Guiming Liu

Background: Gastrointestinal (GI) mucosal injury is a frequent complication of long-term nonsteroidal anti-inflammatory drug (NSAID) use. Effective mucosal healing requires coordinated epithelial migration, proliferation, and angiogenesis, which may be influenced by focal adhesion kinase (FAK). This study aimed to determine whether our newly developed FAK activators promote intestinal mucosal healing by enhancing angiogenesis and whether FAK activation increases resistance to reinjury. Methods: Ischemic jejunal ulcers were induced in C57BL/6 mice. After 24 h, mice received intraperitoneal injections of the FAK activator ZINC40099027 (ZN27, 900 µg/kg every 6 h) or vehicle for 2, 4, or 14 days. Ulcer areas were quantified, and liver and kidney function were assessed. Ulcer and adjacent tissues were analyzed by immunofluorescence staining for angiogenesis and proliferation markers. In vitro, human umbilical vein endothelial cells (HUVECs) were treated with ZN27 to evaluate proliferation, migration, angiogenesis, and intracellular signaling. In a reinjury model, male C57BL/6J mice received continuous infusion of the FAK activator M64HCl (25 mg/kg/day) or vehicle for 7 days, with a single subcutaneous injection of indomethacin (10 mg/kg) on day 1 to induce GI injury. Fourteen days after the first dose of indomethacin, the mice received a second indomethacin challenge, and one day later, total ulcer areas in the pyloric opening and small intestine were quantified. Results: Ulcer areas were significantly smaller in ZN27-treated mice compared with vehicle-treated controls at 3 and 5 days, accompanied by increased expression of angiogenesis and proliferation markers. In vitro, ZN27 enhanced HUVEC migration via FAK activation in an ERK1/2-dependent manner and increased the number of angiogenic sprouts. In the reinjury model, treatment with M64HCl during the initial indomethacin-induced injury resulted in significantly smaller ulcer areas in both the pyloric opening and small intestine after the second indomethacin challenge compared with controls. Conclusions: FAK activation accelerates ischemic ulcer healing, in part by enhancing angiogenesis. Moreover, FAK activation during an initial injury reduces susceptibility to recurrent NSAID-induced intestinal injury, perhaps because it promotes initial higher-quality ulcer repair.

Pathogenic Escherichia coli has a serious impact on animal husbandry. Currently, people mainly prevent pathogenic bacteria by injecting antibiotics into livestock. However, such frequent use of antibiotics accelerates the development of bacterial resistance and affects people’s health. Using bacteriophages to hunt down pathogenic bacteria has become an efficient method. In this study, we identified and characterized the K1 capsular vB_Eco_K1B4 bacteriophage and used RNA-seq analysis to profile the phage transcripts during the E. coli infection phase. The experimental results showed that bacteriophage vB_Eco_K1B4 still had a survival rate of over 50% in a 70 °C water bath for 1 h, and could survive for a short period at low temperatures. Not only that, vB_Eco_K1B4 also has a high tolerance for relatively extreme pH environments, so this bacteriophage has the potential to inhibit pathogenic bacteria. This study further explores the transcriptional regulation mechanism during the interaction between bacteriophages and hosts. Differentially expressed genes analysis, GO enrichment, and other analysis results show that vB_Eco_K1B4 can accurately regulate the host’s transcriptional resources, while inhibiting the expression of genes related to host structural component formation and upregulating the expression of genes related to host energy metabolism. Moreover, vB_Eco_K1B4 also impacts the host’s defense mechanism against bacteriophages. These transcriptome data provide a more thorough understanding of the cellular response of E. coli to phage infection and aid in understanding the phage-host interaction at the transcriptomic level.

花粉过敏近年来患病率呈上升趋势，灰藜花粉量大、致敏性强是夏秋季主要过敏原之一。本研究以灰藜花粉为研究对象，提取其花粉总蛋白，经Western blot初步鉴定灰藜过敏原蛋白分布；利用蛋白质质谱技术，结合灰藜转录组数据预测其潜在的过敏原基因，并构建酵母展示文库；运用酵母表面展示体系，结合高通量测序鉴定灰藜花粉过敏原。结果表明：（1）灰藜的过敏原蛋白分布在15~95 kDa间；（2）成功鉴定位于15 kDa处的灰藜过敏原Che a 4；（3）Che a 4含133个氨基酸残基，蛋白分子量约14.2 kDa，其开放阅读框ORF序列长度为402 bp，属于Profilin家族，与Che a 2氨基酸序列相似性约为76%。本研究利用酵母表面展示体系，结合高通量测序筛选出灰藜花粉过敏原Che a 4，为植物花粉过敏原的鉴定提供技术支持。

Background The escalating threat of antifungal resistance stemming from Trichosporon asahii (T. asahii) biofilms necessitates the pursuit of innovative therapeutic strategies. Among these approaches, 5-aminolevulinic acid (ALA) photodynamic therapy (PDT), an emerging therapeutic modality, has exhibited promising potential in eradicating T. asahii biofilms. Methods The inhibitory activity was evaluated by confocal laser scanning microscopy. To delve deeper into the efficacy of ALA-PDT in eliminating T. asahii biofilms, we conducted a comprehensive transcriptional analysis utilizing transcriptome sequencing. Results ALA-PDT demonstrated a profound inhibitory effect on the viability of T. asahii biofilms. Our investigation unveiled 2720 differentially expressed genes following exposure to ALA-PDT. Subsequent meticulous scrutiny allowed for the annotation of genes with a ≥ twofold change in transcription, focusing on Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways. Particularly noteworthy were the upregulated genes associated with oxidation–reduction processes, oxidoreductase activity, and catalytic activity. Conversely, the downregulated genes were linked to ATP binding, protein phosphorylation, and protein kinase activity. Additionally, we observed a surge in the transcription of genes that may be involved in oxidative stress (e.g., A1Q1_05494) as well as genes that may be involved in morphogenesis and biofilm formation (e.g., A1Q1_04029, A1Q1_01345, A1Q1_08069, and A1Q1_01456) following ALA-PDT treatment. Conclusions Our findings underscore the substantial impact of ALA-PDT on the transcriptional regulation of genes related to oxidative stress, morphogenesis, and biofilm formation, paving the way for novel therapeutic avenues in combating T. asahii biofilms.

Intestinal mucosal injury may arise from various factors. While many drugs target the causative factors, none directly stimulate mucosal wound healing. We found that the specific focal adhesion kinase (FAK) activator, M64HCl, promotes intestinal mucosal healing in mice. This study aims to further validate the therapeutic impact of M64HCl on intestinal mucosal repair in rats as a second species. Wistar rats were assigned to one of four groups: normal control, 1-day injury + vehicle, 4-day injury + vehicle, or 4-day injury + M64HCl. Intestinal injury was induced by serosally applying 75% acetic acid. Immediately after injury, rats received either a continuous infusion of M64HCl (25 mg/kg/day) or its vehicle (saline). Four days post-injury, blood was drawn to measure M64HCl levels and assess liver and kidney function. The intestines were removed and opened, ulcer areas were photographed for size quantification, and tissues were fixed for histological and immunohistochemical analysis. M64HCl substantially reduced ulcer area on gross examination, while histological analysis showed alleviation of pathological changes with M64HCl treatment. Immunohistochemical analysis confirmed increased immunoreactivity for phosphorylated FAK in the epithelium adjacent to the injury in M64HCl-treated rats. However, there was no change in the percentage of Ki67-positive cells in each crypt at the edge of the ulcer area. Serum creatinine, ALT, and AST levels did not differ between the 4-day injury groups with or without M64HCl treatment. M64HCl, a water-soluble FAK activator, promotes acetic acid-induced ulcer healing in rats and may be useful in treating gastrointestinal mucosal injury.

Salix psammophila C. Wang & C. Y. Yang is an important windbreak and sand-fixing shrub species in Northwest China, with excellent characteristics such as resistance to drought, wind, and sand. S. psammophila needs to be stubbed flat after several years of growth to continue to grow, otherwise, its growth rate will slow down and even begin to die. To understand the genetic regulatory mechanism of secondary growth in S. psammophila, cell structure and transcriptome analysis were performed on the secondary xylem and secondary phloem of stems. The results showed that the secondary xylem and the secondary phloem of S. psammophila were well developed at 1, 2, and 3-year-old stages, and the secondary growth changes mainly occurred in the secondary xylem at the 2 to 3-year-old stage, with a faster growth rate. The CSE2 and CSE1 genes that regulate CSE (caffeoyl shikimate esterase) have high sequence similarity (92% and 93%) with the CSE2 and CSE1 genes of the genus Populus, respectively, and regulate lignin biosynthesis. Notably, the expression levels of these two genes decreased in the secondary xylem of 3-year-old S. psammophila, indicating that the rapid growth of S. psammophila may be related to lignin biosynthesis. Weighted gene co-expression network analysis (WGCNA) was utilized to screen candidate TFs and genes involved in the secondary growth processes of S. psammophila, which were categorized into six co-expression modules. A total of 79 genes were selected from these co-expression modules, and co-expression network maps of the genes were constructed. The results indicate that the secondary growth of S. psammophila was regulated by a TF regulatory network. Interestingly, PLATZ TFs were involved in the rapid secondary growth and stress tolerance in S. psammophila. This hints that S. psammophila may promote secondary growth by increasing stress tolerance.

Salix psammophila, commonly known as the sandlive willow, is a vital shrub species within the Salicaceae family, particularly significant for its ecological role in regions susceptible to desertification and sandy soils. In this study, we assembled the complete S. psammophila mitochondrial genome using Pacbio HiFi third-generation sequencing data. The genome was found to be a typical single circular structure, with a total length of 715,555 bp and a GC content of 44.89%. We annotated 33 unique protein-coding genes (PCGs), which included 24 core mitochondrial genes and 9 variable genes, as well as 18 tRNA genes (5 of which were multicopy genes) and 3 rRNA genes. Comparative analysis of the PCGs from the mitochondrial genomes of S. psammophila, Populus deltoides, Populus simonii, Salix wilsonii, and Salix suchowensis revealed that these genes are relatively conserved within the Salicaceae family, with variability primarily occurring in the ribosomal protein genes. The absence of the rps14, which encodes a ribosomal protein, may have played a role in the evolution of stress tolerance in Salicaceae plants. Additionally, we identified 232 SSRs, 19 tandem repeat sequences, and 236 dispersed repeat sequences in the S. psammophila mitochondrial genome, with palindromic and forward repeats being the most abundant. The longest palindromic repeat measured 260 bp, while the longest forward repeat was 86,068 bp. Furthermore, 324 potential RNA editing sites were discovered, all involving C-to-U edits, with the nad4 having the highest number of edits. These findings provide valuable insights into the phylogenetic and genetic research of Salicaceae plants.

Main conclusion In this study, we assembled the first complete mitochondrial genome of Setaria italica and confirmed the multi-branched architecture. Abstract The foxtail millet (Setaria italica) holds significant agricultural importance, particularly in arid and semi-arid regions. It plays a pivotal role in diversifying dietary patterns and shaping planting strategies. Although the chloroplast genome of S. italica has been elucidated in recent studies, the complete mitochondrial genome remains largely unexplored. In this study, we employed PacBio HiFi sequencing platforms to sequence and assemble the complete mitochondrial genome. The mitochondrial genome spans a total length of 446,614 base pairs and harbors a comprehensive set of genetic elements, including 33 unique protein-coding genes (PCGs), encompassing 24 unique mitochondrial core genes and 9 variable genes, along with 20 transfer RNA (tRNA) genes and 3 ribosomal RNA (rRNA) genes. Our analysis of mitochondrial PCGs revealed a pronounced codon usage preference. For instance, the termination codon exhibits a marked preference for UAA, while alanine (Ala) exhibits a preference for GCU, and glutamine (Gln) favors CAA. Notably, the maximum Relative Synonymous Codon Usage (RSCU) values for cysteine (Cys) and phenylalanine (Phe) are both below 1.2, indicating a lack of strong codon usage preference for these amino acids. Phylogenetic analyses consistently place S. italica in close evolutionary proximity to Chrysopogon zizanioides, relative to other Panicoideae plants. Collinearity analysis showed that a total of 39 fragments were identified to display homology with both the mitochondrial and chloroplast genomes. A total of 417 potential RNA-editing sites were discovered across the 33 mitochondrial PCGs. Notably, all these editing events involved the conversion of cytosine (C) to uracil (U). Through the employment of PCR validation coupled with Sanger sequencing for the anticipated editing sites of these codons, RNA-editing events were conclusively identified at two specific loci: nad4L-2 and atp6-1030. The results of this study provide a pivotal foundation for advanced genomic breeding research in foxtail millet. Furthermore, they impart essential insights that will be instrumental for forthcoming investigations into the evolutionary and molecular dynamics of Panicoideae species.

In order to verify the effect of the new fully biodegradable external dressing on the repair of diabetes skin wounds and the promotion of wound healing, this study applied sodium alginate hydrogel dressing products which are supplemented with phage and conotoxin analgesic peptides to the skin lesions of diabetes mice, and comprehensively used the quantitative measurement of serological indicators, Image J Tissue section and other techniques to evaluate the effect of the new hydrogel dressing on the repair of diabetes wounds and the promotion of wound healing. The behavioral observation and analysis of mice did not show obvious regularity and difference. According to the results of serum cytokine analysis, functional hydrogel dressings can promote cell regeneration and wound healing in mice. Image J software analysis showed that the healing results of the experimental group were better than those of the negative control group, and the percentage of collagen fiber content showed an upward trend. Through comprehensive evaluation, it can be observed that the new fully biodegradable external dressing has obvious positive effects on wound healing, collagen fiber reconstruction and wound infection prevention of diabetes. The new biodegradable dressing not only promotes wound healing but also solves environmental pollution problems. It meets the sustainable development needs of society and has broad application prospects.