Preparation and Lithium-Ion Separation Property of ZIF-8 Membrane with Excellent Flexibility.

Metal-organic framework (MOF) membranes exhibit immense potential for separation applications due to their regular pore channels and scalable pore sizes. However, structuring a flexible and high-quality MOF membrane remains a challenge due to its brittleness, which severely restricts its practical application. This paper presents a simple and effective method in which continuous, uniform, defect-free ZIF-8 film layers of tunable thickness are constructed on the surface of inert microporous polypropylene membranes (MPPM). To provide heterogeneous nucleation sites for ZIF-8 growth, an extensive amount of hydroxyl and amine groups were introduced on the MPPM surface using the dopamine-assisted co-deposition technique. Subsequently, ZIF-8 crystals were grown in-situ on the MPPM surface using the solvothermal method. The resultant ZIF-8/MPPM exhibited a lithium-ion permeation flux of 0.151 mol m-2 h-1 and a high selectivity of Li+/Na+ = 1.93, Li+/Mg2+ = 11.50. Notably, ZIF-8/MPPM has good flexibility, and the lithium-ion permeation flux and selectivity remain unchanged at a bending curvature of 348 m-1. These excellent mechanical characteristics are crucial for the practical applications of MOF membranes.

LncRNA MIAT regulates autophagy and apoptosis of macrophage infected by Mycobacterium tuberculosis through the miR-665/ULK1 signaling axis.

Accumulating lines of evidence have revealed the involvement of long non-coding RNAs (lncRNAs) in the control and elimination of invading Mycobacterium tuberculosis (Mtb) by macrophage. In this study, we sought to elucidate the role of MIAT on autophagy and apoptosis of Mtb-infected macrophage and to reveal the molecular mechanism. We observed that the expression of MIAT was heightened while miR-665 level was declined in THP-1 cells with Bacillus Calmette-Guerin (BCG) infection in a time-dependent manner. Functionally, disruption of MIAT effectively facilitated cell viability and restricted apoptosis ability concomitant with the downregulation of Bax and cleaved caspase-3 along with an accumulation of Bcl-2 in BCG-infected THP-1 cells. Concurrently, the interference of MIAT dramatically disinhibited macrophage autophagy as characterized by diminution of autophagy related markers LC3-II and Beclin-1 as well as increment of p62 in THP-1 cells following BCG infection. Concordantly, depletion of MIAT was found to noticeably aggrandize Mtb survival. Importantly, MIAT served as a ceRNA for sponging miR-665 and negatively regulated its expression. ULK1 was identified as an authentic target of miR-665 and modulated by MIAT. Mechanistically, the functional role of MIAT depletion in macrophage apoptosis and autophagy were tremendously abrogated by the depression of miR-665 and enrichment of ULK1. Overall, the preceding observations clearly illuminated that MIAT was elevated in human macrophage response to BCG infection, and functioned as a negative regulator in autophagy and antimicrobial effects by manipulating miR-665/ULK1 axis during Mtb infection, which may provide a promising target for developing an anti-bacterial against TB.

RNF31 mediated ubiquitination of A20 aggravates inflammation and hepatocyte apoptosis through the TLR4/MyD88/NF-κB signaling pathway.

Inflammatory cytokine storm is one of the main pathogenesis of acute liver injury, and accumulating evidence suggests that the E3 ubiquitin ligase ring finger protein 31 (RNF31) plays an important regulatory role in the activation of inflammatory pathways. We found that RNF31 expression was up-regulated in lipopolysaccharide (LPS)-treated HL-7702 cells. Western blotting results showed decreased expression of RNF31 and total ubiquitinated proteins after transfection of si-RNF31. The results of MTT assay indicated that cell viability was enhanced. Flow cytometry analysis showed that cell apoptosis and ROS content was decreased, and ELISA assay results exhibited that the inflammatory factors secretion was reduced. Interestingly, A20 protein expression was inhibited as RNF31 expression was upregulated. On this basis, we performed co-immunoprecipitation assays and found that RNF31 could interact with A20. Actinomycin tracing and proteasome inhibition experiments showed that RNF31 degrades A20 through the proteasome pathway. Furthermore, overexpression of A20 enhanced cell viability, reduced apoptosis, and inhibited ROS generation and inflammatory factor secretion. Mechanistic studies revealed that RNF31 was able to degrade A20, which affected the inflammatory response and hepatocyte apoptosis mediated by the toll like receptor 4 (TLR4)/myeloid differentiation factor88 (MyD88)/nuclear transcription factor-κB (NF-κB) signaling pathway. Moreover, knockdown of RNF31 attenuated the inflammatory response induced by d-Gal/LPS in mice with acute liver injury. In conclusion, RNF31 degrades A20 by ubiquitination and activates the TLR4/MyD88/NF-κB signaling pathway to aggravate acute liver injury.

Effects of post-exercise recovery methods on exercise-induced hormones and blood fatigue factors: a systematic review and meta-analysis.

BACKGROUND: High-intensity exercise consumes a large amount of energy and tends to induce post-exercise fatigue. Promoting physical and psychological recovery after exercise can enable individuals to perform better in subsequent training or competitions and reduce the risk of injury. This study aims to investigate the effects of post-exercise recovery methods on exercise-induced hormones and blood fatigue factors. METHODS: PubMed, Embase and Web of Science databases were queried to collect literature on the correlation between post-exercise recovery methods and the expression of exercise-induced hormones and blood fatigue factors. The search time ranged between inception to July 2020. Stata (version 15.0) was used for meta-analysis. RESULTS: A total of 10 studies were included, involving the data of 278 cases. Among these, 148 people were placed in the study group and assigned active post-exercise recovery measures while 130 people were placed in the control group and assigned no post-exercise recovery measures. The results of this meta-analysis showed that there was significant difference between the study group and the control group [relative risk (RR) =15.62, 95% confidence interval (CI): 3.25, 75.06, P<0.05]. The subgroup analysis on the effect of active and passive recovery on the blood lactate concentration (BLC) and creatine kinase (CK) concentration revealed that the CK concentration [standardized mean difference (SMD) =-0.76, 95% CI: -1.47, -0.04] and BLC (SMD =-1.16, 95% CI: -2.30, -0.02) were significantly lower in the study group compared with the control group. Further analysis on the effect of different post-exercise recovery methods on the BLC and CK concentrations indicated that BLC (SMD =-1.16, 95% CI: -2.30, -0.02) was significantly lower in the group with cold water immersion compared with the control group, while there was no significant difference in the changes of CK concentration. Additionally, food supplementation was shown to reduce CK concentration (SMD =-1.16, 95% CI: -4.69, 2.36). CONCLUSIONS: Recovery measures after high-intensity exercise can accelerate the reduction of BLC and the activity and concentration of CK, thus helping the body quickly return to a pre-exercise state.

Multiple inflammatory profiles of microglia and altered neuroimages in APP/PS1 transgenic AD mice.

Aß plaques of Alzheimer's disease (AD) are believed to precede cognitive deficits or clinical manifestation by decades. However, validated biomarkers for early diagnosis of the AD disease are still not available. In this present study, we combined MRI-based neuroimages and histological assessment of the glial response and altered cytokines, neurogenesis during the early course of Aß deposits in TgAPP/PS1 mice to find potential early biomarkers for AD. We found that microglia and astrocytes were initially activated and clustered around Aß plaques at the age of 6 months and significantly increased with age from 6-12 months of age. Confocal microscope analysis revealed that microglia not astrocytes began to phagocytose Aß in 6-month-old TgAPP/PS1 mice, evidenced by the intracellular Aß in Iba1 positive microglia not in GFAP positive astrocytes. In parallel with these observations, we found that mainly clustered microglia significantly upregulated the production of proinflammatory factors including TNF-α, iNOS and IL-1ß, and anti-inflammatory cytokines including IL-4, TGF-ß and extracellular protecting matrix YM-1 and enzyme arginase 1 (Arg1) at 6-12 months of age. Interestingly, reactive astrocyte did not express these cytokines and YM-1 and Arg1. These results may suggest that microglia rather than astrocytes play crucial roles in clearing Aß and neuroinflammation in early stage of AD. In addition, the number of neural stem cells labeled by BrdU and immature neurons labeled by doublecortin was significantly decreased in 3-month-old TgAPP/PS1 mice ahead of Aß deposits. Finally, DTI conforms that reduced fractional anisotropy (FA) in dentate gyrus of hippocampus and rs-MRI shows an increased connectivity in the networks of somatosensory cortex-caudoputamen and insula in TgAPP/PS1 mice at 6 months. These findings provide a clue to early biomarkers for diagnosis of the AD disease.

TRIM22 regulates macrophage autophagy and enhances Mycobacterium tuberculosis clearance by targeting the nuclear factor-multiplicity κB/beclin 1 pathway.

Autophagy is a crucial host-defense mechanism against Mycobacterium tuberculosis (Mtb) infection by spanning innate and adaptive immune functions. TRIM22 is a member of tripartite motif family protein which involved in innate immunity and autophagy process. However, its role in the modulation of bacterial infection has not been investigated. Here, we demonstrated that TRIM22 is upregulated in a dose-dependent and time-dependent manner during Mtb infection of THP-1 cells. Downregulation of TRIM22 significantly decreased light chain 3 (LC3)-II protein level and the formation of LC3 puncta, while it markedly increased SQSTM1, a marker of autophagic degradation, in Mtb-infected THP-1 cells. What is more, enhanced bacterial survival was observed in TRIM22 knockdown THP-1 cells, while rapamycin abrogated this effect. In the presence of vector containing TRIM22 in THP-1 cells prior to infection, the survival of Mtb was decreased, while BafA restored this effect. Further study demonstrated that TRIM22 expression was regulated by MicroRNA-20b, and that TRIM22 regulates Mtb-infected THP-1 autophagy via the nuclear factor-κB/beclin 1 pathway. Using a nuclear factor-κB inhibitor BAY 11-7082, we found that TRIM22-induced high expression of LC3-II and the formation of LC3 was substantially attenuated, while the TRIM22-induced low expression of SQSTM1 was markedly increased in BAY 11-7082-treatment cells. In addition, the bacterial survival reduced by TRIM22 was significantly reversed by BAY 11-7082. Overall, these results suggest that TRIM22-augmented autophagy prevents intracellular Mtb to evade autophagic clearance, thereby inhibiting the persistence of Mtb infections.

MicroRNA-190b regulates lipid metabolism and insulin sensitivity by targeting IGF-1 and ADAMTS9 in non-alcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is characterized by ectopic lipid accumulation and insulin resistance, yet the underlying molecular mechanisms are poorly understood. MiR-190b is thought to play a role in hepatocellular carcinoma by modulating insulin resistance; however, its role in NAFLD remains unknown. Here, we found that miR-190b expression was significantly increased in the liver tissues of patients with NAFLD, compared to normal tissues. Moreover, miR-190b was upregulated in a high-fat diet NAFLD mouse model and a free fatty acid-induced NAFLD cellular model. Knockdown of miR-190b decreased aspartate transaminase (AST), alanine transaminase (ALT), triglyceride (TG), and total cholesterol (TC). It also reduced expression of the lipogenic genes fatty acid synthase (FAS) and 3-hydroxy-3-methylglutarylCoA reductase (HMGCR), alleviated hepatic steatosis, improved glucose tolerance, elevated insulin sensitivity, and activated insulin receptor substrate (IRS)2/Akt signaling in vivo and/or in vitro. Furthermore, we confirmed that miR-190b directly targeted IGF-1 and ADAMTS9. MiR-190b overexpression suppressed expression of IGF-1 and ADAMTS9, which were increased by miR-190b inhibition. Expression of IGF-1 and ADAMTS9 was inversely correlated with miR-190b in liver tissues of patients with NAFLD, respectively. We also found that IGF-1 or ADAMTS9 inhibition partially reversed the effects of miR-190b on lipid metabolism and insulin signaling in vitro. Taken together, the data reveal that miR-190b inhibition suppressed lipid accumulation and improved insulin sensitivity by targeting IGF-1 and ADAMTS9, suggesting that miR-190b inhibition may be a therapeutic strategy against NAFLD.

[Construction of miR-508-5P lentiviral vector and its targeted effect on S-phase kinase-associated protein-2 gene].

OBJECTIVE: To construct a lentiviral vector overexpressing miR-508-5p and verify its targeted regulating effect on S-phase kinase-associated protein-2 (SKP2) gene. METHODS: The stem-loop structure RNA of miR-508-5p was obtained by chemical synthesis and cloned into the linearized pSicoR plasmid. The positive recombinants, which had been identified by restriction enzyme digestion and DNA sequencing method, were transfected into HEK293T cells. Meanwhile, the potential target gene of SKP2-3'UTR, which was complementary with miR-508-5p, was obtained and cloned into the linearized pMIR-Report plasmid. The targeted effect of miR-508-5p on SKP2 gene was verified by the relative luciferase activity measurement, Western blotting and real-time PCR. RESULTS: The PCR, restriction enzyme digestion and DNA sequencing analysis demonstrated that the recombinant plasmids of pSicoR-miR-508-5p and pMIR-Report-SKP2 3'-UTR were constructed successfully. And it was showed that over-expression of miR-508-5p suppressed the mRNA and protein expression level of SKP2 significantly (P<0.05); and suppression of miR-508-5p expression increased the mRNA and protein expression level of SKP2 significantly (P<0.05). CONCLUSION: We have successfully constructed the lentiviral vector containing miR-508-5p gene. MiR-508-5p can suppress SKP2 gene expression by targeting the specific sequence of SKP2-3'UTR.