Piwi‐interacting RNAs (piRNAs), a novel class of small non‐coding RNAs, were first discovered in germline cells and are thought to silence transposons in spermatogenesis. Recently, piRNAs have also ...been identified in somatic tissues, and aberrant expression of piRNAs in tumor tissues may be implicated in carcinogenesis. However, the function of piR‐823 in colorectal cancer (CRC) remains unclear. Here, we first found that piR‐823 was significantly upregulated in CRC tissues compared with its expression in the adjacent tissues. Inhibition of piR‐823 suppressed cell proliferation, arrested the cell cycle in the G1 phase and induced cell apoptosis in CRC cell lines HCT116 and DLD‐1, whereas overexpression of piR‐823 promoted cell proliferation in normal colonic epithelial cell line FHC. Interestingly, Inhibition of piR‐823 repressed the expression of heat shock protein (HSP) 27, 60, 70. Furthermore, elevated HSPs expression partially abolished the effect of piR‐823 on cell proliferation and apoptosis. In addition, we further demonstrated that piR‐823 increased the transcriptional activity of HSF1, the common transcription factor of HSPs, by binding to HSF1 and promoting its phosphorylation at Ser326. Our study reveals that piR‐823 plays a tumor‐promoting role by upregulating phosphorylation and transcriptional activity of HSF1 and suggests piR‐823 as a potential therapeutic target for CRC.
piR‐823 is up‐regulated in colorectal cancer tissues .piR‐823 promotes proliferation and inhibits apoptosis in colorectal cancer carcinogenesis.piR‐823 elevates the expression of HSP27, 60 and 70 by binding to HSF1 and enhancing its activity.
Background and Purpose
Arctigenin, a major bioactive component of Fructus arctii, has been reported to have antidepressant‐like effects. However, the mechanisms underlying these effects are still ...unclear. Neuroinflammation can be caused by excessive production of proinflammatory cytokines in microglia via high‐mobility group box 1 (HMGB1)/TLR4/NF‐κB and TNF‐α/TNFR1/NF‐κB signalling pathways, leading to depression. In this study, we have investigated the antidepressant mechanism of arctigenin by conducting in vitro and in vivo studies.
Experimental Approach
The effects of chronic unpredictable mild stress (CUMS) on wild‐type (WT) and TLR4−/− mice were examined. Antidepressant‐like effects of arctigenin were tested using the CUMS‐induced model of depression in WT mice. The effects of arctigenin were assessed on the HMGB1/TLR4/NF‐κB and TNF‐α/TNFR1/NF‐κB signalling pathways in the prefrontal cortex (PFC) of mouse brain and HMGB1‐ or TNF‐α‐stimulated primary cultured microglia. The interaction between HMGB1 and TLR4 or TNF‐α and TNFR1 with or without arctigenin was examined by localized surface plasmon resonance (LSPR) and co‐immunoprecipitation assays.
Key Results
The immobility times in the tail suspension test (TST) and forced swimming test (FST) were reduced in TLR4−/− mice, compared with WT mice. Arctigenin exhibited antidepressant‐like effects. Arctigenin also inhibited microglia activation and inflammatory responses in the PFC of mouse brain. Arctigenin inhibited HMGB1 and TLR4 or TNF‐α and TNFR1 interactions, and suppressed both HMGB1/TLR4/NF‐κB and TNF‐α/TNFR1/NF‐κB signalling pathways.
Conclusions and Implications
Arctigenin has antidepressant‐like effects by attenuating excessive microglial activation and neuroinflammation through the HMGB1/TLR4/NF‐κB and TNF‐α/TNFR1/NF‐κB signalling pathways. This suggests that arctigenin has potential as a new drug candidate suitable for clinical trials to treat depression.
Tigecycline is one of the last-resort antibiotics to treat complicated infections caused by both multidrug-resistant Gram-negative and Gram-positive bacteria
. Tigecycline resistance has sporadically ...occurred in recent years, primarily due to chromosome-encoding mechanisms, such as overexpression of efflux pumps and ribosome protection
. Here, we report the emergence of the plasmid-mediated mobile tigecycline resistance mechanism Tet(X4) in Escherichia coli isolates from China, which is capable of degrading all tetracyclines, including tigecycline and the US FDA newly approved eravacycline. The tet(X4)-harbouring IncQ1 plasmid is highly transferable, and can be successfully mobilized and stabilized in recipient clinical and laboratory strains of Enterobacteriaceae bacteria. It is noteworthy that tet(X4)-positive E. coli strains, including isolates co-harbouring mcr-1, have been widely detected in pigs, chickens, soil and dust samples in China. In vivo murine models demonstrated that the presence of Tet(X4) led to tigecycline treatment failure. Consequently, the emergence of plasmid-mediated Tet(X4) challenges the clinical efficacy of the entire family of tetracycline antibiotics. Importantly, our study raises concern that the plasmid-mediated tigecycline resistance may further spread into various ecological niches and into clinical high-risk pathogens. Collective efforts are in urgent need to preserve the potency of these essential antibiotics.
Anaplasma capra is an emerging tickborne human pathogen initially recognized in China in 2015; it has been reported in ticks and in a wide range of domestic and wild animals worldwide. We describe ...whole-genome sequences of 2 A. capra strains from metagenomic sequencing of purified erythrocytes from infected goats in China. The genome of A. capra was the smallest among members of the genus Anaplasma. The genomes of the 2 A. capra strains contained comparable G+C content and numbers of pseudogenes with intraerythrocytic Anaplasma species. The 2 A. capra strains had 54 unique genes. The prevalence of A. capra was high among goats in the 2 endemic areas. Phylogenetic analyses revealed that the A. capra strains detected in this study were basically classified into 2 subclusters with those previously detected in Asia. Our findings clarify details of the genomic characteristics of A. capra and shed light on its genetic diversity.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Haemaphysalis longicornis is drawing attentions for its geographic invasion, extending population, and emerging disease threat. However, there are still substantial gaps in our knowledge of viral ...composition in relation to genetic diversity of H. longicornis and ecological factors, which are important for us to understand interactions between virus and vector, as well as between vector and ecological elements.
We conducted the meta-transcriptomic sequencing of 136 pools of H. longicornis and identified 508 RNA viruses of 48 viral species, 22 of which have never been reported. Phylogenetic analysis of mitochondrion sequences divided the ticks into two genetic clades, each of which was geographically clustered and significantly associated with ecological factors, including altitude, precipitation, and normalized difference vegetation index. The two clades showed significant difference in virome diversity and shared about one fifth number of viral species that might have evolved to "generalists." Notably, Bandavirus dabieense, the pathogen of severe fever with thrombocytopenia syndrome was only detected in ticks of clade 1, and half number of clade 2-specific viruses were aquatic-animal-associated.
These findings highlight that the virome diversity is shaped by internal genetic evolution and external ecological landscape of H. longicornis and provide the new foundation for promoting the studies on virus-vector-ecology interaction and eventually for evaluating the risk of H. longicornis for transmitting the viruses to humans and animals. Video Abstract.
BRI1-EMS suppressor (BES)/brassinazole-resistant (BZR) family transcription factors are involved in a variety of physiological processes, but the biological functions of some BES/BZR transcription ...factors remain unknown; moreover, it is not clear if any of these proteins function in the regulation of plant stress responses. Here, wheat (
) brassinazole-resistant 2 (
)-overexpressing plants exhibited drought tolerant phenotypes, whereas downregulation of
in wheat by RNA interference resulted in elevated drought sensitivity. electrophoretic mobility shift assay and luciferase reporter analysis illustrate that TaBZR2 directly interacts with the gene promoter to activate the expression of
glutathione s-transferase-1 (
), which functions positively in scavenging drought-induced superoxide anions (O
). Moreover, TaBZR2 acts as a positive regulator in brassinosteroid (BR) signaling. Exogenous BR treatment enhanced TaBZR2-mediated O
scavenging and antioxidant enzyme gene expression. Taken together, we demonstrate that a BES/BZR family transcription factor, TaBZR2, functions positively in drought responses by activating
and mediates the crosstalk between BR and drought signaling pathways. Our results thus provide new insights into the mechanisms underlying how BES/BZR family transcription factors contribute to drought tolerance in wheat.
Hard carbon (HC) has emerged as a promising anode material for sodium‐ion batteries (SIBs), whereas it suffers from low initial Coulombic efficiency (ICE) and poor rate capability. Binders endowed ...with high electron/ion transport and strong mechanical integrity are expected to boost the practical application of HC anodes, which cannot be realized via the functional design of commercially available binders. Herein, a trifunctional sodium alginate (SA)/polyethylene oxide (PEO) binder with massive hydrophilic functional groups and abundant Na+ is synthesized via a feasible esterification reaction. The binder forms a passivation film on glucose‐derived carbon (GC) to suppress the electrolyte decomposition and offer stronger adhesion strength. Furthermore, the sluggish Na+ conduction is improved via sufficient ionic transfer channels provided by PEO. Notably, effects of Na+ compensation and interfacial ionic transport of Na+‐containing binder for HC anodes are revealed. Therefore, the SA/PEO binder for the GC anode delivers a high ICE up to 87% and a high capacity of 270 mA h g−1 at 0.1 A g−1, both 10% and 80 mA h g−1 higher than that of poly(vinylidene fluoride) binder, respectively. Significantly, this SA/PEO binder can also be applied to coal‐based and polymer‐based carbon anodes, exhibiting universal applicability.
A trifunctional sodium alginate/polyethylene oxide (SA/PEO) binder is proposed for glucose‐derived carbon anodes, exhibiting excellent sodium storage. The initial Coulombic efficiency and capacity of the carbon anode using the SA/PEO binder are 10% and 80 mAh g−1 higher than that of poly(vinylidene fluoride) binder, respectively, owing to the synergic effects of extra Na+ sources, rich Na+ channels, and stable H‐bonds.
The calcineurin B-like protein (CBL)-interacting protein kinase (CIPK) signaling pathway responds to various abiotic stresses in plants.
Wheat CIPK23, isolated from wheat drought transcriptome data ...set, was induced by multiple abiotic stresses, including drought, salt, and abscisic acid (ABA). Compared with wild-type plants, TaCIPK23-overexpression wheat and Arabidopsis showed an higher survival rate under drought conditions with enhanced germination rate, developed root system, increased accumulation of osmolytes, and reduced water loss rate. Over-expression of TaCIPK23 rendered transgenic plants ABA sensitivity, as evidenced by delayed seed germination and the induction of stomatal closure. Consistent with the ABA-sensitive phenotype, the expression level of drought- and ABA-responsive genes were increased under drought conditions in the transgenic plants. In addition, using yeast two-hybrid system, pull-down and bimolecular fluorescence complementation (BiFc) assays, TaCIPK23 was found to interact with TaCBL1 on the plasma membrane.
These results suggest that TaCIPK23 plays important roles in ABA and drought stress responses, and mediates crosstalk between the ABA signaling pathway and drought stress responses in wheat.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The combination of hetero‐elemental doping and vacancy engineering will be developed as one of the most efficient strategies to design excellent electrocatalysts for hydrogen evolution reaction ...(HER). Herein, a novel strategy for N‐doping coupled with Co‐vacancies is demonstrated to precisely activate inert S atoms adjacent to Co‐vacancies and significantly improve charge transfer for CoS toward accelerating HER. In this strategy, N‐doping favors the presence of Co‐vacancies, due to greatly decreasing their formation energy. The as‐developed strategy realizes the upshift of S 3p orbitals followed by more overlapping between S 3py and H 1s orbitals, which results in the favorable hydrogen atom adsorption free energy change (ΔGH) to activate inert S atoms as newborn catalytical sites. Besides, this strategy synergistically decreases the bandgap of CoS, thereby achieving satisfactory electrical conductivity and low charge‐transfer resistance for the as‐obtained electrocatalysts. With an excellent HER activity of −89.0 mV at 10.0 mA cm−2 in alkaline environments, this work provides a new approach to unlocking inert sites and significantly improving charge transfer toward cobalt‐based materials for highly efficient HER.
A novel strategy for N‐doping coupled with Co‐vacancies is demonstrated to precisely activate inert S atoms adjacent to Co‐vacancies and significantly improve charge transfer for CoS toward accelerating HER. The upshift of the S 3p orbitals and more overlapping between the S 3py and H 1s orbitals are the key reasons for activating such S atoms. Besides, this strategy synergistically decreases the bandgap of CoS, thereby achieving efficient charge transfer during HER.
The anaerobic fermentation gas (AFG) with CO2 removed is a sustainable energy resource, and converting CO2 in AFG to value‐added chemicals can kill two birds with one stone. Herein, an ionic porous ...organic polymer (IPOP‐3) catalyst, with triply synergistic effect of its hydroxide anions, nitrogen activation sites and porous structure, is synthesized. IPOP‐3 exhibits an excellent ability to enrich and convert 50 vol.% CO2 by the reactions with various amines into corresponding formamides. The catalyst is also successfully applied to the N‐formylation of CO2 in AFG, and can be easily recovered and reused. The plausible mechanism for the catalytic N‐formylation is proposed. The hydroxide anion in IPOP‐3 activates the Si−H bond of phenyl silane which reacts with the captured CO2 to form formate anion to facilitate the subsequent conversion into formamide. Our work provides a new idea for the purification of AFG and the resource utilization of CO2.
Purification of Anaerobic Fermentation Gas and Utilization of CO2: Novel ionic porous organic polymer catalyst with triply synergistic catalytic effect is synthesized, and is successfully applied to the direct conversion of CO2 in anaerobic fermentation gas (AFG) into formamides via N‐formylation reaction. The catalyst can be easily recovered and reused. This work provides a new idea for the purification of AFG together with the resource utilization of CO2.
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