bluuebunny/crossref_metadata_2025 huggingface dataset:
Comprehensive Analysis of TRIM Family Genes in Hepatitis Virus B-Related Hepatoma Carcinoma
Authors: Hu Wei , Liu Dongsheng , Li Renjie , Qian Hong , Qiu Wei , Ye Qingwang , Kong Fanyun
Published: July 2022

Background: As significant components of E3 ligases, the tripartite motif (TRIM) proteins participate in various biological processes and facilitate the development of several diseases. Nevertheless, the correlations of TIRMs with hepatitis B virus (HBV)-positive hepatoma carcinoma (HCC) are not well elaborated.

Methods: The expression profile of TRIM genes in HBV-associated HCC and related clinical information were extracted from the Cancer Genome Atla (TCGA) database and the International Cancer Genome Consortium (ICGC) database. Dependent on the ConsensusPathDB and STRING databases, the gene ontology, Reactome pathways, and protein-protein interaction were assessed. Relied on TIMER 2.0 database, the relationship of the TRIMs with immune infiltration was investigated. Using multivariate analysis and Kaplan Meier analysis, the association between TRIM genes and the prognostic value was examined.

Results: A total of 17 TRIM genes, including TRIM16, TRIM17, and TRIM31 with fold change no less than 1.5, were discovered to upregulate in HBV-associated HCC in both TCGA and ICGC cohorts. Relied on gene enrichment analysis, the identified TRIMs were observed to not only be related to the interferon and cytokine signaling but also linked to the adaptive immune system. Particularly, the co-expression patterns of identified TRIMs with other E3 ligase genes and many innate immune genes that are associated with Toll-like receptor signaling, apoptosis, and SUMOylation. Besides, some of identified TRIM expressions were also linked to the infiltration levels of T cells and B cells. Additionally, several TRIM genes were associated with various clinical factors and relevant to the poor survival of HBV-associated HCC.

Conclusion: Our findings could deepen our understanding of TRIMs and their correlations with HBV-associated HCC. Furthermore, some of these TRIMs may be utilized as new prognostic markers of HBV-related HCC prognosis, or act as potential molecular targets for the disease.
Genetic Structure and Forensic Utility of 23 Autosomal STRs of the Ethnic Lao Groups From Laos and Thailand
Authors: Than Khaing Zin , Muisuk Kanha , Woravatin Wipada , Suwannapoom Chatmongkon , Srikummool Metawee , Srithawong Suparat , Lorphengsy Sengvilay , Kutanan Wibhu
Published: July 2022

The Lao Isan and Laotian are the major groups in the area of present-day northeastern Thailand and Laos, respectively. Several previous genetic and forensic studies indicated an admixed genetic structure of Lao Isan with the local Austroasiatic speaking groups, e.g. Khmer, whereas there is a paucity of reporting Laotian’s forensic short tandem repeats (STRs). Here, we newly generated 451 genotypes of seven Lao Isan and three Laotian populations (two Lao Lum and one Lao Thoeng) using 23 autosomal STRs embedded in VerifilerTMplus PCR Amplification kit. We reported allelic frequency and forensic parameters in different dataset: combined ethnic Lao groups, combined Lao Isan populations and combined Laotians. Overall, the forensic parameter results indicate that this set of STRs is suitable for forensic investigation. The anthropological results revealed the genetic homogeneity of Tai-Kadai speaking Lao groups from Thailand and Laos, consistent with previous studies, while the Austroasiatic speaking groups from southern Laos showed genetic relatedness to both Lao Isan and Khmer. In sum, STRs allelic frequency results can provide the genetic backgrounds of populations which is useful for anthropological research and also strengthens the regional forensic database in both countries.
Tuberculosis Phenotypic and Genotypic Drug Susceptibility Testing and Immunodiagnostics: A Review
Authors: Yusoof Kizil A. , García Juan Ignacio , Schami Alyssa , Garcia-Vilanova Andreu , Kelley Holden V. , Wang Shu-Hua , Rendon Adrian , Restrepo Blanca I. , Yotebieng Marcel , Torrelles Jordi B.
Published: July 2022

Tuberculosis (TB), considered an ancient disease, is still killing one person every 21 seconds. Diagnosis of Mycobacterium tuberculosis (M.tb) still has many challenges, especially in low and middle-income countries with high burden disease rates. Over the last two decades, the amount of drug-resistant (DR)-TB cases has been increasing, from mono-resistant (mainly for isoniazid or rifampicin resistance) to extremely drug resistant TB. DR-TB is problematic to diagnose and treat, and thus, needs more resources to manage it. Together with+ TB clinical symptoms, phenotypic and genotypic diagnosis of TB includes a series of tests that can be used on different specimens to determine if a person has TB, as well as if the M.tb strain+ causing the disease is drug susceptible or resistant. Here, we review and discuss advantages and disadvantages of phenotypic vs. genotypic drug susceptibility testing for DR-TB, advances in TB immunodiagnostics, and propose a call to improve deployable and low-cost TB diagnostic tests to control the DR-TB burden, especially in light of the increase of the global burden of bacterial antimicrobial resistance, and the potentially long term impact of the coronavirus disease 2019 (COVID-19) disruption on TB programs.
Protection of Grouper Against Cryptocaryon irritans by Immunization With Tetrahymena thermophila and Protective Cross-Reactive Antigen Identification
Authors: Mo Zequan , Wu Huicheng , Hu Yingtong , Lai Xueli , Guo Wenjie , Duan Yafei , Dan Xueming , Li Yanwei
Published: July 2022

Vaccination is an effective method to prevent Cryptocaryon irritans infection. Although some vaccines have been developed, large-scale production of these vaccines is costly. Development of a heterogenous vaccine generated by low-cost antigens is an alternative method. In the present study, grouper immunized with Tetrahymena thermophila, a free-living ciliate that easily grows in inexpensive culture media at high density, showed protective immunity against C. irritans infection. Higher immobilization against C. irritans theronts was detected in T. thermophila–immunized grouper serum, which suggested the existence of a cross-reactive antibody in the serum. By immunoprecipitation and mass spectrometry analyses, tubulin was identified as a potential cross-reactive antigen between C. irritans and T. thermophila. Recombinant T. thermophila tubulin protein (rTt-tubulin) and its antibody were prepared, and immunofluorescence showed that both C. irritans and T. thermophila cilia were stained by the anti–rTt-tubulin antibody. Grouper immunized with rTt-tubulin showed a reduced infective rate after the C. irritans challenge. An enhanced level of C. irritans–binding immunoglobulin M (IgM) antibody was detected in serum from rTt-tubulin–immunized grouper. Moreover, specific antibodies were also found in the mucus and tissue culture medium from rTt-tubulin–immunized grouper. Overall, these findings suggested that vaccination with T. thermophila elicits cross-reactive protective immunity in grouper against C. irritans, and T. thermophila may be a potential heterologous antigen for vaccine development.
Susceptibility and Severity of COVID-19 Are Both Associated With Lower Overall Viral–Peptide Binding Repertoire of HLA Class I Molecules, Especially in Younger People
Authors: Basir Hamid Reza Ghasemi , Majzoobi Mohammad Mahdi , Ebrahimi Samaneh , Noroozbeygi Mina , Hashemi Seyed Hamid , Keramat Fariba , Mamani Mojgan , Eini Peyman , Alizadeh Saeed , Solgi Ghasem , Di Da
Published: July 2022

An important number of studies have been conducted on the potential association between human leukocyte antigen (HLA) genes and COVID-19 susceptibility and severity since the beginning of the pandemic. However, case–control and peptide-binding prediction methods tended to provide inconsistent conclusions on risk and protective HLA alleles, whereas some researchers suggested the importance of considering the overall capacity of an individual’s HLA Class I molecules to present SARS-CoV-2-derived peptides. To close the gap between these approaches, we explored the distributions of HLA-A, -B, -C, and -DRB1 1st-field alleles in 142 Iranian patients with COVID-19 and 143 ethnically matched healthy controls, and applied in silico predictions of bound viral peptides for each individual’s HLA molecules. Frequency comparison revealed the possible predisposing roles of HLA-A*03, B*35, and DRB1*16 alleles and the protective effect of HLA-A*32, B*58, B*55, and DRB1*14 alleles in the viral infection. None of these results remained significant after multiple testing corrections, except HLA-A*03, and no allele was associated with severity, either. Compared to peptide repertoires of individual HLA molecules that are more likely population-specific, the overall coverage of virus-derived peptides by one’s HLA Class I molecules seemed to be a more prominent factor associated with both COVID-19 susceptibility and severity, which was independent of affinity index and threshold chosen, especially for people under 60 years old. Our results highlight the effect of the binding capacity of different HLA Class I molecules as a whole, and the more essential role of HLA-A compared to HLA-B and -C genes in immune responses against SARS-CoV-2 infection.
Cellular Immune Responses in Islet Xenograft Rejection
Authors: Hu Min , Hawthorne Wayne J. , Yi Shounan , O’Connell Philip J.
Published: July 2022

Porcine islets surviving the acute injury caused by humoral rejection and IBMIR will be subjected to cellular xenograft rejection, which is predominately mediated by CD4+T cells and is characterised by significant infiltration of macrophages, B cells and T cells (CD4+and CD8+). Overall, the response is different compared to the alloimmune response and more difficult to suppress. Activation of CD4+T cells is both by direct and indirect antigen presentation. After activation they recruit macrophages and direct B cell responses. Although they are less important than CD4+T cells in islet xenograft rejection, macrophages are believed to be a major effector cell in this response. Rodent studies have shown that xenoantigen-primed and CD4+T cell-activated macrophages were capable of recognition and rejection of pancreatic islet xenografts, and they destroyed a graftviathe secretion of various proinflammatory mediators, including TNF-α, reactive oxygen and nitrogen species, and complement factors. B cells are an important mediator of islet xenograft rejectionviaxenoantigen presentation, priming effector T cells and producing xenospecific antibodies. Depletion and/or inhibition of B cells combined with suppressing T cells has been suggested as a promising strategy for induction of xeno-donor-specific T- and B-cell tolerance in islet xenotransplantation. Thus, strategies that expand the influence of regulatory T cells and inhibit and/or reduce macrophage and B cell responses are required for use in combination with clinical applicable immunosuppressive agents to achieve effective suppression of the T cell-initiated xenograft response.
A Barrier to Defend - Models of Pulmonary Barrier to Study Acute Inflammatory Diseases
Authors: Herminghaus Anna , Kozlov Andrey V. , Szabó Andrea , Hantos Zoltán , Gylstorff Severin , Kuebart Anne , Aghapour Mahyar , Wissuwa Bianka , Walles Thorsten , Walles Heike , Coldewey Sina M. , Relja Borna
Published: July 2022

Pulmonary diseases represent four out of ten most common causes for worldwide mortality. Thus, pulmonary infections with subsequent inflammatory responses represent a major public health concern. The pulmonary barrier is a vulnerable entry site for several stress factors, including pathogens such as viruses, and bacteria, but also environmental factors e.g. toxins, air pollutants, as well as allergens. These pathogens or pathogen-associated molecular pattern and inflammatory agents e.g. damage-associated molecular pattern cause significant disturbances in the pulmonary barrier. The physiological and biological functions, as well as the architecture and homeostatic maintenance of the pulmonary barrier are highly complex. The airway epithelium, denoting the first pulmonary barrier, encompasses cells releasing a plethora of chemokines and cytokines, and is further covered with a mucus layer containing antimicrobial peptides, which are responsible for the pathogen clearance. Submucosal antigen-presenting cells and neutrophilic granulocytes are also involved in the defense mechanisms and counterregulation of pulmonary infections, and thus may directly affect the pulmonary barrier function. The detailed understanding of the pulmonary barrier including its architecture and functions is crucial for the diagnosis, prognosis, and therapeutic treatment strategies of pulmonary diseases. Thus, considering multiple side effects and limited efficacy of current therapeutic treatment strategies in patients with inflammatory diseases make experimental in vitro and in vivo models necessary to improving clinical therapy options. This review describes existing models for studyying the pulmonary barrier function under acute inflammatory conditions, which are meant to improve the translational approaches for outcome predictions, patient monitoring, and treatment decision-making.
TFNR2 in Ischemia-Reperfusion Injury, Rejection, and Tolerance in Transplantation
Authors: Kouyoumdjian Araz , Tchervenkov Jean , Paraskevas Steven
Published: July 2022

Tumor necrosis factor receptor 2 (TNFR2) has been shown to play a crucial role in CD4+ T regulatory cells (CD4+Tregs) expansion and suppressive function. Increasing evidence has also demonstrated its role in a variety of immune regulatory cell subtypes such as CD8+ T regulatory cells (CD8+ Tregs), B regulatory cells (Bregs), and myeloid-derived suppressor cells (MDSCs). In solid organ transplantation, regulatory immune cells have been associated with decreased ischemia-reperfusion injury (IRI), improved graft survival, and improved overall outcomes. However, despite TNFR2 being studied in the context of autoimmune diseases, cancer, and hematopoietic stem cell transplantation, there remains paucity of data in the context of solid organ transplantation and islet cell transplantation. Interestingly, TNFR2 signaling has found a clinical application in islet transplantation which could guide its wider use. This article reviews the current literature on TNFR2 expression in immune modulatory cells as well as IRI, cell, and solid organ transplantation. Our results highlighted the positive impact of TNFR2 signaling especially in kidney and islet transplantation. However, further investigation of TNFR2 in all types of solid organ transplantation are required as well as dedicated studies on its therapeutic use during induction therapy or treatment of rejection.
Dietary Crude Protein Levels Alter Diarrhea Incidence, Immunity, and Intestinal Barrier Function of Huanjiang Mini-Pigs During Different Growth Stages
Authors: Liu Yating , Azad Md. Abul Kalam , Zhao Xichen , Zhu Qian , Kong Xiangfeng
Published: July 2022

Huanjiang mini-pig is an indigenous pig breed in China; however, the optimal dietary crude protein (CP) levels for this pig breed during different growth stages has not been standardized yet. This study investigated the effects of different CP levels on diarrhea incidence, immunity, and intestinal barrier function in pigs. A total of 360 Huanjiang mini-pigs were assigned to three independent trials and fed the following CP diets: 5−10 kg stage, 14, 16, 18, 20, and 22%; 10−20 kg stage, 12, 14, 16, 18, and 20% and 20−30 kg stage, 10, 12, 14, 16, and 18%. In the 5−10 kg stage, the 22%; diet increased the plasma IL-1β, IL-6, IL-8, and TNF-α concentrations compared to the 14−20% diets and decreased IL-10 and TGF-β; however, these results were fluctuated in the later stages, including the decrease of IL-1β and IL-8 in the 20% group, TNF-α in the 18−20% groups, and the increase of IFN-γ in the 20% group at the 10−20 kg stage and the decrease of TNF-α in the 16% group at the 20−30 kg stage. The 20% diet increased the jejunal and ileal IL-10 concentration compared to the 14% diet at the 5−10 kg stage, as well as in the 16% diet compared to the 12% diet at the 10−20 kg stage. In addition, ileal IL-10 concentration was increased in the 16% diet compared to the 10, 12, and 18% diets at the 20−30 kg stage. Furthermore, the 18% diet at the 5−10 kg stage and the 16% diet at the 10−20 kg stage decreased jejunal IL-6 expression, whereas the 20% diet increased the TNF-α and IFN-γ at the 5−10 kg stage. The 20% diet increased the Claudin, Occludin, ZO-1, ZO-2, Mucin-1, and Mucin-20 expressions at the 5−10 kg stage, as well as TLR-2, TLR-4, and NF-κB in the 22 and 20% diets at the 5−10 and 10−20 kg stages, respectively. Collectively, these findings suggest optimal dietary CP levels of 16, 14, and 12% for Huanjiang mini-pigs during the 5−10, 10−20, and 20−30 kg growth stages, respectively; and provide the guiding significance of dietary CP levels for Huanjiang mini-pigs during different growth stages.
Low IL7R Expression at Diagnosis Predicted Relapse in Adult Acute Myeloid Leukemia Patients With t(8;21)
Authors: Xu Nan , Sun Kai , Wang Ya-Zhe , Chen Wen-Min , Wang Jun , Li Ling-Di , Wang Xu , Hao Yue , Chang Yan , Liu Yan-Rong , Huang Xiao-Jun , Qin Ya-Zhen
Published: July 2022

Background

Acute myeloid leukemia (AML) with t(8;21) needs to be further stratified. In addition to leukemia cells, immune cells in tumor microenvironment participate in tumor initiation, growth and progression. Interleukins (ILs)/interleukin receptors (ILRs) interaction plays important roles in the antitumor immune response. IL7R is reported to be relevant to prognosis in solid tumor and acute lymphoblastic leukemia. However, the prognostic significance of IL7R in t(8;21) AML remains to be clarified.

Methods

Bone marrows collected from 156 newly diagnosed t(8;21) AML patients were used for testing IL7R transcript level by TaqMan-based real-time quantitative PCR (RQ-PCR), and RNAseq were performed in 15 of them. Moreover, IL7R expression at diagnosis were measured by RQ-PCR and flow cytometry (FCM) simultaneously in other 13 t(8;21) AML patients.

Results

t(8;21) AML patients had varied IL7R transcript levels and were categorized into low-expression (IL7R-L) and high-expression (IL7R-H) groups; IL7R-L was significantly associated with a lower relapse-free survival (RFS) rate (P=0.0027) and KITD816/D820 mutation (P=0.0010). Furthermore, IL7R-L was associated with a lower RFS rate in KITD816/D820 group (P=0.013) and IL7R-H/KITD816/D820 patients had similar RFS to KITN822/e8/WT patients (P=0.35). GO analysis enrichment showed that down-regulated genes were predominantly involved in the regulation of T cell and leukocyte activation, proliferation and differentiation in IL7R-L group. IL7R-L had significantly lower levels of Granzymes A/B, CCR7, CD28 and CD27 than IL7R-H group (all P<0.05). FCM analysis showed IL7R protein was primarily expressed in CD4+ T and CD8+ T cell subset. A significant association was found between the transcript level of IL7R and the percentage of CD8+ T cells in nucleated cells (P=0.015) but not CD4+ T cells (P=0.47).

Conclusion

Low IL7R transcript level of bone marrow at diagnosis predicted relapse in t(8;21) AML, which might be caused by the difference in the amount, status and function of T cells.
Insights Into the Pathogenesis of Bullous Pemphigoid: The Role of Complement-Independent Mechanisms
Authors: Cole Connor , Vinay Keshavamurthy , Borradori Luca , Amber Kyle T.
Published: July 2022

Bullous pemphigoid is an autoimmune blistering disease caused by autoantibodies targeting BP180 and BP230. While deposits of IgG and/or complement along the epidermal basement membrane are typically seen suggesting complement -mediated pathogenesis, several recent lines of evidence point towards complement-independent pathways contributing to tissue damage and subepidermal blister formation. Notable pathways include macropinocytosis of IgG-BP180 complexes resulting in depletion of cellular BP180, direct induction of pro-inflammatory cytokines from keratinocytes, as well as IgE autoantibody- and eosinophil-mediated effects. We review these mechanisms which open new perspectives on novel targeted treatment modalities.
A Novel Neuraminidase Virus-Like Particle Vaccine Offers Protection Against Heterologous H3N2 Influenza Virus Infection in the Porcine Model
Authors: Pliasas Vasilis C. , Menne Zach , Aida Virginia , Yin Ji-Hang , Naskou Maria C. , Neasham Peter J. , North J. Fletcher , Wilson Dylan , Horzmann Katharine A. , Jacob Joshy , Skountzou Ioanna , Kyriakis Constantinos S.
Published: July 2022

Influenza A viruses (IAVs) pose a global health threat, contributing to hundreds of thousands of deaths and millions of hospitalizations annually. The two major surface glycoproteins of IAVs, hemagglutinin (HA) and neuraminidase (NA), are important antigens in eliciting neutralizing antibodies and protection against disease. However, NA is generally ignored in the formulation and development of influenza vaccines. In this study, we evaluate the immunogenicity and efficacy against challenge of a novel NA virus-like particles (VLPs) vaccine in the porcine model. We developed an NA2 VLP vaccine containing the NA protein from A/Perth/16/2009 (H3N2) and the matrix 1 (M1) protein from A/MI/73/2015, formulated with a water-in-oil-in-water adjuvant. Responses to NA2 VLPs were compared to a commercial adjuvanted quadrivalent whole inactivated virus (QWIV) swine IAV vaccine. Animals were prime boost vaccinated 21 days apart and challenged four weeks later with an H3N2 swine IAV field isolate, A/swine/NC/KH1552516/2016. Pigs vaccinated with the commercial QWIV vaccine demonstrated high hemagglutination inhibition (HAI) titers but very weak anti-NA antibody titers and subsequently undetectable NA inhibition (NAI) titers. Conversely, NA2 VLP vaccinated pigs demonstrated undetectable HAI titers but high anti-NA antibody titers and NAI titers. Post-challenge, NA2 VLPs and the commercial QWIV vaccine showed similar reductions in virus replication, pulmonary neutrophilic infiltration, and lung inflammation compared to unvaccinated controls. These data suggest that anti-NA immunity following NA2 VLP vaccination offers comparable protection to QWIV swine IAV vaccines inducing primarily anti-HA responses.
Lactobacillus Ameliorates SD-Induced Stress Responses and Gut Dysbiosis by Increasing the Absorption of Gut-Derived GABA in Rhesus Monkeys
Authors: Zhao Ning , Shu Yan , Jian Chenxing , Zhou Zili , Bao Haijun , Li Xianguo , Cheng Xukai , Zhao Ying , Jin Si , Shu Xiaogang
Published: July 2022

Sleep deprivation (SD) has become a health problem in the modern society. Although probiotics supplementation has been proven to improve SD-induced gut dysbiosis, the potential neuroendocrine mechanisms remain elusive. In this study, thirty rhesus monkeys (RMs) were recruited. Paradoxical sleep, bright light, and noise were used to build an RM SD model. We examined the plasma γ-aminobutyric acid (GABA), stress hormones, and inflammatory cytokines using ELISAs. 16S ribosomal DNA sequencing and untargeted metabolomics sequencing were employed to detect gut microbial community and metabolites, respectively. The results of our study showed that RMs subjected to SD had elevated plasma stress hormones (such as cortisol and norepinephrine) and proinflammatory cytokines (such as TNF-α, IL-6, and IL-8), and a decreased anti‐inflammatory cytokine IL-10 level. Additionally, SD could give rise to a significant change in gut microbiota and metabolites. The differential gut microbiota and metabolites caused by SD were enriched in the signaling pathways related to GABA metabolism. Pearson correlation analysis revealed that there is a significant correlation between plasma GABA and SD-induced stress responses and gut dysbiosis. The supplementation of GABA-producing probiotics could significantly increase the relative abundance of Lactobacillus and plasma GABA levels, and reverse SD‐induced stress responses and gut dysbiosis. Therefore, we speculated that SD-induced stress response and gut dysbiosis might be an outcome of reduced gut-derived GABA absorption. The supplementation of GABA-producing Lactobacillus might be beneficial for the treatment of SD-induced intestinal dysfunction.
Oral Immunization With a M Cell-Targeting Recombinant L. Lactis Vaccine LL-plSAM-FVpE Stimulate Protective Immunity Against H. Pylori in Mice
Authors: Guo Le , Zhang Furui , Wang Shue , Li Runle , Zhang Lele , Zhang Zhen , Yin Runting , Liu Hongpeng , Liu Kunmei
Published: July 2022

There are many virulence factors of H. pylori that contribute in diverse ways to gastric disease. Therefore, designing multivalent epitope vaccines against many key virulence factors virulence factors of H. pylori is a promising strategy to control H. pylori infection. In previous studies, we constructed a multivalent epitope vaccine FVpE against four key virulence factors of H. pylori (Urease, CagA, VacA, and NAP), and oral immunization with the FVpE vaccine plus a polysaccharide adjuvant (PA) containing lycium barbarum polysaccharide and chitosan could provide protection against H. pylori infection in the Mongolian gerbil model. Oral vaccines have many advantages over injected vaccines, such as improved safety and compliance, and easier manufacturing and administration. However, the harsh gastrointestinal (GI) environment, such as gastric acid and proteolytic enzymes, limits the development of oral vaccines to some extent. Oral vaccines need a gastrointestinal delivery system with high safety, low price and promoting vaccine antigen to stimulate immune response in the gastrointestinal mucosa. Lactic acid bacteria are gastrointestinal probiotics that have unique advantages as a delivery system for oral vaccines. In this study, a M cell-targeting surface display system for L. lactis named plSAM was designed to help vaccine antigens to stimulate effective immune responses in the gastrointestinal tract, and a M cell-targeting recombinant L. lactis vaccine LL-plSAM-FVpE was constructed by using the surface display system plSAM. recombinant L. lactis vaccine LL-plSAM-FVpE could secretively express the SAM-FVpE protein and display it on the bacterial surface. Moreover, experimental results confirmed that LL-plSAM-FVpE had an enhanced M cell-targeting property. In addition, LL-plSAM-FVpE had excellent M cell-targeting property to promote the phagocytosis and transport of the antigen SAM-FVpE by gastrointestinal M cells. More importantly, oral immunization of LL-plSAM-FVpE or SAM-FVpE plus PA can stimulate IgG and sIgA antibodies and CD4+ T cell immune responses against four virulence factors of H. pylori (Urease, CagA, VacA, and NAP), thus providing protective immunity against H. pylori infection in mice. The M cell-targeting recombinant L. lactis vaccine against various key H. pylori virulence factors could be a promising vaccine candidate for controlling H. pylori infection.
TGF-β Enhances Immunosuppression of Myeloid-Derived Suppressor Cells to Induce Transplant Immune Tolerance Through Affecting Arg-1 Expression
Authors: Cao Peng , Sun Zejia , Zhang Feilong , Zhang Jiandong , Zheng Xiang , Yu Baozhong , Zhao Yong , Wang Wei , Wang Wei
Published: July 2022

Myeloid-derived suppressor cells (MDSCs) are a class of heterogeneous myeloid cells, which play an important role in immunosuppression. We intended to find an effective method that can produce MDSCs with significantly better efficiency and promote immune tolerance for transplant rejection through cell therapy. It has been reported that granulocyte and macrophage colony-stimulating factor (GM-CSF) could induce MDSCsin vitroto cause immunosuppression. In the present study, transforming growth factor β (TGF-β) was added to the induction system, and flow cytometry analysis was used to detect the phenotypes of induced MDSCs. Their potential immunosuppressive function and mechanisms were determined by co-culturing MDSCs with stimulated T cellsin vitroand transferring MDSCs to the skin grafted C57BL/6J mouse modelsin vivo. It was found that the addition of TGF-β could effectively cause bone marrow cells to differentiate into a group of cells with stronger immunosuppressive functions, thereby inhibiting the proliferation of stimulated T cells. The population of CD11b+Gr-1+MDSCs also increased significantly as compared with GM-CSF alone treatment. While detecting for immunosuppressive effectors, we found that expression of arginase 1 (Arg-1) was significantly upregulated in these MDSCs, and inhibitor of Arg-1 significantly suppressed their immunosuppressive capabilities. Moreover, an adoptive transfer of these cells significantly prolonged survival of allo-skin and improved immune tolerancein vivo. These findings indicated that TGF-β + GM-CSF could serve as an effective and feasible method to induce powerful immunosuppressive MDSCsin vitro. Thus, TGF-β + GM-CSF–induced MDSCs may have a promising role in prevention of the graft rejection.
Effects of Small Peptide Supplementation on Growth Performance, Intestinal Barrier of Laying Hens During the Brooding and Growing Periods
Authors: Zhao Xiyu , Zhang Yao , He Wentao , Wei Yuanhang , Han Shunshun , Xia Lu , Tan Bo , Yu Jie , Kang Houyang , Ma Mengen , Zhu Qing , Yin Huadong , Cui Can
Published: July 2022

The growing period is a critical period for growth and development in laying hens. During this period, chicks grow rapidly, but are accompanied by unstable digestive function, incomplete organ development, and high mortality. Small peptide, a feed additive, which has been proved to promote intestinal development and immunity in poultry. In order to elucidate the effects of small peptides on growth performance, immunity, antioxidant capacity, and intestinal health of growing laying hens, a total of 900 Tianfu green shell laying hens (1-day-old) were randomly divided into 5 treatments with 6 replicates of 30 birds each in this 18-week trial. Dietary treatments included a corn-soybean meal-based diet supplemented with 0 g/kg, 1.5 g/kg, 3.0 g/kg, 4.5 g/kg and 6.0 g/kg small peptide, respectively. The results showed that the supplementation of small peptides significantly increased growth rate (P<0.05) in laying hens, as well as elevated the serum immunoglobulins (P<0.05) and antioxidant indices (P<0.05), however, it decreased inflammation parameters (P<0.05). The supplementation of small peptides enhanced the intestinal function by promoting gut development (P<0.05) and improving gut integrity (P<0.05), barrier function (P<0.05) and the diversity of gut microbiota (P<0.05) in the growing hens. The best performance was recorded among the hens fed 4.5 g/kg level of small peptide. Taken together, these results showed that small peptide supplementation could improve the economic value of growing hens by promoting growth rate, disease resistance, and the optimal amount of addition for Tianfu green shell laying hens was 4.5 g/kg.
Immunomodulatory Role of Surfactant Protein-D in a Transgenic Adenocarcinoma of Mouse Prostate (TRAMP) Model
Authors: Ganguly Kasturi , Kishore Uday , Metkari Siddhanath M. , Madan Taruna
Published: July 2022

Surfactant protein D (SP-D), a pattern recognition molecule, is emerging as a potent anti-tumoural innate immune defense molecule in a range of cancers. Previously, SP-D expression was found to be significantly downregulated at the malignant sites of human prostate adenocarcinoma and associated with an increasing Gleason score and severity. We recently reported selective induction of intrinsic apoptosis by a recombinant fragment of human SP-D (rfhSP-D) in the human Prostate cancer (PCa) biopsy explants and cells with glucose regulated protein of 78 (GRP78) as one of the key interacting partners. The present study evaluated the expression of SP-D in early and advanced stages of PCa using transgenic adenocarcinoma of mouse prostate (TRAMP) model. Both early and late stages of PCa showed significantly decreased SP-D mRNA expression and increased proteolytic degradation of SP-D protein. Systemic and tumoural immunophenotyping of TRAMP model revealed increased serine proteases producing granulocytes and polymorphonuclear myeloid-derived suppressor cells (PMN MDSCs) in the late stage; the serine proteases secreted by these cells could be involved in the degradation of SP-D. Susceptibility of rfhSP-D to elastase-mediated proteolysis provided the rationale to use an elastase-inhibitor to sustain intact rfhSP-D in the tumour microenvironment. The study revealed an immunomodulatory potential of rfhSP-D and elastase inhibitor, sivelestat, to induce macrophage polarization towards M1 with downregulation of PMN MDSCs in ex-vivo cultured TRAMP tumours. Furthermore, rfhSP-D induced immunogenic cell death in murine PCa cells and in TRAMP explants. The findings highlight that SP-D plays an anti-tumourigenic role in PCa by inducing immunogenic cell death and immunomodulation while the prostate tumour milieu adversely impacts SP-D by inhibiting its transcription, and enhancing its proteolytic degradation. Transformation of an immunologically “cold tumour” into a “hot tumour” implicates therapeutic potential of rfhSP-D in PCa.
A Guide to International Climate Mitigation Policy and Finance Frameworks Relevant to the Protection and Restoration of Blue Carbon Ecosystems
Authors: Vanderklift Mathew A. , Herr Dorothée , Lovelock Catherine E. , Murdiyarso Daniel , Raw Jacqueline L. , Steven Andrew D. L.
Published: July 2022

The protection, management and restoration of vegetated ecosystems on land and in the ocean (‘natural climate solutions’) can be a useful strategy for reducing net greenhouse gas emissions to help limit global warming. Their potential contribution to reducing net emissions has led to the development of policies and financial incentives for their protection and restoration. These have in turn created a set of expectations among some stakeholders, and interest in expanding these to encompass other ecosystems. However, there are specific rules about how abatement is calculated in international policy and climate finance, and the frameworks and terminology associated with them are often complex. This can be a barrier to stakeholders who want to leverage the potential of natural climate solutions, sometimes leading to incongruence between realised and anticipated benefits. In this article, we attempt to outline some of the key international policy and carbon market frameworks for coastal ‘blue carbon’ ecosystems, and the extent to which different ecosystems are accommodated. Currently, among the coastal ecosystems, only mangrove forests, seagrass meadows, and tidal marshes are typically considered in international policy and carbon market frameworks. The defining feature of these ecosystems is that the foundation species are plants that grow in sediment (soil). They are the only coastal ecosystems currently included in IPCC guidelines for national greenhouse gas inventories, and in compliance and voluntary carbon markets. There is interest in potentially including other marine ecosystems, such as kelp forests and unvegetated tidal flats, into carbon accounting frameworks, but there are unresolved questions about whether sequestration and storage of carbon by these ecosystems meets the rigorous standards required. Voluntary carbon markets have greater flexibility than mechanisms linked to national greenhouse gas inventories, and so might be early implementers of expanding methods to include other ecosystems. Incorporating coastal ecosystems into national greenhouse gas inventory is a useful action countries can take that will likely help generate incentives for protection and restoration of these important ecosystems.
Campylobacter jejuni-Associated Hemophagocytic Lymphohistiocytosis and Guillain-Barre Syndrome: A Case Report
Authors: Shi Fang-e , Chen Mei-fang , Li Yong-jie , Dong Gui-ying , Zhu Ji-hong
Published: July 2022

Campylobacter jejuni (C. jejuni), a Gram-negative bacterium, belongs to microaerobic bacteria. We reported a 21-year-old male patient diagnosed with hemophagocytic lymphohistiocytosis (HLH) due to C. jejuni infection, who presented with multiple clinical manifestations of peripheral nerve injury, such as ophthalmoplegia, facial paralysis, and urinary retention during the treatment. Electromyography showed neurogenic injury and the final diagnosis was Guillain-Barre Syndrome (GBS). After treatment of dexamethasone combined with immunoglobulin, the patient was discharged from the hospital with partial recovery of neurological symptoms.
A Preliminary in vitro and in vivo Evaluation of the Effect and Action Mechanism of 17-AAG Combined With Azoles Against Azole-Resistant Candida spp.
Authors: Liu Luyao , Zhang Xueying , Kayastha Shruti , Tan Lihua , Zhang Heng , Tan Jingwen , Li Linyun , Mao Jinghua , Sun Yi
Published: July 2022

Invasive candidiasis is the primary reason for the increased cases of mortality in a medical environment. The resistance spectra of Candida species to antifungal drugs have gradually expanded. Particularly, the resistance spectra of Candida auris are the most prominent. Hsp90 plays a protective role in the stress response of fungi and facilitates their virulence. In contrast, Hsp90 inhibitors can improve the resistance of fungi to antifungal drugs by regulating the heat resistance of Hsp90, which destroys the integrity of the fungal cell walls. Hsp90 inhibitors thus offer a great potential to reduce or address fungal drug resistance. The drugs tested for the resistance include itraconazole, voriconazole, posaconazole, fluconazole, and 17-AAG. A total of 20 clinical strains of Candida were investigated. The broth microdilution checkerboard technique, as adapted from the CLSI M27-A4 method, was applied in this study. We found that 17-AAG alone exerted limited antifungal activity against all tested strains. The MIC range of 17-AAG was 8 to >32 μg/ml. A synergy was observed among 17-AAG and itraconazole, voriconazole, and posaconazole against 10 (50%), 7 (35%), and 13 (65%) of all isolates, respectively. Moreover, the synergy between 17-AAG and fluconazole was observed against 5 (50%) strains of azole-resistant Candida. However, no antagonism was recorded overall. Our result adequately verifies the influence of 17-AAG on the formation of Candida spp. biofilm. Moreover, we determined that with the use of rhodamine 6G to detect drug efflux and that of dihydrorhodamine-123 to detect intracellular reactive oxygen species (ROS), treatment with 17-AAG combined with azole drugs could inhibit the efflux pump of fungi and promote the accumulation of ROS in the fungal cells, thereby inducing fungal cell apoptosis. Thus, the mechanism of 17-AAG combined with azoles can kill fungi. Our results thus provide a new idea to further explore drugs against drug-resistant Candida spp.
Targeted Antimicrobial Agents as Potential Tools for Modulating the Gut Microbiome
Authors: Chou Shuli , Zhang Shiqing , Guo Huating , Chang Yung-fu , Zhao Wenjing , Mou Xiangyu
Published: July 2022

The gut microbiome plays a pivotal role in maintaining the health of the hosts; however, there is accumulating evidence that certain bacteria in the host, termed pathobionts, play roles in the progression of diseases. Although antibiotics can be used to eradicate unwanted bacteria, the side effects of antibiotic treatment lead to a great need for more targeted antimicrobial agents as tools to modulate the microbiome more precisely. Herein, we reviewed narrow-spectrum antibiotics naturally made by plants and microorganisms, followed by more targeted antibiotic agents including synthetic peptides, phage, and targeted drug delivery systems, from the perspective of using them as potential tools for modulating the gut microbiome for favorable effects on the health of the host. Given the emerging discoveries on pathobionts and the increasing knowledge on targeted antimicrobial agents reviewed in this article, we anticipate targeted antimicrobial agents will emerge as a new generation of a drug to treat microbiome-involved diseases.
Inoculum Concentration and Mineral Fertilization: Effects on the Endophytic Microbiome of Soybean
Authors: dos Santos Roberta Mendes , Cueva-Yesquén Luis Gabriel , Garboggini Fabiana Fantinatti , Desoignies Nicolas , Rigobelo Everlon Cid
Published: July 2022

Soybean crops are of great economic importance worldwide and in Brazil. This crop is a commodity that provides large amounts of financial resources to the country. Soybean productivity is influenced by several biotic and abiotic factors, and most of these factors cannot be controlled by agricultural practices. Due to the soybean cultivars used and their required yields, the soybean crop, similar to other agriculturally important crops, requires large amounts of mineral fertilizers. There are several microorganisms that colonize soybean plant roots without causing symptoms or damage. These microorganisms that colonize plant tissues are called endophytes and can often promote plant growth and development. Little is known about the factors that influence endophyticism. The aim of the present study was to evaluate whether Bacillus subtilis inoculant concentrations and levels of mineral fertilization recommended for the crop have any influence on the endophytic microbiome of soybean plant roots. The results show that B. subtilis inoculations did not affect the endophytic community of the roots; however, the evaluation of the microbial community structure according to the alpha diversity metrics observed richness, Chao1 index, Shannon index and Simpson index showed that microbial diversity of endophytes was higher at fertilization levels of 50 and 100%, with a significant difference (p < 0.05) between 0 and 50% and 0 and 100% fertilization.
Melatonin Attenuates the Urea-Induced Yields Improvement Through Remodeling Transcriptome and Rhizosphere Microbial Community Structure in Soybean
Authors: Xiao Renhao , Han Qin , Liu Yu , Zhang Xuehai , Hao Qingnan , Chai Qingqing , Hao Yongfang , Deng Junbo , Li Xia , Ji Hongtao
Published: July 2022

Foliar application of nitrogen to enhance crop productivity has been widely used. Melatonin is an effective regulator in promoting plant growth. However, the effects of melatonin and the combination of melatonin and nitrogen on soybeans yields production remain largely unknown. In this study, a field experiment was conducted to evaluate the effects and mechanisms of spraying leaves with melatonin and urea on soybeans. Foliar application of urea significantly increased soybean yields and melatonin did not affect the yields, while combination of melatonin and urea significantly reduced the yields compared to the application of urea alone. A leaf transcriptional profile was then carried out to reveal the underlying mechanism and found that foliar spraying of urea specifically induced the expression of genes related to amino acid transport and nitrogen metabolism. However, foliar application of melatonin significantly changed the transcriptional pattern established by urea application and increased the expression of genes related to abiotic stress signaling pathways. The effects of melatonin and urea treatment on soil microbiome were also investigated. Neither melatonin nor urea application altered the soil microbial alpha diversity, but melatonin application changed rhizosphere microbial community structure, whereas the combination of melatonin and urea did not. Melatonin or urea application altered the abundance of certain taxa. The number of taxa changed by melatonin treatment was higher than urea treatment. Collectively, our results provide new and valuable insights into the effects of foliar application of melatonin to urea and further show that melatonin exerts strong antagonistic effects on urea-induced soybean yields, gene expression and certain soil microorganisms.
Hepatitis B Virus Reactivation Increased the Risk of Developing Hepatic Failure and Mortality in Cirrhosis With Acute Exacerbation
Authors: Zhu Ying , Li Hai , Wang Xianbo , Zheng Xin , Huang Yan , Chen Jinjun , Meng Zhongji , Gao Yanhang , Qian Zhiping , Liu Feng , Lu Xiaobo , Shi Yu , Shang Jia , Yan Huadong , Zheng Yubao , Qiao Liang , Zhang Yan , Xiang Xiaomei , Dan Yunjie , Sun Shuning , Hou Yixin , Zhang Qun , Xiong Yan , Li Sumeng , Chen Jun , Huang Zebing , Li Beiling , Jiang Xiuhua , Luo Sen , Chen Yuanyuan , Gao Na , Liu Chunyan , Ji Liujuan , Yuan Wei , Li Jing , Li Tao , Zheng Rongjiong , Zhou Xinyi , Ren Haotang , Zhou Yi , Xu Baoyan , Yu Rentao , Tan Wenting , Deng Guohong
Published: July 2022

Background and Aims

Hepatitis B virus (HBV) reactivation is a serious condition and has been extensively described in chemotherapeutic immunosuppressive population. However, little is known about HBV reactivation in immunocompetent patients with chronic hepatitis B (CHB). In this study, we evaluated the prevalence and the clinical significance of HBV reactivation in CHB patients with acute exacerbations.

Method

Patients were screened from two prospective multicenter observational cohorts (CATCH-LIFE cohort). A total of 1,020 CHB patients with previous antiviral treatment history were included to assess the prevalence, risk factors, clinical characteristics of HBV reactivation, and its influence on the progression of chronic liver disease.

Results

The prevalence of HBV reactivation was 51.9% in CHB patients with acute exacerbations who had antiviral treatment history in our study. Among the 529 patients with HBV reactivation, 70.9% of them were triggered by discontinued antiviral treatment and 5.9% by nucleos(t)ide analogs (NUCs) resistance. The prevalence of antiviral treatment disruption and NUCs resistance in patients with HBV reactivation is much higher than that in the patients without (70.9% vs. 0.2%, and 5.9% vs. 0, respectively, both p < 0.001). Stratified and interaction analysis showed that HBV reactivation was correlated with high short-term mortality in cirrhosis subgroup (HR = 2.1, p < 0.001). Cirrhotic patients with HBV reactivation had a significantly higher proportion of developing hepatic failure (45.0% vs. 20.3%, p < 0.001), acute-on-chronic liver failure (ACLF; 31.4% vs. 21.8%, p = 0.005), and short-term death (14.0% vs. 5.9% for 28-day, and 23.3% vs. 12.4% for 90-day, both p < 0.001) than those without. HBV reactivation is an independent risk factor of 90-day mortality for cirrhosis patients (OR = 1.70, p = 0.005), as well as hepatic encephalopathy, ascites, and bacterial infection.

Conclusion

This study clearly demonstrated that there was a high prevalence of HBV reactivation in CHB patients, which was mainly triggered by discontinued antiviral treatment. The HBV reactivation strongly increased the risk of developing hepatic failure, ACLF and short-term death in HBV-related cirrhotic patients, which may suggest that HBV reactivation would be a new challenge in achieving the WHO target of 65% reduction in mortality from hepatitis B by 2030.
Sources and Fluxes of Organic Carbon and Energy to Microorganisms in Global Marine Sediments
Authors: Bradley James A. , Arndt Sandra , Amend Jan P. , Burwicz-Galerne Ewa , LaRowe Douglas E.
Published: July 2022

Marine sediments comprise one of the largest microbial habitats and organic carbon sinks on the planet. However, it is unclear how variations in sediment physicochemical properties impact microorganisms on a global scale. Here we investigate patterns in the distribution of microbial cells, organic carbon, and the amounts of power used by microorganisms in global sediments. Our results show that sediment on continental shelves and margins is predominantly anoxic and contains cells whose power utilization decreases with sediment depth and age. Sediment in abyssal zones contains microbes that use low amounts of power on a per cell basis, across large gradients in sediment depth and age. We find that trends in cell abundance, POC storage and degradation, and microbial power utilization are mainly structured by depositional setting and redox conditions, rather than sediment depth and age. We also reveal distinct trends in per-cell power regime across different depositional settings, from maxima of ∼10–16 W cell–1 in recently deposited shelf sediments to minima of <10–20 W cell–1 in deeper and ancient sediments. Overall, we demonstrate broad global-scale connections between the depositional setting and redox conditions of global sediment, and the amounts of organic carbon and activity of deep biosphere microorganisms.