Selective regulation of IFN-γ and IL-4 co-producing unconventional T cells by purinergic signaling.

Unconventional T cells, including mucosal-associated invariant T (MAIT), natural killer T (NKT), and gamma-delta T (γδT) cells, comprise distinct T-bet+, IFN-γ+ and RORγt+, IL-17+ subsets which play differential roles in health and disease. NKT1 cells are susceptible to ARTC2-mediated P2X7 receptor (P2RX7) activation, but the effects on other unconventional T-cell types are unknown. Here, we show that MAIT, γδT, and NKT cells express P2RX7 and are sensitive to P2RX7-mediated cell death.

Discovery of highly potent and ALK2/ALK1 selective kinase inhibitors using DNA-encoded chemistry technology.

Activin receptor type 1 (ACVR1; ALK2) and activin receptor like type 1 (ACVRL1; ALK1) are transforming growth factor beta family receptors that integrate extracellular signals of bone morphogenic proteins (BMPs) and activins into Mothers Against Decapentaplegic homolog 1/5 (SMAD1/SMAD5) signaling complexes. Several activating mutations in ALK2 are implicated in fibrodysplasia ossificans progressiva (FOP), diffuse intrinsic pontine gliomas, and ependymomas. The ALK2 R206H mutation is also present in a subset of endometrial tumors, melanomas, non-small lung cancers, and colorectal cancers, and ALK2 expression is elevated in pancreatic cancer.

Dietary intakes of vitamin B, folate, vitamin B and erectile dysfunction: a national population-based study.

Background: While deficiencies in vitamin B, folate, and vitamin B are linked to various human diseases, including anemia, depression, peripheral neuropathy, and cardiovascular disease (CVD), literature regarding the association between vitamin B, folate, and vitamin B and erectile dysfunction (ED) is scarce. We aimed to determine the dietary intake of vitamin B, folate, and vitamin B and ED in the United States population.

Methods: We extracted data from the 2001-2004 cycles of the National Health and Nutrition Examination Survey (NHANES).

Generation of antitumor chimeric antigen receptors incorporating T cell signaling motifs.

Chimeric antigen receptor (CAR) T cells have been used to successfully treat various blood cancers, but adverse effects have limited their potential. Here, we developed chimeric adaptor proteins (CAPs) and CAR tyrosine kinases (CAR-TKs) in which the intracellular ζ T cell receptor (TCRζ) chain was replaced with intracellular protein domains to stimulate signaling downstream of the TCRζ chain. CAPs contain adaptor domains and the kinase domain of ZAP70, whereas CAR-TKs contain only ZAP70 domains.

Bispecific CAR-T cells targeting FAP and GPC3 have the potential to treat hepatocellular carcinoma.

Chimeric antigen receptor (CAR) T cell therapy has demonstrated robust efficacy against hematological malignancies, but there are still some challenges regarding treating solid tumors, including tumor heterogeneity, antigen escape, and an immunosuppressive microenvironment. Here, we found that SNU398, a hepatocellular carcinoma (HCC) cell line, exhibited high expression levels of fibroblast activation protein (FAP) and Glypican 3 (GPC3), which were negatively correlated with patient prognosis. The HepG2 HCC cell line highly expressed GPC3, while the SNU387 cell line exhibited high expression of FAP.

Gsα Regulates Macrophage Foam Cell Formation During Atherosclerosis.

Background: Many cardiovascular pathologies are induced by signaling through G-protein-coupled receptors via Gsα (G protein stimulatory α subunit) proteins. However, the specific cellular mechanisms that are driven by Gsα and contribute to the development of atherosclerosis remain unclear.

Methods: High-throughput screening involving data from single-cell and bulk sequencing were used to explore the expression of Gsα in atherosclerosis.

Resolvin E1/ChemR23 Protects Against Hypertension and Vascular Remodeling in Angiotensin II-Induced Hypertensive Mice.

Background: Inflammation plays a critical role in the development of hypertension and vascular remodeling. Resolvin E1 (RvE1), as one of the specialized proresolving lipid mediators, promotes inflammation resolution by binding with a G protein-coupled receptor, ChemR23 (chemerin receptor 23). However, whether RvE1/ChemR23 regulates hypertension and vascular remodeling is unknown.

Three-dimensional High-Resolution Dark-Blood Late Gadolinium Enhancement Imaging for Improved Atrial Scar Evaluation.

Background Radiofrequency ablation (RFA) is a widely used treatment for atrial fibrillation, reducing the risk of cardiac arrhythmia. Detailed visualization and quantification of atrial scarring has the potential to improve preprocedural decision-making and postprocedural prognosis. Conventional bright-blood late gadolinium enhancement (LGE) MRI can help detect atrial scars; however, its suboptimal myocardium to blood contrast inhibits accurate scar estimation.

Optogenetic Spreading Depolarizations Do Not Worsen Acute Ischemic Stroke Outcome.

Background: Spreading depolarizations (SDs) are believed to contribute to injury progression and worsen outcomes in focal cerebral ischemia because exogenously induced SDs have been associated with enlarged infarct volumes. However, previous studies used highly invasive methods to trigger SDs that can directly cause tissue injury (eg, topical KCl) and confound the interpretation. Here, we tested whether SDs indeed enlarge infarcts when induced via a novel, noninjurious method using optogenetics.

Association of Lifestyle With Incidence of Heart Failure According to Metabolic and Genetic Risk Status: A Population-Based Prospective Study.

Background: Whether lifestyle factors are similarly associated with risk of heart failure (HF) for individuals with different metabolic or genetic risk status remains unclear.

Methods: We included 464 483 participants from UK Biobank who were free of major cardiovascular disease or HF during baseline recruitment. Healthy lifestyle factors included avoidance of smoking, no obesity, regular physical activity, and healthy diet.

Dynamic trafficking patterns of IL-17-producing γδ T cells are linked to the recurrence of skin inflammation in psoriasis-like dermatitis.

Background: Psoriasis recurrence is a clinically challenging issue. However, the underlying mechanisms haven't been fully understood.

Methods: RNAseq analysis from affected skin of psoriatic patients treated with topical glucocorticoid (GC) with different outcomes was performed.

Live Birth with or without Preimplantation Genetic Testing for Aneuploidy.

Background: Embryo selection with preimplantation genetic testing for aneuploidy (PGT-A) may improve pregnancy outcomes after initial embryo transfer. However, it remains uncertain whether PGT-A improves the cumulative live-birth rate as compared with conventional in vitro fertilization (IVF).

Methods: In this multicenter, randomized, controlled trial, we randomly assigned subfertile women with three or more good-quality blastocysts to undergo either PGT-A or conventional IVF; all the women were between 20 and 37 years of age.

Efficacy of Acupuncture for Chronic Prostatitis/Chronic Pelvic Pain Syndrome : A Randomized Trial.

Background: Acupuncture has promising effects on chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), but high-quality evidence is scarce.

Objective: To assess the long-term efficacy of acupuncture for CP/CPPS.

Design: Multicenter, randomized, sham-controlled trial.

Global evolution of research on green energy and environmental technologies:A bibliometric study.

To better grasp developments and trends in research on green energy and environmental technologies, the published literatures in the Web of Science Core Collection database from 1998 to 2020 were utilized to reveal critical information and guidance on what has been investigated, and what are the changes in research interests using a bibliometric method. Herein, yearly quantitative distribution of literatures, author contribution and collaboration, productive and influential institutions and countries/territories, co-citation analysis, keywords co-occurrence analysis, and research frontier identification are analyzed via information visualization technology. The results show that the publications on green energy and environmental technologies have grown exponentially, that China, the USA, and Italy are the most active countries, but the global cooperation is not close at present.

No Associations Between Regular Use of Proton Pump Inhibitors and Risk of All-Cause and Cause-Specific Mortality: A Population-Based Cohort of 0.44 Million Participants.

Introduction: The association between proton pump inhibitors' (PPIs) use and mortality remains unclear.

Methods: This was a prospective analysis of 440,840 UK residents and 13,154 deaths. We evaluated the associations with multivariate Cox regression.

The Soluble (Pro)Renin Receptor in Health and Diseases: Foe or Friend?

The (pro)renin receptor (PRR) is a single-transmembrane protein that regulates the local renin-angiotensin system and participates in various intracellular signaling pathways, thus exhibiting a significant physiopathologic relevance in cellular homeostasis. A soluble form of PRR (sPRR) is generated through protease-mediated cleavage of the full-length PRR and secreted into extracellular spaces. Accumulating evidence indicates pivotal biologic functions of sPRR in various physiopathological processes.

Liver metastasis restrains immunotherapy efficacy via macrophage-mediated T cell elimination.

Metastasis is the primary cause of cancer mortality, and cancer frequently metastasizes to the liver. It is not clear whether liver immune tolerance mechanisms contribute to cancer outcomes. We report that liver metastases diminish immunotherapy efficacy systemically in patients and preclinical models.

A Universal Design of Betacoronavirus Vaccines against COVID-19, MERS, and SARS.

Vaccines are urgently needed to control the ongoing pandemic COVID-19 and previously emerging MERS/SARS caused by coronavirus (CoV) infections. The CoV spike receptor-binding domain (RBD) is an attractive vaccine target but is undermined by limited immunogenicity. We describe a dimeric form of MERS-CoV RBD that overcomes this limitation.

Jasmonate Signaling Enhances RNA Silencing and Antiviral Defense in Rice.

Small RNA-mediated RNA silencing is an important antiviral mechanism in higher plants. It has been shown that RNA silencing components can be upregulated by viral infection. However, the mechanisms underlying the upregulation remain largely unknown.

Progress on combat damage control resuscitation/surgery and its application in the Chinese People's Liberation Army.

Damage control resuscitation (DCR) and damage control surgery (DCS) has now been developed as a well-established standard of care for severely injured civilian patients worldwide. On the other hand, the application of combat DCR/DCS has saved the lives of thousands of severely injured casualties in several wars during the last two decades. This article describes the great progress on DCR/DCS in the last two decades and its application in the Chinese People's Liberation Army (PLA).

Regulation of Atrial Fibrosis by the Bone.

MR (mineralocorticoid receptor) antagonists have been demonstrated to provide beneficial effects on preventing atrial fibrosis. However, the underlying cellular and molecular mechanisms remain unclear. We aim to determine the role of osteoblast MR in atrial fibrosis and to explore the underlying mechanism.

Regenerative Potential of Neonatal Porcine Hearts.

Background: Rodent hearts can regenerate myocardium lost to apical resection or myocardial infarction for up to 7 days after birth, but whether a similar window for myocardial regeneration also exists in large mammals is unknown.

Methods: Acute myocardial infarction (AMI) was surgically induced in neonatal pigs on postnatal days 1, 2, 3, 7, and 14 (ie, the P1, P2, P3, P7, and P14 groups, respectively). Cardiac systolic function was evaluated before AMI and at 30 days post-AMI via transthoracic echocardiography.

Hierarchically Aligning 10 Legume Genomes Establishes a Family-Level Genomics Platform.

Mainly due to their economic importance, genomes of 10 legumes, including soybean (), wild peanut ( and ), and barrel medic (), have been sequenced. However, a family-level comparative genomics analysis has been unavailable. With grape () and selected legume genomes as outgroups, we managed to perform a hierarchical and event-related alignment of these genomes and deconvoluted layers of homologous regions produced by ancestral polyploidizations or speciations.