A vascularized adipose organoid model using stromal vascular fraction cells from ruminant animals.

In vitro cell culture serves as an efficient system for studying animal cell behavior in a controlled setting. Here, we present a 3D culture model for forming ruminant adipose organoids using stromal vascular fraction cells. We describe steps for forming cell spheroids and growing them on a Matrigel-coated surface. We then detail procedures for inducing organoids to undergo angiogenesis and adipogenesis followed by capillary sprouting. This protocol can be utilized to study the interaction between blood vessels and adipocytes. For complete details on the use and execution of this protocol, please refer to Yu et al.1.

Characterization of Probiotic Properties and Whole-Genome Analysis of Lactobacillus johnsonii N5 and N7 Isolated from Swine.

In our previous microbiome profiling analysis, Lactobacillus (L.) johnsonii was suggested to contribute to resistance against chronic heat stress-induced diarrhea in weaned piglets. Forty-nine L. johnsonii strains were isolated from these heat stress-resistant piglets, and their probiotic properties were assessed. Strains N5 and N7 exhibited a high survival rate in acidic and bile environments, along with an antagonistic effect against Salmonella. To identify genes potentially involved in these observed probiotic properties, the complete genome sequences of N5 and N7 were determined using a combination of Illumina and nanopore sequencing. The genomes of strains N5 and N7 were found to be highly conserved, with two N5-specific and four N7-specific genes identified. Multiple genes involved in gastrointestinal environment adaptation and probiotic properties, including acidic and bile stress tolerance, anti-inflammation, CAZymes, and utilization and biosynthesis of carbohydrate compounds, were identified in both genomes. Comparative genome analysis of the two genomes and 17 available complete L. johnsonii genomes revealed 101 genes specifically harbored by strains N5 and N7, several of which were implicated in potential probiotic properties. Overall, this study provides novel insights into the genetic basis of niche adaptation and probiotic properties, as well as the genome diversity of L. johnsonii.

Stenotrophomonas maltophilia contributes to smoking-related emphysema through IRF1-triggered PANoptosis of alveolar epithelial cells.

Cigarette smoke (CS), the main source of indoor air pollution and the primary risk factor for respiratory diseases, contains chemicals that can perturb microbiota through antibiotic effects. Although smoking induces a disturbance of microbiota in the lower respiratory tract, whether and how it contributes to initiation or promotion of emphysema are not well clarified. Here, we demonstrated an aberrant microbiome in lung tissue of patients with smoking-related COPD. We found that Stenotrophomonas maltophilia (S. maltophilia) was expanded in lung tissue of patients with smoking-related COPD. We revealed that S. maltophilia drives PANoptosis in alveolar epithelial cells and represses formation of alveolar organoids through IRF1 (interferon regulatory factor 1). Mechanistically, IRF1 accelerated transcription of ZBP1 (Z-DNA Binding Protein 1) in S. maltophilia-infected alveolar epithelial cells. Elevated ZBP1 served as a component of the PANoptosome, which triggered PANoptosis in these cells. By using of alveolar organoids infected by S. maltophilia, we found that targeting of IRF1 mitigated S. maltophilia-induced injury of these organoids. Moreover, the expansion of S. maltophilia and the expression of IRF1 negatively correlated with the progression of emphysema. Thus, the present study provides insights into the mechanism of lung dysbiosis in smoking-related COPD, and presents a potential target for mitigation of COPD progression.

Ficus awkeotsang Makino pectin in acidic environments: Insights into pectin structure, gelation behavior, and gel properties.

This study demonstrated the gelation capacity, gelation behavior, and mechanism of Ficus awkeotsang Makino pectin (JFSP) in acidic media (pH 3.4-4.5). JFSP exhibited an extraordinary ability to spontaneously form a gel at a low polymer concentration (0.3 %, w/v) within the pH range of 3.75-4.05 at room temperature, without the need to introduce exogenous metal ions or co-solutes. Analysis of zeta potential and carboxyl dissociation extent revealed the protonation of free carboxyl groups within JFSP under acidic conditions. Atomic force microscopy and small angle X-ray scattering elucidated the aggregation morphology and folding conformation of JFSP. At pH 3.8, the correlation length (ξ) of JFSP chains decreased to around 1.67 nm. Rheological experiments confirmed the formation of a stronger gel network at pH 3.8 and 4.0, with good thermal and freeze-thaw stability. Isothermal Titration Calorimetry (ITC), temperature sweeps, and gelation force analyses emphasized the pivotal role of hydrogen bonds in JFSP gels at pH 3.8 and 4.0. Further reducing the pH to 3.4-3.6 disrupted the dynamic equilibrium of gel-driving forces, leading to the formation of a flocculated gel network. These findings deepen our understanding of JFSP behavior in low-acid conditions, which may be useful for further food formulations at these conditions.

Dermatophagoides farinae microRNAs released to external environments via exosomes regulate inflammation-related gene expression in human bronchial epithelial cells.

Background: Dermatophagoides farinae (DFA) is an important species of house dust mites (HDMs) that causes allergic diseases. Previous studies have focused on allergens with protein components to explain the allergic effect of HDMs; however, there is little knowledge on the role of microRNAs (miRNAs) in the allergic effect of HDMs. This study aimed to unravel the new mechanism of dust mite sensitization from the perspective of cross-species transport of extracellular vesicles-encapsulated miRNAs from HDMs. Methods: Small RNA (sRNA) sequencing was performed to detect miRNAs expression profiles from DFA, DFA-derived exosomes and DFA culture supernatants. A quantitative fluorescent real-time PCR (qPCR) assay was used to detect miRNAs expression in dust specimens. BEAS-2B cells endocytosed exosomes were modeled in vitro to detect miRNAs from DFA and the expression of related inflammatory factors. Representative dfa-miR-276-3p and dfa-novel-miR2 were transfected into BEAS-2B cells, and then differentially expressed genes (DEGs) were analyzed by RNA sequencing. Protein-protein interaction (PPI) network analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) terms enrichment analyses were performed on the first 300 nodes of DEGs. Results: sRNA sequencing identified 42 conserved miRNAs and 66 novel miRNAs in DFA, DFA-derived exosomes, and DFA culture supernatants. A homology analysis was performed on the top 18 conserved miRNAs with high expression levels. The presence of dust mites and miRNAs from HDMs in living environment were also validated. Following uptake of DFA-derived exosomes by BEAS-2B cells, exosomes transported miRNAs from DFA to target cells and produced pro-inflammatory effects in corresponding cells. RNA sequencing identified DEGs in dfa-miR-276-3p and dfa-novel-miR2 transfected BEAS-2B cells. GO and KEGG enrichment analyses revealed the role of exosomes with cross-species transporting of DFA miRNAs in inflammatory signaling pathways, such as JAK-STAT signaling pathway, PI3K/AKT signaling pathway and IL-6-mediated signaling pathway. Conclusion: Our findings demonstrate the miRNAs expression profiles in DFA for the first time. The DFA miRNAs are delivered into living environments via exosomes, and engulfed by human bronchial epithelial cells, and cross-species regulation may contribute to inflammation-related processes.

Relationship between Components, Intestinal Microbiota, and Mechanism of Hypoglycemic Effect of the Saggy Ink Cap Medicinal Mushroom (Coprinus Comatus, Agaricomycetes): A Review.

Coprinus comatus is rich in a variety of nutrients, which has been reported to display a good hypoglycemic effect. However, there is no consensus on the hypoglycemic mechanism of this mushroom. Intestinal microbiota, a complex and intrinsic system, is closely related to metabolism. In this review, we discussed the potential relationship between certain components of C. comatus and intestinal microbiota to illustrate the possible hypoglycemic mechanism of C. comatus through intestinal microbiota. It will provide a new perspective for the study of hypoglycemic mechanism of C. comatus and promote the development and utilization of this mushroom.

Expression Profiles of circRNAs and Identification of hsa_circ_0007608 and hsa_circ_0064656 as Potential Biomarkers for COPD-PH Patients.

Introduction: Pulmonary hypertension (PH) is a common complication of chronic obstructive pulmonary disease (COPD), which can worsen the prognosis and increase the mortality of COPD patients. Circular RNA (circRNA) has been discovered to participate in the occurrence and progression of PH in COPD and may have significant prospects for advanced diagnostics and prognosis evaluation. However, the expression profile of circRNAs in human lung tissues with definite diagnosis of COPD-PH remains to be further explored and validated. Methods: Twelve human lung tissue samples (6 each from COPD-PH and control groups) were collected and subjected to high-throughput sequencing. QRT-PCR was performed to validate the differential expression levels of the top 10 dysregulated circRNAs in patients' plasma samples, HPAECs and HPASMCs. Functional and pathway enrichment analysis on target genes was performed to explore the potential functions and pathways of those circRNAs. Hub genes obtained after conducting bioinformatics analysis on the predicted target mRNAs were verified by qRT-PCR in HPAECs and HPASMCs, and then we selected VCAN as a potential key gene involved in the pathogenesis of COPD-PH for immunohistochemistry validation in lung tissue. Results: A total of 136 circRNAs (39 up-regulated and 97 down-regulated) were differentially expressed between the two groups. Following qRT-PCR validation, two circRNAs (hsa_circ_0007608 and hsa_circ_0064656) were believed to be involved in the pathogenesis. GO and KEGG pathway analysis suggested that these two DECs were mainly related to the celluar proliferation, migration and EndMT. PPI network revealed 11 pairs of key mRNAs. VCAM1, VCAN and THBS1, three hub mRNAs with the highest reliability among all, were validated and proven to be up-regulated in COPD-PH. We innovatively found that VCAN may be involved in COPD-PH. Conclusion: This study identified the functional circRNAs, providing insights into the molecular mechanisms and predictions of COPD-PH, and may provide potential diagnostic biomarkers or therapeutic targets for COPD-PH.

Exosomes Derived from Dermatophagoides farinae Induce Allergic Airway Inflammation.

House dust mites (HDMs) are a major source of indoor allergens that cause airway allergic disease. Dermatophagoides farinae, a predominant species of HDMs in China, has demonstrated pathogenic role in allergic disorders. Exosomes derived from human bronchoalveolar lavage fluid have been strongly associated with allergic respiratory diseases progression. However, the pathogenic role of D. farinae-derived exosomes in allergic airway inflammation has remained unclear until now. Here, D. farinae was stirred overnight in phosphate-buffered saline, and the supernatant was used to extract exosomes by ultracentrifugation. Then, shotgun liquid chromatography-tandem mass spectrometry and small RNA sequencing were performed to identify proteins and microRNAs contained in D. farinae exosomes. Immunoblotting, Western blotting, and enzyme-linked immunosorbent assay demonstrated the specific immunoreactivity of D. farinae-specific serum IgE antibody against D. farinae exosomes, and D. farinae exosomes were found to induce allergic airway inflammation in a mouse model. In addition, D. farinae exosomes invaded 16-HBE bronchial epithelial cells and NR8383 alveolar macrophages to release the inflammation-related cytokines interleukin-33 (IL-33), thymic stromal lymphopoietin, tumor necrosis factor alpha, and IL-6, and comparative transcriptomic analysis of 16-HBE and NR8383 cells revealed that immune pathways and immune cytokines/chemokines were involved in the sensitization of D. farinae exosomes. Taken together, our data demonstrate that D. farinae exosomes are immunogenic and may induce allergic airway inflammation via bronchial epithelial cells and alveolar macrophages. IMPORTANCE Dermatophagoides farinae, a predominant species of house dust mites in China, has displayed pathogenic role in allergic disorders, and exosomes derived from human bronchoalveolar lavage fluid have been strongly associated with allergic respiratory diseases progression. However, the pathogenic role of D. farinae-derived exosomes in allergic airway inflammation has remained unclear until now. This study, for the first time, extracted exosomes from D. farinae, and sequenced their protein cargo and microRNAs using shotgun liquid chromatography-tandem mass spectrometry and small RNA sequencing. D. farinae-derived exosomes trigger allergen-specific immune responses and present satisfactory immunogenicity, as revealed by immunoblotting, Western blotting, and enzyme-linked immunosorbent assay and may induce allergic airway inflammation via bronchial epithelial cells and alveolar macrophages. Our data provide insights into the mechanisms of allergic airway inflammation caused with D. farinae-derived exosomes and the treatment of house dust mite-induced allergic airway inflammation.

NOD1 mediated D. pteronyssinus-induced allergic airway inflammation through RIP2/NF-κB.

BACKGROUND: Dermatophagoides pteronyssinus (D. pteronyssinus) is the main cause of allergic airway inflammation. As the earliest intracytoplasmic pathogen recognition receptors (PRR), NOD1 has been identified as key inflammatory mediator in NOD-like receptor (NLR) family. OBJECTIVE: Our primary aim is to elucidate whether NOD1 and its downstream regulatory proteins mediate D. pteronyssinus-induced allergic airway inflammation. METHODS: Mouse and cell models of D. pteronyssinus-induced allergic airway inflammation were established. NOD1 was inhibited in bronchial epithelium cells (BEAS-2B cells) and mice by cell transfection or application of inhibitor. The change of downstream regulatory proteins was detected by quantitative real-time PCR (qRT-PCR) and Western blot. The relative expression of inflammatory cytokines was evaluated by ELISA. RESULTS: The expression level of NOD1 and its downstream regulatory proteins increased in BEAS-2B cells and mice after treating with D. pteronyssinus extract, followed by the aggravation of inflammatory response. Moreover, inhibition of NOD1 decreased the inflammatory response, which also downregulated the expression of downstream regulatory proteins and inflammatory cytokines. CONCLUSIONS: NOD1 involves in the development of D. pteronyssinus-induced allergic airway inflammation. Inhibition of NOD1 reduces D. pteronyssinus-induced airway inflammation.

Poly-pathways metabolomics for high-yielding cordycepin of Cordyceps militaris.

Cordycepin is an important quality control marker in Cordyceps militaris. This study aimed to explain the metabolic mechanisms for high-yielding cordycepin of C. militaris. In this study, high-yielding strains of cordycepin were obtained by ultraviolet mutagenesis, and the polysaccharide and protein contents were also changed. In high-yielding strains, the protein content significantly increased, whereas the polysaccharide content decreased. Simultaneously, metabolic differences for high- and low-yielding cordycepin strains were detected by metabolomics. Metabolomics results showed that the relative content of most metabolites decreased in high-yielding cordycepin strains. Various metabolic pathways have been altered in high-yielding cordycepin strains, such as the citric acid cycle, purine metabolism, and pyrimidine metabolism, leading to an increase in cordycepin content. In addition, changes in metabolic poly-pathways related to polysaccharide and protein synthesis, such as galactose metabolism and amino acid metabolism, promoted an increase in cordycepin content. This study analyzes the high yield of cordycepin in C. militaris at the metabolic level and provides a theoretical basis for further increasing cordycepin content.

A balanced gut microbiota is essential to maintain health in captive sika deer.

Certain animals harbor a high proportion of pathogens, particular the zoonotic pathogens, in their gut microbiome but are usually asymptomic; however, their carried pathogens may seriously threaten the public health. By understanding how the microbiome overcomes the negative effects of pathogens to maintain host health, we can develop novel solutions to control animal-mediated pathogen transmission including identification and application of beneficial microbes. Here, we analyzed the gut microbiota of 10 asymptomic captive sika deer individuals by full-length 16S rDNA sequencing. Twenty-nine known pathogens capable of infecting humans were identified, and the accumulated proportions of the identified pathogens were highly variable among individuals (2.33 to 39.94%). The relative abundances of several beneficial bacteria, including Lactobacillus and Bifidobacterium, were found to be positively correlated with the relative abundances of accumulated pathogens. Whole-genome metagenomic analysis revealed that the beneficial- and pathogenic-associated functions, such as genes involved in the synthesis of short chain fatty acids and virulence factors, were also positively correlated in the microbiome, indicating that the beneficial and pathogenic functions were maintained at a relatively balanced ratio. Furthermore, the bacteriophages that target the identified pathogens were found to be positively correlated with the pathogenic content in the microbiome. Several high-quality genomes of beneficial bacteria affiliated with Lactobacillus and Bifidobacterium and bacteriophages were recovered from the metagenomic data. Overall, this study provides novel insights into the interplay between beneficial and pathogenic content to ensure maintenance of a healthy gut microbiome, and also contributes to discovery of novel beneficial microbes and functions that control pathogens. KEY POINTS: • Certain asymptomic captive sika deer individuals harbor relatively high amounts of zoonotic pathogens. • The beneficial microbes and the beneficial functions are balanced with the pathogenic contents in the gut microbiome. • Several high-quality genomes of beneficial bacteria and bacteriophages are recovered by metagenomics.

A Novel Preparation of Special-Shaped Phosphors-in-Glass by Gel Casting with Isobam for High-Power WLEDs Lighting.

Phosphors-in-glass (PiGs) regarded as a promising phosphor-converter for white light emitting diodes (WLEDs) is being researched widely. However, there are few reports on the effect of changing the shape of PiGs on the color rendering index (CRI) and heat dissipation of WLEDs. In this paper, gel casting with Isobam was first attempted in preparing special-shaped PiGs successfully. It exhibited that 76 wt.% was the optimum solid content based on the rheological properties of slurry and the shrinkage of green bodies. The sintering rate should be kept at a low speed and glass transition temperature (Tg) of glass powders must be higher than sublimation temperatures (Ts) of APS and Isobam. The CRI of PiGs was increased by about 27% after changing the shape of PiGs from cylinder to dome. Most importantly, operating temperature also reduced effectively the increase of the surface area of PiGs. Therefore, changing the shape of PiGs by gel casting with Isobam is a creative way for high-power WLEDs lighting.

Prophage-mediated genome differentiation of the Salmonella Derby ST71 population.

Although Salmonella Derby ST71 strains have been recognized as poultry-specific by previous studies, multiple swine-associated S. Derby ST71 strains were identified in this long-term, multi-site epidemic study. Here, 15 representative swine-associated S. Derby ST71 strains were sequenced and compared with 65 (one swine-associated and 64 poultry-associated) S. Derby ST71 strains available in the NCBI database at a pangenomic level through comparative genomics analysis to identify genomic features related to the differentiation of swine-associated strains and previously reported poultry-associated strains. The distribution patterns of known Salmonella pathogenicity islands (SPIs) and virulence factor (VF) encoding genes were not capable of differentiating between the two strain groups. The results demonstrated that the S. Derby ST71 population harbours an open pan-genome, and swine-associated ST71 strains contain many more genes than the poultry-associated strains, mainly attributed to the prophage sequence contents in the genomes. The numbers of prophage sequences identified in the swine-associated strains were higher than those in the poultry-associated strains. Prophages specifically harboured by the swine-associated strains were found to contain genes that facilitate niche adaptation for the bacterial hosts. Gene deletion experiments revealed that the dam gene specifically present in the prophage of the swine-associated strains is important for S. Derby to adhere onto the host cells. This study provides novel insights into the roles of prophages during the genome differentiation of Salmonella.

Application and mechanism of probiotics in skin care: A review.

BACKGROUND: Skin problems have been the focus of attention in recent years. Skin aging, wrinkles, pigmentation, dryness has been a problem that makes people feel troubled. Researchers have been devoted to find ways to solve these skin problems. Micro-ecological skin care is a popular concept these days, and improving skin health through the use of probiotics is a hot topic of discussion. OBJECTIVE: Many experimental studies have shown that probiotics have a good effect on improving skin problems. This paper aims to comprehensively review the application and mechanism of probiotics in skin care and provide theoretical basis for the application of probiotics in skin care. METHODS: Literatures in this review were searched in PubMed, China National Knowledge Infrastructure (CNKI), Web of Science, and Science Direct. RESULTS: Probiotics have potent effects on skin whitening, moisturizing, anti-aging, anti-wrinkle and removing body odor. CONCLUSIONS: The effects of probiotics on skin whitening, skin moisturizing, anti-aging, improving skin wrinkles and removing body odor were reviewed, which provided a new basis for the extensive application of probiotics in skin care.

Regulatory T cell deficiency in patients with eosinophilic asthma.

BACKGROUND: There is a lack of information about regulatory T cells (Tregs) and inflammatory phenotypes in patients with asthma. In this study, we aimed to compare the characteristics of Tregs in patients with eosinophilic asthma. METHODS: Forty healthy and 120 stable asthmatic patients were recruited. Sputum and airway inflammatory phenotypes were assessed, and all patients were followed for one year. Human peripheral blood mononuclear cells (PBMCs) were collected and stimulated with phytohemagglutinin (PHA) and Dermatophagoides farina (Derp) to detect CD4+CD25+FOXP3+T cells and Foxp3 levels. Interleukin (IL)-13, IL-5, IL-17, IL-9, and interferon (IFN)-γ levels were measured. RESULTS: 38.33% of patients had eosinophilic asthma, 13.33% had neutrophilic asthma, 6.67% had mixed granulocytic asthma, and 41.67% had pauci-granulocytic asthma. The eosinophilic asthma patients had a relatively high Asthma Control Test (ACT) score, an increased prediction and improvement FEV1 (%) rate, and elevated total IgE serum levels (P < 0.05). T helper cell 2 (Th2) cytokines IL-13 and IL-5 were predominantly expressed in the eosinophilic phenotype, while the Th1 cytokine IFN-γ and Th17 cytokine were found in the neutrophilic phenotype. IL-10 was significantly lower in eosinophilic asthmatic patients compared to the controls (P < 0.05). CD4+CD25+FOXP3+T cells (%Tregs) and Foxp3 gene expression in the PHA stimulated eosinophilic asthma samples were significantly lower compared to the control samples (P < 0.05). The airway inflammation phenotypes remained stable after one-year of therapy. CONCLUSION: Asthmatic patients with the eosinophilic phenotype in this study were deficient in Tregs, as characterized by a Th2 cell-biased pattern.

Clinical characteristics and genetic analysis of a Chinese pedigree of type 2 diabetes complicated with interstitial lung disease.

Purpose: Diabetes mellitus is a systemic metabolic disorder which may target the lungs and lead to interstitial lung disease. The clinical characteristics and mechanisms of type 2 diabetes mellitus (T2DM) complicated with interstitial lung disease (ILD) have been studied. However, little work has been done to assess genetic contributions to the development of T2DM complicated with ILD. Method: A pedigree of T2DM complicated with ILD was investigated, and the whole genome re-sequencing was performed to identify the genetic variations in the pedigree. According to the literature, the most valuable genetic contributors to the pathogenesis of T2DM complicated with ILD were screened out, and the related cellular functional experiments were also performed. Results: A large number of SNPs, InDels, SVs and CNVs were identified in eight subjects including two diabetic patients with ILD, two diabetic patients without ILD, and four healthy subjects from the pedigree. After data analysis according to the literature, MUC5B SNP rs2943512 (A > C) was considered to be an important potentially pathogenic gene mutation associated with the pathogenesis of ILD in T2DM patients. In vitro experiments showed that the expression of MUC5B in BEAS-2B cells was significantly up-regulated by high glucose stimulation, accompanied by the activation of ERK1/2 and the increase of IL-1ß and IL-6. When silencing MUC5B by RNA interference, the levels of p-ERK1/2 as well as IL-1ß and IL-6 in BEAS-2B cells were all significantly decreased. Conclusion: The identification of these genetic variants in the pedigree enriches our understanding of the potential genetic contributions to T2DM complicated with ILD. MUC5B SNP rs2943512 (A > C) or the up-regulated MUC5B in bronchial epithelial cells may be an important factor in promoting ILD inT2DM patients, laying a foundation for future exploration about the pathogenesis of T2DM complicated with ILD.

Rapid and Accurate Campylobacter jejuni Detection With CRISPR-Cas12b Based on Newly Identified Campylobacter jejuni-Specific and -Conserved Genomic Signatures.

Campylobacter jejuni is among the most prevalent foodborne zoonotic pathogens leading to diarrheal diseases. In this study, we developed a CRISPR-Cas12b-based system to rapidly and accurately detect C. jejuni contamination. Identification of C. jejuni-specific and -conserved genomic signatures is a fundamental step in development of the detection system. By comparing C. jejuni genome sequences with those of the closely related Campylobacter coli, followed by comprehensive online BLAST searches, a 20-bp C. jejuni-conserved (identical in 1024 out of 1037 analyzed C. jejuni genome sequences) and -specific (no identical sequence detected in non-C. jejuni strains) sequence was identified and the system was then assembled. In further experiments, strong green fluorescence was observed only when C. jejuni DNA was present in the system, highlighting the specificity of this system. The assay, with a sample-to-answer time of ∼40 min, positively detected chicken samples that were contaminated with a dose of approximately 10 CFU C. jejuni per gram of chicken, which was >10 times more sensitive than the traditional Campylobacter isolation method, suggesting that this method shows promise for onsite C. jejuni detection. This study provides an example of bioinformatics-guided CRISPR-Cas12b-based detection system development for rapid and accurate onsite pathogen detection.

Genome-Wide Identification of Genes Involved in Acid Stress Resistance of Salmonella Derby.

Resistance to and survival under acidic conditions are critical for Salmonella to infect the host. As one of the most prevalent serotypes identified in pigs and humans, how S. Derby overcomes acid stress remains unclear. Here, we de novo sequenced the genome of a representative S. Derby strain 14T from our S. Derby strain stock and identified its acid resistance-associated genes using Tn-seq analysis. A total of 35 genes, including those belonging to two-component systems (TCS) (cpxAR), the CRISPR-Cas system (casCE), and other systems, were identified as essential for 14T to survive under acid stress. The results demonstrated that the growth curve and survival ability of ΔcpxA and ΔcpxR were decreased under acid stress, and the adhesion and invasion abilities to the mouse colon cancer epithelial cells (MC38) of ΔcpxR were also decreased compared with the wild type strain, suggesting that the TCS CpxAR plays an essential role in the acid resistance and virulence of S. Derby. Also, CasC and CasE were found to be responsible for acid resistance in S. Derby. Our results indicate that acid stress induces multiple genes' expression to mediate the acid resistance of S. Derby and enhance its pathogenesis during an infection.

Role of HDAC6 inhibition in sepsis-induced acute respiratory distress syndrome (Review).

Acute respiratory distress syndrome (ARDS) induced by sepsis contributes remarkably to the high mortality rate observed in intensive care units, largely due to a lack of effective drug therapies. Histone deacetylase 6 (HDAC6) is a class-IIb deacetylase that modulates non-nuclear protein functions via deacetylation and ubiquitination. Importantly, HDAC6 has been shown to exert anti-cancer, anti-neurodegeneration, and immunological effects, and several HDAC6 inhibitors have now entered clinical trials. It has also been recently shown to modulate inflammation, and HDAC6 inhibition has been demonstrated to markedly suppress experimental sepsis. The present review summarizes the role of HDAC6 in sepsis-induced inflammation and endothelial barrier dysfunction in recent years. It is proposed that HDAC6 inhibition predominantly ameliorates sepsis-induced ARDS by directly attenuating inflammation, which modulates the innate and adaptive immunity, transcription of pro-inflammatory genes, and protects endothelial barrier function. HDAC6 inhibition protects against sepsis-induced ARDS, thereby making HDAC6 a promising therapeutic target. However, HDAC inhibition may be associated with adverse effects on the embryo sac and oocyte, necessitating further studies.

Microecology research: a new target for the prevention of asthma.

The incidence and prevalence of asthma have increased remarkably in recent years. There are lots of factors contributing to the occurrence and development of asthma. With the improvement of sequencing technology, it has been found that the microbiome plays an important role in the formation of asthma in early life. The roles of the microbial environment and human microbiome in the occurrence and development of asthma have attracted more and more attention. The environmental microbiome influences the occurrence of asthma by shaping the human microbiome. The specific mechanism may be related to the immune regulation of Toll-like receptors and T cells (special Tregs). Intestinal microbiome is formed and changed by regulating diet and lifestyle in early life, which may affect the development and maturation of the pulmonary immune system through the intestinal-pulmonary axis. It is well-recognized that both environmental microbiomes and human microbiomes can influence the onset of asthma. This review aims to summarize the recent advances in the research of microbiome, its relationship with asthma, and the possible mechanism of the microbiome in the occurrence and development of asthma. The research of the microbial environment and human microbiome may provide a new target for the prevention of asthma in children who have high-risk factors to allergy. However, further study of "when and how" to regulate microbiome is still needed.