SARS-CoV-2 is the cause of the ongoing Coronavirus Disease 2019 (COVID-19) pandemic. Understanding of the RNA virus and its interactions with host proteins could improve therapeutic interventions for COVID-19. Using icSHAPE, we determined the structural landscape of SARS-CoV-2 RNA in infected human cells and from refolded RNAs, as well as of the regulatory untranslated regions of SARS-CoV-2 and six other coronaviruses. We validated several structural elements predicted in silico and discovered structural features that affect the translation and abundance of subgenomic viral RNAs in cells. The structural data informed a deep learning tool to predict 42 host proteins that bind to SARS-CoV-2 RNA. Strikingly, antisense oligonucleotides targeting the structural elements and FDA-approved drugs inhibiting the SARS-CoV-2 RNA binding proteins dramatically reduced SARS-CoV-2 infection in cells derived from human liver and lung tumors. Our findings thus shed light on coronavirus and reveal multiple candidate therapeutics for COVID-19 treatment.

The gut microbiota has been implicated in glucose intolerance and its progression towards type-2 diabetes mellitus (T2DM). Relevant randomized clinical trial with prebiotic intervention was inadequate. We sought to evaluate the impact of fructooligosaccharides (FOS) and galactooligosaccharides (GOS) on glycemia during oral glucose tolerance test (OGTT) and intestinal microbiota. A randomized double-blind cross-over study was performed with 35 adults treated with FOS and GOS for 14 days (16 g/day). Faeces sampling, OGTT and anthropometric parameters were performed. Short-term intake of high-dose prebiotics had adverse effect on glucose metabolism, as in FOS intervention demonstrated by OGTT (P < 0.001), and in GOS intervention demonstrated by fasting glucose (P < 0.05). A significant increase in the relative abundance of Bifidobacterium was observed both in FOS and GOS group, while the butyrate-producing bacteria like Phascolarctobacterium in FOS group and Ruminococcus in GOS group were decreased. A random forest model using the initial microbiota was developed to predict OGTT levels after prebiotic intervention with relative success (R = 0.726). Our study alerted even though FOS and GOS increased Bifidobacterium, they might have adverse effect on glucose metabolism by reducing butyrate-producing microbes. Individualized prebiotics intervention based on gut microbiome needs to be evaluated in future.

Nasopharyngeal carcinoma (NPC) is a rare malignancy worldwide, but it is endemic in a few areas including Southern China, Southeast Asia, North Africa and the Arctic. The underlying mechanisms behind this remarkable geographic distribution remain unclear. Although Epstein-Barr virus (EBV) infection has been suggested as a necessary cause of undifferentiated NPC, EBV itself is not sufficient to cause this malignancy. Other co-factors, such as environmental risk factors, and/or genetic susceptibility, may interact with EBV to play a role in the carcinogenesis of NPC. Survival rates differ significantly between NPC patients in early stages and late stages. Due to the close associations between EBV infection and NPC risk, EBV-related biomarkers have been used for early detection and screening for NPC in a few high-incidence areas. In the present review article the latest updates are discussed.

Lactobacilli are recognized as probiotics on account of their health-promoting effects in the host. The aim of this review is to summarize current knowledge of the mechanisms of the adaption factors and main functions of lactobacilli that exert health-promoting effects in the host and to discuss important applications in animal and human health. The adaption mechanisms of lactobacilli facilitate interactions with the host and directly contribute to the beneficial nutritional, physiological, microbiological, and immunological effects in the host. Besides, the application of probiotic lactobacilli will increase our understanding of practical uses based on the roles of these organisms in immunoregulation, antipathogenic activities, and enhancement of the epithelial barrier.

In contrast to the extensive research about viral protein–host protein interactions that has revealed major insights about how RNA viruses engage with host cells during infection, few studies have examined interactions between host factors and viral RNAs (vRNAs). Here, we profiled vRNA–host protein interactomes for three RNA virus pathogens (SARS-CoV-2, Zika, and Ebola viruses) using ChIRP-MS. Comparative interactome analyses discovered both common and virus-specific host responses and vRNA-associated proteins that variously promote or restrict viral infection. In particular, SARS-CoV-2 binds and hijacks the host factor IGF2BP1 to stabilize vRNA and augment viral translation. Our interactome-informed drug repurposing efforts identified several FDA-approved drugs (e.g., Cepharanthine) as broad-spectrum antivirals in cells and hACE2 transgenic mice. A co-treatment comprising Cepharanthine and Trifluoperazine was highly potent against the newly emerged SARS-CoV-2 B.1.351 variant. Thus, our study illustrates the scientific and medical discovery utility of adopting a comparative vRNA–host protein interactome perspective.

In this study, we investigated the microbiota dynamics during two industrial-scale traditional solid-state fermentation (SSF) processes of Daqu starters. Similar evolution profiles of environmental parameters, enzymatic activities, microbial amounts, and communities were observed during the medium temperature SSF (MTSSF) and low temperature SSF (LTSSF) processes. Orders of Rickettsiales and Streptophyta only dominated the initial 2 days, and Eurotiales only predominated from days 10 to 24, however, phylotypes of Enterobacteriales, Lactobacillales, Bacillales, Saccharomycetales, and Mucorales both prevailed throughout the MTSSF and LTSSF processes. Nevertheless, the pH in MTSSF process on day 5 were 5.28, while in LTSSF process (4.87) significantly lower (P < 0.05). The glucoamylase activities in MTSSF process dropped from 902.71 to 394.33 mg glucose g-1 h-1 on days 5 to 24, while significantly lower (P < 0.05) in LTSSF process and decreased from 512.25 to 268.69 mg glucose g-1 h-1. The relative abundance of Enterobacteriales and Lactobacillales in MTSSF process constituted from 10.30 to 71.73% and 2.34 to 16.68%, while in LTSSF process ranged from 3.16 to 41.06% and 8.43 to 57.39%, respectively. The relative abundance of Eurotiales in MTSSF process on days 10 to 24 decreased from 36.10 to 28.63%, while obviously higher in LTSSF process and increased from 52.00 to 72.97%. Furthermore, lower bacterial richness but higher fungal richness were displayed, markedly differences in bacterial communities but highly similarities in fungal communities were exhibited, during MTSSF process comparatively to the LTSSF process. Canonical correspondence analysis revealed microbial structure transition happened at thermophilic stages under environmental stress of moisture, pH, acidity, and pile temperature. These profound understanding might help to effectively control the traditional Daqu SSF process by adjusting relevant environmental parameters.

Integrins are an important family of adhesion molecules that were first discovered two decades ago. Integrins are transmembrane heterodimeric glycoprotein receptors consisting of α and β subunits, and are comprised of an extracellular domain, a transmembrane domain, and a cytoplasmic tail. Therein, integrin cytoplasmic domains may associate directly with numerous cytoskeletal proteins and intracellular signaling molecules, which are crucial for modulating fundamental cell processes and functions including cell adhesion, proliferation, migration, and survival. The purpose of this review is to describe the unique structure of each integrin subunit, primary cytoplasmic association proteins, and transduction signaling pathway of integrins, with an emphasis on their biological functions.

In this study, we sought to investigate the role of soybean agglutinin (SBA) in mediating membrane permeability and the mechanical barrier function of intestinal epithelial cells. The IPEC-J2 cells were cultured and treated with 0, 0.5, 1.0, 1.5, 2.0, 2.5, or 3.0 mg/mL SBA. Transepithelial electrical resistance (TEER) and alkaline phosphatase (AP) activity were measured to evaluate membrane permeability. The results showed a significant decrease in TEER values (p < 0.05) in a time- and dose-dependent manner, and a pronounced increase in AP activity (p < 0.05). Cell growth and cell morphology were used to evaluate the cell viability. A significant cell growth inhibition (p < 0.05) and alteration of morphology were observed when the concentration of SBA was increased. The results of western blotting showed that the expression levels of occludin and claudin-3 were decreased by 31% and 64% compared to those of the control, respectively (p < 0.05). In addition, immunofluorescence labeling indicated an obvious decrease in staining of these targets and changes in their localizations. In conclusion, SBA increased the membrane permeability, inhibited the cell viability and reduced the levels of tight junction proteins (occludin and claudin-3), leading to a decrease in mechanical barrier function in intestinal epithelial cells.