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Background and Aims: Human studies suggest that a high intake of polyunsaturated fatty acid (PUFA) is associated with an increased risk of inflammatory bowel disease (IBD). PUFA is highly prone to oxidation. To date, it is unclear whether unoxidized or oxidized PUFA is involved in the development of IBD. Here, we aim to compare the effects of unoxidized PUFA vs. oxidized PUFA on the development of IBD and associated colorectal cancer., Methods: We evaluated the effects of unoxidized and oxidized PUFA on dextran sodium sulfate (DSS)- and IL-10 knockout-induced colitis, and azoxymethane (AOM)/DSS-induced colon tumorigenesis in mice. Additionally, we studied the roles of gut microbiota and Toll-like receptor 4 (TLR4) signaling involved., Results: Administration of a diet containing oxidized PUFA, at human consumption-relevant levels, increases the severity of colitis and exacerbates the development of colitis-associated colon tumorigenesis in mice. Conversely, a diet rich in unoxidized PUFA doesn't promote colitis. Furthermore, oxidized PUFA worsens colitis-associated intestinal barrier dysfunction and leads to increased bacterial translocation, and it fails to promote colitis in Toll-like receptor 4 (TLR4) knockout mice. Finally, oxidized PUFA alters the diversity and composition of gut microbiota, and it fails to promote colitis in mice lacking the microbiota., Conclusions: These results support that oxidized PUFA promotes the development of colitis and associated tumorigenesis in mouse models via TLR4- and gut microbiota-dependent mechanisms. Our findings highlight the potential need to update regulation policies and industrial standards for oxidized PUFA levels in food., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Transcription factors (TFs) are crucial pre-transcriptional regulatory mechanisms that can modulate the expression of downstream genes by binding to their promoter regions. DOF (DNA binding with One Finger) proteins are a unique class of TFs with extensive roles in plant growth and development. Our previous research indicated that iron content varies among bamboo leaves of different colors. However, to our knowledge, genes related to iron metabolism pathways in bamboo species have not yet been studied. Therefore, in the current study, we identified iron metabolism related (IMR) genes in bamboo and determined the TFs that significantly influence them. Among these, DOFs were found to have widespread effects and potentially significant impacts on their expression. We identified specific DOF members in Dendrocalamus latiflorus with binding abilities through homology with Arabidopsis DOF proteins, and established connections between some of these members and IMR genes using RNA-seq data. Additionally, molecular docking confirmed the binding interactions between these DlDOFs and the DOF binding sites in the promoter regions of IMR genes. The co-expression relationship between the two gene sets was further validated using q-PCR experiments. This study paves the way for research into iron metabolism pathways in bamboo and lays the foundation for understanding the role of DOF TFs in D. latiflorus .

Objective: To investigate the effect of zirconia personalized gingival structure on peri-implant soft and hard tissue stability after single-tooth implant restorations in patients with thin gingival biotypes in the anterior region, with a view to provide a clinical guideline. Methods: This retrospective study included 20 patients with thin gingival biotype and implant restorations in the anterior region. These patients included 9 males and 11 females, and the age was (35.2± 10.3) years. The patients were from the Department of Periodontal Implantology, Stomatology Hospital, Southern Medical University from January 2018 to December 2022. Computer-aided design/computer-aided manufacturing (CAD/CAM) techniques were used to fabricate a titanium base zirconia personalized gingival structure to maintain the soft-tissue perforated gingival contour of the anterior esthetic zone. This structure consists of two modalities: titanium base + zirconia outer crown or titanium base personalized zirconia abutment + zirconia outer crown. Clinical outcomes were recorded immediately and after delivery of the final restorations. Implant retention was recorded, esthetic scoring was performed using the pink esthetic index, the amount of bone resorption at the implant margins was measured based on digitized apical radiographs, and periodontal health was evaluated using the modified plaque index and the modified bleeding index. Results: The survival rate of the 20 implants was 100% after 3 years of wearing the final restorations, with a pink aesthetic score of 9.3±0.9. Bone resorption at the proximal and distal mesial margins of the implants was 0.09 (-0.21, 0.20) mm, 0.17 (-0.12, 0.27) mm after 3 years, respectively, and the difference was not statistically significant when compared to bone resorption immediately after placement of the final restoration [0(0, 0) mm] ( Z =-1.03, P =0.394; Z =-2.05, P =0.065). Conclusions: Zirconia personalized gingival structure maintains the stability of peri-implant hard and soft tissues of thin gingival biotypes in the anterior region.

This study aims to explore the effect of Lycii Fructus and Salviae Miltiorrhizae Radix et Rhizoma(LFSMR), a drug pair possesses the function of nourishing Yin, promoting blood circulation, and brightening the eyes, in treating retinitis pigmentosa(RP)by inhibiting the gliosis of Müller cells(MCs) and inducing their reprogramming and differentiation into various types of retinal nerve cells. Twelve C57 mice were used as the normal control group, and 48 transgenic RP(rd10) mice were randomly divided into the model group, positive control group, and low and high dose LFSMR groups, with 12 mice in each group. HE staining was used to detect pathological changes in the retina, and an electroretinogram was used to detect retinal function. Retinal optical coherence tomography was used to detect retinal thickness and perform fundus photography, and laser speckle perfusion imaging was used to detect local retinal blood flow. Digital PCR was used to detect gene expression related to retinal nerve cells, and immunofluorescence was used to detect protein expression related to retinal nerve cells. LFSMR could significantly improve the pathological changes, increase the amplitude of a and b waves, increase the retinal thickness, restore retinal damage, and increase retinal blood flow in mice with RP lesions. LFSMR could also significantly inhibit the m RNA expression of the glial fibrillary acidic protein( GFAP) during the pathogenesis of RP and upregulate m RNA expression of sex determining region Y box protein 2(SOX2), paired box protein 6(Pax6),rhodopsin, protein kinase C-α(PKCα), syntaxin, and thymic cell antigen 1. 1(Thy1. 1). LFSMR could significantly inhibit GFAP protein expression and enhance protein expression of SOX2, Pax6, rhodopsin, PKCα, syntaxin, and Thy1. 1. It could also reverse the pathological changes in the retina of rd10 mice, improve retinal function and fundus performance, increase retinal thickness, enhance local retinal blood flow, and exert therapeutic effects on RP. The mechanism of action of LFSMR may be related to inhibiting the gliosis of MCs and promoting their reprogramming and differentiation into various types of retinal nerve cells.

The gut microbiota promotes immune system development in early life, but the interactions between the gut metabolome and immune cells in the neonatal gut remain largely undefined. Here, we demonstrate that the neonatal gut is uniquely enriched with neurotransmitters, including serotonin, and that specific gut bacteria directly produce serotonin while down-regulating monoamine oxidase A to limit serotonin breakdown. We found that serotonin directly signals to T cells to increase intracellular indole-3-acetaldehdye and inhibit mTOR activation, thereby promoting the differentiation of regulatory T cells, both ex vivo and in vivo in the neonatal intestine. Oral gavage of serotonin into neonatal mice resulted in long-term T cell-mediated antigen-specific immune tolerance toward both dietary antigens and commensal bacteria. Together, our study has uncovered an important role for specific gut bacteria to increase serotonin availability in the neonatal gut and identified a function of gut serotonin in shaping T cell response to dietary antigens and commensal bacteria to promote immune tolerance in early life.

Bulbophyllum is one of the largest genera and presents some of the most intricate taxonomic problems in the family Orchidaceae, including species of ornamental and medical importance. The lack of knowledge regarding the characterization of Bulbophyllum chloroplast (cp) genomes has imposed current limitations on our study. Here, we report the complete cp genomes of seven Bulbophyllum species, including B . ambrosia , B . crassipes , B . farreri , B . hamatum , B . shanicum , B . triste , and B . violaceolabellum , and compared with related taxa to provide a better understanding of their genomic information on taxonomy and phylogeny. A total of 28 Bulbophyllum cp genomes exhibit typical quadripartite structures with lengths ranging from 145,092 bp to 165,812 bp and a GC content of 36.60% to 38.04%. Each genome contained 125-132 genes, encompassing 74-86 protein-coding genes, 38 tRNA genes, and eight rRNA genes. The genome arrangements, gene contents, and length were similar, with differences observed in ndh gene composition. It is worth noting that there were exogenous fragment insertions in the IR regions of B . crassipes . A total of 18-49 long repeats and 38-80 simple sequence repeats (SSRs) were detected and the single nucleotide (A/T) was dominant in Bulbophyllum cp genomes, with an obvious A/T preference. An analysis of relative synonymous codon usage (RSCU) revealed that leucine (Leu) was the most frequently used codon, while cysteine (Cys) was the least used. Six highly variable regions ( rpl32 - trnL UAG > trnT UGU - trnL UAA > trnF GAA - ndhJ > rps15 - ycf1 > rbcL - accD > psbI - trnS GCU ) and five coding sequences ( ycf1 > rps12 > matK > psbK > rps15 ) were identified as potential DNA markers based on nucleotide diversity. Additionally, 31,641 molecular diagnostic characters (MDCs) were identified in complete cp genomes. A phylogenetic analysis based on the complete cp genome sequences and 68 protein-coding genes strongly supported that 28 Bulbophyllum species can be divided into four branches, sects. Brachyantha , Cirrhopetalum , and Leopardinae , defined by morphology, were non-monophyly. Our results enriched the genetic resources of Bulbophyllum , providing valuable information to illustrate the complicated taxonomy, phylogeny, and evolution process of the genus.

The diversity of leaf characteristics, particularly leaf color, underscores a pivotal area of inquiry within plant science. The synthesis and functionality of chlorophyll, crucial for photosynthesis, largely dictate leaf coloration, with varying concentrations imparting different shades of green. Complex gene interactions regulate the synthesis and degradation of chlorophyll, and disruptions in these pathways can result in abnormal chlorophyll production, thereby affecting leaf pigmentation. This study focuses on Bambusa multiplex f. silverstripe , a natural variant distinguished by a spectrum of leaf colors, such as green, white, and green-white, attributed to genetic variations influencing gene expression. By examining the physiological and molecular mechanisms underlying chlorophyll anomalies and genetic factors in Silverstripe, this research sheds light on the intricate gene interactions and regulatory networks that contribute to leaf color diversity. The investigation includes the measurement of photosynthetic pigments and nutrient concentrations across different leaf color types, alongside transcriptomic analyses for identifying differentially expressed genes. The role of key genes in pathways such as ALA biosynthesis, chlorophyll synthesis, photosynthesis, and sugar metabolism is explored, offering critical insights for advancing research and plant breeding practices.

Ethnopharmacological Relevance: The deposition of lipids in macrophages and the subsequent formation of foam cells significantly increase the risk of developing atherosclerosis (As). Targeting ATP-binding cassette transporter A1/G1 (ABCA1/ABCG1)-mediated reverse cholesterol transport is crucial for regulating foam cell formation. Therefore, the search for natural chemical components with the ability to regulate ABCA1/G1 is a potential drug target to combat the development of atherosclerosis. Gypenoside XVII (GP-17), a gypenoside monomer extracted from gynostemma pentaphyllum, presents an efficient anti-atherosclerosis function. However, the suppressed formation mechanism of foam cells by GP-17 remains elusive., Aim of Study: To explore the protective activities of GP-17 in ox-LDL-induced THP-1 macrophage-derived foam cells through modulating the promotion of cholesterol efflux and alleviation of inflammation., Materials and Methods: MTT was used to detect cell viability. Bodipy493/503 and oil red O staining were performed to measure cell lipid deposition. Enzymatic assay was used to measure intracellular cholesterol measurement. Cholesterol efflux/uptake were determined by cholesterol efflux assay and Dil-ox-LDL uptake assay. Inflammatory cytokines were measured by ELISA. Bioinformatics prediction and dual luciferase reporter assay were performed to validate miR-182-5p targeting HDAC9. Relative protein levels were evaluated by immunoblotting and relative gene levels were determined by quantitative real-time PCR., Results: Our results showed that GP-17 upregulated the expression of ABCA1, ABCG1 and miR-182-5p, but reduced HDAC9 expression levels in lipid-loaded macrophages, which promoted cholesterol efflux and inhibited lipid deposition. Additionally, GP-17 promoted the M2 phenotype of the macrophage and suppressed the inflammatory response in THP-1 macrophage-derived foam cells. Overexpression of HDAC9 or suppression of miR-182-5p eliminated the effects of ABCA1/G1 expression, lipid deposition and pro-inflammatory response., Conclusion: These findings suggest that GP-17 exerts a beneficial effect on macrophage lipid deposition and inflammation responses through activating the miR-182-5p/HDAC9 signaling pathway., Competing Interests: Declaration of competing interest We the undersigned declare that this manuscript entitled “Gypenoside XVII inhibits ox-LDL-induced macrophage inflammatory responses and promote cholesterol efflux in macrophage through the miR-182–5p/HDAC9 pathway” is original, has not been published before and is not currently being considered for publication elsewhere. We confirm that the manuscript has been read and approved by all named authors and that there are no other persons who satisfied the criteria for authorship but are not listed. We further confirm that the order of authors listed in the manuscript has been approved by all of us., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Multiple sclerosis shows a strong sex bias, with unclear mechanisms. In this issue of Immunity, Peng et al. elucidate a female-biased increase in intestinal dopamine signaling that diminishes protective Lactobacillus and exacerbates inflammation in a mouse model of multiple sclerosis., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023. Published by Elsevier Inc.)

Background: Chiloschista (Orchidaceae, Aeridinae) is an epiphytic leafless orchid that is mainly distributed in tropical or subtropical forest canopies. This rare and threatened orchid lacks molecular resources for phylogenetic and barcoding analysis. Therefore, we sequenced and assembled seven complete plastomes of Chiloschista to analyse the plastome characteristics and phylogenetic relationships and conduct a barcoding investigation., Results: We are the first to publish seven Chiloschista plastomes, which possessed the typical quadripartite structure and ranged from 143,233 bp to 145,463 bp in size. The plastomes all contained 120 genes, consisting of 74 protein-coding genes, 38 tRNA genes and eight rRNA genes. The ndh genes were pseudogenes or lost in the genus, and the genes petG and psbF were under positive selection. The seven Chiloschista plastomes displayed stable plastome structures with no large inversions or rearrangements. A total of 14 small inversions (SIs) were identified in the seven Chiloschista plastomes but were all similar within the genus. Six noncoding mutational hotspots (trnN GUU -rpl32 > rpoB-trnC GCA > psbK-psbI > psaC-rps15 > trnE UUC -trnT GGU > accD-psaI) and five coding sequences (ycf1 > rps15 > matK > psbK > ccsA) were selected as potential barcodes based on nucleotide diversity and species discrimination analysis, which suggested that the potential barcode ycf1 was most suitable for species discrimination. A total of 47-56 SSRs and 11-14 long repeats (> 20 bp) were identified in Chiloschista plastomes, and they were mostly located in the large single copy intergenic region. Phylogenetic analysis indicated that Chiloschista was monophyletic. It was clustered with Phalaenopsis and formed the basic clade of the subtribe Aeridinae with a moderate support value. The results also showed that seven Chiloschista species were divided into three major clades with full support., Conclusion: This study was the first to analyse the plastome characteristics of the genus Chiloschista in Orchidaceae, and the results showed that Chiloschista plastomes have conserved plastome structures. Based on the plastome hotspots of nucleotide diversity, several genes and noncoding regions are suitable for phylogenetic and population studies. Chiloschista may provide an ideal system to investigate the dynamics of plastome evolution and DNA barcoding investigation for orchid studies., (© 2023. The Author(s).)

The Elsholtzieae, comprising ca. 7 genera and 70 species, is a small tribe of Lamiaceae (mint family). Members of Elsholtzieae are of high medicinal, aromatic, culinary, and ornamentals value. Despite the rich diversity and value of Elsholtzieae, few molecular markers or plastomes are available for phylogenetics. In the present study, we employed high-throughput sequencing to assemble two Mosla plastomes, M. dianthera and M. scabra , for the first time, and compared with other plastomes of Elsholtzieae. The plastomes of Elsholtzieae exhibited a quadripartite structure, ranging in size from 148,288 bp to 152,602 bp. Excepting the absence of the pseudogene rps19 in Elsholtzia densa , the exhaustive tally revealed the presence of 132 genes (113 unique genes). Among these, 85 protein-coding genes (CDS), 37 tRNA genes, 8 rRNA genes, and 2 pseudogenes ( rps19 and ycf1 ) were annotated. Comparative analyses showed that the plastomes of these species have minor variations at the gene level. Notably, the E. eriostchya plastid genome exhibited increased GC content regions in the LSC and SSC, resulting in an increased overall GC content of the entire plastid genome. The E. densa plastid genome displayed modified boundaries due to inverted repeat (IR) contraction. The sequences of CDS and intergenic regions (IGS) with elevated variability were identified as potential molecular markers for taxonomic inquiries within Elsholtzieae. Phylogenetic analysis indicated that four genera formed monophyletic entities, with Mosla and Perilla forming a sister clade. This clade was, in turn, sister to Collinsonia , collectively forming a sister group to Elsholtzia . Both CDS, and CDS + IGS could construct a phylogenetic tree with stronger support. These findings facilitate species identification and DNA barcoding investigations in Elsholtzieae and provide a foundation for further exploration and resource utilization within this tribe.

Trichoglottis exhibits a range of rich variations in colors and shapes of flower and is a valuable ornamental orchid genus. The genus Trichoglottis has been expanded by the inclusion of Staurochilus , but this Trichoglottis sensu lato (s.l.) was recovered as a non-monophyletic genus based on molecular sequences from one or a few DNA regions. Here, we present phylogenomic data sets, incorporating complete plastome sequences from seven species (including five species sequenced in this study) of Trichoglottis s.l. (including two species formerly treated as Staurochilus ), to compare plastome structure and to reconstruct the phylogenetic relationships of this genus. The seven plastomes possessed the typical quadripartite structure of angiosperms and ranged from 149,402 bp to 149,841 bp with a GC content of 36.6-36.7%. These plastomes contain 120 genes, which comprise 74 protein-coding genes, 38 tRNA genes, and 8 rRNA genes, all ndh genes were pseudogenized or lost. A total of 98 ( T . philippinensis ) to 134 ( T . ionosma ) SSRs and 33 ( T . subviolacea ) to 46 ( T . ionosma ) long repeats were detected. The consistent and robust phylogenetic relationships of Trichoglottis were established using a total of 25 plastid genomes from the Aeridinae subtribe. The genus Trichoglottis s.l. was strongly supported as a monophyletic group, and two species formerly treated as Staurochilus were revealed as successively basal lineages. In addition, five mutational hotspots ( trnN GUU - rpl32 , trnL UAA , trnS GCU - trnG UCC , rbcL - accD , and trnT GGU - psbD ) were identified based on the ranking of PI values. Our research indicates that plastome data is a valuable source for molecular identification and evolutionary studies of Trichoglottis and its related genera.

Epidendrum , one of the three largest genera of Orchidaceae, exhibits significant horticultural and ornamental value and serves as an important research model in conservation, ecology, and evolutionary biology. Given the ambiguous identification of germplasm and complex evolutionary relationships within the genus, the complete plastome of this genus (including five species) were firstly sequenced and assembled to explore their characterizations. The plastomes exhibited a typical quadripartite structure. The lengths of the plastomes ranged from 147,902 bp to 150,986 bp, with a GC content of 37.16% to 37.33%. Gene annotation revealed the presence of 78-82 protein-coding genes, 38 tRNAs, and 8 rRNAs. A total of 25-38 long repeats and 130-149 SSRs were detected. Analysis of relative synonymous codon usage (RSCU) indicated that leucine (Leu) was the most and cysteine (Cys) was the least. The consistent and robust phylogenetic relationships of Epidendrum and its closely related taxa were established using a total of 43 plastid genomes from the tribe Epidendreae. The genus Epidendrum was supported as a monophyletic group and as a sister to Cattleya . Meanwhile, four mutational hotspots ( trnC GCA - petN , trnD GUC - trnY GUA , trnS GCU - trnG UCC , and rpl32 - trnL UAG ) were identified for further phylogenetic studies. Our analysis demonstrates the promising utility of plastomes in inferring the phylogenetic relationships of Epidendrum .

One new species of the genus Pseudopoda Jäger, 2000, Pseudopodadeformis Gong & Zhong, sp. nov. (♂, ♀), is described and documented with digital images from Shennongjia Forestry District, Hubei Province, China, based on morphology and DNA barcodes. This new species is separated from other Pseudopoda species by the unique type of internal ducts of the female vulva that are curved longitudinally, forming a narrow triangle or trapezoidal shape. In addition, DNA barcodes for this species are provided., (Li-jun Gong, Meng-yun Zeng, Yang Zhong, Hui-liang Yu.)

Background: In utero transmission of SARS coronavirus 2 (SARS-CoV-2) has not been fully investigated. We investigated whether newborns of mothers with COVID-19 during pregnancy might harbor SARS-CoV-2 in the gastrointestinal tract., Methods: This cohort study investigated stool from 14 newborns born at 25-41 weeks admitted at delivery to our urban academic hospital whose mothers had COVID-19 during pregnancy. Eleven mothers had COVID-19 resolved more than 10 weeks before delivery. Newborn stool was evaluated for SARS-CoV-2 RNA, Spike protein, and induction of inflammatory cytokines interleukin-6 (IL-6) and interferon-γ (IFN-γ) in macrophages., Results: Despite negative SARS CoV-2 nasal PCRs from all newborns, viral RNAs and Spike protein were detected in the stool of 11 out of 14 newborns as early as the first day of life and increased over time in 6. Stool homogenates from all 14 newborns elicited elevated inflammatory IL-6 and IFN-γ from macrophages. Most newborns were clinically well except for one death from gestational autoimmune liver disease and another who developed necrotizing enterocolitis., Conclusions: These findings suggest in utero transmission of SARS-CoV-2 and possible persistent intestinal viral reservoirs in the newborns. Further investigation is required to understand the mechanisms and their clinical implications., Impact: SARS-CoV-2 RNAs or Spike protein was detected in the stool of 11 out of 14 preterm newborns born to mothers with resolved COVID-19 weeks prior to delivery despite negative newborn nasal PCR swabs. These novel findings suggest risk of in utero SARS-CoV-2 transmission to the fetal intestine during gestation. The presence of SARS-CoV-2 RNAs and Spike protein in the intestines of newborns may potentially impact the development of the gut microbiome and the immune system; the long-term health impact on the preterm infants should be further investigated., (© 2022. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

For salt-sensitive hypertension (SSH), salt restriction and angiotensin-converting enzyme (ACE) inhibitors are essential treatments, but their effect on the function of resistance arteries is unclear. Here, we present an intravital study to detect the effect of salt restriction and ACE inhibitors on the function of the mesenteric small artery (MSA) in SSH. Dahl salt-sensitive rats were randomized into the following groups: ACE inhibitor gavage, salt restriction, ACE inhibitor combined with salt restriction, and high-salt diet. After a 12-week intervention, the mesenteric vessels maintained their perfusion in vivo , and the changes in the diameter and blood perfusion of the MSAs to norepinephrine (NE) and acetylcholine (ACh) were detected. Switching from a high-salt diet to a low-salt diet (i.e., salt restriction) attenuated the vasoconstriction of the MSAs to NE and promoted the vasodilatation to ACh, while ACE inhibitor improved the vasodilatation more obviously. Pathologically, changes in local ACE, AT1R, and eNOS expression were involved in these processes induced by a high-salt diet. Our study suggests that salt restriction and ACE inhibitor treatment improve high salt intake-induced MSA dysfunction in SSH, and salt restriction is a feasible and effective treatment. Our findings may provide a scientific basis for the treatment of hypertension., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

There has been growing interest in the complex host-microbe interactions within the human gut and the role these interactions play in systemic health and disease. As an essential metabolic organ, the liver is intimately coupled to the intestinal microbial environment via the portal venous system. Our understanding of the gut-liver axis comes almost exclusively from studies of adults; the gut-liver axis in children, who have unique physiology and differing gut microbial communities, remains poorly understood. Here, we provide a comprehensive overview of common pediatric hepatobiliary conditions and recent studies exploring the contributions of the gut microbiota to these conditions or changes of the gut microbiota due to these conditions. We examine the current literature regarding the microbial alterations that take place in biliary atresia, pediatric non-alcoholic fatty liver disease, Wilson's disease, cystic fibrosis, inflammatory bowel disease, and viral hepatitis. Finally, we propose potential therapeutic approaches involving modulation of the gut microbiota and the gut-liver axis to mitigate the progression of pediatric liver disease.

In this study, we examined the effect of the GP130-targeting molecule, LMT-28, on lipopolysaccharide- (LPS-) induced bone resorption around implants in diabetic models using in vitro and rat animal experiments. First, LMT-28 was added to osteoblasts stimulated by LPS and advanced glycation end products (AGEs), and nuclear factor- κ B receptor-activating factor ligand (RANKL) and associated pathways were evaluated. Then, LMT-28 was administered by gavage at 0.23 mg/kg once every 5 days for 2 weeks to type 2 diabetic rats with peri-implantitis induced by LPS injection and silk ligature. The expression of IL-6 and RANKL was evaluated by immunohistochemistry, and the bone resorption around implants was evaluated by microcomputed tomography. The results showed that LMT-28 downregulated the expression of RANKL through the JAK2/STAT3 signaling pathway in osteoblasts stimulated by LPS and AGEs, reduced bone resorption around implants with peri-implantitis, decreased the expression of IL-6 and RANKL, and decreased osteoclast activity in type 2 diabetic rats. This study confirmed the ability of LMT-28 to reduce LPS-induced bone resorption around implants in diabetic rats., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2023 Qi-qi Liu et al.)

One new species of the genus Sinopoda Jäger, 1999, S.muyuensis sp. nov. (♂, ♀), is described and figured from the Shennongjia Forestry District, Hubei Province, China. In addition, the male of Sinopodawuyiensis Liu, 2021 is described for the first time from the Wuyishan National Nature Reserve, Fujian Province, China., (Yang Zhong, Meng-Yun Zeng, Chao-Lan Gu, Hui-Liang Yu, Jing-Yuan Yang.)

The gut microbiome elicits antigen-specific immunoglobulin G (IgG) at steady state that cross-reacts to pathogens to confer protection against systemic infection. The role of gut microbiome-specific IgG antibodies in the development of the gut microbiome and immunity against enteric pathogens in early life, however, remains largely undefined. In this study, we show that gut microbiome-induced maternal IgG is transferred to the neonatal intestine through maternal milk via the neonatal Fc receptor and directly inhibits Citrobacter rodentium colonization and attachment to the mucosa. Enhanced neonatal immunity against oral C. rodentium infection was observed after maternal immunization with a gut microbiome-derived IgG antigen, outer membrane protein A, or induction of IgG-inducing gut bacteria. Furthermore, by generating a gene-targeted mouse model with complete IgG deficiency, we demonstrate that IgG knockout neonates are more susceptible to C. rodentium infection and exhibit alterations of the gut microbiome that promote differentiation of interleukin-17A-producing γδ T cells in the intestine, which persist into adulthood and contribute to increased disease severity in a dextran sulfate sodium-induced mouse model of colitis. Together, our studies have defined a critical role for maternal gut microbiome-specific IgG antibodies in promoting immunity against enteric pathogens and shaping the development of the gut microbiome and immune cells in early life.

The gut microbiome is intricately coupled with immune regulation and metabolism, but its role in Coronavirus Disease 2019 (COVID-19) is not fully understood. Severe and fatal COVID-19 is characterized by poor anti-viral immunity and hypercoagulation, particularly in males. Here, we define multiple pathways by which the gut microbiome protects mammalian hosts from SARS-CoV-2 intranasal infection, both locally and systemically, via production of short-chain fatty acids (SCFAs). SCFAs reduced viral burdens in the airways and intestines by downregulating the SARS-CoV-2 entry receptor, angiotensin-converting enzyme 2 (ACE2), and enhancing adaptive immunity via GPR41 and 43 in male animals. We further identify a novel role for the gut microbiome in regulating systemic coagulation response by limiting megakaryocyte proliferation and platelet turnover via the Sh2b3-Mpl axis. Taken together, our findings have unraveled novel functions of SCFAs and fiber-fermenting gut bacteria to dampen viral entry and hypercoagulation and promote adaptive antiviral immunity.

Goodyerinae are one of phylogenetically unresolved groups of Orchidaceae. The lack of resolution achieved through the analyses of previous molecular sequences from one or a few markers has long confounded phylogenetic estimation and generic delimitation. Here, we present large-scale phylogenomic data to compare the plastome structure of the two main clades (Goodyera and Cheirostylis) in this subtribe and further adopt two strategies, combining plastid coding sequences and the whole plastome, to investigate phylogenetic relationships. A total of 46 species in 16 genera were sampled, including 39 species in 15 genera sequenced in this study. The plastomes of heterotrophic species are not drastically reduced in overall size, but display a pattern congruent with a loss of photosynthetic function. The plastomes of autotrophic species ranged from 147 to 165 kb and encoded from 132 to 137 genes. Three unusual structural features were detected: a 1.0-kb inversion in the large single-copy region of Goodyera schlechtendaliana; the loss and/or pseudogenization of ndh genes only in two species, Cheirostylis chinensis and C. montana; and the expansion of inverted repeat regions and contraction of small single-copy region in Hetaeria oblongifolia. Phylogenomic analyses provided improved resolution for phylogenetic relationships. All genera were recovered as monophyletic, except for Goodyera and Hetaeria, which were each recovered as non-monophyletic. Nomenclatural changes are needed until the broader sampling and biparental inherited markers. This study provides a phylogenetic framework of Goodyerinae and insight into plastome evolution of Orchidaceae., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Inflammation, the main factor in the progression of osteoarthritis (OA), impairs the chondrogenesis of bone mesenchymal stem cells (BMSCs), which is an appealing process to target to regenerate impaired articular cartilage. This article aimed to investigate whether SP600125, a competitive ATP-specific inhibitor of the JNK pathway, could promote the chondrogenesis of BMSCs by enhancing their anti-inflammatory capacity. Chondrogenic differentiation was assessed by Alcian blue staining, immunofluorescence staining, and Western blot. The inflammation level was associated with the expression of matrix metalloproteinases (Mmp), evaluated by Western blot. Intra-articular injection of BMSCs pretreated with or without SP600125 was carried out on C57BL/6 mice after inducing OA by surgical destabilization of the medial meniscus. Safranin O-fast green (SO) and hematoxylin-eosin staining were employed to evaluate the cartilage destruction and immunohistochemical analysis was adopted to detect the expression of Col2 and Mmp-13 proteins in the mouse knee joint. We showed that SP600125 could inhibit inflammation induced by tumor necrosis factor-α (TNF-α) and promote the chondrogenesis of BMSCs. In the presence of TNF-α, the expression of aggrecan (Agc) and collagen type II alpha 1 (Col2) was significantly decreased compared with that in the control group and increased with the addition of SP600125. Moreover, the expression of Mmp-1, Mmp-3, and Mmp-13 was increased in BMSCs treated only with TNF-α and downregulated in SP600125-treated BMSCs. In vivo study showed that SP600125 could enhance protective effects of BMSCs on OA mice. Our results indicated that SP600125 rescued the chondrogenesis of BMSCs by inhibiting inflammation induced by TNF-α, which provides a theoretical basis for solving the problem of cartilage repair under inflammatory conditions.

The complete plastid genome of Bulbophyllum pingnanense , a critically endangered species, was determined and analyzed in this study. The complete genome was 151,224 bp in length, consisting of a large single-copy region (LSC) of 86,017 bp, a small single-copy region (SSC) of 13,497 bp, and two inverted repeat (IR) regions of 25,855 bp. The genome contained 127 genes, including 81 protein-coding genes, 38 transfer RNA (tRNA) genes, and eight ribosomal RNA (rRNA) genes. Phylogenetic analysis indicated that B. pingnanense is sister to B. inconspicuum ., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Pregnancy induces unique changes in maternal immune responses and metabolism. Drastic physiologic adaptations, in an intricately coordinated fashion, allow the maternal body to support the healthy growth of the fetus. The gut microbiome plays a central role in the regulation of the immune system, metabolism, and resistance to infections. Studies have reported changes in the maternal microbiome in the gut, vagina, and oral cavity during pregnancy; it remains unclear whether/how these changes might be related to maternal immune responses, metabolism, and susceptibility to infections during pregnancy. Our understanding of the concerted adaption of these different aspects of the human physiology to promote a successful pregnant remains limited. Here, we provide a comprehensive documentation and discussion of changes in the maternal microbiome in the gut, oral cavity, and vagina during pregnancy, metabolic changes and complications in the mother and newborn that may be, in part, driven by maternal gut dysbiosis, and, lastly, common infections in pregnancy. This review aims to shed light on how dysregulation of the maternal microbiome may underlie obstetrical metabolic complications and infections.

Early life is a critical time window for the neonatal gut to be progressively populated with different bacterial species that collectively promote gut maturation. A fully developed and healthy gut microbiome in neonates is an important driver for the development of other aspects of health. Unlike the relatively stable gut microbiome in adults, the developing gut microbiome in neonates exhibits higher plasticity and adaptability. This also underscores the unique window of opportunity for intervention or preventive measures to improve long-term health through modulations of the gut microbiome in early life. Better understanding of the neonatal gut microbiome - how it arises and how it impacts immune cell development - will help us appreciate the underpinnings of immune-related diseases. Here, we examine recent findings on the neonatal gut microbiome and discuss their implications for understanding this important driver of the maturation of the immune system and immunity against infections in early life., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The Cleisostoma-Gastrochilus clades are among the most speciose and diverse groups of Asian orchids and are a taxonomically problematic group. Phylogenetic relationships among the genera of these clades have remained unresolved with traditional sequences from one or a few markers. We present large-scale phylogenomic data sets, incorporating complete chloroplast genome sequences from 53 species (including 41 species sequenced in this study), to compare plastome structure and to resolve the phylogenetic relationships of these clades. The plastomes of Cleisostoma-Gastrochilus clades possessed the quadripartite structure and plastome genes of typical angiosperms with sizes ranging from 142 to 149 kb and encoding a set of 118-120 genes. Unusual structural features were detected in the plastome of Uncifera acuminata, including the presence of a large 17-kb inversion (19 genes) in the Large Single-Copy region and the loss of the rpl32 gene in Cleisostoma fuerstenbergianum. The pseudogenization of ndh genes was widespread in these clades. Phylogenomic analyses, including 68 plastid protein-coding genes, showed that these clades can be subdivided into three major groupings and six subgroupings: Vandopsis undulata, the Gastrochilus clade (including the Trichoglottis and Gastrochilus subclades) and the Cleisostoma clade (including the Vandopsis, Diploprora, Cleisostoma and Schoenorchis subclades). Two genera, Vandopsis and Cleisostoma, were not monophyletic. A new genus, Cymbilabia, was proposed to avoid non-monophyly of Vandopsis. Our results demonstrate the power of plastid phylogenomics to improve the phylogenetic relationships of intricate groups and provide new insight into plastome evolution in Orchidaceae., (Copyright © 2020 Elsevier Inc. All rights reserved.)

N-doped SnO₂ nanowires were synthesized via chemical vapor deposition in the presence of NH₃ gas with SnO₂ nanowires as the precursor. All samples exhibited room-temperature ferromagnetism (FM). X-ray diffraction measurement showed that the FM is intrinsic. Results of vibrating sample magnetometry indicated that FM decreased along with increasing NH₃ flow rate. Further analysis by X-ray photoelectron spectroscopy showed that the N atom was substituted at the lattice site of O, and NH₃ was chemisorbed in the surface of samples. The chemisorbed NH₃ was the dominant ingredient and main factor causing the significant decrease in FM. However, the FM of the samples after etching was enhanced due to the doped N atoms.

Sinomenine (SN) has been used in the clinical treatment of systemic lupus erythematosus and rheumatoid arthritis for many years. Studies showed that SN held protective effects such as anti-inflammation, scavenging free radicals and suppressing immune response in many autoimmune diseases. The purpose of the present study is to explore the mechanism of anti-inflammation of SN on lipopolysaccharide (LPS)-induced macrophages activation and investigate whether the TLR4/NF-κB signaling pathway participated in. Macrophages isolated from mouse peritoneal cavity were stimulated by 1 µg/mL LPS for 24 h. And then the cells were treated with various concentrations of SN, TLR4 inhibitor respectively for additional 48 h. Drug toxicity was detected by MTT assay and Transwell experiment was used to assess chemotaxis. Furthermore, TLR4 and MyD88 mRNA levels were detected by real-time PCR. Western blotting was used to examine TLR4, MyD88 and phosphorylated IκB protein expression in macrophages. Immunofluorescence assay was applied to observe p65 NF-κB protein expression in macrophage nucleus. We extracted macrophages with high purity and activity from the abdominal cavity of mice. SN remarkably inhibited the chemotaxis and secretion function of LPS-stimulated macrophages. It also down-regulated both the protein levels of inflammatory cytokines (TNF-α, IL-1β and IL-6) and the RNA and protein levels of the key factors (TLR4, MyD88, P-IκB) in TLR4 pathway. The expression of p65 NF-κB protein in nuclei was down-regulated, which was correlated with a similar decrease in P-IκB protein level. In conclusion, SN can inhibit the LPS induced immune responses in macrophages by blocking the activated TLR4/NF-κB signaling pathway. These results may provide a therapeutic approach to regulate inflammatory responses.

The neonatal gut microbiome undergoes dynamic changes in response to many nutritional and environmental variables. A recent study by Singer et al. in Nature Medicine elucidates several mechanisms to inhibit the expansion of gut-derived pathobionts in a dysbiotic neonatal gut and prevent these pathobionts from disseminating systemically and causing sepsis in neonatal mice., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To study the clinical characteristics of outpatients with hand, foot and mouth disease (HFMD) caused by different serotypes of enteroviruses. Methods: This was a prospective study. From February 2017 to March 2018, 563 outpatients with HFMD were enrolled by systematic sampling in the Department of Infectious Diseases, Henan Children's Hospital. Throat swabs were collected to determine the serotypes via PCR. Demographic, clinical, and laboratory data were collected by standard questionnaire. All cases were followed up twice at 2 and 9 weeks after the initial outpatient visit through telephone interview. A total of 563 cases were enrolled and 555 (98.6%) cases were positive for human enteroviruses, including 338 (60.9%) males. Analyses were stratified by enterovirus serotypes, Chi square test or Fisher's exact test, Rank sum test was used for comparison among different groups. Results: The age of 555 cases was 24.2 (16.4, 41.3) months. Among them 44.0% (224 cases) were identified as coxsackievirus (CV)-A6, while 189 cases, 35 cases, 14 cases and 73 cases were identified as CV-A16, enterovirus (EV)-A71, CV-A10 and other serotypes, respectively. Fever (≥37.5 ℃) was present in 51.4% (285/555) of laboratory confirmed cases. The proportions of fever in cases of CV-A6 (68.9%(168/244)) and CV-A10 (12/14) were significantly higher than those in cases of CV-A16 (31.7%(60/189),χ(2)=57.344,14.313,both P= 0.000), other serotypes (43.8%(32/73),χ(2)=15.101 and 8.242, P= 0.000 and 0.004) and EV-A71 (37.1%(13/35), χ(2)=13.506 and 9.441, P= 0.000 and 0.002) respectively. There was no significant difference between CV-A6 and CV-A10 in presentation of fever (χ(2)=1.785, P= 0.182). There were 359 cases (64.7%) with eruptions in mouth, hands, feet and buttocks. Cases infected with EV-A71 had the highest proportions (74.3%(26/35)) of rash emerging simultaneously in mouth, hands, feet, and buttocks. The proportion in cases of CV-A16, CV-A6, CVA10 and other serotype were 73.5% (139/189), 61.9% (151/244), 7/14 and 49.3% (36/73), respectively. The proportion of rash on other parts of body, such as face, limbs or torso in cases infected with CV-A6 (16.8% (41/244)) was the higherest and the proportion in cases of CV-A16, EV-A71, CV-A10 or other serotypes were 8.5% (16/189) , 5.7% (2/35) , 1/14, 6.8% (5/73) , respectively. None of these cases developed serious complications. Desquamation occurred in 45.5% (179/393) cases 7.5 (5.0, 9.0) days after disease onset and 13.5% (53/393) cases showed onychomadesis 31.0 (18.0, 33.5) days after disease onset. The proportion of desquamation and onychomadesis associated with CV-A6 (64.2% (95/148) and 31.8% (47/148)) was significantly higher than CV-A16 (31.8% (49/154) and 1.3% (2/154), χ(2)=33.601 and 52.482, both P= 0.000) and other serotypes (38.0%(19/50) and 6.0%(3/50),χ(2)=10.236 and 12.988, P= 0.001 and 0.000). Desquamation appeared more in cases of CV-A6 than in cases of CV-A10 (2/11,χ(2)=9.386, P= 0.002), with the proportion of onychomadesis higher in CV-A6 than in EV-A71 (3.3% (1/30),χ(2)=11.088, P= 0.001). Conclusion: Clinical manifestation such as fever, rash emerging parts, desquamation and onychomadesis are different among outpatient HFMD cases infected with CV-A16, CV-A6, EV-A71, CV-A10 and other enteroviruses.

Neutrophils are phagocytic innate immune cells essential for killing bacteria via activation of a wide variety of effector responses and generation of large amounts of reactive oxygen species (ROS). Majority of the ROS in neutrophils is generated by activation of the superoxide-generating enzyme nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Independent of their anti-microbial function, NADPH oxidase-derived ROS have emerged as key regulators of host immune responses and neutrophilic inflammation. Data from patients with inherited defects in the NADPH oxidase subunit alleles that ablate its enzyme function as well as mouse models demonstrate profound dysregulation of host inflammatory responses, neutrophil hyper-activation and tissue damage in response to microbial ligands or tissue trauma. A large body of literature now demonstrates how oxidants function as essential signaling molecules that are essential for the regulation of neutrophil responses during priming, degranulation, neutrophil extracellular trap formation, and apoptosis, independent of their role in microbial killing. In this review we summarize how NADPH oxidase-derived oxidants modulate neutrophil function in a cell intrinsic manner and regulate host inflammatory responses. In addition, we summarize studies that have elucidated possible roles of oxidants in neutrophilic responses within the oral mucosa and periodontal disease., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Owing to immature immune systems and impaired colonization resistance mediated by the microbiota, infants are more susceptible to enteric infections. Maternal antibodies can provide immunity, with maternal vaccination offering a protective strategy. We find that oral infection of adult females with the enteric pathogen Citrobacter rodentium protects dams and offspring against oral challenge. Parenteral immunization of dams with heat-inactivated C. rodentium reduces pathogen loads and mortality in offspring but not mothers. IgG, but not IgA or IgM, transferred through breast milk to the intestinal lumen of suckling offspring, coats the pathogen and reduces intestinal colonization. Protective IgG largely recognizes virulence factors encoded within the locus of enterocyte effacement (LEE) pathogenicity island, including the adhesin Intimin and T3SS filament EspA, which are major antigens conferring protection. Thus, pathogen-specific IgG in breast milk induced during maternal infection or immunization protects neonates against infection with an attaching and effacing pathogen., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Microfold cells (M-cells) are specialized cells of the intestine that sample luminal microbiota and dietary antigens to educate the immune cells of the intestinal lymphoid follicles. The function of M-cells in systemic inflammatory responses are still unclear. Here we show that epithelial non-canonical NFkB signaling mediated by NFkB-inducing kinase (NIK) is highly active in intestinal lymphoid follicles, and is required for M-cell maintenance. Intestinal NIK signaling modulates M-cell differentiation and elicits both local and systemic IL-17A and IgA production. Importantly, intestinal NIK signaling is active in mouse models of colitis and patients with inflammatory bowel diseases; meanwhile, constitutive NIK signaling increases the susceptibility to inflammatory injury by inducing ectopic M-cell differentiation and a chronic increase of IL-17A. Our work thus defines an important function of non-canonical NFkB and M-cells in immune homeostasis, inflammation and polymicrobial sepsis.

Atherosclerosis is a dyslipidemia disease characterized by foam cell formation driven by the accumulation of lipids. Visceral adipose tissue-derived serine protease inhibitor (vaspin) is known to suppress the development of atherosclerosis via its anti-inflammatory properties, but it is not yet known whether vaspin affects cholesterol efflux in THP-1 macrophage-derived foam cells. Here, we investigated the effects of vaspin on ABCA1 expression and cholesterol efflux, and further explored the underlying mechanism. We found that vaspin decreased miR-33a levels, which in turn increased ABCA1 expression and cholesteorl efflux. We also found that inhibition of NF-κB reduced miR-33a expression and vaspin suppressed LPS-mediated NF-κB phosphorylation. Our findings suggest that vaspin is not only a regular of inflammasion but also a promoter of cholesterol efflux., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The phagocyte reduced NAD phosphate (NADPH) oxidase generates superoxide, the precursor to reactive oxygen species (ROS) that has both antimicrobial and immunoregulatory functions. Inactivating mutations in NADPH oxidase alleles cause chronic granulomatous disease (CGD), characterized by enhanced susceptibility to life-threatening microbial infections and inflammatory disorders; hypomorphic NADPH oxidase alleles are associated with autoimmunity. Impaired apoptotic cell (AC) clearance is implicated as an important contributing factor in chronic inflammation and autoimmunity, but the role of NADPH oxidase-derived ROS in this process is incompletely understood. Here, we demonstrate that phagocytosis of AC (efferocytosis) potently activated NADPH oxidase in mouse peritoneal exudate macrophages (PEMs). ROS generation was dependent on macrophage CD11b, Toll-like receptor 2 (TLR2), TLR4, and myeloid differentiation primary response 88 (MyD88), and was also regulated by phosphatidylinositol 3-phosphate binding to the p40 phox oxidase subunit. Maturation of efferosomes containing apoptotic neutrophils was significantly delayed in CGD PEMs, including acidification and acquisition of proteolytic activity, and was associated with slower digestion of apoptotic neutrophil proteins. Treatment of wild-type macrophages with the vacuolar-type H+ ATPase inhibitor bafilomycin also delayed proteolysis within efferosomes, showing that luminal acidification was essential for efficient digestion of efferosome proteins. Finally, cross-presentation of AC-associated antigens by CGD PEMs to CD8 T cells was increased. These studies unravel a key role for the NADPH oxidase in the disposal of ACs by inflammatory macrophages. The oxidants generated promote efferosome maturation and acidification that facilitate the degradation of ingested ACs., (© 2018 by The American Society of Hematology.)

Hepatitis E (HE) is a zoonotic viral disease caused by hepatitis E virus (HEV). The objective of this study was to investigate the prevalence of HEV infection among dogs and humans exposed to dogs in the south-west region of China. A total of 4,490 dog serum samples and 2,206 relative practitioner serum samples were collected from 18 pet hospitals and dog farms in Yunnan, Sichuan and Guizhou province, and the anti-HEV IgG antibodies were detected by ELISA. The results showed that the total positive rate of anti-HEV antibodies was 36.55% with the highest rate in city stray dogs, and the differences in distinct species and growth phases were significant. The positive rate of anti-HEV antibody in veterinarian and farm staff-related practitioners was significantly higher than the general population. The finding of the present survey suggested that high HEV seroprevalence in dogs and humans exposed to dogs in the south-west area of China poses a significant public health concern. It is urgent to improve integrated strategies to detect, prevent and control HEV infection in dogs and humans exposed to dogs in this area., (© 2017 Blackwell Verlag GmbH.)

The intestinal tract of mammals is colonized by a large number of microorganisms including trillions of bacteria that are referred to collectively as the gut microbiota. These indigenous microorganisms have co-evolved with the host in a symbiotic relationship. In addition to metabolic benefits, symbiotic bacteria provide the host with several functions that promote immune homeostasis, immune responses, and protection against pathogen colonization. The ability of symbiotic bacteria to inhibit pathogen colonization is mediated via several mechanisms including direct killing, competition for limited nutrients, and enhancement of immune responses. Pathogens have evolved strategies to promote their replication in the presence of the gut microbiota. Perturbation of the gut microbiota structure by environmental and genetic factors increases the risk of pathogen infection, promotes the overgrowth of harmful pathobionts, and the development of inflammatory disease. Understanding the interaction of the microbiota with pathogens and the immune system will provide critical insight into the pathogenesis of disease and the development of strategies to prevent and treat inflammatory disease., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Enteric pathogens including Salmonella enteric serovar Typhimurium can breach the epithelial barrier of the host and spread to systemic tissues. In response to infection, the host activates innate immune receptors via the signaling molecule MyD88, which induces protective inflammatory and antimicrobial responses. Most of these innate immune responses have been studied in hematopoietic cells, but the role of MyD88 signaling in other cell types remains poorly understood. Surprisingly, we found that Dermo1-Cre;Myd88 fl/fl mice with mesenchymal cell-specific deficiency of MyD88 were less susceptible to orogastric and i.p. S Typhimurium infection than their Myd88 fl/fl littermates. The reduced susceptibility of Dermo1-Cre;Myd88 fl/fl mice to infection was associated with lower loads of S. Typhimurium in the liver and spleen. Mutant analyses revealed that S. Typhimurium employs its virulence type III secretion system 2 to promote its growth through MyD88 signaling pathways in mesenchymal cells. Inflammatory monocytes function as a major cell population for systemic dissemination of S. Typhimurium Mechanistically, mesenchymal cell-specific MyD88 signaling promoted CCL2 production in the liver and spleen and recruitment of inflammatory monocytes to systemic organs in response to S Typhimurium infection. Consistently, MyD88 signaling in mesenchymal cells enhanced the number of phagocytes including Ly6C hi Ly6G - inflammatory monocytes harboring S Typhimurium in the liver. These results suggest that S. Typhimurium promotes its systemic growth and dissemination through MyD88 signaling pathways in mesenchymal cells., (Copyright © 2017 by The American Association of Immunologists, Inc.)

Many benefits provided by the gut microbiota to the host rely on its intricate interactions with host cells. Perturbations of the gut microbiota, termed gut dysbiosis, affect the interplay between the gut microbiota and host cells, resulting in dysregulation of inflammation that contributes to the pathogenesis of chronic inflammatory diseases, including inflammatory bowel disease, multiple sclerosis, allergic asthma and rheumatoid arthritis. In this review, we provide an overview of how gut bacteria modulates host metabolic and immune functions, summarize studies that examined the roles of gut dysbiosis in chronic inflammatory diseases, and finally discuss measures to correct gut dysbiosis as potential therapeutics for chronic inflammatory diseases.

The gut microbiota has diverse and essential roles in host metabolism, development of the immune system and as resistance to pathogen colonization. Perturbations of the gut microbiota, termed gut dysbiosis, are commonly observed in diseases involving inflammation in the gut, including inflammatory bowel disease, infection, colorectal cancer and food allergies. Importantly, the inflamed microenvironment in the gut is particularly conducive to blooms of Enterobacteriaceae, which acquire fitness benefits while other families of symbiotic bacteria succumb to environmental changes inflicted by inflammation. Here we summarize studies that examined factors in the inflamed gut that contribute to blooms of Enterobacterieaceae, and highlight potential approaches to restrict Enterobacterial blooms in treating diseases that are otherwise complicated by overgrowth of virulent Enterobacterial species in the gut.

Objective: To observe the clinical efficacy of Kangle Decoction in the treatment of erectile dysfunction (ED) with liver-qi stagnation and kidney deficiency., Methods: A total of 79 ED patients with liver-qi stagnation and kidney deficiency were randomly assigned to an experimental group (aged ［36.62±8.05］ yr and with a disease course of ［18.15±6.41］ mo) and a control group (aged ［37.44±8.10］ yr and with a disease course of ［17.51±6.79］ mo), the former treated orally with Kangle Decoction at 0.5 dose bid while the latter with Cialis at 10 mg qd alt, both for 8 weeks. Before treatment, after 4 and 8 weeks of medication, and at 4 weeks after drug withdrawal, we obtained the scores of the patients in the International Index of Erectile Function-5 (IIEF-5), Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS), and Short-Form Psychological and Interpersonal Relationship Scales (SF-PAIRS), and compared the indexes between the two groups of patients., Results: The IIEF-5 score was dramatically increased in both the treatment and control groups after 4 weeks (13.40±2.42 and 16.00±2.68) and 8 weeks of medication (18.60±3.50 and 18.59±3.80) and at 4 weeks after drug withdrawal (17.00±3.05 and 13.95±2.61) as compared with the baseline (10.78±2.28 and 10.77±2.33) (P<0.05 ), even higher in the treatment than in the control group after drug withdrawal (P<0.05 ). The EDITS scores in the treatment and control groups were (28.88±3.31 and 28.90±3.31) after 4 weeks of intervention, (29.68±3.30 and 29.13±3.32) after 8 weeks of intervention, and (29.20±2.92 and 26.82±3.23) at 4 weeks after drug withdrawal, all significantly higher in the former than in the latter group after drug withdrawal (P<0.05 ). The sexual self-confidence score (SSCS), sexual spontaneity score (SSS), and sexual time-concern score (STCS) were all improved in the treatment and control groups after medication as compared with the baseline (P<0.05 ), even higher in the former than in the latter group after drug withdrawal (P<0.05 )., Conclusions: Kangle Decoction has a definite efficacy in the treatment of ED with liver-qi stagnation and kidney deficiency, with few adverse reactions and long-term post-withdrawal effect, and therefore deserves a wide clinical application.

Rationale: Previous studies have shown that apolipoprotein-1 (apoA-1) binding protein (AIBP) is highly associated with the regulation of apoA-1 metabolism, suggesting its role in the treatment of atherosclerosis. However, how AIBP regulates foam cell formation remains largely unexplored., Objective: To investigate the mechanisms underlying AIBP inhibition of foam cell formation from macrophages., Methods and Results: THP-1-derived macrophages were incubated without or with apoA-1 and AIBP, followed by assessing the formation of foam cells and the potential mechanisms. Our results showed that AIBP and apoA-1 enhanced cholesterol efflux, altered the levels of cellular free cholesterol and cholesterol ester and prevented lipid accumulation so as to reduce the formation of foam cells. Meanwhile, lack of AIBP 115-123 amino acids resulted in the loss of AIBP binding to apoA-1. Moreover, our chemiluminescent analysis showed that AIBP promoted biotin-labeled apoA-1 binding to macrophages. Besides with AIBP, more apoA-1 bound to ABCA1, a key transporter responsible for cholesterol efflux to apoA-1, as indicated by our co-immunoprecipitation assay. Our results also showed that AIBP did not regulate ABCA1 mRNA expression, but stabilized its protein from CSN2-mediated degradation., Conclusions: AIBP promotes apoA-1 binding to ABCA1 on the cell membrane of macrophages and prevents ABCA1 protein from CSN2-mediated degradation so as to prevent foam cell formation. AIBP 115-123 amino acids is at least partially responsible for its binding to apoA-1., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

The gut microbiota is compartmentalized in the intestinal lumen and induces local immune responses, but it remains unknown whether the gut microbiota can induce systemic response and contribute to systemic immunity. We report that selective gut symbiotic gram-negative bacteria were able to disseminate systemically to induce immunoglobulin G (IgG) response, which primarily targeted gram-negative bacterial antigens and conferred protection against systemic infections by E. coli and Salmonella by directly coating bacteria to promote killing by phagocytes. T cells and Toll-like receptor 4 on B cells were important in the generation of microbiota-specific IgG. We identified murein lipoprotein (MLP), a highly conserved gram-negative outer membrane protein, as a major antigen that induced systemic IgG homeostatically in both mice and humans. Administration of anti-MLP IgG conferred crucial protection against systemic Salmonella infection. Thus, our findings reveal an important function for the gut microbiota in combating systemic infection through the induction of protective IgG., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Inflammasomes are intracellular protein complexes that drive the activation of inflammatory caspases. So far, four inflammasomes involving NLRP1, NLRP3, NLRC4 and AIM2 have been described that recruit the common adaptor protein ASC to activate caspase-1, leading to the secretion of mature IL-1β and IL-18 proteins. The NLRP3 inflammasome has been implicated in the pathogenesis of several acquired inflammatory diseases as well as cryopyrin-associated periodic fever syndromes (CAPS) caused by inherited NLRP3 mutations. Potassium efflux is a common step that is essential for NLRP3 inflammasome activation induced by many stimuli. Despite extensive investigation, the molecular mechanism leading to NLRP3 activation in response to potassium efflux remains unknown. Here we report the identification of NEK7, a member of the family of mammalian NIMA-related kinases (NEK proteins), as an NLRP3-binding protein that acts downstream of potassium efflux to regulate NLRP3 oligomerization and activation. In the absence of NEK7, caspase-1 activation and IL-1β release were abrogated in response to signals that activate NLRP3, but not NLRC4 or AIM2 inflammasomes. NLRP3-activating stimuli promoted the NLRP3-NEK7 interaction in a process that was dependent on potassium efflux. NLRP3 associated with the catalytic domain of NEK7, but the catalytic activity of NEK7 was shown to be dispensable for activation of the NLRP3 inflammasome. Activated macrophages formed a high-molecular-mass NLRP3-NEK7 complex, which, along with ASC oligomerization and ASC speck formation, was abrogated in the absence of NEK7. NEK7 was required for macrophages containing the CAPS-associated NLRP3(R258W) activating mutation to activate caspase-1. Mouse chimaeras reconstituted with wild-type, Nek7(-/-) or Nlrp3(-/-) haematopoietic cells showed that NEK7 was required for NLRP3 inflammasome activation in vivo. These studies demonstrate that NEK7 is an essential protein that acts downstream of potassium efflux to mediate NLRP3 inflammasome assembly and activation.

The leukocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase generates reactive oxygen species essential in microbial killing and regulation of inflammation. Inactivating mutations in this enzyme lead to chronic granulomatous disease (CGD), associated with increased susceptibility to both pyogenic infections and to inflammatory disorders. The role of the NADPH oxidase in regulating inflammation driven by nonmicrobial stimuli is poorly understood. Here, we show that NADPH oxidase deficiency enhances the early local release of interleukin-1α (IL-1α) in response to damaged cells, promoting an excessive granulocyte colony-stimulating factor (G-CSF)-regulated neutrophilic response and prolonged inflammation. In peritoneal inflammation elicited by tissue injury, X-linked Cybb-null (X-CGD) mice exhibited increased release of IL-1α and IL-1 receptor -mediated G-CSF production. In turn, higher levels of systemic G-CSF increased peripheral neutrophilia, which amplified neutrophilic peritoneal inflammation in X-CGD mice. Dampening early neutrophil recruitment by neutralization of IL-1α, G-CSF, or neutrophil depletion itself promoted resolution of otherwise prolonged inflammation in X-CGD. IL-1β played little role. Thus, we identified an excessive IL-1α/G-CSF response as a major driver of enhanced sterile inflammation in CGD in the response to damaged cells. More broadly, these results provide new insights into the regulation of sterile inflammation, and identify the NADPH oxidase in regulating the amplitude of the early neutrophilic response., (© 2015 by The American Society of Hematology.)