by Bcl-3 in allergic asthma.

Inactive PARP1 causes embryonic lethality and genome instability in a dominant-negative manner.

PARP1 (poly-ADP ribose polymerase 1) is recruited and activated by DNA strand breaks, catalyzing the generation of poly-ADP-ribose (PAR) chains from NAD+. PAR relaxes chromatin and recruits other DNA repair factors, including XRCC1 and DNA Ligase 3, to maintain genomic stability. Here we show that, in contrast to the normal development of Parp1-null mice, heterozygous expression of catalytically inactive Parp1 (E988A, ) acts in a dominant-negative manner to disrupt murine embryogenesis.

ATR kinase supports normal proliferation in the early S phase by preventing replication resource exhaustion.

The ATR kinase, which coordinates cellular responses to DNA replication stress, is also essential for the proliferation of normal unstressed cells. Although its role in the replication stress response is well defined, the mechanisms by which ATR supports normal cell proliferation remain elusive. Here, we show that ATR is dispensable for the viability of G0-arrested naïve B cells.

Phosphorylation of DNA-PKcs at the S2056 cluster ensures efficient and productive lymphocyte development in XLF-deficient mice.

The nonhomologous end-joining (NHEJ) pathway is a major DNA double-strand break repair pathway in mammals and is essential for lymphocyte development. Ku70 and Ku80 heterodimer (KU) initiates NHEJ, thereby recruiting and activating the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs). While DNA-PKcs deletion only moderately impairs end-ligation, the expression of kinase-dead DNA-PKcs completely abrogates NHEJ.

ATR kinase supports normal proliferation in the early S phase by preventing replication resource exhaustion.

The ATR kinase, which coordinates cellular responses to DNA replication stress, is also essential for the proliferation of normal unstressed cells. Although its role in the replication stress response is well defined, the mechanisms by which ATR supports normal cell proliferation remain elusive. Here, we show that ATR is dispensable for the viability of G0-arrested naïve B cells.

Microbiota-derived short-chain fatty acids may participate in post-stroke depression by regulating host's lipid metabolism.

Background: Post-stroke depression (PSD) is a common mental disorder of stroke survivors, its pathogenesis remains elusive. Previous studies suggested a role of the microbiota-gut-brain (MGB) axis in stroke and depression. In this study, we characterized microbial composition and function, and gut-brain metabolic signatures, in PSD rats.

Laccase-mediated formation of hydrogels based on silk-elastin-like protein polymers with ultra-high molecular weight.

As artificial extracellular matrix-like materials, silk-elastin-like protein (SELP) hydrogels, with excellent mechanical properties, high tunability, favorable biocompatibility, and controlled degradability, have become an important candidate in biomedical materials. In this study, SELP is composed of silk-like (GAGAGS) and elastin-like (GXGVP) tandem repeats, in which X residues are set as tyrosine and lysine. Furthermore, SELP polymers are prepared via SpyTag/SpyCatcher.

An expressway traffic congestion measurement under the influence of service areas.

Identifying traffic congestion accurately is crucial for improving the expressway service level. Because the distributions of microscopic traffic quantities are highly sensitive to slight changes, the traffic congestion measurement is affected by many factors. As an essential part of the expressway, service areas should be considered when measuring the traffic state.

SREBP signaling is essential for effective B cell responses.

Our previous study using systems vaccinology identified an association between the sterol regulatory binding protein (SREBP) pathway and humoral immune response to vaccination in humans. To investigate the role of SREBP signaling in modulating immune responses, we generated mice with B cell- or CD11c antigen-presenting cell (APC)-specific deletion of SCAP, an essential regulator of SREBP signaling. Ablation of SCAP in CD11c APCs had no effect on immune responses.

Aberrant expression of polo-like kinase 4 in renal cell carcinoma: Association with clinicopathological characteristics and long-term survival.

Polo-like kinase 4 (PLK4) promotes tumorigenesis and is associated with the prognosis of several solid tumors, while its clinical role in patients with renal cell carcinoma (RCC) remains unidentified. The present study aimed to analyze the association of PLK4 with clinicopathological characteristics and long-term prognosis in patients with RCC. The present study detected PLK4 protein and mRNA expression using immunohistochemical and reverse transcription-quantitative PCR assays in 120 patients with RCC.

Whole-Genome Sequencing and Analysis of the White-Rot Fungus Reveals Its Phylogenetic Status and the Genetic Basis of Lignocellulose Degradation and Terpenoid Synthesis.

is an endophytic white-rot fungus that has lignocellulolytic and terpenoid-biosynthetic abilities. However, little is known about the genomic architecture of this fungus, even at the genus level. In this study, we present the first genome assembly of (CGMCC No.

[Recent progress in ergothioneine biosynthesis: a review].

Ergothioneine is a multifunctional physiological cytoprotector, with broad application in foods, beverage, medicine, cosmetics and so on. Biosynthesis is an increasingly favored method in the production of ergothioneine. This paper summarizes the new progress in the identification of key pathways, the mining of key enzymes, and the development of natural edible mushroom species and high-yield engineering strains for ergothioneine biosynthesis in recent years.

Alteration of Glycerophospholipid Metabolism in Hippocampus of Post-stroke Depression Rats.

Post-stroke depression (PSD) is the most common mental disorder in stroke survivors. However, its specific pathophysiology remains largely unknown. Previous studies suggested a role of hippocampus in PSD.

PARP inhibitors trap PARP2 and alter the mode of recruitment of PARP2 at DNA damage sites.

Dual-inhibitors of PARP1 and PARP2 are promising anti-cancer drugs. In addition to blocking PARP1&2 enzymatic activity, PARP inhibitors also extend the lifetime of DNA damage-induced PARP1&2 foci, termed trapping. Trapping is important for the therapeutic effects of PARP inhibitors.

Potential markers for predicting delayed encephalopathy in patients with acute carbon monoxide poisoning.

Background: Acute carbon monoxide poisoning (ACOP) commonly results in delayed neuropsychiatric sequelae (DNS). Currently, there are no reliable predictors. The aim of this article is to establish a practical model for predicting the development of delayed encephalopathy clinically.

Alteration of Gut Microbiome and Correlated Lipid Metabolism in Post-Stroke Depression.

Background: The pathogenesis of post-stroke depression (PSD) remains largely unknown. There is growing evidence indicating that gut microbiota participates in the development of brain diseases through the gut-brain axis. Here, we aim to determine whether and how microbial composition and function altered among control, stroke and PSD rats.

Misidentification of Acute Psychiatric Symptoms in the Emergency Room: Clinical Experience in China.

Patients who come to the emergency department because of acute psychiatric symptoms are often not admitted to the correct department timely. The purpose of this study is to identify the clinical characteristics of patients with acute psychiatric symptoms in order to achieve early and correct triage in the emergency room. We conducted a cross-analysis of inpatients who first came to the emergency department with acute psychiatric symptoms and then admitted to the department of neurology or psychiatry between years 2012 and 2018.

GPRC5A reduction contributes to pollutant benzo[a]pyrene injury via aggravating murine fibrosis, leading to poor prognosis of IIP patients.

Air pollution exposure is recently reported to be one of the drivers of exacerbation in idiopathic pulmonary fibrosis (IPF). But there was a lack of direct evidence between pollution and lung fibrosis. Here, our data show effects of pollutant benzo[a]pyrene (BaP) and protein G-protein-coupled receptor family C group 5 type A (GPRC5A) on pulmonary fibrosis, which might help limit potential pollutant injury and disease progression.