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Butyric acid (BA) can potentially enhance the function of the intestinal barrier. However, the mechanisms by which BA protects the intestinal mucosal barrier remain to be elucidated. Given that the Ras homolog gene family, member A (RhoA)/Rho-associated kinase 2 (ROCK2)/Myosin light chain kinase (MLCK) signaling pathway is crucial for maintaining the permeability of the intestinal epithelium, we further investigated whether BA exerts a protective effect on epithelial barrier function by inhibiting this pathway in LPS-induced Caco2 cells. First, we aimed to identify the optimal treatment time and concentration for BA and Lipopolysaccharide (LPS) through a CCK-8 assay. We subsequently measured Trans-epithelial electrical resistance (TEER), FITC-Dextran 4 kDa (FD-4) flux, and the mRNA expression of ZO-1, Occludin, RhoA, ROCK2, and MLCK, along their protein expression levels, and average fluorescence intensity following immunofluorescence staining. We then applied the ROCK2 inhibitor Y-27632 and reevaluated the TEER, FD-4 flux, and mRNA, and protein expression of ZO-1, Occludin, RhoA, ROCK2, and MLCK, as well as their distribution in Caco2 cells. The optimal treatment conditions were determined to be 0.2 mmol/L BA and 5 μg/mL LPS for 24 hours. Compared with LPS treatment alone, BA significantly mitigated the reduction in the TEER, decreased FD-4 flux permeability, increased the mRNA expression of ZO-1 and Occludin, and normalized the distribution of ZO-1 and Occludin in Caco2 cells. Furthermore, BA inhibited the expression of RhoA, ROCK2, and MLCK, and normalized their localization within Caco2 cells. Following treatment with Y-27632, the epithelial barrier function, along with the mRNA and protein expression and distribution of ZO-1 and Occludin were further normalized upon inhibition of the pathway. These findings contribute to a deeper understanding of the potential mechanisms through which BA attenuates LPS-induced impairment of the intestinal epithelial barrier. [ABSTRACT FROM AUTHOR]

Sclerotinia sclerotiorum is a fungal pathogen with a broad range of hosts, which can cause diseases and pose a great threat to many crops. Fungal-specific Zn2Cys6 transcription factors (TFs) constitute a large family prevalent among plant pathogens. However, the function of Zn2Cys6 TFs remains largely unknown. In this study, we identified and characterized SsZNC1, a Zn2Cys6 TF in S. sclerotiorum, which is involved in virulence, sclerotial development, and osmotic stress response. The expression of SsZNC1 was significantly up-regulated in the early stages of S. sclerotiorum infection on Arabidopsis leaves. The target deletion of SsZNC1 resulted in reduced virulence on Arabidopsis and oilseed rape. In addition, sclerotial development ability and growth ability under hyperosmotic conditions of SsZNC1 knockout transformants were reduced. A transcriptomic analysis unveiled its regulatory role in key cellular functions, including cellulose catabolic process, methyltransferase activity, and virulence, etc. Together, our results indicated that SsZNC1, a core regulatory gene involved in virulence, sclerotial development and stress response, provides new insight into the transcription regulation and pathogenesis of S. sclerotiorum. [ABSTRACT FROM AUTHOR]

Objectives: Immunoglobulin A vasculitis (IgAV), previously known as Henoch–Schönlein purpura, is the most common vasculitis that has a classical skin manifestation of palpable purpuric rash. Factors pertinent to IgAV remain inadequately understood. Here, we aimed to examine the gut microbiome shifts associated with IgAV and its recovery. Methods: Stool samples were collected from 10 children with IgAV (6–14 years old) before and after a multi‐drug therapy, along with 9 age‐matched healthy children. The samples were subjected to metagenomic analyses to investigate the taxonomic and functional shifts of the gut microbiome. Results: The analyses revealed that compared with healthy controls, treatment‐naïve patients exhibited substantial taxonomic and functional alterations of gut microbiota, including 104 IgAV‐depleted species and 7 IgAV‐elevated species (FDR < 0.05). After treatment, the IgAV patients displayed a partial restoration of the microbiota shifts, as the relative abundances of some biomarkers (e.g. 9 genera and 22 species) became comparable (FDR > 0.1) between the patients and healthy controls. The treatment‐responsive features included Weissella, Faecalibacterium prausnitzii and Bifidobacterium pseudocatenulatum and three components of a putative glutamine transport system. Importantly, gram‐positive bacteria accounted for over 85% of the numbers and total relative abundance of the species that were associated with IgAV and responsive to the treatment. In addition, of the 122 IgAV‐depleted bacterial genes, 82 were mainly contributed by gram‐positive bacteria and 12 by gram‐negative bacteria. Conclusions: Gram‐positive bacteria are the main drivers underlying the gut microbiome shifts of IgAV, which may assist rational management of the disease. [ABSTRACT FROM AUTHOR]

Threshold segmentation has been widely used in recent years due to its simplicity and efficiency. The method of segmenting images by the two-dimensional maximum entropy is a species of the useful technique of threshold segmentation. However, the efficiency and stability of this technique are still not ideal and the traditional search algorithm cannot meet the needs of engineering problems. To mitigate the above problem, swarm intelligent optimization algorithms have been employed in this field for searching the optimal threshold vector. An effective technique of lightning attachment procedure optimization (LAPO) algorithm based on a two-dimensional maximum entropy criterion is offered in this paper, and besides, a chaotic strategy is embedded into LAPO to develop a new algorithm named CLAPO. In order to confirm the benefits of the method proposed in this paper, the other seven kinds of competitive algorithms, such as Ant–lion Optimizer (ALO) and Grasshopper Optimization Algorithm (GOA), are compared. Experiments are conducted on four different kinds of images and the simulation results are presented in several indexes (such as computational time, maximum fitness, average fitness, variance of fitness and other indexes) at different threshold levels for each test image. By scrutinizing the results of the experiment, the superiority of the introduced method is demonstrated, which can meet the needs of image segmentation excellently. [ABSTRACT FROM AUTHOR]

Multi-level image thresholding is the most direct and effective method for image segmentation, which is a key step for image analysis and computer vision, however, as the number of threshold values increases, exhaustive search does not work efficiently and effectively and evolutionary algorithms often fall into a local optimal solution. In the paper, a meta-heuristics algorithm based on the breeding mechanism of Chinese hybrid rice is proposed to seek the optimal multi-level thresholds for image segmentation and Renyi's entropy is utilized as the fitness function. Experiments have been run on four scanning electron microscope images of cement and four standard images, moreover, it is compared with other six classical and novel evolutionary algorithms: genetic algorithm, particle swarm optimization algorithm, differential evolution algorithm, ant lion optimization algorithm, whale optimization algorithm, and salp swarm algorithm. Meanwhile, some indicators, including the average fitness values, standard deviation, peak signal to noise ratio, and structural similarity index are used as evaluation criteria in the experiments. The experimental results show that the proposed method prevails over the other algorithms involved in the paper on most indicators and it can segment cement scanning electron microscope image effectively. [ABSTRACT FROM AUTHOR]

Rhizoctonia solani AG-1 IA is one of the most important fungal pathogens that causes severe yield losses in rice-growing regions worldwide. Catechol (1, 2-benzenediol) is a natural catecholamine which can induce melanization of fungi and contribute to enhanced virulence and fungal resistance to diverse environments. In this study, the effects of catechol on growth, activities of antioxidant enzymes such as catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), glutathione S-transferase (GSH-ST), glutathione peroxidase (GSH-PX) and glutathione reductase (GR), as well as expression of melanin biosynthesis genes in R. solani AG-1 IA, were evaluated by culturing the fungus in catechol-containing nutrient media. The results showed that the activities of CAT, POD, SOD, GSH-ST, GSH-PX and GR were decreased in the presence of 12.5-50 μg mL−1 catechol, while GSH-PX activity was significantly increased (by 310%) in the presence of 50 µg mL−1 catechol. The growth rates of R. solani AG-1 IA on potato dextrose agar (PDA) containing catechol were significantly decreased, whereas the pathogenicity to rice of R. solani AG-1 IA cultured on PDA containing different concentrations of catechol was enhanced when compared with the catechol-free control. Quantitative RT-PCR results showed that the expression of four melanin biosynthesis genes, i.e. protein tyrosine phosphatase (Ptp), chorismate mutase (Cm), peroxidase (Per) and phenol hydroxylase (Ph), was significantly down-regulated in R. solani AG-1 IA cultured in catechol-containing PDB at 100 µg mL−1. These results suggest that catechol was utilized by the fungus to synthesize melanin, and it could also induce the activities of antioxidant enzymes and melanization in R. solani AG-1 IA. Our results provide strong evidence to support the view that melanin contributes to virulence directly through fungal antioxidant defence systems in which melanization is induced by oxidative stress. [ABSTRACT FROM AUTHOR]

High-dose methotrexate (HDMTX) chemotherapy is generally accepted as an effective method for the treatment and prevention of extramedullary leukemia in children. However, it is unknown whether HDMTX chemotherapy kills intestinal bacteria on a large scale, thus causing dysbacteriosis, which may in turn influence the progress or prognosis of leukemia. The aim of this study was to examine changes in intestinal flora in children with acute lymphoblastic leukemia (ALL) treated with HDMTX chemotherapy. Bacterial DNA in stool from 36 healthy children and 36 ALL children were tested at A(260) with a spectrophotometer before and after HDMTX chemotherapy. The primers of Bifidobacteria, Lactobacillus and Escherichia coli were designed according to the 16SrRNA/DNA bacterial sequences. Bacteria were qualitatively and quantitatively confirmed by routine polymerase chain reaction (PCR) and fluorescent quantitative PCR, respectively. Our data showed that the total amount of flora in the stools of children with ALL was decreased by 29.6% compared with healthy children (P < 0.01). The total amount of flora in the stools of children with ALL on the third and seventh days after chemotherapy were 1496.5 ± 577.1 and 1966.6 ± 598.3 ng/μL, respectively, which was notably less than before chemotherapy (2436.3 ± 768.6 ng/μL). The amount of Bifidobacteria, Lactobacillus and E. coli in the intestinal tract in the ALL group after chemotherapy had an apparent change, which decreased most clearly on the third day, and partially recovered on the seventh day after chemotherapy. HDMTX chemotherapy can cause intestinal dysbacteriosis in children with ALL. The amount of Bifidobacteria, Lactobacillus and E. coli decreased significantly compared with the control group.

Background: Rotavirus infection is the most common cause of infectious diarrhea and gastroenteritis among children worldwide. The viral proteins (VP), especially VP4- and VP7-induced neutralizing antibodies, were considered to be critical in protective immunity to rotavirus disease. However, whether the antibody to rotavirus nonstructural protein 4 (NSP4) protects against rotavirus-induced diarrhea directly is not completely clear, especially for the protective time course., Materials and Methods: To obtain direct evidence, 12-day-old ICR mice were treated with NSP4 and entire rotavirus to induce diarrhea., Results: Both NSP4 and rotavirus-treated mice developed diarrhea, which was accompanied by histological changes in the small intestine compared to age-matched control mice. Anti-NSP4 antibody demonstrated protection against both entire rotavirus-induced diarrhea and NSP4-induced diarrhea. The histological changes in the small intestinal were reversible. These data show that early intervention with anti-NSP4 antibody can prevent rotavirus-induced diarrhea in mice; late intervention with anti-NSP4 antibody could halt diarrhea progression in mice., Conclusions: Our findings demonstrate for the first time that administration of anti-NSP4 antibody is effective both prior to and during the time course of rotavirus infection. These observations extend our knowledge of rotavirus infection and its therapeutic options.