Transcription factor Ascl2 promotes germinal center B cell responses by directly regulating AID transcription.

During germinal center (GC) reactions, activated B cells undergo clonal expansion and functional maturation to produce high-affinity antibodies and differentiate into plasma and memory cells, accompanied with class-switching recombination (CSR) and somatic hypermutation (SHM). Activation-induced cytidine deaminase (AID) is responsible for both CSR and SHM in GC B cells. Transcriptional mechanisms underlying AID regulation and GC B cell reactions are still not well understood.

Tart Cherry (Fruit of ) Concentrated Powder (TCcp) Ameliorates Glucocorticoid-Induced Muscular Atrophy in Mice.

: The present study investigated the beneficial effects of tart cherry (fruit of ) concentrated powder (TCcp) on glucocorticoid (GLU)-induced catabolic muscular atrophy in the skeletal muscle of mice. Furthermore, its potential mechanism was also studied. : Changes in calf thickness, calf muscle weight, calf muscle strength, body weight, gastrocnemius muscle histology, immunohistochemistry, serum creatinine, creatine kinase, lactate dehydrogenase, and antioxidant defense systems were measured.

Evidence of Cooperation between Hippo Pathway and Mutation in Thyroid Carcinomas.

Thyroid cancer incidences have been steadily increasing worldwide and are projected to become the fourth leading cancer diagnosis by 2030. Improved diagnosis and prognosis predictions for this type of cancer depend on understanding its genetic bases and disease biology. mutations have been found in a wide range of thyroid tumors, from benign to aggressive thyroid carcinomas.

The Rab7 effector WDR91 promotes autophagy-lysosome degradation in neurons by regulating lysosome fusion.

The effectors of the Rab7 small GTPase play multiple roles in Rab7-dependent endosome-lysosome and autophagy-lysosome pathways. However, it is largely unknown how distinct Rab7 effectors coordinate to maintain the homeostasis of late endosomes and lysosomes to ensure appropriate endolysosomal and autolysosomal degradation. Here we report that WDR91, a Rab7 effector required for early-to-late endosome conversion, is essential for lysosome function and homeostasis.

Chrom-Lasso: a lasso regression-based model to detect functional interactions using Hi-C data.

Hi-C is a genome-wide assay based on Chromosome Conformation Capture and high-throughput sequencing to decipher 3D chromatin organization in the nucleus. However, computational methods to detect functional interactions utilizing Hi-C data face challenges including the correction for various sources of biases and the identification of functional interactions with low counts of interacting fragments. We present Chrom-Lasso, a lasso linear regression model that removes complex biases assumption-free and identifies functional interacting loci with increased power by combining information of local reads distribution surrounding the area of interest.

Association of cardiovascular disease with 30-day hospital readmission in Chinese patients receiving maintenance dialysis.

Background: Previous studies have shown cardiovascular disease (CVD) to be a risk factor in the prediction of 30-day hospital readmission among patients receiving dialysis. However, studies of Asian populations are limited. In the present study, we examined the association between CVD and 30-day hospital readmission in Chinese patients receiving maintenance dialysis.

De novo transcriptome analysis for examination of the nutrition metabolic system related to the evolutionary process through which stick insects gain the ability of flight (Phasmatodea).

Objective: Insects are the most evolutionarily successful groups of organisms, and this success is largely due to their flight ability. Interestingly, some stick insects have lost their flight ability despite having wings. To elucidate the shift from wingless to flying forms during insect evolution, we compared the nutritional metabolism system among flight-winged, flightless-winged, and flightless-wingless stick insect groups.

Effect of CTLA4-Ig on Obliterative Bronchiolitis in a Mouse Intrapulmonary Tracheal Transplantation Model.

Objectives: One of the serious problems after lung transplantation is chronic lung allograft dysfunction (CLAD). Most CLAD patients pathologically characterized by obliterative bronchiolitis (OB). Cytotoxic T-lymphocyte-associated antigen 4 (CTLA4)-Ig is a combination protein of the Fc fragment of human IgG1 linked to the extracellular domain of CTLA4.

Lysosome biogenesis: Regulation and functions.

Lysosomes are degradation centers and signaling hubs in cells and play important roles in cellular homeostasis, development, and aging. Changes in lysosome function are essential to support cellular adaptation to multiple signals and stimuli. Therefore, lysosome biogenesis and activity are regulated by a wide variety of intra- and extracellular cues.

Identification of candidate PAX2-regulated genes implicated in human kidney development.

PAX2 is a transcription factor essential for kidney development and the main causative gene for renal coloboma syndrome (RCS). The mechanisms of PAX2 action during kidney development have been evaluated in mice but not in humans. This is a critical gap in knowledge since important differences have been reported in kidney development in the two species.

Disrupting tumor onset and growth via selective cell tagging (SeCT) therapy.

This study presents the early framework of selective cell tagging (SeCT) therapy, which is the concept of preferentially labeling specific cells in vivo with chemical moieties that can elicit a therapeutic response. Using glycosylated artificial metalloenzyme (GArM)-based protein labeling, this study reports two separate functional strategies. In one approach, early tumor onset can be suppressed by tagging cancer cells in living mice with an integrin-blocking cyclic-Arg-Gly-Asp (cRGD) moiety, thereby disrupting cell adhesion onto the extracellular matrix.

Surgery may not benefit patients with locally advanced rectal cancer who achieved clinical complete response following neoadjuvant chemoradiotherapy.

Purpose: We compared the long-term outcome of the watch and wait (WW) strategy and surgery in patients with locally advanced rectal cancer.

Patients And Methods: This prospective cohort study included 84 patients who achieved clinical complete response (cCR) after neoadjuvant chemoradiotherapy (NCRT). They were divided into the WW group (n = 58) and surgery group (SG, n = 26).

Single-cell transcriptomics of human embryos identifies multiple sympathoblast lineages with potential implications for neuroblastoma origin.

Characterization of the progression of cellular states during human embryogenesis can provide insights into the origin of pediatric diseases. We examined the transcriptional states of neural crest- and mesoderm-derived lineages differentiating into adrenal glands, kidneys, endothelium and hematopoietic tissue between post-conception weeks 6 and 14 of human development. Our results reveal transitions connecting the intermediate mesoderm and progenitors of organ primordia, the hematopoietic system and endothelial subtypes.

Targeting stanniocalcin-1-expressing tumor cells elicits efficient antitumor effects in a mouse model of human lung cancer.

Lung cancer is the most common cause of cancer-related death in developed countries; therefore, the generation of effective targeted therapeutic regimens is essential. Recently, gene therapy approaches toward malignant cells have emerged as attractive molecular therapeutics. Previous studies have indicated that stanniocalcin-1 (STC-1), a hormone involved in calcium and phosphate homeostasis, positively regulates proliferation, apoptosis resistance, and glucose metabolism in lung cancer cell lines.

Unmanipulated haploidentical hematopoietic stem cell transplantation is an excellent option for children and young adult relapsed/refractory Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia after CAR-T-cell therapy.

Although chimeric antigen receptor T-cell (CAR-T) therapy produces a high complete remission rate among patients with relapsed/refractory B-cell acute lymphoblastic leukemia, relapse remains an urgent issue. It is uncertain whether consolidative haploidentical-allogeneic hematopoietic stem cell transplantation (haplo-HSCT) is suitable for achieving sustainable remission. Therefore, we aimed to assess the efficacy and safety of bridging CAR-T therapy to haplo-HSCT.

Human Endogenous Natural Products.

Natural products are a class of chemical compounds that are biosynthesized by living organisms, including humans. Endogenous natural products are produced by human cells as well as by the human microbiome. This contribution describes the current understanding and recent progress made on endogenous natural products that are produced by human cells, including amines, steroids, and fatty acid-derived natural products.

Anti-inflammatory, expectorant, and antitussive properties of in ICR mice.

Context: (KOG) is a traditional mixed herb preparation consisting of CA Meyer (Araliaceae), Wolf (Polyporaceae), (Gaertner) Liboschitz ex Steudel (Orobanchaceae), and honey. Various pharmacological effects of KOG are reported, but the efficacy on respiratory diseases has not been evaluated.

Objective: The anti-inflammatory, expectorant, and antitussive properties of KOG were examined using animal models of respiratory diseases.

Development of a rapid scabies immunodiagnostic assay based on transcriptomic analysis of Sarcoptes scabiei var. nyctereutis.

Scabies is a highly contagious skin disease caused by the mite Sarcoptes scabiei that affects many mammals. However, the sensitivity of traditional tests for scabies diagnosis in humans is less than 50%. To simplify the diagnosis of scabies, methods that are simple, sensitive, specific, and cost-effective are required.

Cyst formation in proximal renal tubules caused by dysfunction of the microtubule minus-end regulator CAMSAP3.

Epithelial cells organize an ordered array of non-centrosomal microtubules, the minus ends of which are regulated by CAMSAP3. The role of these microtubules in epithelial functions, however, is poorly understood. Here, we show that the kidneys of mice in which Camsap3 is mutated develop cysts at the proximal convoluted tubules (PCTs).

Decoding Neuronal Diversification by Multiplexed Single-cell RNA-Seq.

Cellular reprogramming is driven by a defined set of transcription factors; however, the regulatory logic that underlies cell-type specification and diversification remains elusive. Single-cell RNA-seq provides unprecedented coverage to measure dynamic molecular changes at the single-cell resolution. Here, we multiplex and ectopically express 20 pro-neuronal transcription factors in human dermal fibroblasts and demonstrate a widespread diversification of neurons based on cell morphology and canonical neuronal marker expressions.

A review of the pharmacology and clinical profile of lumateperone for the treatment of schizophrenia.

Schizophrenia is associated with a tremendous individual and societal burden. The disease is characterized by a complex set of symptoms including psychosis, hallucinations, delusions and related positive symptoms combined with social function deficits, cognitive disturbances and, often, devastating mood disorder, such as comorbid depression. Management of the disease often requires lifelong pharmacotherapy.

Structural Basis for Pore Blockade of the Human Cardiac Sodium Channel Na 1.5 by the Antiarrhythmic Drug Quinidine*.

Na 1.5, the primary voltage-gated Na (Na ) channel in heart, is a major target for class I antiarrhythmic agents. Here we present the cryo-EM structure of full-length human Na 1.