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ABSTRACTMacroautophagy/autophagy has been recognized as a central antiviral defense mechanism in plant, which involves complex interactions between viral proteins and host factors. Rhabdoviruses are single-stranded RNA viruses, and the infection causes serious harm to public health, livestock, and crop production. However, little is known about the role of autophagy in the defense against rhabdovirus infection by plant. In this work, we showed that Rice stripe mosaic cytorhabdovirus(RSMV) activated autophagy in plants and that autophagy served as an indispensable defense mechanism during RSMV infection. We identified RSMV glycoprotein as an autophagy inducer that interacted with OsSnRK1B and promoted the kinase activity of OsSnRK1B on OsATG6b. RSMV glycoprotein was toxic to rice cells and its targeted degradation by OsATG6b-mediated autophagy was essential to restrict the viral titer in plants. Importantly, SnRK1-glycoprotein and ATG6-glycoprotein interactions were well-conserved between several other rhabdoviruses and plants. Together, our data support a model that SnRK1 senses rhabdovirus glycoprotein for autophagy initiation, while ATG6 mediates targeted degradation of viral glycoprotein. This conserved mechanism ensures compatible infection by limiting the toxicity of viral glycoprotein and restricting the infection of rhabdoviruses.Abbreviations:AMPK: adenosine 5‘-monophosphate (AMP)-activated protein kinase; ANOVA: analysis of variance; ATG: autophagy related; AZD: AZD8055; BiFC: bimolecular fluorescence complementation; BYSMV: barley yellow striate mosaic virus; Co-IP: co-immunoprecipitation; ConA: concanamycin A; CTD: C-terminal domain; DEX: dexamethasone; DMSO: dimethyl sulfoxide; G: glycoprotein; GFP: green fluorescent protein; MD: middle domain; MDC: monodansylcadaverine; NTD: N-terminal domain; OE: over expression; Os: Oryza sativa; PBS: phosphate-buffered saline; PtdIns3K: class III phosphatidylinositol-3-kinase; qRT-PCR: quantitative real-time reverse-transcription PCR; RFP: red fluorescent protein; RSMV: rice stripe mosaic virus; RSV: rice stripe virus; SGS3: suppressor of gene silencing 3; SnRK1: sucrose nonfermenting1-related protein kinase1; SYNV: sonchus yellow net virus; TEM: transmission electron microscopy; TM: transmembrane region; TOR: target of rapamycin; TRV: tobacco rattle virus; TYMaV: tomato yellow mottle-associated virus; VSV: vesicular stomatitis virus; WT: wild type; Y2H: yeast two-hybrid; YFP: yellow fluorescent protein.

Transcription factors respond to multilevel stimuli and co-occupy promoter regions of target genes to activate RNA polymerase (RNAP) in a cooperative manner. To decipher the molecular mechanism, here we report two cryo-electron microscopy structures of Anabaenatranscription activation complexes (TACs): NtcA-TAC composed of RNAP holoenzyme, promoter and a global activator NtcA, and NtcA–NtcB-TAC comprising an extra context-specific regulator, NtcB. Structural analysis showed that NtcA binding makes the promoter DNA bend by ∼50°, which facilitates RNAP to contact NtcB at the distal upstream NtcB box. The sequential binding of NtcA and NtcB induces looping back of promoter DNA towards RNAP, enabling the assembly of a fully activated TAC bound with two activators. Together with biochemical assays, we propose a ‘DNA looping’ mechanism of cooperative transcription activation in bacteria.

Candida albicansis one of the most common species of Candida, which cause various mucosal and systemic infectious diseases. However, the resistance rate to existing clinical antifungal drugs gradually increases in C. albicans. Therefore, new antifungal drugs must be developed to solve the current problem. This study discovered that the solid fermented ethyl acetate crude extract of Microporus vernicipeshad inhibitory activity on C. albicans. This study determined that the Mv5 components had significantly inhibited the activity of C. albicansusing column chromatography separation component screening. The components included 23 compounds of fatty acids and their derivatives, alkaloids, phenols, and other classes using ultra-high performance liquid chromatography tandem high-resolution mass spectrometry (UHPLC-HR-MS) analysis, with fatty acids constituting the primary components. The mechanism of action showed that the minimum inhibitory concentration (MIC) of Mv5 components against C. albicanswas 15.63 μg/mL, while minimum fungicidal concentration (MFC) was 31.25 μg/mL. Mv5 components can inhibit the early biofilm formation and destroy the mature biofilm structure. It can inhibit the germ tube growth of C. albicans, thereby inhibiting the transformation of yeast morphology to hyphae. We detected 193 differentially expressed genes, including 156 upregulated and 37 downregulated genes in the Mv5 components of the MIC concentration group. We detected 391 differentially expressed genes, including 334 upregulated and 57 downregulated expression genes in the MFC concentration group. Among these differentially expressed genes, the genes related to mycelium and biofilm formation were significantly downregulated. GO enrichment analysis presented that single-organism process metabolic process, and cellular processes were the biological processes with the most gene enrichment. Kyoto Encyclopedia of Genes and Genomes (KEGG)of Mv5 components were mainly enriched in metabolic pathways, such as meiosis yeast and amino acid metabolism. Therefore, it is believed that the fermentation extract of M. vernicipesinhibits C. albicans, which can provide clues for developing effective antifungal drugs.

The echo from shipborne high-frequency surface wave radar (HFSWR) is significantly influenced by the movement of the shipborne platform, and the accurate estimation of antenna displacement on the shipborne platform is a key factor in reflecting the echo model for shipborne HFSWR. However, the existing echo models for shipborne HFSWR mainly use ideal periodic motion to estimate the antenna displacement, which cannot meet the actual requirements. In this letter, a modified first-order ocean surface echo model for shipborne HFSWR in the time domain is proposed based on fusion estimation of multiple antenna displacements, which fuses the attitude and global navigation satellite system (NSS) information to improve the accuracy of the estimation of antenna displacement. Simulations were conducted in both anchor and navigation states to validate the effectiveness of the proposed modified model. The simulation results demonstrate that the proposed fusion method can more accurately estimate antenna displacement than the method using only attitude information. The modified echo model can more accurately reconstruct the first-order ocean surface echo spectrum, making it easier to accurately distinguish motion-induced peaks and extract echo spectrum information. This helps to facilitate the application of shipborne HFSWR for ocean state inversion and target detection.

Efficient and accurate termination is required for gene transcription in all living organisms1,2. Cellular RNA polymerases in both bacteria and eukaryotes can terminate their transcription through a factor-independent termination pathway3,4—called intrinsic termination transcription in bacteria—in which RNA polymerase recognizes terminator sequences, stops nucleotide addition and releases nascent RNA spontaneously. Here we report a set of single-particle cryo-electron microscopy structures of Escherichia colitranscription intrinsic termination complexes representing key intermediate states of the event. The structures show how RNA polymerase pauses at terminator sequences, how the terminator RNA hairpin folds inside RNA polymerase, and how RNA polymerase rewinds the transcription bubble to release RNA and then DNA. These macromolecular snapshots define a structural mechanism for bacterial intrinsic termination and a pathway for RNA release and DNA collapse that is relevant for factor-independent termination by all RNA polymerases.

The complex preparation, weak wet tissue adhesion, and limited biological activity of traditional oral wound dressings usually impede their efficient treatment and healing for diabetic oral mucosal defects. To overcome these problems, a novel hydrogel adhesive (named CFT hydrogel) is rapidly constructed using a one‐step method based on dual‐dynamic covalent cross‐linking. Compared with the commercial oral patches, the CFT hydrogel shows superior in vivo (rat tongue) wet tissue adhesion performance. Additionally, the CFT hydrogel exhibits unique acid‐responsive properties, thereby facilitating the release of bioactive molecule tannic acid in the acidic diabetic wound microenvironment. And a series of in vitro experiments substantiate the favorable biocompatibility and bioactivity properties (including antibacterial, antioxidative, anti‐inflammatory, and angiogenetic effects) exhibited by CFT hydrogel. Moreover, in vivo experiments conducted on a diabetic rat model with oral mucosal defects demonstrate that the CFT hydrogel exhibits significant efficacy in protecting against mucosal wounds, alleviating inflammatory reactions, thereby facilitating the wound‐healing process. Taken together, this study provides a promising and comprehensive therapeutic option with great potential for the clinical management of oral mucosa defects in diabetic patients. A novel CFT hydrogel is constructed as a multifunctional dressing material for diabetic oral mucosa defects healing. The CFT hydrogels exhibit good in vivo wet tissue adhesion performance, acid‐responsive tannic acid release properties, as well as favorable antimicrobial, antioxidant, anti‐inflammatory, and angiogenic activity.

The MerR-family transcription factors (TFs) are a large group of bacterial proteins responding to cellular metal ions and multiple antibiotics by binding within central RNA polymerase-binding regions of a promoter. While most TFs alter transcription through protein–protein interactions, MerR TFs are capable of reshaping promoter DNA. To address the question of which mechanism prevails, we determined two cryo-EM structures of transcription activation complexes (TAC) comprising Escherichia coliCueR (a prototype MerR TF), RNAP holoenzyme and promoter DNA. The structures reveal that this TF promotes productive promoter–polymerase association without canonical protein–protein contacts seen between other activator proteins and RNAP. Instead, CueR realigns the key promoter elements in the transcription activation complex by clamp-like protein–DNA interactions: these induce four distinct kinks that ultimately position the -10 element for formation of the transcription bubble. These structural and biochemical results provide strong support for the DNA distortion paradigm of allosteric transcriptional control by MerR TFs.

Effective extraction of lithium from high Mg2+/Li+ratio brine lakes is of great challenge. In this work, organic–inorganic hybrid silica nanofiltration (NF) membranes were prepared by dip-coating a 1,2-bis(triethoxysilyl)ethane (BTESE)-derived separation layer on tubular TiO2support, for efficient separation of LiCl and MgCl2salt solutions. We found that the membrane calcinated at 400 °C (M1–400) could exhibit a narrow pore size distribution (0.63–1.66 nm) owing to the dehydroxylation and the thermal degradation of the organic bridge groups. All as-prepared membranes exhibited higher rejections to LiCl than to MgCl2, which was attributed to the negative charge of the membrane surfaces. The rejection for LiCl and MgCl2followed the order: LiCl > MgCl2, revealing that Donnan exclusion effect dominated the salt rejection mechanism. In addition, the triple-coated membrane calcined at 400 °C (M3–400) exhibited a permeability of about 9.5 L∙m−2∙h−1∙bar−1for LiCl or MgCl2solutions, with rejections of 74.7% and 20.3% to LiCl and MgCl2,respectively, under the transmembrane pressure at 6 bar. Compared with the previously reported performance of NF membranes for Mg2+/Li+separation, the overall performance of M3–400 is highly competitive. Therefore, this work may provide new insight into designing robust silica-based ceramic NF membranes with negative charge for efficient lithium extraction from salt lakes.

This work reports a non noble metal catalyst for the oxygen reduction reaction (ORR) in alkaline. The catalyst is nitrogen doped graphitic carbon synthesized by the pyrolysis of microalgae in ammonia with ferrous chloride as the graphitization catalyst. The morphology, crystalline structure, defects and nitrogen groups of the catalyst are studied to reveal the origin of the high activity in ORR. The mechanism and kinetics of ORR are studied. The nitrogen doped graphitic carbon is more stable compared with commercial Pt/C catalyst. The high performance and low cost of the nitrogen doped graphitic carbon make it a promising candidate for applications in fuel cell and other energy devices.

Abstract

Burns, trauma, surgery and chronic diabetic ulcers are the most common reasons causing skin wounds in clinic. Thus, developing a functional wound dressing has been an imperative issue. Herein, functional wound dressing (poly(l‐lactic acid) PLLA‐((tanic acid (TA)/europium (Eu))n) is fabricated through a facile polyphenol–europium ion assembly to ameliorate wound microenvironment via scavenging excessive reactive oxygen species (ROS) and promoting angiogenesis. The physicochemical characterization indicates that the multicycle assembled TA/Eu is uniformly deposited on PLLA‐(TA/Eu)nnanofiber mats surface. In vitro 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) antioxidant tests display good antioxidant ability by scavenging more than 75% ROS, and significantly increasing the antioxidant enzyme levels in vivo. Cytocompatibility experiments illustrate that PLLA‐(TA/Eu)nnanofiber mats can promote the adhesion and proliferation of human umbilical vein endothelial cells (HUVECs) and L929 cells. Meanwhile, real‐time quantitative polymerase chain reaction (PCR) (RT‐qPCR) and western blot assays illustrate that it can stimulate proangiogenesis by elevating the expression of angiogenesis‐related genes and proteins. In vivo Sprague–Dawley (SD) rats experiments indicate that PLLA‐(TA/Eu)nnanofiber mats can significantly promote wound healing by improving both angiogenesis and antioxidant activity. Taken together, the functional PLLA‐(TA/Eu)nnanofiber mats can offer significant promise as wound dressing for accelerated wound healing. A functional wound dressing (poly(l‐lactic acid) (PLLA)‐((tanic acid (TA)/europium (Eu))n)) is fabricated through a facile polyphenol–europium ion assembly, which can ameliorate wound microenvironment through scavenging excessive reactive oxygen species (ROS) and promoting angiogenesis. In detail, it displays good antioxidant ability and cytocompatibility. In vivo experiments, it can promote wound healing by improving both angiogenesis and antioxidant activity.

Objective: To observe the effect of Bushen Conger (BSCE) tablet, a pure Chinese herbal medicine for reinforcing Kidney, removing blood stasis and opening apertures, in treating sensorineural deafness.Methods: Three hundred and ten patients were treated by BSCE tablet and the effects were observed. At the same time the effects of BSCE tablet on hearing, SOD, LPO, etc. were also assayed in guinea pigs.Results: The clinical total effective rate of BSCE tablet was 71.9%. Animal experiment proved that the drug was effective in preventing and treating toxic deafness induced by aminoglycoside antibiotics.Conclusion: BSCE tablet could cure sensorineural deafness through adjusting the cochlear cyclic neucleotides as well as its SOD level, reducing the LPO level, and raising the thyroid and sexual glandular functions.