bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploration of the core gene signatures and mechanisms between NAFLD and sarcopenia through transcriptomic level
Authors: Xu Ziying , Yu Zihui , Li Shang , Tian Ziyan , Yuan Jing , You Fuping
Published: March 2023

Introduction

The increased prevalence of non-alcoholic fatty liver disease (NAFLD) and sarcopenia among the elderly are facing a significant challenge to the world’s health systems. Our study aims to identify the coexpressed genes in NAFLD and sarcopenia patients.

Methods

We downloaded the transcriptome data of NAFLD tissue from patients, as well as muscle tissues from sarcopenia patients, from the GEO database in order to investigate the shared transcriptional regulation mechanisms between these two diseases. Then, focusing on the genes that were frequently expressed in these diseases, together with GSVA and WGCNA, we utilized a range of analysis methods to identify the main co-expressed genes in both diseases by taking intersections. We investigated these changes after learning that they mostly affected lipid metabolism and oxidative stress injury pathways.

Results

By analyzing these genes and their interactions with transcription factors and proteins, we were able to identify 8 genes that share common patterns. From these 8 genes, we were possible to forecast potential future medicines. Our research raises the possibility of NAFLD and sarcopenia transcriptome regulatory pathways in aging populations.

Discussion

In conclusion, a complete transcription pattern mapping was carried out in order to identify the core genes, underlying biological mechanisms, and possible therapeutic targets that regulate aging in NAFLD and sarcopenia patients. It provides novel insights and proof in favor of decreasing the increased prevalence of sarcopenia in the elderly caused by NAFLD.
Pericytes modulate islet immune cells and insulin secretion through Interleukin-33 production in mice
Authors: Burganova Guzel , Schonblum Anat , Sakhneny Lina , Epshtein Alona , Wald Tomer , Tzaig Mika , Landsman Limor
Published: March 2023

Introduction

Immune cells were recently shown to support β-cells and insulin secretion. However, little is known about how islet immune cells are regulated to maintain glucose homeostasis. Administration of various cytokines, including Interleukin-33 (IL-33), was shown to influence β-cell function. However, the role of endogenous, locally produced IL-33 in pancreatic function remains unknown. Here, we show that IL-33, produced by pancreatic pericytes, is required for glucose homeostasis.

Methods

To characterize pancreatic IL-33 production, we employed gene expression, flow cytometry, and immunofluorescence analyses. To define the role of this cytokine, we employed transgenic mouse systems to delete the Il33 gene selectively in pancreatic pericytes, in combination with the administration of recombinant IL-33. Glucose response was measured in vivo and in vitro, and morphometric and molecular analyses were used to measure β-cell mass and gene expression. Immune cells were analyzed by flow cytometry.

Resuts

Our results show that pericytes are the primary source of IL-33 in the pancreas. Mice lacking pericytic IL-33 were glucose intolerant due to impaired insulin secretion. Selective loss of pericytic IL-33 was further associated with reduced T and dendritic cell numbers in the islets and lower retinoic acid production by islet macrophages.

Discussion

Our study demonstrates the importance of local, pericytic IL-33 production for glucose regulation. Additionally, it proposes that pericytes regulate islet immune cells to support β-cell function in an IL-33-dependent manner. Our study reveals an intricate cellular network within the islet niche.
Numerical study on flow separation and force evolution in liquid nitrogen cavitating flow
Authors: Liu Yi , Zhang JinLing , Sun Lilong , An LiLi , Wang XunMing , Cai Jie , Zhang Wei , Chen Feng
Published: March 2023

In this paper, a two-phase flow model and the improved thermal cavitation model are used to study the flow characteristics and the evolution of vorticity force for liquid nitrogen cavitation flow. The results are validated against the experimental data from NASA, which shows that the flow re-attachment occurs in the area where the boundary vorticity flux begins to decrease from its positive value. Alternatively, the flow separation occurs near the area with low boundary vorticity fluxes. Besides, the boundary vorticity flux changes typically from negative to positive around the cavity. The development of the cavity affects the surrounding vortex structure, which leads to the evolution of vorticity force and the fluctuations of lateral force and drag force. The results show that the drag force is magnified by the cavitation, and it first decreases and then increases in a typical cycle of cavity evolution. The negative resistance unit is mainly produced in the front of the cavity, and the positive resistance unit is also made in the rear of the cavity. When the attached cavity is shed, the positive drag elements decrease, and the drag force drops to its minimum. When the attached cavity is growing, the positive resistance elements behind the cavity increase, making the resistance force gradually increase. For the lateral force, the existence of the cavity produces lift elements pointing out of the surface outside the cavity, and the unsymmetrical distribution of the cavity leads to the fluctuation of the lateral force.
Proud of you, so act for you? The role of national pride in promoting individual pro-environmental tendencies
Authors: Wang Pengcheng , Dong Zhiqiang , Cai Shenggang , Xiao Min
Published: March 2023

The promotion of pro-environment behaviors is important for achieving national and global environmental protection goals. However, there is a gap between the government’s environmental will and the people’s pro-environmental tendencies. National pride has been identified as a critical pathway to achieving individual behaviors desired by the government. Here, we investigate the role of national pride in promoting individuals’ pro-environmental tendencies (PET). A large-scale survey and two experiments in the Chinese context were conducted to investigate the relationship between national pride and PET and the tools for promoting national pride and PET. The results show that national pride is positively associated with individuals’ PET. Priming with national achievements promotes individuals’ PET by inspiring their national pride. Both political-economic achievements and historical-cultural achievements can inspire Chinese people’s national pride, but political-economic achievements are more effective. Moreover, priming national pride combined with highlighting national environmental norm information could more effectively increase PET. Our findings illuminate the relationship between individuals’ national pride and PET, suggesting a potential means for translating national environmental will into individuals’ pro-environmental actions.
A united model for diagnosing pulmonary tuberculosis with random forest and artificial neural network
Authors: Zhu Qingqing , Liu Jie
Published: March 2023

Background: Pulmonary tuberculosis (PTB) is a chronic infectious disease and is the most common type of TB. Although the sputum smear test is a gold standard for diagnosing PTB, the method has numerous limitations, including low sensitivity, low specificity, and insufficient samples.

Methods: The present study aimed to identify specific biomarkers of PTB and construct a model for diagnosing PTB by combining random forest (RF) and artificial neural network (ANN) algorithms. Two publicly available cohorts of TB, namely, the GSE83456 (training) and GSE42834 (validation) cohorts, were retrieved from the Gene Expression Omnibus (GEO) database. A total of 45 and 61 differentially expressed genes (DEGs) were identified between the PTB and control samples, respectively, by screening the GSE83456 cohort. An RF classifier was used for identifying specific biomarkers, following which an ANN-based classification model was constructed for identifying PTB samples. The accuracy of the ANN model was validated using the receiver operating characteristic (ROC) curve. The proportion of 22 types of immunocytes in the PTB samples was measured using the CIBERSORT algorithm, and the correlations between the immunocytes were determined.

Results: Differential analysis revealed that 11 and 22 DEGs were upregulated and downregulated, respectively, and 11 biomarkers specific to PTB were identified by the RF classifier. The weights of these biomarkers were determined and an ANN-based classification model was subsequently constructed. The model exhibited outstanding performance, as revealed by the area under the curve (AUC), which was 1.000 for the training cohort. The AUC of the validation cohort was 0.946, which further confirmed the accuracy of the model.

Conclusion: Altogether, the present study successfully identified specific genetic biomarkers of PTB and constructed a highly accurate model for the diagnosis of PTB based on blood samples. The model developed herein can serve as a reliable reference for the early detection of PTB and provide novel perspectives into the pathogenesis of PTB.
Bivariate quantitative Bayesian LASSO for detecting association of rare haplotypes with two correlated continuous phenotypes
Authors: Sajal Ibrahim Hossain , Biswas Swati
Published: March 2023

In genetic association studies, the multivariate analysis of correlated phenotypes offers statistical and biological advantages compared to analyzing one phenotype at a time. The joint analysis utilizes additional information contained in the correlation and avoids multiple testing. It also provides an opportunity to investigate and understand shared genetic mechanisms of multiple phenotypes. Bivariate logistic Bayesian LASSO (LBL) was proposed earlier to detect rare haplotypes associated with two binary phenotypes or one binary and one continuous phenotype jointly. There is currently no haplotype association test available that can handle multiple continuous phenotypes. In this study, by employing the framework of bivariate LBL, we propose bivariate quantitative Bayesian LASSO (QBL) to detect rare haplotypes associated with two continuous phenotypes. Bivariate QBL removes unassociated haplotypes by regularizing the regression coefficients and utilizing a latent variable to model correlation between two phenotypes. We carry out extensive simulations to investigate the performance of bivariate QBL and compare it with that of a standard (univariate) haplotype association test, Haplo.score (applied twice to two phenotypes individually). Bivariate QBL performs better than Haplo.score in all simulations with varying degrees of power gain. We analyze Genetic Analysis Workshop 19 exome sequencing data on systolic and diastolic blood pressures and detect several rare haplotypes associated with the two phenotypes.
Pan-cancer analysis reveals signal transducer and activator of transcription (STAT) gene family as biomarkers for prognostic prediction and therapeutic guidance
Authors: Cheng Mei , Liu Yifan , Guo Yangkun , Li Man , Xian Shuyuan , Qin Hengwei , Yang Yiting , Qian Weijin , Tang Jieling , Lu Yuwei , Yao Yuntao , Zhang Mengyi , Jin Minghao , Xu Long , Huang Runzhi , Xu Dayuan
Published: March 2023

Background: The signal transducer and activator of transcription (STAT) gene family have been widely found to regulate cell proliferation, differentiation, apoptosis, and angiogenesis through complex signaling pathways, and thus impacting tumor formation and development in different types of tumor. However, the roles of STATs on prognostic prediction and therapeutic guidance in pan-cancer remain unexplored.

Materials and Methods: The dataset of 33 types of TCGA tumor, para-carcinoma and normal tissues, was obtained from the UCSC Xena database, including the gene expression profiles in the formats of FPKM value, demographic characteristics, clinical information, and survival data of STATs. Differential expression and co-expression analyses, WGCNA, clinical relevance analysis, immune subtype analysis, tumor stemness analysis, tumor purity analysis, immune infiltration analysis, immunotherapy related analysis, tumor mutation related analysis, and drug sensitivity analysis were performed by R software.

Results: Differential expression of STAT1 was found between normal and BRCA tissues (p < 0.001, log2FC = 0.895). Additionally, the strongest correlation among STATs lied between STAT1 and STAT2 (correlation coefficient = 0.6). Moreover, high expression levels of STAT1 (p = 0.031) were revealed to be notably correlated with poor prognosis in KIRP. In addition, STAT1 expressed the highest value in immune subtypes C1, C2, C3, and C6 in LUAD. What’s more, strong negative correlations were demonstrated between expression of STAT6 and mDNAss and mRNAss of TGCT. Additionally, STAT4 expression was characterized to be significantly negatively correlated with tumor purity of the majority of cancer types. Moreover, STAT1 and STAT3 were shown to be generally high-expressed in pan-cancer myeloid cells, and STATs all had positive correlation with the infiltration of the majority of immune cells. In addition, STATs were revealed to be closely linked with immunotherapy response. What’s more, STAT4 expression was identified to have a strong negative correlation with TMB value in DLBC. Last but not least, positive correlations were accessed between STAT5 and sensitivity of Nelarabine (cor = 0.600, p < 0.001).

Conclusion: In the present study, we identified STATs as biomarkers for prognostic prediction and therapeutic guidance in pan-cancer. Hopefully our findings could provide a valuable reference for future STATs research and clinical applications.
Role of regulation of PD-1 and PD-L1 expression in sepsis
Authors: Zhang Teng , Yu-Jing Li , Ma Tao
Published: March 2023

Long term immunosuppression is problematic during sepsis. The PD-1 and PD-L1 immune checkpoint proteins have potent immunosuppressive functions. Recent studies have revealed several features of PD-1 and PD-L1 and their roles in sepsis. Here, we summarize the overall findings of PD-1 and PD-L1 by first reviewing the biological features of PD-1 and PD-L1 and then discussing the mechanisms that control the expression of PD-1 and PD-L1. We then review the functions of PD-1 and PD-L1 in physiological settings and further discuss PD-1 and PD-L1 in sepsis, including their involvement in several sepsis-related processes and their potential therapeutic relevance in sepsis. In general, PD-1 and PD-L1 have critical roles in sepsis, indicating that their regulation may be a potential therapeutic target for sepsis.
Knowledge mapping of autophagy in osteoarthritis from 2004 to 2022: A bibliometric analysis
Authors: Liao Jiahe , Yu Xinbo , Chen Jiaqi , Wu Zihua , He Qian , Zhang Yan , Song Weijiang , Luo Jing , Tao Qingwen
Published: March 2023

Background

Autophagy in osteoarthritis (OA) has become an active area of research with substantial value and potential. Nevertheless, few bibliometric studies have systematically analyzed the available research in the field. The main goal of this study was to map the available literature on the role of autophagy in OA and identify global research hotspots and trends.

Methods

The Web of Science Core Collection and Scopus databases were interrogated for studies of autophagy in OA published between 2004 and 2022. Microsoft Excel, VOSviewer and CiteSpace software were used to analyze and visualize the number of publications and associated citations, and reveal global research hotspots and trends in the autophagy in OA field.

Results

732 outputs published by 329 institutions from 55 countries/regions were included in this study. From 2004 to 2022, the number of publications increased. China produced the most publications (n=456), prior to the USA (n=115), South Korea (n=33), and Japan (n=27). Scripps Research Institute (n=26) was the most productive institution. Martin Lotz (n=30) was the highest output author, while Caramés B (n=302) was the highest output author. Osteoarthritis and Cartilage was the most prolific and most co-cited journal. Currently, the autophagy in OA research hotspots include chondrocyte, transforming growth factor beta 1 (TGF-β1), inflammatory response, stress, and mitophagy. The emerging research trends in this field are AMPK, macrophage, senescence, apoptosis, tougu xiaotong capsule (TXC), green tea extract, rapamycin, and dexamethasone. Novel drugs targeting specific molecule such as TGF-β and AMPK have shown therapeutic potential but are still in the preclinical stage of development.

Conclusions

Research on the role of autophagy in OA is flourishing. Martin Lotz, Beatriz Caramés, and Osteoarthritis and Cartilage have made outstanding contributions to the field. Prior studies of OA autophagy mainly focused on mechanisms underlying OA and autophagy, including AMPK, macrophages, TGF-β1, inflammatory response, stress, and mitophagy. Emerging research trends, however, are centered around the relationship between autophagy, apoptosis, and senescence, as well as drug candidates such as TXC and green tea extract. The development of new targeted drugs that enhance or restore autophagic activity is a promising strategy for the treatment of OA.
Inducible nitric oxide synthase-expressing myeloid-derived suppressor cells regulated by interleukin 35 contribute to the pathogenesis of psoriasis
Authors: Zhang Junfeng , Zhang Yunsheng , Yang Zhiya , Cheng Dalei , Zhang Hui , Wei Li , Liu Chen , Yan Fenglian , Li Chunxia , Dong Guanjun , Wang Changying , Shi Dongmei , Xiong Huabao
Published: March 2023

Although psoriasis is classified as a T cell-mediated inflammatory disease, the contribution of myeloid cells to the pathogenesis of psoriasis is not fully understood. In the present study, we demonstrated that the expression of the anti-inflammatory cytokine interleukin-35 (IL-35) was significantly increased in patients with psoriasis with a marked increase in the number of myeloid-derived suppressor cells (MDSCs). Similar results were obtained in an imiquimod-induced psoriasis mouse model. IL-35 reduced the total number of MDSCs and their subtypes in the spleens and psoriatic skin lesions, ameliorating psoriasis. IL-35 also reduced the expression of inducible nitric oxide synthase in MDSCs, although it had no significant effect on interleukin-10 expression. Adoptive transfer of MDSCs from imiquimod-challenged mice aggravated the disease and weakened the effect of IL-35 in the recipient mice. In addition, mice transferred with MDSCs isolated from inducible nitric oxide synthase knockout mice had milder disease than those with wild-type MDSCs. Furthermore, wild-type MDSCs reversed the effects of IL-35, while MDSCs isolated from inducible nitric oxide synthase knockout mice did not affect IL-35 treatment. In summary, IL-35 may play a critical role in the regulation of iNOS-expressing MDSCs in the pathogenesis of psoriasis, highlighting IL-35 as a novel therapeutic strategy for patients with chronic psoriasis or other cutaneous inflammatory diseases.
A cis-element at the Rorc locus regulates the development of type 3 innate lymphoid cells
Authors: Chang Dehui , Zhang Hao , Ge Jing , Xing Qi , Guo Xinyi , Wang Xiaohu , Dong Chen
Published: March 2023

Background

As an important early source of IL-17A and IL-22 in immune responses, type 3 innate lymphoid cells (ILC3s) are critically regulated by the transcription factor retinoic-acid-receptor-related orphan receptor gamma t (RORγt). Previously, we have identified a crucial role of the conserved non-coding sequence 9 (CNS9), located at +5,802 to +7,963 bp of the Rorc gene, in directing T helper 17 differentiation and related autoimmune disease. However, whether cis-acting elements regulate RORγt expression in ILC3s is unknown.

Results

Here we show that CNS9 deficiency in mice not only decreases ILC3 signature gene expression and increases ILC1-gene expression features in total ILC3s, but also leads to generation of a distinct CD4+NKp46+ ILC3 population, though the overall numbers and frequencies of RORγt+ ILC3s are not affected. Mechanistically, CNS9 deficiency selectively decreases RORγt expression in ILC3s, which thus alters ILC3 gene expression features and promotes cell-intrinsic generation of CD4+NKp46+ ILC3 subset.

Conclusion

Our study thus identifies CNS9 as an essential cis-regulatory element controlling the lineage stability and plasticity of ILC3s through modulating expression levels of RORγt protein.
Microbiota-ear-brain interaction is associated with generalized anxiety disorder through activation of inflammatory cytokine responses
Authors: Feng Renyi , Zhu Qingyong , Li Qingchen , Zhai Yanping , Wang Jiuqi , Qin Chi , Liang Dongxiao , Zhang Rui , Tian Haiyan , Liu Han , Chen Yongkang , Fu Yu , Wang Xuejing , Ding Xuebing
Published: March 2023

Introduction

Generalized anxiety disorder (GAD) is one of the most enduring anxiety disorders, being associated with increased systemic inflammation. However, the trigger and mechanisms underlying the activation of inflammatory cytokine responses in GAD remain poorly understood.

Materials and methods

We characterized the ear canal microbiome in GAD patients through 16S rRNA gene sequencing and metagenomic sequencing and identified the serum inflammatory markers in GAD patients. Spearman correlations were applied to test the relationship between the microbiota changes and systemic inflammation.

Results

Our findings showed the higher microbial diversity, accompanied with the significantly increased abundance of Proteobacteria, and decreased abundance of Firmicutes in the ear canal of GAD participants compared to that of the age- and sex-matched healthy controls (HC). Metagenomic sequencing showed that Pseudomonas aeruginosa were significantly increased at species-level in GAD patients. Furthermore, we observed the relative abundance of Pseudomonas aeruginosa was positively associated with elevated systemic inflammatory markers and the severity of disease, suggesting that these ear canal microbiota alterations might be correlated with GAD by activating the inflammatory response.

Conclusions

These findings indicate that microbiota-ear-brain interaction via upregulating inflammatory reaction involve in the development of GAD, as well as suggest that ear canal bacterial communities may be a target for therapeutic intervention.
Differentiation-related genes in tumor-associated macrophages as potential prognostic biomarkers in non-small cell lung cancer
Authors: Li Zhaoxun , Zhou Bin , Zhu Xinsheng , Yang Fujun , Jin Kaiqi , Dai Jie , Zhu Yuming , Song Xiao , Jiang Gening
Published: March 2023

Background

The purpose of this study was to evaluate the role of differentiation-related genes (DRGs) in tumor-associated macrophages (TAMs) in non-small cell lung cancer (NSCLC).

Methods

Single cell RNA-seq (scRNA-seq) data from GEO and bulk RNA-seq data from TCGA were analyzed to identify DRGs using trajectory method. Functional gene analysis was carried out by GO/KEGG enrichment analysis. The mRNA and protein expression in human tissue were analyzed by HPA and GEPIA databases. To investigate the prognostic value of these genes, three risk score (RS) models in different pathological types of NSCLC were generated and predicted NSCLC prognosis in datasets from TCGA, UCSC and GEO databases.

Results

1,738 DRGs were identified through trajectory analysis. GO/KEGG analysis showed that these genes were predominantly related to myeloid leukocyte activation and leukocyte migration. 13 DRGs (C1QB, CCL4, CD14, CD84, FGL2, MS4A6A, NLRP3, PLEK, RNASE6, SAMSN1, SPN, TMEM176B, ZEB2) related to prognosis were obtained through univariate Cox analysis and Lasso regression. C1QB, CD84, FGL2, MS4A6A, NLRP3, PLEK, SAMSN1, SPN, and ZEB2 were downregulated in NSCLC compared to non-cancer tissue. The mRNA of 13 genes were significantly expressed in pulmonary macrophages with strong cell specificity. Meanwhile, immunohistochemical staining showed that C1QB, CCL4, SPN, CD14, NLRP3, SAMSN1, MS4A6A, TMEM176B were expressed in different degrees in lung cancer tissues. ZEB2 (HR=1.4, P<0.05) and CD14 (HR=1.6, P<0.05) expression were associated with a worse prognosis in lung squamous cell carcinoma; ZEB2 (HR=0.64, P<0.05), CD84 (HR=0.65, P<0.05), PLEK (HR=0.71, P<0.05) and FGL2 (HR=0.61, P<0.05) expression were associated with a better prognosis in lung adenocarcinoma. Three RS models based on 13 DRGs both showed that the high RS was significantly associated with poor prognosis in different pathological types of NSCLC.

Conclusions

This study highlights the prognostic value of DRGs in TAMs in NSCLC patients, providing novel insights for the development of therapeutic and prognostic targets based on TAM functional differences.
Porcine anti-human lymphocyte immunoglobulin depletes the lymphocyte population to promote successful kidney transplantation
Authors: Zhang Limin , Zou Haoyong , Lu Xia , Shi Huibo , Xu Tao , Gu Shiqi , Yu Qinyu , Yin Wenqu , Chen Shi , Zhang Zhi , Gong Nianqiao
Published: March 2023

Introduction

Porcine anti-human lymphocyte immunoglobulin (pALG) has been used in kidney transplantation, but its impacts on the lymphocyte cell pool remain unclear.

Methods

We retrospectively analyzed 12 kidney transplant recipients receiving pALG, and additional recipients receiving rabbit anti-human thymocyte immunoglobulin (rATG), basiliximab, or no induction therapy as a comparison group.

Results

pALG showed high binding affinity to peripheral blood mononuclear cells (PBMCs) after administration, immediately depleting blood lymphocytes; an effect that was weaker than rATG but stronger than basiliximab. Single-cell sequencing analysis showed that pALG mainly influenced T cells and innate immune cells (mononuclear phagocytes and neutrophils). By analyzing immune cell subsets, we found that pALG moderately depleted CD4+T cells, CD8+T cells, regulatory T cells, and NKT cells and mildly inhibited dendritic cells. Serum inflammatory cytokines (IL-2, IL-6) were only moderately increased compared with rATG, which might be beneficial in terms of reducing the risk of untoward immune activation. During 3 months of follow-up, we found that all recipients and transplanted kidneys survived and showed good organ function recovery; there were no cases of rejection and a low rate of complications.

Discussion

In conclusion, pALG acts mainly by moderately depleting T cells and is thus a good candidate for induction therapy for kidney transplant recipients. The immunological features of pALG should be exploited for the development of individually-optimized induction therapies based on the needs of the transplant and the immune status of the patient, which is appropriate for non-high-risk recipients.
Peripheral blood mononuclear cells reactivity in recent-onset type I diabetes patients is directed against the leader peptide of preproinsulin, GAD65271-285 and GAD65431-450
Authors: Jores Rita D. , Baldera Davide , Schirru Enrico , Muntoni Sandro , Rossino Rossano , Manchinu Maria F. , Marongiu Maria F. , Caria Cristian A. , Ripoli Carlo , Ricciardi Maria R. , Cucca Francesco , Congia Mauro
Published: March 2023

Introduction

T cell reactivity against pancreatic autoantigens is considered one of the main contributors to the destruction of insulin-producing cells in type 1 diabetes (T1D). Over the years, peptide epitopes derived from these autoantigens have been described in NOD mice and in both HLA class II transgenic mice and humans. However, which ones are involved in the early onset or in the progressive phases of the disease is still unclear.

Methods

In this work we have investigated, in early-onset T1D pediatric patients and HLA-matched controls from Sardinia, the potential of preproinsulin (PPI) and glutamate decarboxylase 65 (GAD65)-derived peptides to induce spontaneous T cell proliferation responses of peripheral blood mononuclear cells (PBMCs).

Results

Significant T cell responses against PPI1-18, PPI7-19 and PPI31-49, the first two belonging to the leader sequence of PPI, and GAD65271-285 and GAD65431-450, were found in HLA-DR4, -DQ8 and -DR3, -DQ2 T1D children.

Conclusions

These data show that cryptic epitopes from the leader sequence of the PPI and GAD65271-285 and GAD65431-450 peptides might be among the critical antigenic epitopes eliciting the primary autoreactive responses in the early phases of the disease. These results may have implications in the design of immunogenic PPI and GAD65 peptides for peptide-based immunotherapy.
Immunogenicity and protective efficacy of OmpA subunit vaccine against Aeromonas hydrophila infection in Megalobrama amblycephala: An effective alternative to the inactivated vaccine
Authors: Zhang Minying , Zhang Ting , He Yang , Cui Hujun , Li Hong , Xu Zehua , Wang Xu , Liu Yunlong , Li Hongping , Zhao Xiaoheng , Cheng Hanliang , Xu Jianhe , Chen Xiangning , Ding Zhujin
Published: March 2023

Aeromonas hydrophila is a kind of zoonotic pathogen, which can cause bacterial septicemia in fish and bring huge economic losses to global aquaculture. Outer membrane proteins (Omps) are conserved antigens of Aeromonas hydrophila, which can be developed as subunit vaccines. To evaluate the protective efficacy of inactivated vaccine and recombinant outer membrane protein A (OmpA) subunit vaccine against A. hydrophila in juvenile Megalobrama amblycephala, the present study investigated the immunogenicity and protective effects of both vaccines, as well as the non-specific and specific immune response of M. amblycephala. Compared with the non-vaccinated group, both inactivated and OmpA subunit vaccines improved the survival rate of M. amblycephala upon infection. The protective effects of OmpA vaccine groups were better than that of the inactivated vaccine groups, which should be attributed to the reduced bacterial load and enhanced host immunity in the vaccinated fish. ELISA assay showed that the titer of serum immunoglobulin M (IgM) specific to A. hydrophila up-regulated significantly in the OmpA subunit vaccine groups at 14 d post infection (dpi), which should contribute to better immune protective effects. In addition, vaccination enhanced host bactericidal abilities might also attribute to the regulation of the activities of hepatic and serum antimicrobial enzymes. Moreover, the expression of immune-related genes (SAA, iNOS, IL-1 β, IL-6, IL-10, TNF α, C3, MHC I, MHC II, CD4, CD8, TCR α, IgM, IgD and IgZ) increased in all groups post infection, which was more significant in the vaccinated groups. Furthermore, the number of immunopositive cells exhibiting different epitopes (CD8, IgM, IgD and IgZ) that were detected by immunohistochemical assay had increased in the vaccinated groups post infection. These results show that vaccination effectively stimulated host immune response (especially OmpA vaccine groups). In conclusion, these results indicated that both the inactivated vaccine and OmpA subunit vaccine could protect juvenile M. amblycephala against A. hydrophila infection, of which OmpA subunit vaccine provided more effective immune protection and can be used as an ideal candidate for the A. hydrophila vaccine.
Causal relationships between gut microbiota and programmed cell death protein 1/programmed cell death-ligand 1: A bidirectional Mendelian randomization study
Authors: Huang Yu-Feng , Zhang Wei-Ming , Wei Zhi-Song , Huang Huan , Mo Qi-Yan , Shi Dan-Li , Han Lu , Han Yu-Yuan , Nong Si-Kai , Lin Guo-Xiang
Published: March 2023

Background

Multiple clinical studies have indicated that the gut microbiota influences the effects of immune checkpoint blockade (ICB) therapy comprising PD-1/PD-L1 inhibitors, but the causal relationship is unclear. Because of numerous confounders, many microbes related to PD-1/PD-L1 have not been identified. This study aimed to determine the causal relationship between the microbiota and PD-1/PD-L1 and identify possible biomarkers for ICB therapy.

Method

We used bidirectional two-sample Mendelian randomization with two different thresholds to explore the potential causal relationship between the microbiota and PD-1/PD-L1 and species-level microbiota GWAS to verify the result.

Result

In the primary forward analysis, genus_Holdemanella showed a negative correlation with PD-1 [βIVW = -0.25; 95% CI (-0.43 to -0.07); PFDR = 0.028] and genus_Prevotella9 showed a positive correlation with PD-1 [βIVW = 0.2; 95% CI (0.1 to 0.4); PFDR = 0.027]; order_Rhodospirillales [βIVW = 0.2; 95% CI (0.1 to 0.4); PFDR = 0.044], family_Rhodospirillaceae [βIVW = 0.2; 95% CI (0 to 0.4); PFDR = 0.032], genus_Ruminococcaceae_UCG005 [βIVW = 0.29; 95% CI (0.08 to 0.5); PFDR = 0.028], genus_Ruminococcus_gnavus_group [βIVW = 0.22; 95% CI (0.05 to 0.4); PFDR = 0.029], and genus_Coprococcus_2 [βIVW = 0.4; 95% CI (0.1 to 0.6); PFDR = 0.018] were positively correlated with PD-L1; and phylum_Firmicutes [βIVW = -0.3; 95% CI (-0.4 to -0.1); PFDR = 0.031], family_ClostridialesvadinBB60group [βIVW = -0.31; 95% CI (-0.5 to -0.11), PFDR = 0.008], family_Ruminococcaceae [βIVW = -0.33; 95% CI (-0.58 to -0.07); PFDR = 0.049], and genus_Ruminococcaceae_UCG014 [βIVW = -0.35; 95% CI (-0.57 to -0.13); PFDR = 0.006] were negatively correlated with PD-L1. The one significant species in further analysis was species_Parabacteroides_unclassified [βIVW = 0.2; 95% CI (0-0.4); PFDR = 0.029]. Heterogeneity (P > 0.05) and pleiotropy (P > 0.05) analyses confirmed the robustness of the MR results.
Dietary supplementation of coated sodium butyrate improves growth performance of laying ducks by regulating intestinal health and immunological performance
Authors: Zeng Tao , Sun Hanxue , Huang Manman , Guo Rongbing , Gu Tiantian , Cao Yongqing , Li Chengfeng , Tian Yong , Chen Li , Li Guoqin , Lu Lizhi
Published: March 2023

Introduction

This study was conducted to assess the effects of dietary supplementation of coated sodium butyrate (CSB) on the growth performance, serum antioxidant, immune performance, and intestinal microbiota of laying ducks.

Methods

A total of 120 48-week-old laying ducks were randomly divided into 2 treatment groups: the control group (group C fed a basal diet) and the CSB-treated group (group CSB fed the basal diet + 250 g/t of CSB). Each treatment consisted of 6 replicates, with 10 ducks per replicate, and the trial was conducted for 60 days.

Results

Compared with the group C, the group CSB showed a significant increase in the laying rate (p<0.05) of the 53-56 week-old ducks. Additionally, the serum total antioxidant capacity, superoxide dismutase activity and immunoglobulin G level were significantly higher (p<0.05), while the serum malondialdehyde content and tumor necrosis factor (TNF)-a level were significantly lower (p<0.05) in the serum of the group CSB compared to the group C. Moreover, the expression of IL-1b and TNF-a in the spleen of the group CSB was significantly lower (p<0.05) compared to that of the group C. In addition, compared with the group C, the expression of Occludin in the ileum and the villus height in the jejunum were significantly higher in the group CSB (p<0.05). Furthermore, Chao1, Shannon, and Pielou-e indices were higher in the group CSB compared to the group C (p<0.05). The abundance of Bacteroidetes in the group CSB was lower than that in the group C (p<0.05), while the abundances of Firmicutes and Actinobacteria were higher in the group CSB compared to the group C (p<0.05).

Conclusions

Our results suggest that the dietary supplementation of CSB can alleviate egg-laying stress in laying ducks by enhancing immunity and maintaining the intestinal health of the ducks.
Transcriptional control of ILC identity
Authors: Korchagina Anna A. , Shein Sergey A. , Koroleva Ekaterina , Tumanov Alexei V.
Published: March 2023

Innate lymphoid cells (ILCs) are heterogeneous innate immune cells which participate in host defense, mucosal repair and immunopathology by producing effector cytokines similarly to their adaptive immune cell counterparts. The development of ILC1, 2, and 3 subsets is controlled by core transcription factors: T-bet, GATA3, and RORγt, respectively. ILCs can undergo plasticity and transdifferentiate to other ILC subsets in response to invading pathogens and changes in local tissue environment. Accumulating evidence suggests that the plasticity and the maintenance of ILC identity is controlled by a balance between these and additional transcription factors such as STATs, Batf, Ikaros, Runx3, c-Maf, Bcl11b, and Zbtb46, activated in response to lineage-guiding cytokines. However, how interplay between these transcription factors leads to ILC plasticity and the maintenance of ILC identity remains hypothetical. In this review, we discuss recent advances in understanding transcriptional regulation of ILCs in homeostatic and inflammatory conditions.
International cruise research advances and hotspots: Based on literature big data
Authors: Meng Shuhan , Li Hua , Wu Xianhua
Published: March 2023

This paper makes a systematic visual analysis of cruise research literature collected in science network database from 1996 to 2019. The results show that: the overall number of published literatures on cruise research are growing; North American states, Europe, and Asia are the main regions of cruise research. The evolutionary of theme development of cruise research has three stages, and the current hot topics of cruise research can be summarized as cruise tourism, luxury cruises, cruise passengers, destination ports, environmental and biological conservation, and cruise diseases. Future research in the cruise field is in the areas of cruise supply chain, technology in cruise, children’s cruise experience, itinerary design, planning and optimization, brand reputation and luxury cruises, public transportation in destinations, environmental responsibility of passengers and corporate social responsibility, optimization of energy systems, climate change in relation to the cruise industry, the Chinese cruise market and risk management of cruise diseases.
Selective feeding of the mullet larvae Liza haematocheila during ontogeny in Laizhou Bay, Bohai Sea, China: The importance of small copepods in mesozooplankton as prey
Authors: Sun Xiaohong , Song Minpeng , Li Zhengguang , Song Yan , Yuan Xiaonan , Dong Bing , Zhang Lu , Zhu Lixin , Liang Zhenlin
Published: March 2023

The mullet Liza haematocheila is widely distributed in low-salinity waters around the world and has high economic value. However, details regarding the foraging ecology of mullet larvae remain unclear. Larvae of L. haematocheila were sampled in Laizhou Bay of the Bohai Sea, China, in May 2016, and diet composition was detected using gut content analysis to compare differences in feeding parameters and diet shift in dominant prey during ontogeny. The results showed no linear relationship between gape size (GS) and standard length (SL) at larva length <7 mm (flexion larvae, FL), but linear increase was observed for SL >7 mm (post-flexion larvae, PFL). Maximum prey size (MPS) overlapped with GS during the FL stage but was never higher than GS during the PFL stage. Trends of increasing MPS and prey size range (PSR) during the PFL stage were lower than those during the FL stage, but prey number (PN) increased significantly during the PFL stage. Diet composition analyses in mullet larvae showed a total of 10 mesozooplankton species (or categories), of which 8 species were copepods (including copepods nauplii and copepodites), and showed the dominance of 4 small copepods (<1 mm). Analyses of the numerical proportion of dominant copepods showed that the largest prey (Paracalanus parvus) gradually increased as GS increased; conversely, the smallest prey (nauplii of Calanus sinicus) decreased. Collectively, these results suggest that PFL tends to exhibit increased PN but not prey size or size range, and diet shifts from smaller to larger prey during ontogeny in mullet larvae. All these indicate that PFL has higher prey selection ability compared with FL, specifically switching the diet to include larger small copepods during the PFL stage and increasing the prey number instead of increasing prey size. These determine the importance of small copepods in mesozooplankton as dominant prey and facilitate predictions of the impact of climate change on mesozooplankton and fish larvae.
A novel submersible-mounted sediment pressure-retaining sampler at full ocean depth
Authors: He Shudong , Qiu Sawei , Tang Wenbo , Peng Youduo , Jin Yongping
Published: March 2023

High-efficiency pressure-retaining sampling technology for obtaining seabed sediments is required for studying marine geological history, the survival principles of marine microorganisms, and the evolution of earth life. In this paper, a novel submersible-mounted sampler capable of collecting pressure-retained samples at a full ocean depth is designed. The structure scheme is first presented, including the sampling unit, pressure-retaining unit, and pressure-compensation unit. The sampling kinematics model is then established, and the influences of pressing velocity, and the length and inner diameter of pressure pipe on the pressing force of the mechanical arm are determined, providing important guidance for the design of the sealing structure. The maximum working depth of the sampler is 11,000 m, the coring diameter of the sampler is 54 mm, the maximum coring depth is 500 mm, and obtained samples can keep close to in-situ pressures. The sampler can be mounted on a submersible and operated using a single mechanical arm. During cruise TS-21 from August to October 2021, the sampler was deployed 4 times at depth of 7700 m in the West Philippine Basin, and the high pressure sediment samples were successfully collected. The pressure change of the samples remained within ±6%, which verified the rationality of the design and the feasibility of this novel submersible-mounted pressure-retaining sampler.
Study of electrical properties and detection mechanism of a practical novel 3D-Spherical Electrode Detector
Authors: Tan Zewen , Li Zheng , Li Xinqing , Cai Xinyi , Liu Manwen , Wang Hongfei
Published: March 2023

Among the 3D electrode Si detectors for high energy particle and X-ray detection, the traditional 3D-Trench electrode Si detector is a semiconductor detector that is widely used and discussed. Aiming at removing the shortcomings of the traditional 3D-Trench electrode Si detectors such as uneven electric field distribution, asymmetric electric potential, and the existence of some dead zone, we propose a new type 3D-Spherical Electrode Detectors and carry out extensive and systematic studies of their physical properties. We simulated detector electric field, electric potential, electron concentration distribution, full depletion voltage, leakage current, capacitance, the incident particle induced transient current and the weighting field. We systematically studied and analyzed detector’s electrical characteristics. By comparing with the traditional 3D-Trench electrode Si detectors, the new detector structure has more uniform electric field and potential, and less depletion voltage, leakage current and capacitance.
Constructing a prediction model of inflammatory bowel disease recurrence based on factors affecting the quality of life
Authors: Li Maojuan , Tao Yan , Sun Yang , Wu Jing , Zhang Fengrui , Wen Yunling , Gong Min , Yan Jingxian , Liang Hao , Bai Xinyu , Niu Junkun , Miao Yinglei
Published: March 2023

Aim

This study aimed to determine the factors affecting the quality of life of patients with inflammatory bowel disease (IBD) and to construct a disease recurrence prediction model based on these influencing factors.

Methods

A prospective, single-center study in China was conducted between October 2020 and March 2021. The quality of life of patients was assessed using the Inflammatory Bowel Disease Questionnaire (IBDQ). Multiple stepwise regression analysis was used to analyze the factors influencing the quality of life of patients with IBD. The chi-square test and the point-biserial correlation analysis were performed to identify factors associated with clinical recurrence. A binary logistic regression model was constructed to predict the recurrence. The receiver operating characteristic curve was used to evaluate the prediction model. Patients with IBD from April 2021 to June 2021 were randomly included for model verification to evaluate the disease recurrence prediction model.

Results

The average IBDQ score of patients with IBD was 172.2 ± 35.0 (decreased by 23.2%). The scores of all dimensions of the IBDQ were decreased, especially emotional function and systemic symptoms. Disease activity, age, extraintestinal manifestations (EIMs), and annual household income were important factors influencing the IBDQ scores of patients with ulcerative colitis, and these accounted for ~57.0% of the factors affecting the quality of life. Disease activity, EIMs, and occupational stress were important factors influencing the IBDQ scores of patients with Crohn's disease, and they accounted for approximately 75.1% of the factors affecting the quality of life. Annual household income, occupational stress, and IBDQ scores were independent risk factors for recurrence. The area under the curve of the recurrence prediction model was 81.1%. The sensitivity and specificity were 81.7 and 71.7%, respectively. The Youden index of the model was 0.534. The established recurrence prediction model has good discriminant validity in the validation cohort.

Conclusion

The quality of life of patients with IBD was generally poor. The use of factors affecting the quality of life to predict disease recurrence has high predictive value and can support the management of IBD by selecting patients at a higher risk for relapse.
Niche-mediated bacterial community composition in continental glacier alluvial valleys under cold and arid environments
Authors: Chen Xianke , Qi Xiangning , Ren Ge , Chang Ruiying , Qin Xiang , Liu Guohua , Zhuang Guoqiang , Ma Anzhou
Published: March 2023

Introduction

Bacteria are an essential component of glacier-fed ecosystems and play a dominant role in driving elemental cycling in the hydrosphere and pedosphere. However, studies of bacterial community composition mechanisms and their potential ecological functions from the alluvial valley of mountain glaciers are extremely scarce under cold and arid environments.

Methods

Here, we analyzed the effects of major physicochemical parameters related to soil on the bacterial community compositions in an alluvial valley of the Laohugou Glacier No. 12 from the perspective of core, other, and unique taxa and explored their functional composition characteristics.

Results and discussion

The different characteristics of core, other, and unique taxa highlighted the conservation and difference in bacterial community composition. The bacterial community structure of the glacial alluvial valley was mainly affected by the above sea level, soil organic carbon, and water holding capacity. In addition, the most common and active carbon metabolic pathways and their spatial distribution patterns along the glacial alluvial valley were revealed by FAPTOTAX. Collectively, this study provides new insights into the comprehensive assessment of glacier-fed ecosystems in glacial meltwater ceasing or glacier disappearance.