Period circadian clock 3 is crucial for regulation of IL-22-producing type 3 innate lymphoid cells by flavonoids from Shen Ling Bai Zhu San to alleviate colitis.

Type 3 Innate lymphoid cells (ILC3s) functions bear complex response during Inflammatory bowel diseases (IBD). Here, our study first analyzed the main pharmacological components in Shen Ling Bai Zhu San n-butanol extracts (S-Nb), and then explored whether S-Nb administrated immune response of ILC3s, and how it regulates ILC3s. Shen Ling Bai Zhu San (SLBZS) or S-Nb were administrated for 7 days to analyze the frequency of ILC3s and their produced cytokine.

LncRNA SNHG16 Inhibits Intracellular Growth Involving Cathelicidin Pathway, Autophagy, and Effector Cytokines Production.

Long noncoding small nucleolar RNA (LncRNA) host gene 16 (SNHG16) is associated with certain diseases, including cancers. However, its role and mechanism in () infection remain unclear. Here, we demonstrated that SNHG16 expression levels were suppressed in peripheral blood mononuclear cells (PBMCs) and CD14 monocytes of tuberculosis (TB) patients.

FMT and TCM to treat diarrhoeal irritable bowel syndrome with induced spleen deficiency syndrome- microbiomic and metabolomic insights.

Background: Diarrheal irritable bowel syndrome (IBS-D) is a functional bowel disease with diarrhea, and can be associated with common spleen deficiency syndrome of the prevelent traditional Chinese medicine (TCM) syndrome. Fecal microbiota transplantation (FMT) could help treating IBS-D, but may provide variable effects. Our study evaluated the efficacy of TCM- shenling Baizhu decoction and FMT in treating IBS-D with spleen deficiency syndrome, with significant implications on gut microbiome and serum metabolites.

Membrane Associated RNA-Containing Vesicles Regulate Cortical Astrocytic Microdomain Calcium Transients in Awake Ischemic Stroke Mice.

Astrocytic processes minutely regulate neuronal activity via tripartite synaptic structures. The precision-tuning of the function of astrocytic processes is garnering increasing attention because of its significance in promoting brain repair following ischemic stroke. Microdomain calcium (Ca) transients in astrocytic processes are pivotal for the functional regulation of these processes.

CD137 expression and signal function drive pleiotropic γδ T-cell effector functions that inhibit intracellular M. tuberculosis growth.

Co-activation signal that induces/sustains pleiotropic effector functions of antigen-specific γδ T cells remains unknown. Here, Mycobacteria tuberculosis (Mtb) tuberculin administration during tuberculosis (TB) skin test resulted in rapid expression of co-activation signal molecules CD137 and CD107a by fast-acting Vγ2Vδ2 T cells in TB-resistant subjects (Resisters), but not patients with active TB. And, anti-CD137 agonistic antibody treatment experiments showed that CD137 signaling enabled Vγ2Vδ2 T cells to produce more effector cytokines and inhibit intracellular Mtb growth in macrophages (Mɸ).

Macrophage targeted iron oxide nanodecoys augment innate immunological and drug killings for more effective Mycobacterium Tuberculosis clearance.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb) infection, is still one of the top killers worldwide among infectious diseases. The escape of Mtb from immunological clearance and the low targeting effects of anti-TB drugs remain the substantial challenges for TB control. Iron is particularly required for Mtb growth but also toxic for Mtb in high dosages, which makes iron an ideal toxic decoy for the 'iron-tropic' Mtb.

Evaluation of RNAi therapeutics VIR-2218 and ALN-HBV for chronic hepatitis B: Results from randomized clinical trials.

Background & Aims: Current therapy for chronic hepatitis B virus (cHBV) infection involves lifelong treatment. New treatments that enable HBV functional cure would represent a clinically meaningful advance. ALN-HBV and VIR-2218 are investigational RNA interference therapeutics that target all major HBV transcripts.

Gut Microbiota and Bile Acids Mediate the Clinical Benefits of YH1 in Male Patients with Type 2 Diabetes Mellitus: A Pilot Observational Study.

Our previous clinical trial showed that a novel concentrated herbal extract formula, YH1 ( and Shen-Ling-Bai-Zhu-San), improved blood glucose and lipid control. This pilot observational study investigated whether YH1 affects microbiota, plasma, and fecal bile acid (BA) compositions in ten untreated male patients with type 2 diabetes (T2D), hyperlipidemia, and a body mass index ≥ 23 kg/m. Stool and plasma samples were collected for microbiome, BA, and biochemical analyses before and after 4 weeks of YH1 therapy.

Adjunctive Zoledronate + IL-2 administrations enhance anti-tuberculosis Vγ2Vδ2 T-effector populations, and improve treatment outcome of multidrug-resistant tuberculosis.

Multidrug-resistant tuberculosis (MDR-TB) is a refractory disease with high mortality rate due to no or few choices of antibiotics. Adjunctive immunotherapy may help improve treatment outcome of MDR-TB. Our decade-long studies demonstrated that phosphoantigen-specific Vγ2Vδ2 T cells play protective roles in immunity against TB.

Discovery of Potential Therapeutic Drugs for COVID-19 Through Logistic Matrix Factorization With Kernel Diffusion.

Coronavirus disease 2019 (COVID-19) is rapidly spreading. Researchers around the world are dedicated to finding the treatment clues for COVID-19. Drug repositioning, as a rapid and cost-effective way for finding therapeutic options from available FDA-approved drugs, has been applied to drug discovery for COVID-19.

Nanocages engineered from Bacillus Calmette-Guerin facilitate protective Vγ2Vδ2 T cell immunity against Mycobacterium tuberculosis infection.

Tuberculosis (TB), induced by Mycobacterium tuberculosis (Mtb) infection, remains a top killer among infectious diseases. While Bacillus Calmette-Guerin (BCG) is the sole TB vaccine, the clumped-clustered features of BCG in intradermal immunization appear to limit both the BCG protection efficacy and the BCG vaccination safety. We hypothesize that engineering of clumped-clustered BCG into nanoscale particles would improve safety and also facilitate the antigen-presenting-cell (APC)'s uptake and the following processing/presentation for better anti-TB protective immunity.

MIR337-3p Enhances Mycobacterial Pathogenicity Involving TLR4/MYD88 and STAT3 Signals, Impairing VDR Antimicrobial Response and Fast-Acting Immunity.

Active form of vitamin D (VitD) enhances human innate immunity against () infection. Our previous studies showed that MIR337-3p was highly expressed in lymphocytes of tuberculosis (TB) patients. Here, we identified the mechanism of MIR337-3p in the regulation of fast-acting anti-TB immunity by inhibiting VitD-dependent antimicrobial response pathways.

VDA-RWLRLS: An anti-SARS-CoV-2 drug prioritizing framework combining an unbalanced bi-random walk and Laplacian regularized least squares.

Background: A new coronavirus disease named COVID-19, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is rapidly spreading worldwide. However, there is currently no effective drug to fight COVID-19.

Methods: In this study, we developed a Virus-Drug Association (VDA) identification framework (VDA-RWLRLS) combining unbalanced bi-Random Walk, Laplacian Regularized Least Squares, molecular docking, and molecular dynamics simulation to find clues for the treatment of COVID-19.

The Genetic Architecture of Depression in Individuals of East Asian Ancestry: A Genome-Wide Association Study.

Importance: Most previous genome-wide association studies (GWAS) of depression have used data from individuals of European descent. This limits the understanding of the underlying biology of depression and raises questions about the transferability of findings between populations.

Objective: To investigate the genetics of depression among individuals of East Asian and European descent living in different geographic locations, and with different outcome definitions for depression.

Genetics and Functional Mechanisms of STAT3 Polymorphisms in Human Tuberculosis.

Signal transducer and activator of transcription-3 (STAT3) plays an important role in biological balance. Our and others previous studies implied that STAT3 had a great effect on fast-acting innate immunity against tuberculosis (TB). We hypothesized that SNP down-regulation of STAT3 leads to a change in susceptibility to TB in humans.

Involvement of HECTD1 in LPS-induced astrocyte activation via σ-1R-JNK/p38-FOXJ2 axis.

Background: Astrocytes participate in innate inflammatory responses within the mammalian central nervous system (CNS). HECT domain E3 ubiquitin protein ligase 1 (HECTD1) functions during microglial activation, suggesting a connection with neuroinflammation. However, the potential role of HECTD1 in astrocytes remains largely unknown.

PARP14 inhibits microglial activation via LPAR5 to promote post-stroke functional recovery.

Stroke is a major public health problem leading to high rates of death and disability worldwide, but no effective pharmacological therapy is currently available except for the use of PLAT (plasminogen activator, tissue). Here we show that PARP14 (poly (ADP-ribose) polymerase family, member 14) level was significantly increased in the peri-infarct zone of photothrombotic stroke (PT) mice. Genetic knockdown and pharmacological inhibition of PARP14 aggravated functional impairment and increased infarct volume in PT mice, while overexpression of PARP14 displayed the opposite effects.

MIR155HG Knockdown Inhibited the Progression of Cervical Cancer by Binding SRSF1.

Background: As the fourth most common cancer among women worldwide, cervical cancer lead to 311,000 deaths in 2018. Although the treatments have been developed, the survival rate of cervical cancer remains unsatisfactory. In this study, we aimed to identify differentially expressed lncRNAs (DEIncRNAs) between cervical cancer and adjacent normal tissues using bioinformatics analysis, and further to investigate the biological function of the DEIncRNAs in vitro and in vivo.

Risk factors and incidence of suction loss during small incision lenticule extraction (SMILE) in 8493 eyes.

Background: To report the incidence and risk factors of suction loss during small incision lenticule extraction (SMILE).

Methods: This retrospective comparative case control study included 8493 eyes of 4261 patients. Patients underwent SMILE surgery between January 2014 and September 2019 were included.

Fast-acting γδ T-cell subpopulation and protective immunity against infections.

Unique Vγ2Vδ2 (Vγ9Vδ2) T cells existing only in human and non-human primates, account for the majority of circulating γδ T cells in human adults. Vγ2Vδ2 T cells are the sole γδ T-cell subpopulation capable of recognizing the microbial (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP) produced by selected pathogens during infections. Recent seminal studies in non-human primate models have demonstrated that the unique HMBPP-specific Vγ2Vδ2 T cells are fast-acting, multi-functional, and protective during infections.

BTLA-Expressing Dendritic Cells in Patients With Tuberculosis Exhibit Reduced Production of IL-12/IFN-α and Increased Production of IL-4 and TGF-β, Favoring Th2 and Foxp3 Treg Polarization.

Little is known about how tuberculosis (TB) impairs dendritic cell (DC) function and anti-TB immune responses. We previously showed that the B and T lymphocyte attenuator (BTLA), an immune inhibitory receptor, is involved in TB pathogenesis. Here, we examined whether BTLA expression in TB affects phenotypic and functional aspects of DCs.

Author Correction: Bis-biguanide dihydrochloride inhibits intracellular replication of M. tuberculosis and controls infection in mice.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.