TRIM21 Promotes Rabies Virus Production by Degrading IRF7 through Ubiquitination.

Rabies, a highly fatal zoonotic disease, is a significant global public health threat. Currently, the pathogenic mechanism of rabies has not been fully elucidated, and no effective treatment for rabies is available. Increasing evidence shows that the tripartite-motif protein (TRIM) family of proteins participates in the host's regulation of viral replication. Studies have demonstrated the upregulated expression of tripartite-motif protein 21 (TRIM21) in the brain tissue of mice infected with the rabies virus. Related studies have shown that TRIM21 knockdown inhibits RABV replication, while overexpression of TRIM21 exerted the opposite effect. Knockdown of interferon-alpha and interferon-beta modulates the inhibition of RABV replication caused by TRIM21 knockdown and promotes the replication of the virus. Furthermore, our previous study revealed that TRIM21 regulates the secretion of type I interferon during RABV infection by targeting interferon regulatory factor 7 (IRF7). IRF7 knockdown reduced the inhibition of RABV replication caused by the knockdown of TRIM21 and promoted viral replication. TRIM21 regulates RABV replication via the IRF7-IFN axis. Our study identified TRIM21 as a novel host factor required by RABV for replication. Thus, TRIM21 is a potential target for rabies treatment or management.

Self-adhesive PMIA membranes with chitosan porous beads immobilized pullulanase for efficient biological aging of beer.

A novel pulluanase@chitosan porous beads/Poly (m-phthaloyl-m-phenylenediamine) (PULL@CPB/PMIA) membrane with good separation and biocatalysis properties was prepared by a self-adhesive method by introducing an immobilized enzyme (PULL@CPB) onto the PMIA membrane. The combination of PULL@CPB and PMIA could increase the one-step refining of protoplasmic beer as well as the ability of biocatalysis to lower the alcohol-to-ester ratio. The experimental results showed that the addition of PULL@CPB and the increase in the ratio of EtOH/water in the coagulation bath both increased the load of pullulanase on the membrane surface, while excessive addition decreased the activity of pullulanase. Under the amount of PULL@CPB is 0.5 g·L-1 and the ratio of EtOH/water is 60%, the relative activity of pullulanase in PULL@CPB modified PMIA membrane was the highest, which was 91.7% of the initial activity. The interception rates of protein and macromolecular ß-glucan were 92.2% and 87.3%, respectively, under the condition of beer flux (162.3 L·m-2·h-1). At the same time, the PULL@CPB/PMIA membrane has strong antibacterial performance and thus plays a role in extending the shelf life of beer. Compared with free pullulanase, the thermal stability, pH stability, organic solvent stability, and storing stability of immobilized pullulanase were significantly improved. The effects of PULL@CPB dosage and operating temperature on biocatalysis efficiency were discussed. The immobilized pullulanase activity on the membrane remained at 70.8% after 10 continuous uses. Therefore, the PMIA membrane is an excellent carrier of pullulanase, so its bioactive membrane has a wide range of prospects in food, medicine, and other fields.

Study on the mechanism of Yupingfeng powder in the treatment of immunosuppression based on UPLC⁃QTOF⁃MS, network pharmacology and molecular biology verification.

AIMS: The current study aims to investigate the effect of Yupingfeng (YPF) powder on immunosuppression, and explore the possible mechanisms. MAIN METHODS: Firstly, the monomer components of YPF powder were analyzed by UPLC-QTOF-MS combined with UNIFI automatic analysis platform, then the mechanism of YPF on immunosuppressive treatment was investigated using network pharmacological method, and finally the prediction was verified in a Candida albicans (Can)-induced immunosuppressive BALB/c mouse model. KEY FINDINGS: 98 monomer compounds in YPF were obtained. Through virtual analysis and screening on the oral utilization and drug likeness properties of the components, 47 effective components were got. 9 core targets obtained were enriched in IL-17 signaling pathway. In the mouse model, YPF could reduce the number of Can and alleviate Can-induced inflammation in the kidney effectively, upregulate Can-induced low proportion of CD4+/CD8+ of splenic lymphocytes, and increase Can-induced low activity of IL-17 pathway. SIGNIFICANCE: These results demonstrate that YPF could improve the immunity of Can-induced immunosuppression in BALB/c mice through upregulating the activity of IL-17 pathway.

Designing of a novel polyvinylidene fluoride/TiO2/UiO-66-NH2 membrane with photocatalytic antifouling properties using modified zirconium-based metal-organic framework.

Novel polyvinylidene fluoride/TiO2/UiO-66-NH2 (PVDF/TiUN) membranes were produced by the delay phase separation method via introducing the TiO2/UiO-66-NH2 (TiUN) nanocomposite into PVDF casting solution. Interconnection of TiO2 and UiO-66-NH2 improved photocatalysis capacity and endowed PVDF/TiUN membranes with self-cleaning capability. Quantitative measurements showed that, firstly, PVDF/TiUN membranes exhibited improved photodegradation kinetics and efficiency (up to 88.1%) to Rhodamine B (RhB). Secondly, the performances of bovine serum albumin (BSA) rejection and permeation of PVDF/TiUN membranes outperformed those of other check samples, indicating enhanced hydrophilicity. Thirdly, rejection rate of BSA reached a breathtaking 98.14% and flux recovery ratio (FRR) of BSA reached a breathtaking 95.37%. Thus, given their excellent anti-contamination property and separation performance, the PVDF/TiUN membrane is very likely to be a novel water treatment membrane.

Jiaolong capsule protects SD rats against 2,4,6-trinitrobenzene sulfonic acid induced colitis.

ETHNOPHARMACOLOGICAL RELEVANCE: Jiaolong capsule (JLC) was approved for the therapy of gastrointestinal diseases by the State Food and Drug Administration (SFDA) of China. It has a satisfactory curative effect in the treatment of patients with inflammatory bowel disease, however, the mechanism remains to be elucidated. AIM OF THE STUDY: In current study, the effects and possible mechanisms of JLC on 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis were investigated. MATERIALS AND METHODS: Sulfasalazine and JLC were administrated orally and initialized 6 h after TNBS enema, once a day for seven consecutive days. The effect of JLC on intestinal microbial populations and LPS/TLR-4/NF-κB pathway was observed and assessed. Thirty female SD rats were distributed into six groups randomly and equally, namely, control, TNBS, TNBS + sulfasalazine (625 mg/kg), and TNBS + three different doses of JLC (25, 50, and 100 mg/kg) groups. RESULTS: The effect of JLC on restoring normal structures of colorectum and repairing colonic damage were superior to that of sulfasalazine. JLC showed a positive effect in re-balancing intestinal bacteria population of colitis, and suppressed the activation of LPS/TLR-4/NF-κB pathway. CONCLUSION: The results suggest that JLC demonstrated a beneficial effect on treating colitis in a rat model. The possible mechanisms may be through the regulatory effect of intestinal commensal bacteria and down-regulation of LPS/TLR-4/NF-κB pathway.

GanMeijian ameliorates lipid accumulation and oxidative damage in alcoholic fatty liver disease in Wistar rats.

Alcoholic fatty liver disease (AFLD), a major public health problem, has drawn clinical and scientific attention. The study aims to investigate the effect of Ganmeijian [crude extract of malt root, phosphoesterase complex (Pho)] on AFLD, and explore the possible mechanisms. An AFLD rat model was made. 30 and 60 mg/kg Pho were administrated through intestinal fistula for 5 weeks. Compared with those in model group, AST, LDL-C and TC in 30 mg/kg Pho group and TC in 60 mg/kg Pho group decreased. The mRNA level of Fas, Gpat1 and Srebp-1c in Pho groups was significantly reduced. The level of GSH-Px was increased, mitochondrial activity was improved, and the level of MDA and ROS was reduced in Pho groups. Pho shows a beneficial effect on AFLD. The mechanisms are possibly related to Pho inhibiting the expression of fat synthesis genes, protecting the function and increasing the activity of mitochondria in hepatocytes, then reducing the accumulation of ROS and the level of oxidative stress in the liver.

Novel ß-CD@ZIF-8 Nanoparticles-Doped Poly(m-phenylene isophthalamide) (PMIA) Thin-Film Nanocomposite (TFN) Membrane for Organic Solvent Nanofiltration (OSN).

Organic solvent nanofiltration (OSN) membranes are always troubled by the "trade-off" effect between solvent flux and solute rejection. Hence, a rapid, convenient, and effective way to synthesize novel ß-cyclodextrin-enhanced zeolite imidazole framework-8 (ß-CD@ZIF-8) nanoparticles was first proposed and the nanoparticles were doped into both selective layer and poly(m-phenylene isophthalamide) support for fabricating thin-film nanocomposite membranes. Transmission/scanning electron microscopy images and X-ray photoelectron spectroscopy results demonstrate the successful synthesis of ß-CD@ZIF-8. Atomic force microscopy images illustrate the more rougher surface compared to the pristine membrane, while the pure acetone flux reached 62.3 ± 2.3 L m-2 h-1, and Rose Bengal rejection achieved 96.6 ± 1.8 and 94.5 ± 0.5% in methanol (MeOH) and tetrahydrofuran at 0.6 MPa, respectively, when the dosage was 0.05% (w/v). The molecular weight cutoff around 574 Da of PPA2505 containing ß-CD@ZIF-8 in both support and selective layers shows the optimum properties and outstanding OSN performances in erythromycin concentration and purification in MeOH and butyl acetate. Additionally, polyimide nanofiber and the formed net structure may offer a potential way to fabricate "ultrathin" film in the OSN industry.

IL-23, rather than IL-17, is crucial for the development of ovalbumin-induced allergic rhinitis.

Interleukin-23 (IL-23) and IL-17 are involved in the pathogenesis of allergic rhinitis (AR). However, the roles of IL-23 and IL-17 in ovalbumin (OVA)-induced AR remain unclear. Therefore in this study we aim to investigate the precise roles of IL-23 and IL-17 in a mouse model of OVA-induced AR. We found that during OVA-induced AR, eosinophil and goblet cells in the nose were significantly decreased in IL-23-deficient, but not in IL-17-deficient mice. However, there was no difference in the serum IgE and IgG1 levels between IL-23-deficient or IL-17-deficient and wild-type mice. Moreover, IL-4 levels in lymph node cell culture supernatants were significantly decreased in IL-23-deficient, but not IL-17-deficient, compared with wild-type mice. Furthermore, OVA-induced AR developed similarly in wild-type mice transferred with either IL-23-deficient BM cells or wild-type BM cells. These findings suggest that IL-23, but not IL-17 is crucial for the development of OVA-induced AR, and IL-23 neutralization may be a potential approach for treatment of OVA-induced AR in humans.

Quantitative study of the dynamic tumor-endothelial cell interactions through an integrated microfluidic coculture system.

The interaction between tumor and endothelial cells is crucial to cancer metastasis and angiogenesis. We developed a novel microfluidic device to assess the cell-cell interaction quantitatively at the single cell resolution. This integrated chip offers 16 coculture experiments in parallel with controllable microenvironments to study interactions between cells dynamically. We applied this approach to model the tumor invasion using Hela cells and human umbilical vein endothelial cells (HUVECs) and monitored the migration of both. We observed the retreatment of HUVECs upon the approach of Hela cells during coculture, indicating that the interaction between two cells was mediated by soluble factors. This interaction was further analyzed through quantitatively processing the phase-contrast microscopic time-lapse images of each individual coculture chamber. We also confirmed this paracrine effect by varying the frequency of medium change. This microfluidic technique is highly controllable, contamination free, fully automatic, and inexpensive. This approach not only offers a unique way to quantitatively study the interaction between cells but also provides accurate spatial-temporal tunability of microenvironments for cell coculture. We believe this method, intrinsically high-throughput and quantitative, will greatly facilitate the study of cell-cell interactions and communications.

Sustainable membrane operation design for the treatment of the synthetic coke wastewater in SMBR.

Membrane fouling in the membrane bioreactor (MBR) is typically caused by the interaction of microbial characteristics, hydrodynamic behavior, operation environment, wastewater characteristics and membrane properties, which result in the deterioration of performance and increasing energy consumption and cost of membrane replacement. The effect of the crucial MBR parameters (the microbial loading and characteristics, dissolved oxygen (DO), hydraulic retention time (HRT), backwashing conditions and membrane characteristics) on membrane fouling was investigated in a submerged membrane bioreactor (SMBR) during the long term treatment of synthetic coke wastewater. Also the optimum operation strategies were further utilized in order to satisfy the minimal membrane fouling operation through a long-term evaluation of the MBR performance. It has been demonstrated that with application of these optimal designed conditions, significant membrane fouling improvements were achieved over a long operating time, so it was possible to perform in sustainable operation for MBR. In this study, the upper limit of the sustainable flux is found to be as much as 18.6 L/m(2) h and the optimum sustainable flux value should be 50 approximately 75% of critical flux to satisfy the desired sustainable operation period.