Search

The treatment and prevention of pathogenic diseases by lactic acid bacteria (LAB) has attracted more and more attention. As a special LAB, Levilactobacillus brevis (L. brevis) has relatively less research on its antibacterial infection in vivo, and its protective effect and mechanism still need to be fully studied. In this study, we selected L. brevis 23017, which can regulate the intestinal immunity of the host animal and resist pathogen infection, to evaluate its protective role and potential molecular mechanisms in the mouse model of S. typhimurium C7731 infection. As expected, we confirmed that L. brevis 23017 reduced the diarrhea rate and increased the daily weight gain and survival rate of the mouse model, and inhibited S. typhimurium colonization in the jejunum and liver. It also reduced the level of oxidative damage and protected the integrity of intestinal tissue by increasing the activity of intestinal antioxidant enzymes (SOD, GSH-Px and T-AOC). From the perspective of intestinal mucosal barrier injury and repair, it was confirmed that L. brevis 23017 could increase the expression levels of intestinal tight junction proteins (ZO-1 and OCLN). Our research results also show that L. brevis 23017 inhibits the inflammatory response and promotes the occurrence of cellular immunity in the body by promoting the increase in IL-10 and inhibiting IL-13 in serum and intestinal tissue. Notably, L. brevis 23017 increased total secretory immunoglobulin A (SIgA) levels in the intestine, which were closely associated with elevated levels of IL-5, IL-13, pIgR, j-chain, and IgAα-chain. In addition, L. brevis 23017 increased the expression of antioxidant proteins Nrf2, NQO1, and HO-1 associated with Nrf2 signaling to inhibit intestinal oxidative damage. This mechanism may be responsible for its protective effect against S. typhimurium-infected intestine. Our study provides new evidence and theoretical support for the analysis of the anti-bacterial infection effect and mechanism of L. brevis, which will contribute to the development of L. brevis and the treatment of pathogenic bacteria intestinal infection. [ABSTRACT FROM AUTHOR]

Enterococci resistance is increasing sharply, which poses a serious threat to public health. Rhamnolipids are a kind of amphiphilic compound used for its bioactivities, while the combination of nontraditional drugs to restore linezolid activity is an attractive strategy to treat infections caused by these pathogens. This study aimed to investigate the activity of linezolid in combination with the rhamnolipids against Enterococcus faecium. Here, we determined that the rhamnolipids could enhance the efficacy of linezolid against enterococci infections by a checkerboard MIC assay, a time–kill assay, a combined disk test, an anti-biofilm assay, molecular simulation dynamics, and mouse infection models. We identified that the combination of rhamnolipids and linezolid restored the linezolid sensitivity. Anti-biofilm experiments show that our new scheme can effectively inhibit biofilm generation. The mouse infection model demonstrated that the combination therapy significantly reduced the bacterial load in the feces, colons, and kidneys following subcutaneous administration. This study showed that rhamnolipids could play a synergistic role with linezolid against Enterococcus. Our combined agents could be appealing candidates for developing new combinatorial agents to restore antibiotic efficacy in the treatment of linezolid-resistant Enterococcus infections. [ABSTRACT FROM AUTHOR]

Enterotoxigenic Escherichia coli (ETEC) is a significant contributor to diarrhea. To determine whether ETEC-catecholamine hormone interactions contribute to the development of diarrhea, we tested the effects of catecholamine hormones acting on ETEC in vitro. The results showed that in the presence of norepinephrine (NE) and epinephrine (Epi), the growth of 9 out of 10 ETEC isolates was promoted, the MICs of more than 60% of the isolates to 6 antibiotics significantly increased, and the biofilm formation ability of 10 ETEC isolates was also promoted. In addition, NE and Epi also significantly upregulated the expression of the virulence genes feaG, estA, estB, and elt. Transcriptome analysis revealed that the expression of 290 genes was affected by NE. These data demonstrated that catecholamine hormones may augment the diarrhea caused by ETEC. [ABSTRACT FROM AUTHOR]

In view of the insufficient utilization of dependent syntactic information in aspect-level sentiment analysis, as well as the separate learning of contextual information and dependent syntactic information, a research method of aspectlevel sentiment analysis integrating prior knowledge and pre-training model is proposed. Firstly, this method inputs the dependent syntax information as prior knowledge and the sentence into the pre-training model. Through the pre-training model, the long- distance information between aspect words and emotional words of dependent syntactic modeling is learned while learning the context information of the sentence. Secondly, the dependency distance representation is further used to match the dynamic weight of the pre-training word vector, so as to make full use of the syntactic information. Thirdly, the part of speech information and the dependency label information are learned through self- attention mechanism, and using two auxiliary information to enhance sentence representation. Lastly, three kinds of information are spliced as the input of sentiment classifier. Compared with other aspect-level sentiment analysis methods, the accuracy and F1 value are increased on the four benchmark data sets, which verifies the effectiveness of prior knowledge fusion and dynamic weight matching proposed by this method, and has a great application value in aspect-level sentiment analysis tasks. [ABSTRACT FROM AUTHOR]

There is an increasing interest in the use of spore-forming Bacillus spp. as probiotic ingredients on the market. However, probiotics Bacillus species are insufficient, and more safe Bacillus species were required. In the study, traditional fermented foods and soil samples were collected from more than ten provinces in China, and 506 Bacillus were selected from 109 samples. Using the optimized procedure, we screened nine strains, which successfully passed the acid, alkali, bile salt, and trypsin resistance test. Drug sensitivity test results showed that three Bacillus out of the nine isolates exhibited antibiotic sensitivity to more than 29 antibiotics. The three strains sensitive to antibiotics were identified by 16S ribosomal RNA, recA, and gyrB gene analysis, two isolates (38,327 and 38,328) belong to the species Lysinibacillus capsici and one isolate (37,326) belong to Bacillus halotolerans. Moreover, the three strains were confirmed safe through animal experiments. Finally, L. capsici 38,327 and 38,328 showed protections in the Salmonella typhimurium infection mouse model, which slowed down weight loss, reduced bacterial load, and improved antioxidant capacity. Altogether, our data demonstrated that selected L. capsici strains can be used as novel probiotics for intestinal health. [ABSTRACT FROM AUTHOR]

Background: Tissue-resident CD8+T cells (CD103+CD8+T cells) are the essential effector cell population of anti-tumor immune response in tissue regional immunity. And we have reported that IL-33 can promote the proliferation and effector function of tissue-resident CD103+CD8+T cells. As of now, the immunolocalization and the prognostic values of tissue-resident CD8+T cells in human hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) still remain to be illustrated. Methods: In our present study, we used the tissue microarrays of HCC and ICC, the multicolor immunohistochemistry (mIHC), and imaging analysis to characterize the tissue-resident CD8+T cells in HCC and ICC tissues. The prognostic values and clinical associations were also analyzed. We also studied the biological functions and the cell–cell communication between tumor-infiltrating CD103+CD8+T cells and other cell types in HCC and ICC based on the published single-cell RNA sequencing (scRNA-seq) data. Results: Our work unveiled the expressions of CD8 and CD103 and immunolocalization of tissue-resident CD8+T cells in human HCC and ICC. Elevated CD8+T cells indicated a better overall survival (OS) rate, implying that tumor-infiltrating CD8+T cells in HCC and ICC could serve as an independent prognostic factor. Moreover, the number of CD103+CD8+T cells was increased in HCC and ICC tissues compared with adjacent normal tissues. HCC patients defined as CD8highCD103high had a better OS, and the CD8lowCD103low group tended to have a poorer prognosis in ICC. Evaluation of the CD103+CD8+T-cell ratio in CD8+T cells could also be a prognostic predictor for HCC and ICC patients. A higher ratio of CD103+CD8+T cells over total CD8+T cells in HCC tissues was negatively and significantly associated with the advanced pathological stage. The percentage of higher numbers of CD103+CD8+T cells in ICC tissues was negatively and significantly associated with the advanced pathological stage. In contrast, the higher ratio of CD103+CD8+T cells over total CD8+T cells in ICC tissues was negatively and significantly associated with the advanced pathological stage. In addition, single-cell transcriptomics revealed that CD103+CD8+T cells were enriched in genes associated with T-cell activation, proliferation, cytokine function, and T-cell exhaustion. Conclusion: The CD103+ tumor-specific T cells signified an important prognostic marker with improved OS, and the evaluation of the tissue-resident CD103+CD8+T cells might be helpful in assessing the on-treatment response of liver cancer. [ABSTRACT FROM AUTHOR]

Aims: Lactobacillus strains have protective effects against heavy metals while relieving oxidative stress and modulating the immune response. Mechanisms that ameliorate heavy metal toxicity and the relationship between probiotics and gut barrier protection in the process of heavy metal pathogenesis was poorly understood. Methods and Results: In this study, Lactobacillus brevis 23017 (LAB, L. brevis 23017), a selected probiotics strain with strong mercury binding capacities, was applied to evaluate the efficiency against mercury toxicity in a mouse model. Histopathological results along with HE stains show that L. brevis 23017 protects the integrity of the small intestinal villus, which slows weight loss in response to Hg exposure. The qRT-PCR results demonstrate that L. brevis 23017 maintains a normal mucosal barrier via modulation of tight junction proteins. Importantly, the present study demonstrates that L. brevis 23017 effectively ameliorates injury of the small intestine by reducing intestinal inflammation and alleviating oxidative stress in animal models. Moreover, L. brevis 23017 blocks oxidative stress and inflammation through MAPK and NF-κB pathways, as shown by western blot. Conclusions: Together, these results reveal that L. brevis 23017 may have applications in the prevention and treatment of oral Hg exposure with fermented functional foods by protecting gut health in daily life. [ABSTRACT FROM AUTHOR]

ContextChebulae Fructus is used as an herbal remedy for diarrhoea in traditional Chinese medicine. However, there is no scientific evidence to support its antidiarrhoeal activity. ObjectiveThis study evaluates the antidiarrhoeal properties of Chebulae Fructus aqueous extract (CFAE) and determines the active fraction. Materials and methodsThe antidiarrhoeal effect of CFAE (200–800 mg/kg) was investigated by determining the wet dropping, intestinal transit in BALB/c mice and enteropooling in Wister rats. The protective effects of the CFAE on the intestinal and liver were tested by histopathological analyses. The antidiarrhoeal fraction was determined by castor oil-induced diarrhoea and its main constituents were identified by HPLC-ESI-MS. ResultsThe extract at doses of 200, 400 and 800 mg/kg reduced the diarrhoea by 9.1, 40.0 and 58.2% and inhibited intestinal transit by 18.3, 24.1 and 35.7%, respectively. Additionally, the CFAE (200, 400 and 800 mg/kg) decreased the volume of enteropooling by 47.1, 58.8 and 64.7%, respectively. Mice treated with castor oil presented morphological alterations in the small intestine and the liver. However, the lesions of mice treated with CFAE were alleviated. Moreover, the ethyl acetate fraction was the active fraction of CFAE, the fraction (41.7, 83.4 and 166.8 mg/kg) reduced the diarrhoea by 9.1, 38.2 and 54.5%, respectively. The major components of the ethyl acetate fraction were tannins, including gallic acid, 3, 4, 6-tri-O-galloyl-β-d-Glc, corilagin and ellagic acid according to the HPLC-ESI-MS analysis. ConclusionThe CFAE possessed antidiarrhoeal property and the ethyl acetate fraction was its main active fraction. [ABSTRACT FROM PUBLISHER]

The codon-optimized Eimeria tenella 3-1E gene was introduced into the lactic acid bacterial vector pTX8048 to construct plasmid pTX8048-3-1E. The plasmid pTX8048-3-1E was transformed into Lactococcus lactis NZ9000 by electroporation to create the strain of L. lactis pTX8048-3-1E. The expression of objective protein was verified by Western blot. The live bacteria L. lactis pTX8048-3-1E were administered orally, and an animal challenge experiment was carried out to evaluate the protective efficacy. The results indicated the strain of L. lactis pTX8048-3-1E was constructed successfully. Oral immunization to specific pathogen-free (SPF) chickens with L. lactis pTX8048-3-1E provided partial protection against homologous challenge including significant increased oocyst decrease ratio, reduced average lesion score in cecum, and improved body weight gain compared to control bacteria L. lactis pTX8048. These results demonstrate the use of Lactococcus as live vector for delivery of Eimeria antigen is feasible and promising method to control coccidiosis in poultry. [ABSTRACT FROM AUTHOR]

Palladium supported on different shaped iron oxides has been synthesized and tested in glycerol hydrogenolysis in order to investigate the morphological effect of the support on catalytic performance. The plate-like iron oxide support exhibits a much higher activity due to the presence of more basic sites (oxygen vacancies) on its predominant polar surface. Thus, by tailoring the shape of the crystallized support, we show that bifunctional metal-oxide catalysis at the interface, like in the present example, can be significantly manipulated. [ABSTRACT FROM AUTHOR]

Abstract: Using sodium caprylate as a model molecule, in the present work, we unraveled the gelation mechanism of sodium soaps in organic solvents from its correlation with the microstructure morphology. It is interesting to find that both the formation of organogels and radiation-like gel fibers are controlled by Na+ concentration in the system. As the gel-activator, the sodium ions not only accelerate the gelation process and enhance the gel networks, but also induce the morphology transformation from fibers to radiative nanoribbons. TEM and XRD characterization reveals that the Na+ enhanced effect should be ascribed to the structure transformation of sodium caprylate from layers to hexagonal packing, due to its reduced inter-separation after the addition of Na+. Based on these results, the gelation mechanism of sodium soaps has been also proposed. [Copyright &y& Elsevier]

A novel CoIII(salen)-based pseudohomogeneous catalyst exhibits both extremely high activity at low H 2 O/epoxide ratio and surprising recyclability without regeneration in propylene oxide hydration due to its unusual bisubstrate-directly-activated cooperative mechanism. [Display omitted] • A novel pseudohomogeneous catalyst was developed for epoxide hydration. • The catalyst exhibits unexpectedly enhanced activity at low H 2 O/epoxide ratio. • The catalyst shows surprising recyclability without regeneration between runs. • An unusual bisubstrate-directly-activated cooperative mechanism has been proposed. Due to high H 2 O/epoxide molar ratio for non-catalytic hydration, industrial production of bulk chemicals 1,2-diols is much energy-intensive. As a very promising route to produce 1,2-diols with low energy consumption, catalytic hydration of epoxides has aroused much interest from both academy and industry. The key is to develop a catalyst with high activity and stability at a low H 2 O/epoxide molar ratio. It has been demonstrated that encapsulating a homogeneous catalytic species into the cavity of porous material is a very efficient way to obtain a high-performance heterogeneous catalyst. Herein, a novel pseudohomogeneous catalyst with the distinctive Co(salen)-PF 6 encapsulated in nanocages of a typical mesoporous material FDU-12 has been successfully developed, which exhibits both unexpectedly tremendously enhanced activity at the low H 2 O/epoxide molar ratio close to stoichiometric ratio and unique surprising recyclability without regeneration between runs in propylene oxide hydration. Especially, based on the systematic experimental design/implementation, particular structural characterizations and in-depth calculations, the pathway the newly developed catalyst going through has been investigated and determined to be an unusual bisubstrate-directly-activated cooperative mechanism (i.e. a bimolecular cooperative activation mechanism not involving Co(salen)–OH). The cooperative activation effect gives rise to the unexpectedly tremendously enhanced activity of our new catalyst, while no involving of Co(salen)–OH during the catalytic process leads to its best and unique catalytic stability in epoxide hydration among all the reported CoIII(salen)-based heterogeneous catalyst. It is believed that this study and the developed catalyst are of great significance for developing the catalytic hydration technology with low energy consumption and for developing high-performance heterogeneous catalysts. [ABSTRACT FROM AUTHOR]

Bacterium-like particles (BLP) are the peptidoglycan skeleton particles of lactic acid bacteria, which have high safety, mucosal delivery efficiency, and adjuvant effect. It has been widely used in recent years in the development of vaccines. Existing anchoring proteins for BLP surfaces are few in number, so screening and characterization of new anchoring proteins are necessary. In this research, we created the OACD (C-terminal domain of Escherichia coli outer membrane protein A) to serve as an anchoring protein on the surface of BLP produced by the immunomodulatory bacteria Levilactobacillus brevis 23017. We used red fluorescent protein (RFP) to demonstrate the novel surface display system's effectiveness, stability, and ability to be adapted to a wide range of lactic acid bacteria. Furthermore, this study employed this surface display method to develop a novel vaccine (called COB17) by using the multi-epitope antigen of Clostridium perfringens as the model antigen. The vaccine can induce more than 50% protection rate against C. perfringens type A challenge in mice immunized with a single dose and has been tested through three routes. The vaccine yields protection rates of 75% for subcutaneous, 50% for intranasal, and 75% for oral immunization. Additionally, it elicits a strong mucosal immune response, markedly increasing levels of specific IgG, high-affinity IgG, specific IgA, and SIgA antibodies. Additionally, we used protein anchors (PA) and OACD simultaneous to show several antigens on the BLP surface. The discovery of novel BLP anchoring proteins may expand the possibilities for creating mucosal immunity subunit vaccines. Additionally, it may work in concert with PA to provide concepts for the creation of multivalent or multiple vaccines that may be used in clinical practice to treat complex illnesses., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Niu, Gao, Ren, De, Jiang, Zhou, Liu, Li, Duan, Zhang, Wang and Ge.)

Exhausted CD8 + T cells represent a distinct cellular lineage that emerges during both chronic infections and cancers. Recent studies have shown that persistent antigen exposure can drive the differentiation of precursor exhausted CD8 + T cells, termed T pex cells, which are characterized as TCF-1 + PD-1 + CD8 + T cells. Elevated T pex cell frequencies in the tumor microenvironment (TME) are associated with improved overall survival (OS) in cancer patients and heightened responsiveness to anti-PD-1 therapy. In our present study, we utilized multi-color immunohistochemistry (mIHC) to determine the localization and clinical implications of tumor-infiltrating T pex cells within the TME of human colorectal cancer (CRC) tissues. We also conducted a multi-omics integrative analysis using single-cell RNA sequencing (scRNA-seq) data derived from both the murine MC38 tumor model and human CRC tissues. This analysis helped delineate the transcriptional and functional attributes of T pex cells within the CRC TME. Furthermore, we employed spatial transcriptome sequencing data from CRC patients to investigate the interactions between T pex cells and other immune cell subsets within the TME. In conclusion, our study not only established a method for T pex cell detection using mIHC technology but also confirmed that assessing T pex cells within the CRC TME could be indicative of patients' survival. We further uncovered the transcriptional and functional characteristics of T pex cells in the TME and ascertained their pivotal role in the efficacy of immunotherapy against CRC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Huang, Ge, Fang, Wu, Jiang, Lang, Chen, Xiao, Xu, Liu, Chen, Zheng and Jiang.)

Background: Immune-based therapies are commonly employed to combat hepatocellular carcinoma (HCC). However, the presence of immune-regulating elements, especially regulatory T cells (Tregs), can dramatically impact the treatment efficacy. A deeper examination of the immune-regulation mechanisms linked to these inhibitory factors and their impact on HCC patient outcomes is warranted., Methods: We employed multicolor fluorescence immunohistochemistry (mIHC) to stain Foxp3, cytokeratin, and nuclei on an HCC tissue microarray (TMA). Leveraging liver cancer transcriptome data from TCGA, we built a prognostic model focused on Treg-associated gene sets and represented it with a nomogram. We then sourced liver cancer single-cell RNA sequencing data (GSE140228) from the GEO database, selectively focusing on Treg subsets, and conducted further analyses, including cell-to-cell communication and pseudo-time trajectory examination., Results: Our mIHC results revealed a more substantial presence of Foxp3 + Tregs in HCC samples than in adjacent normal tissue samples ( P < .001). An increased presence of Foxp3 + Tregs in HCC samples correlated with unfavorable patient outcomes ( HR = 1.722, 95% CI :1.023-2.899, P = .041). The multi-factorial prognosis model we built from TCGA liver cancer data highlighted Tregs as a standalone risk determinant for predicting outcomes ( HR = 3.84, 95% CI: 2.52-5.83, P < .001). Re-analyzing the scRNA-seq dataset (GSE140228) showcased distinctive gene expression patterns in Tregs from varying tissues. Interactions between Tregs and other CD4 + T cell types were predominantly governed by the CXCL13/CXCR3 signaling pathway. Communication pathways between Tregs and macrophages primarily involved MIF-CD74/CXCR4, LGALS9/CD45, and PTPRC/MRC1. Additionally, macrophages could influence Tregs via HLA-class II and CD4 interactions., Conclusion: An elevated presence of Tregs in HCC samples correlated with negative patient outcomes. Elucidating the interplay between Tregs and other immune cells in HCC could provide insights into the modulatory role of Tregs within HCC tissues., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

TMP269, a small molecular inhibitor of IIa histone deacetylase, plays a vital role in cancer therapeutic. However, the effect of TMP269 on the regulation of viral replication has not been studied. In the present study, we found that TMP269 treatment significantly inhibited RABV replication at concentrations without significant cytotoxicity in a dose-dependent manner. In addition, TMP269 can reduce the viral titers and protein levels of RABV at an early stage in the viral life cycle. RNA sequencing data revealed that immune-related pathways and autophagy-related genes were significantly downregulated after RABV infection treated with TMP269. Further exploration shows that autophagy enhances RABV replication in HEK-293T cells, while TMP269 can inhibit autophagy to decrease RABV replication. Together, these results provide a novel treatment strategy for rabies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yin, Wang, Ren, Liang, Ge, Sun, Yin and Wang.)