Single-Atom 3d Transition Metals on SnO2 as Model Cell for Conversion Mechanism: Revealing Thermodynamic Catalytic Effects on Enhanced Na Storage of Heterostructures.

Since the discovery in 2000, conversion-type materials have emerged as a promising negative-electrode candidate for next-generation batteries with high capacity and tunable voltage, limited by low reversibility and severe voltage hysteresis. Heterogeneous construction stands out as a cost-effective and efficient approach to reducing reaction barriers and enhancing energy density. However, the second term introduced by conventional heterostructure inevitably complicates the electrochemical analysis and poses great challenges to harvesting systematic insights and theoretical guidance. A model cell is designed and established herein for the conversion reactions between Na and TMSA-SnO2, where TMSA-SnO2 represents single atom modification of eight different 3d transition elements (V, Cr, Mn, Fe, Co, Ni, Cu or Zn). Such a model unit fundamentally eliminates the interference from the second phase and thus enables independent exploration of activation manifestations of the heterogeneous architecture. For the first time, a thermodynamically dependent catalytic effect is proposed and verified through statistical data analysis. The mechanism behind the unveiled catalytic effect is further elucidated by which the active d orbitals of transition metals weaken the surface covalent bonds and lower the reaction barriers. This research provides both theoretical insights and practical demonstrations of the advanced heterogeneous electrodes.

Broad antiviral and anti-inflammatory activity of Qingwenjiere mixture against SARS-CoV-2 and other human coronavirus infections.

BACKGROUND: Qingwenjiere Mixture (QJM) is a traditional Chinese medicine (TCM) that has been shown to have remarkable clinical efficacy against COVID-19. However, little is known about the antiviral and anti-inflammatory activities of QJM against a wider range of human coronavirus (HCoV) strains. PURPOSE: The study aims to investigate the antiviral and anti-inflammatory activities of QJM, as well as the underlying mechanisms against HCoV infections. METHODS: The chemical compositions from QJM were analyzed by LC-MS. The inhibitory effect of QJM on infections of HCoV-OC43, HCoV-229E, HCoV-NL63, and SARS-CoV-2 was evaluated in HRT-18 cells, Huh7 cells, LLC-MK2 cells, and Vero-E6 cells, respectively, by using cytopathic effect (CPE) inhibition assay or RT-qPCR detection of viral n, s, or RdRp/Hel genes. The expression of pro-inflammatory cytokines induced by HCoV-OC43, HCoV-229E, and SARS-CoV-2, as well as the host ace2 gene was also determined by RT-qPCR assay. Furthermore, the expression of key molecules in the NF-κB/MAPKs signaling pathways was determined by western blot. RESULTS: In alcohol-extraction groups of QJM and reference decoction pieces, 53 similar ion peaks were identified, the majority of which were phenylpropanoids, iridoids, and flavonoids. In addition, QJM reduced CPE caused by HCoVs and the expression of viral n genes or N protein. Pretreatment with QJM also exerted inhibitory effect on viral n gene expression. QJM also inhibited the expression of RdRp/Hel and s genes of SARS-CoV-2, as well as the host ace2 gene. Besides, QJM markedly reduced virus-induced mRNA expression of a panel of pro-inflammatory cytokines, such as IL-6, CXCL-8/IL-8, CXCL-10/IP-10, CCL-5/RANTES, TNF-α, IFN-α, CCL-2/MCP-1, CXCL-9/MIG, and IL1-α. We further showed that QJM inhibited the phosphorylation of NF-κB p65, and JNK, ERK 1/2, and p38 MAPKs in HCoV-OC43-infected HRT-18 cells. CONCLUSIONS: QJM has broad antiviral and anti-inflammatory activity against both common and newly emerged HCoVs possibly by inhibiting the activation of key components in NF-κB/MAPKs signaling pathway. QJM also has a prevention effect against HCoV infections and inhibits the host receptor required for virus entry. These results indicate that QJM may have the therapeutic potential in the treatment of diseases caused by a broad range of HCoVs.

Recapitulating Zika Virus Infection in Vagina of Tree Shrew (Tupaia belangeri).

Sexual transmission of Zika Virus (ZIKV) elevates the risk of its dissemination in the female reproductive tract and causes a serious threat to the fetus. However, the available animal models are not appropriate to investigate sexual transmission, dynamics of ZIKV infection, replication, and shedding. The use of tree shrew as a small animal model of ZIKV vaginal infection was assessed in this study. A total of 23 sexually mature female tree shrews were infected with ZIKV GZ01 via the intravaginal route. There was no significant difference in change of body weight, and the temperature between ZIKV infected and control animals. Viral RNA loads were detected in blood, saliva, urine, and vaginal douching. ZIKV RNA was readily detected in vaginal lavage of 22 animals (95.65%, 22/23) at 1 dpi, and viral load ranged from 104.46 to 107.35 copies/ml, and the peak of viral load appeared at 1 dpi. The expression of key inflammatory genes, such as IL6, 8, CCL5, TNF-a, and CXCL9, was increased in the spleen of ZIKV infected animals. In the current study, female tree shrews have been successfully infected with ZIKV through the vaginal route for the first time. Interestingly, at first, ZIKV replicates at the local site of infection and then spreads throughout the host body to develop a robust systemic infection and mounted a protective immune response. This small animal model is not only valuable for exploring ZIKV sexual transmission and may also help to explain the cause of debilitating manifestations of the fetus in vivo.

Polymers via Reversible Addition-Fragmentation Chain Transfer Polymerization with High Thiol End-Group Fidelity for Effective Grafting-To Gold Nanoparticles.

End-group fidelity is the most important property for end-functional polymers. Compared to other controlled living polymerization methods, reversible addition-fragmentation chain transfer (RAFT) polymerization often yields polymers with a lower end-group fidelity, which greatly affects their applications. Herein, we report a staged-thermal-initiation RAFT polymerization for the synthesis of polymers with high thiol end-group fidelity and their high efficiencies for grafting to various gold nanoparticles (GNPs). We experimentally prove that the decrease of end-group fidelity with their molecular weight is caused by the gradual decomposition of the initiator rather than the degradation of chain-transfer agents. We show that the staged-thermal-initiation RAFT polymerization is more effective for synthesis of polymers with high thiol end-group fidelity. The grafting-to assays for various GNPs illustrate the positive correlation between the end-group fidelity of polymers and grafting-to efficiency. This work highlights the prospects for synthesis of high end-group fidelity polymers and their application in the preparation of nanoparticles-polymer hybrid materials.

Infectivity of Zika virus on primary cells support tree shrew as animal model.

Zika virus (ZIKV) is a mosquito-borne flavivirus that caused the public health emergency. Recently, we have proved a novel small animal tree shrew was susceptive to ZIKV infection and presented the most common rash symptoms as ZIKV patients. Here we further cultured the primary cells from different tissues of this animal to determine the tissue tropism of ZIKV infection in vitro. The results showed that the primary cells from tree shrew kidney, lung, liver, skin and aorta were permissive to ZIKV infection and could support viral replication by the detection of viral specific RNA intra- and extra-cells. In comparing, the skin fibroblast and vascular endothelial cells were highly permissive to ZIKV infection with high releasing of active virus particles in supernatants proved by its infectivity in established neonatal mouse model. The expressions of ZIKV envelop and nonstructural protein-1, and the effects and strong immune response of primary tree shrew cells were also detected followed by ZIKV infection. These findings provide powerful in vitro cell-level evidence to support tree shrew as animal model of ZIKV infection and may help to explain the rash manifestations in vivo.

miR­494­BAG­1 axis is involved in cinobufacini­induced cell proliferation and apoptosis in gastric cancer.

Cinobufacini is widely used in the treatment of advanced cancers. It has been previously reported that microRNA (miR)­494 was upregulated in cinobufacini­treated gastric cancer cells; however, the detailed role of miR­494 in the anti­tumor activity of cinobufacini is unclear. The present study aimed to clarify the function of miR­494 in cinobufacini­induced cell behavior changes. Cell viability and proliferation ability were investigated using a Cell Counting Kit­8 assay. Flow cytometry was performed to investigate the apoptosis rate of gastric cancer (GC) cells. The mRNA expression levels of microRNA (miR)­494 and BCL2 associated athanogene 1 (BAG­1) were investigated using reverse transcription­quantitative polymerase chain reaction, and the protein expression level of BAG­1 was investigated using western blot assays. The results demonstrated that treatment with cinobufacini suppressed proliferation and promoted apoptosis of gastric cancer cells. miR­494 acts as a tumor suppressor gene in gastric cancer. In cinobufacini­treated cells, miR­494 and BAG­1 exhibited opposing expression trends. Furthermore, knockdown of miR­494 in cinobufacini­treated cells upregulated the protein expression level of BAG­1, promoted cell proliferation and inhibited cell apoptosis. In addition, inhibition of BAG­1 using small interfering RNA in cinobufacini­treated cells partially abrogated the effects of miR­494 inhibitor on cell proliferation and apoptosis. Thus, these results suggest that cinobufacini suppresses GC cells proliferation and promotes apoptosis partially through the regulation of miR­494­BAG­1 axis, which may provide a novel insight into the functional mechanism of cinobufacini.

Overexpression of miR-15b-5p promotes gastric cancer metastasis by regulating PAQR3.

Gastric cancer (GC) is the fifth most common cancer in the world, with 952,000 new cases diagnosed in 2012. Tumor metastasis is the major cause of cancer recurrence and death. miR-15b-5p has been reported to be dysregulated in numerous types of cancers. However, the role of miR-15b-5p in GC metastasis remains unclear. An miRNA microarray was adopted to analyze the miRNA expression profile. By employing quantitative real-time polymerase chain reaction (qRT-PCR), miR-15b-5p expression levels were detected in GC cell lines, tissues and plasma samples. In addition, the effects of miR-15b-5p on cell proliferation, migration and invasion were studied by applying gain-of-function approaches. Moreover, the target of miR-15b-5p was assessed by dual-luciferase assay, and the mechanism underlying the regulation of GC metastasis by miR-15b-5p was assessed by rescue experiments. The results revealed that miR-15b-5p was upregulated in GC cell lines, tissues and plasma samples. A high plasma level of miR-15b-5p was correlated with distant tumor metastasis. In addition, overexpression of miR­15b-5p in GC cells promoted cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT). Moreover, progestin and adipoQ receptor family member 3 (PAQR3) was found to be a direct target of miR-15b-5p and re-expression of PAQR3 in miR-15b-5p-overexpressing GC cells partly attenuated the proliferation, migration and invasion. These findings revealed that miR-15b-5p promotes the metastasis of GC cells through PAQR3 and may represent a potential biomarker of GC.

Cinobufacin suppresses cell proliferation via miR-494 in BGC- 823 gastric cancer cells.

Cinobufacin is used clinically to treat patients with many solid malignant tumors. However, the mechanisms underlying action remain to be detailed. Our study focused on miRNAs involved in cinobufacin inhibition of GC cell proliferation. miRNA microarray analysis and real time PCR identified miR-494 as a significant cinobufacin- associated miRNA. In vivo, ectopic expression of miR-494 inhibited the proliferation and induced apoptosis of BGC-823 cells on CCK-8 and flow cytometry analysis. Further study verified BAG-1 (anti-apoptosis gene) to bea target of miR-494 by luciferase reporter assay and Western blotting. In summary, our study demonstrated that cinobufacin may inhibit the proliferation and promote the apoptosis of BGC-823 cells. Cinobufacin-associated miR-494 may indirectly be involved in cell proliferation and apoptosis by targeting BAG-1, pointing to use as a potential molecular target of cinobufacin in gastric cancer therapy.

Hsa-miR-181a-5p expression and effects on cell proliferation in gastric cancer.

PURPOSE: MicroRNAs (miRNAs) are small endogenous, non-coding, single-stranded RNAs (approximately 22 nt). Accumulating evidence has shown that aberrant miRNA expression is pronounced and correlated with gastric cancer genesis and progression. MATERIALS AND METHODS: Expression levels of miR-181a-5p in GC tissues and cell lines were assessed by qRT-PCR and tested for correlation with clinical features. In addition, effects of miR-181a-5p on GC cell growth were investigated. RESULTS: Our findings indicate that miR-181a-5p is upregulated in GC, in correlation with lymph node invasion, nerve invasion and vascular invasion (P<0.05). Enforced expression of miR-181a -5p promoted cell proliferation ability. CONCLUSIONS: This study suggested that increased miR-181a-5p is related to GC progression. MiR-181a-5p may represent a potential therapeutic target for GC.