bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical value of M1 macrophage-related genes identification in bladder urothelial carcinoma and in vitro validation
Authors: Yu Yang , Huang Yuexi , Li Chen , Ou Santao , Xu Chaojie , Kang Zhengjun
Published: November 2022

Background: Tumor microenvironment (TME) takes a non-negligible role in the progression and metastasis of bladder urothelial carcinoma (BLCA) and tumor development could be inhibited by macrophage M1 in TME. The role of macrophage M1-related genes in BLCA adjuvant therapy has not been studied well.

Methods: CIBERSOR algorithm was applied for identification tumor-infiltrating immune cells (TICs) subtypes of subjects from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) data sets. We identified potential modules of M1 macrophages by weighted gene co-expression network analysis (WGCNA). Nomogram was determined by one-way Cox regression and lasso regression analysis for M1 macrophage genes. The data from GEO are taken to verify the models externally. Kaplan-Meier and receiver operating characteristic (ROC) curves validated prognostic value of M1 macrophage genes. Finally, we divided patients into the low-risk group (LRG) and the high-risk group (HRG) based on the median risk score (RS), and the predictive value of RS in patients with BLCA immunotherapy and chemotherapy was investigated. Bladder cancer (T24, 5637, and BIU-87) and bladder uroepithelial cell line (SV-HUC-1) were used for in vitro validation. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was employed to validate the associated genes mRNA level.

Results: 111 macrophage M1-related genes were identified using WGCNA. RS model containing three prognostically significant M1 macrophage-associated genes (FBXO6, OAS1, and TMEM229B) was formed by multiple Cox analysis, and a polygenic risk model and a comprehensive prognostic line plot was developed. The calibration curve clarified RS was a good predictor of prognosis. Patients in the LRG were more suitable for programmed cell death protein 1 (PD1) and cytotoxic T lymphocyte associate protein-4 (CTLA4) combination immunotherapy. Finally, chemotherapeutic drug models showed patients in the LRG were more sensitive to gemcitabine and mitomycin. RT-qPCR result elucidated the upregulation of FBXO6, TMEM229B, and downregulation of OAS1 in BLCA cell lines.

Conclusion: A predictive model based on M1 macrophage-related genes can help guide us in the treatment of BLCA.
Transcriptomic responses to thermal stress in hybrid abalone (Haliotis discus hannai ♀ × H. fulgens ♂)
Authors: Zhang Qian , Huang Jianfang , Yang Chenyu , Chen Jianming , Wang Wei
Published: November 2022

China is the world’s largest abalone producing country. Currently, summer mortality caused by high temperature, is one of the biggest challenges for abalone aquaculture industry. The hybrid abalone (Haliotis discus hannai ♀ × H. fulgens ♂) was conferred on the “new variety”. It has heterosis for thermal tolerance and has been cultured at large-scale in southern China. In this study, a transcriptome analysis was performed to identify the related genes in this hybrid abalone under thermal stress and recovery stage. Compared to control group (18°C), a total of 75, 2173, 1050, 1349, 2548, 494, and 305 differentially expressed genes (DEGs) were identified at 21°C, 24°C, 27°C, 30°C, 32°C, 29°C, and 26°C, respectively. In this study, 24°C is the critical temperature at which the abalone is subjected to thermal stress. With the temperature rising, the number of stress-responsive genes increased. During the temperature recovering to the optimum, the number of stress-responsive genes decreased gradually. Thus, this hybrid abalone has a rapid response and strong adaptability to the temperature. Under the thermal stress, the abalone triggered a complicated regulatory network including degrading the misfolded proteins, activating immune systems, negative regulation of DNA replication, and activating energy production processes. The more quickly feedback regulation, more abundant energy supply and more powerful immune system might be the underlying mechanisms to fight against thermal stress in this hybrid abalone. These findings could provide clues for exploring the thermal-response mechanisms in abalone. The key genes and pathways would facilitate biomarker identification and thermal-tolerant abalone breeding studies.
Siglec10—An immunosuppressor and negative predictor of survival prognosis in gliomas
Authors: Wang Hesong , Feng Yanyan , Zhang Yuxiang , Wang Ting , Xu Heng , Zhi Yuxing , Feng Yuyin , Tian Lichun , Yuan Kai
Published: November 2022

Glioma is a type of tumor occurring in the central nervous system. In recent decades, specific gene mutations and molecular aberrations have been used to conduct the glioma classification and clinical decisions. Siglec10 is a member of the sialic acid-binding immunoglobulin superfamily. In this study, we investigated the expression and functions of siglec10 in gliomas. We analyzed the siglec10 expression in glioma patients with immunohistochemical (IHC) staining and evaluated the survival prognosis. The high siglec10 expression had a shorter survival prognosis than the low siglec10 expression in patients, especially in malignant gliomas. Bioinformatic datasets, including TCGA and CGGA, validated the IHC results and discovered the expression of siglec10 was higher in the malignant subtype than a benign subtype of gliomas. So, siglec10 is associated with the poor prognosis of gliomas. Furthermore, the related mechanisms of siglec10 in gliomas were investigated by functional enrichment analysis, including GSEA, GO, and KEGG analysis. Siglec10 was correlated with inflammatory mediators, inflammatory cells, and inflammatory pathways in gliomas. Siglec10 might take part in the immune response in the tumor microenvironment to induce glioma’s progression and metastasis. This study showed siglec10 was a biomarker in glioma, and it might be the potential target of glioma immunotherapy in the future.
Single-cell sequencing reveals the landscape of the tumor microenvironment in a skeletal undifferentiated pleomorphic sarcoma patient
Authors: Yuan Liu-Liu , Chen Zhong , Qin Jian , Qin Cheng-Jiao , Bian Jing , Dong Rui-Fang , Yuan Tang-Bo , Xu Yi-Ting , Kong Ling-Yi , Xia Yuan-Zheng
Published: November 2022

Skeletal undifferentiated pleomorphic sarcoma (SUPS) is an invasive pleomorphic soft tissue sarcoma with a high degree of malignancy and poor prognosis. It is prone to recur and metastasize. The tumor microenvironment (TME) and the pathophysiology of SUPS are barely described. Single-cell RNA sequencing (scRNA-seq) provides an opportunity to dissect the landscape of human diseases at an unprecedented resolution, particularly in diseases lacking animal models, such as SUPS. We performed scRNA-seq to analyze tumor tissues and paracancer tissues from a SUPS patient. We identified the cell types and the corresponding marker genes in this SUPS case. We further showed that CD8+ exhausted T cells and Tregs highly expressed PDCD1, CTLA4 and TIGIT. Thus, PDCD1, CTLA4 and TIGIT were identified as potential targets in this case. We applied copy number karyotyping of aneuploid tumors (CopyKAT) to distinguish malignant cells from normal cells in fibroblasts. Our study identified eight malignant fibroblast subsets in SUPS with distinct gene expression profiles. C1-malignant Fibroblast and C6-malignant Fibroblast in the TME play crucial roles in tumor growth, angiogenesis, metastasis and immune response. Hence, targeting malignant fibroblasts could represent a potential strategy for this SUPS therapy. Intervention via tirelizumab enabled disease control, and immune checkpoint inhibitors (ICIs) of PD-1 may be considered as the first-line option in patients with SUPS. Taken together, scRNA-seq analyses provided a powerful basis for this SUPS treatment, improved our understanding of complex human diseases, and may afforded an alternative approach for personalized medicine in the future.
Cytokine/Chemokine assessment as a complementary diagnostic tool for inflammatory skin diseases
Authors: Liu Timothy J. , Lin Lynlee L. , McMeniman Erin , Wu Jason , Kao Yung-Ching , Kumari Snehlata , Boyle Glen M. , Wells James W. , Soyer H. Peter , Gonzalez-Cruz Jazmina L.
Published: November 2022

Inflammatory skin conditions are the 4th leading cause of non-fatal health burden in the general population worldwide. The diagnosis of skin lesions due to systemic drug reactions, viral or bacterial exanthems, or in patients with psoriasis, atopic dermatitis or contact dermatitis is often difficult and relies heavily upon conventional histopathologic examination. Conversely, it is widely accepted that the cutaneous profile of inflammatory markers, or ‘inflammatory signature’, is differentially expressed in various skin conditions. In this pilot study, we investigated the possibility of inflammatory skin disease diagnosis from an immunological perspective in small punch biopsies. We collected lesional and perilesional punch biopsies from 139 patients suffering from a variety of inflammatory skin conditions and attending the Dermatology Department at the Princess Alexandra Hospital in Brisbane, Australia. Using bead-based immunoassays we were able to measure 13 out of 17 inflammatory markers from a pre-selected multi-analyte panel and to detect significant differences between lesional and perilesional biopsies from each individual patient. Hierarchical and unbiased clustering methods based on inflammatory signatures grouped psoriasis and atopic dermatitis lesions into individual clusters in contrast to other skin conditions, highlighting the potential of inflammatory signatures to be used as diagnostic differentiators and to inform alternative targets in anti-inflammatory treatment strategies.
Combined impact of the inter and intra-patient variability of tacrolimus blood level on allograft outcomes in kidney transplantation
Authors: Park Yohan , Lee Hanbi , Eum Sang Hun , Ko Eun Jeong , Min Ji Won , Yoon Se-Hee , Hwang Won-Min , Yun Sung-Ro , Yang Chul Woo , Shin Jieun , Chung Byung Ha
Published: November 2022

Introduction

Tacrolimus (TAC) has been widely used as an immunosuppressant after kidney transplantation (KT); however, the combined effects of intra-patient variability (IPV) and inter-patient variability of TAC-trough level (C0) in blood remain controversial. This study aimed to determine the combined impact of TAC-IPV and TAC inter-patient variability on allograft outcomes of KT.

Methods

In total, 1,080 immunologically low-risk patients who were not sensitized to donor human leukocyte antigen (HLA) were enrolled. TAC-IPV was calculated using the time-weighted coefficient variation (TWCV) of TAC-C0, and values > 30% were classified as high IPV. Concentration-to-dose ratio (CDR) was used for calculating TAC inter-patient variability, and CDR < 1.05 ng•mg/mL was classified as rapid metabolizers (RM). TWCV was calculated based on TAC-C0 up to 1 year after KT, and CDR was calculated based on TAC-C0 up to 3 months after KT. Patients were classified into four groups according to TWCV and CDR: low IPV/non-rapid metabolizer (NRM), high IPV/NRM, low IPV/RM, and high IPV/RM. Subgroup analysis was performed for pre-transplant panel reactive antibody (PRA)-positive and -negative patients (presence or absence of non-donor-specific HLA-antibodies). Allograft outcomes, including deathcensored graft loss (DCGL) and biopsy-proven allograft rejection (BPAR), were compared.

Results

The incidences of DCGL, BPAR, and overall graft loss were the highest in the high-IPV/RM group. In addition, a high IPV/RM was identified as an independent risk factor for DCGL. The hazard ratio of high IPV/RM for DCGL and the incidence of active antibody-mediated rejection were considerably increased in the PRA-positive subgroup.

Discussion

High IPV combined with RM (inter-patient variability) was closely related to adverse allograft outcomes, and hence, more attention must be given to pre-transplant PRA-positive patients.
Multiplex flow cytometry-based assay for quantifying tumor- and virus-associated antibodies induced by immunotherapies
Authors: Minott Jessica A. , van Vloten Jacob P. , Yates Jacob G. E. , Chan Lily , Wood Geoffrey A. , Viloria-Petit Alicia M. , Karimi Khalil , Petrik James J. , Wootton Sarah K. , Bridle Byram W.
Published: November 2022

Novel immunotherapies continue to be developed and tested for application against a plethora of diseases. The clinical translation of immunotherapies requires an understanding of their mechanisms. The contributions of antibodies in driving long-term responses following immunotherapies continue to be revealed given their diverse effector functions. Developing an in-depth understanding of the role of antibodies in treatment efficacy is required to optimize immunotherapies and improve the chance of successfully translating them into the clinic. However, analyses of antibody responses can be challenging in the context of antigen-agnostic immunotherapies, particularly in the context of cancers that lack pre-defined target antigens. As such, robust methods are needed to evaluate the capacity of a given immunotherapy to induce beneficial antibody responses, and to identify any therapy-limiting antibodies. We previously developed a comprehensive method for detecting antibody responses induced by antigen-agnostic immunotherapies for application in pre-clinical models of vaccinology and cancer therapy. Here, we extend this method to a high-throughput, flow cytometry-based assay able to identify and quantify isotype-specific virus- and tumor-associated antibody responses induced by immunotherapies using small sample volumes with rapid speed and high sensitivity. This method provides a valuable and flexible protocol for investigating antibody responses induced by immunotherapies, which researchers can use to expand their analyses and optimize their own treatment regimens.
The dichotomous outcomes of TNFα signaling in CD4+ T cells
Authors: Skartsis Nikolaos , Ferreira Leonardo M. R. , Tang Qizhi
Published: November 2022

TNFa blocking agents were the first-in-class biologic drugs used for the treatment of autoimmune disease. Paradoxically, however, exacerbation of autoimmunity was observed in some patients. TNFa is a pleiotropic cytokine that has both proinflammatory and regulatory effects on CD4+T cells and can influence the adaptive immune response against autoantigens. Here, we critically appraise the literature and discuss the intricacies of TNFa signaling that may explain the controversial findings of previous studies. The pleiotropism of TNFa is based in part on the existence of two biologically active forms of TNFa, soluble and membrane-bound, with different affinities for two distinct TNF receptors, TNFR1 and TNFR2, leading to activation of diverse downstream molecular pathways involved in cell fate decisions and immune function. Distinct membrane expression patterns of TNF receptors by CD4+T cell subsets and their preferential binding of distinct forms of TNFα produced by a diverse pool of cellular sources during different stages of an immune response are important determinants of the differential outcomes of TNFa-TNF receptor signaling. Targeted manipulation of TNFa-TNF receptor signaling on select CD4+T cell subsets may offer specific therapeutic interventions to dampen inflammation while fortifying immune regulation for the treatment of autoimmune diseases.
NETosis is critical in patients with severe community-acquired pneumonia
Authors: Zhang Yiming , Li Yan , Sun Na , Tang Hanqi , Ye Jun , Liu Yang , He Quan , Fu Yangyang , Zhu Huadong , Jiang Chengyu , Xu Jun
Published: November 2022

Pneumonia is the fourth leading cause of death globally, and the reason for the high mortality rate of patients with severe community-acquired pneumonia (SCAP) remains elusive. Corticosteroid treatment reduces mortality in adults with SCAP but can cause numerous adverse events. Therefore, novel therapeutic targets need to be explored and new adjunctive immune drugs are urgently required. We analyzed the transcriptome data of peripheral blood leukocytes from patients with SCAP and healthy controls from three perspectives: differentially expressed genes, predicted functions of differentially expressed long non-coding RNAs, and transcriptional read-through. We discovered that the NETosis pathway was top-ranked in patients with SCAP caused by diverse kinds of pathogens. This provides a potential therapeutic strategy for treating patients. Furthermore, we calculated the correlation between the expression of genes involved in NETosis and the ratio of arterial oxygen partial pressure to fractional inspired oxygen. We identified four novel potential therapeutic targets for NETosis in patients with SCAP, including H4C15, H3-5, DNASE1, and PRKCB. In addition, a higher occurrence of transcriptional read-through is associated with a worse outcome in patients with SCAP, which probably can explain the high mortality rate of patients with SCAP.
Protective interaction of human phagocytic APC subsets with Cryptococcus neoformans induces genes associated with metabolism and antigen presentation
Authors: Nelson Benjamin N. , Daugherty Cheyenne S. , Sharp Rachel R. , Booth J. Leland , Patel Vineet I. , Metcalf Jordan P. , Jones Kenneth L. , Wozniak Karen L.
Published: November 2022

Cryptococcal meningitis is the most common cause of meningitis among HIV/AIDS patients in sub-Saharan Africa, and worldwide causes over 223,000 cases leading to more than 181,000 annual deaths. Usually, the fungus gets inhaled into the lungs where the initial interactions occur with pulmonary phagocytes such as dendritic cells and macrophages. Following phagocytosis, the pathogen can be killed or can replicate intracellularly. Previous studies in mice showed that different subsets of these innate immune cells can either be antifungal or permissive for intracellular fungal growth. Our studies tested phagocytic antigen-presenting cell (APC) subsets from the human lung against C. neoformans. Human bronchoalveolar lavage was processed for phagocytic APCs and incubated with C. neoformans for two hours to analyze the initial interactions and fate of the fungus, living or killed. Results showed all subsets (3 macrophage and 3 dendritic cell subsets) interacted with the fungus, and both living and killed morphologies were discernable within the subsets using imaging flow cytometry. Single cell RNA-seq identified several different clusters of cells which more closely related to interactions with C. neoformans and its protective capacity against the pathogen rather than discrete cellular subsets. Differential gene expression analyses identified several changes in the innate immune cell’s transcriptome as it kills the fungus including increases of TNF-α (TNF) and the switch to using fatty acid metabolism by upregulation of the gene FABP4. Also, increases of TNF-α correlated to cryptococcal interactions and uptake. Together, these analyses implicated signaling networks that regulate expression of many different genes – both metabolic and immune - as certain clusters of cells mount a protective response and kill the pathogen. Future studies will examine these genes and networks to understand the exact mechanism(s) these phagocytic APC subsets use to kill C. neoformans in order to develop immunotherapeutic strategies to combat this deadly disease.
PET image enhancement using artificial intelligence for better characterization of epilepsy lesions
Authors: Flaus Anthime , Deddah Tahya , Reilhac Anthonin , Leiris Nicolas De , Janier Marc , Merida Ines , Grenier Thomas , McGinnity Colm J. , Hammers Alexander , Lartizien Carole , Costes Nicolas
Published: November 2022

Introduction

[18F]fluorodeoxyglucose ([18F]FDG) brain PET is used clinically to detect small areas of decreased uptake associated with epileptogenic lesions, e.g., Focal Cortical Dysplasias (FCD) but its performance is limited due to spatial resolution and low contrast. We aimed to develop a deep learning-based PET image enhancement method using simulated PET to improve lesion visualization.

Methods

We created 210 numerical brain phantoms (MRI segmented into 9 regions) and assigned 10 different plausible activity values (e.g., GM/WM ratios) resulting in 2100 ground truth high quality (GT-HQ) PET phantoms. With a validated Monte-Carlo PET simulator, we then created 2100 simulated standard quality (S-SQ) [18F]FDG scans. We trained a ResNet on 80% of this dataset (10% used for validation) to learn the mapping between S-SQ and GT-HQ PET, outputting a predicted HQ (P-HQ) PET. For the remaining 10%, we assessed Peak Signal-to-Noise Ratio (PSNR), Structural Similarity Index Measure (SSIM), and Root Mean Squared Error (RMSE) against GT-HQ PET. For GM and WM, we computed recovery coefficients (RC) and coefficient of variation (COV). We also created lesioned GT-HQ phantoms, S-SQ PET and P-HQ PET with simulated small hypometabolic lesions characteristic of FCDs. We evaluated lesion detectability on S-SQ and P-HQ PET both visually and measuring the Relative Lesion Activity (RLA, measured activity in the reduced-activity ROI over the standard-activity ROI). Lastly, we applied our previously trained ResNet on 10 clinical epilepsy PETs to predict the corresponding HQ-PET and assessed image quality and confidence metrics.

Results

Compared to S-SQ PET, P-HQ PET improved PNSR, SSIM and RMSE; significatively improved GM RCs (from 0.29 ± 0.03 to 0.79 ± 0.04) and WM RCs (from 0.49 ± 0.03 to 1 ± 0.05); mean COVs were not statistically different. Visual lesion detection improved from 38 to 75%, with average RLA decreasing from 0.83 ± 0.08 to 0.67 ± 0.14. Visual quality of P-HQ clinical PET improved as well as reader confidence.

Conclusion

P-HQ PET showed improved image quality compared to S-SQ PET across several objective quantitative metrics and increased detectability of simulated lesions. In addition, the model generalized to clinical data. Further evaluation is required to study generalization of our method and to assess clinical performance in larger cohorts.
A prognostic signature based on cuprotosis-related long non-coding RNAs predicts the prognosis and sensitivity to chemotherapy in patients with colorectal cancer
Authors: Li Wei , Yang Guiyun , Dong Hao , Zhu Jiajing , Liu Tongjun
Published: November 2022

Cuprotosis, a newly proposed mechanism of cell death, can trigger acute oxidative stress that leads to cell death by mediating protein lipidation in the tricarboxylic acid cycle. However, cuprotosis-related long non-coding RNAs (CRLNCs) and their relationship with prognosis and the immunological landscape of colorectal cancer (CRC) are unclear. We have developed a lncRNA signature to predict survival time, immune infiltration, and sensitivity to chemotherapy. CRLNCs were screened using the Cor function of the R software and the differentially expressed lncRNAs were collected with the limma package. Differentially expressed long non-coding RNAs (lncRNAs) associated with prognosis were selected using univariate regression analysis. A prognostic signature was developed using the least absolute shrinkage and selection operator (LASSO) and multivariate regression analysis. Patients with CRC were divided into two groups based on the risk score. The low-risk group had a more favorable prognosis, higher expression of immune checkpoints, and a higher level of immune cell infiltration compared with the high-risk group. Furthermore, there was a close association between the risk score and the clinical stage, tumor mutational burden, cancer stem cell index, and microsatellite instability. We also assessed chemotherapy response in the two risk groups. Our study analyzed the role of CRLNCs in CRC and provided novel targets and strategies for CRC chemotherapy and immunotherapy.
Intention to give birth in the health institutions and associated factors among women who gave birth in the last 6 months in Debre Berhan town, North Showa zone, Ethiopia: A community-based cross-sectional study
Authors: Amare Nakachew Sewnet , Mekuriyaw Abebayehu Melesew , Tesema Getaye Worku , Ambaw Yeshinat Lakew
Published: November 2022

Background

Institutional delivery is a proxy for skilled birth attendance, which is an important intervention to reduce maternal and neonatal mortality. Even though institutional delivery has such importance, significant numbers of women in Ethiopia do not prefer to give birth in health institutions. This study aimed to assess women’s intention to give birth in health institutions and associated factors among women who gave birth in the last 6 months in Debre Berhan town, North Showa Zone, Ethiopia, 2020.

Materials and methods

A community-based cross-sectional study was conducted among women who gave birth in the last 6 months in Debre Berhan town from October 30 to November 30, 2020. A cluster sampling technique was used to select study participants. Pretested semi-structured interviewer-administered questionnaires were administered. A logistic regression model was performed, and adjusted odds ratios with a 95% confidence interval based on p < 0.05 were used to identify statistically significant variables.

Result

This study found that a total of 689 (88.8%) (95% CI: 86.6, 91%) respondents intended to deliver in the health facility. Being multiparous [AOR = 0.18 (95% CI: 0.08, 0.36)], having planned pregnancy [AOR = 3.1 (95% CI: 1.6, 5.9)], had no complications during previous delivery (AOR = 6.0 (95% CI: 3.5, 10.4)], and received respectful maternity care (RMC) during preceding delivery [AOD = 1.8 (95% CI: 1.05, 3.10)] are significantly associated with women’s intention to give birth in the health institution.

Conclusion

Childbirth is a special event that requires the safest place to save the lives of both the mother and newborn. In this study, the number of women who do not have the intention to give birth in the health institution is still high. Strategies to promote planned pregnancy, reduce complications during childbirth and provide RMC during childbirth should be designed and interventions should be implemented for all childbearing women.
A study on the method and effect of the construction of a humanized mouse model of fecal microbiota transplantation
Authors: Wang Yaru , Zhang Zhenzhen , Liu Bin , Zhang Chunzhi , Zhao Junying , Li Xianping , Chen Lijun
Published: November 2022

The gestation period is critical for the health of the mother and fetus. Malnutrition or over nutrition during pregnancy may cause gestational diseases that can result in adverse pregnancy outcomes. Fecal microbiota transplantation (FMT) can be used to re-establish new gut microbiota to treat a variety of diseases and construct a model to investigate the nutritional health during pregnancy. Therefore, this study investigated whether human-derived gut microbiota during pregnancy could colonize the intestines of mice. Moreover, we determined the time and method of intervention for FMT. Based on this information, a humanized mouse model of FMT was constructed to simulate the human intestinal microecology during pregnancy, and serve as a useful animal model for the study of nutritional health and disease during pregnancy. Germ-free (GF) and specific pathogen free (SPF) C57BL/6J mice were selected for humanized gestational FMT and the transplantation outcomes were evaluated. The results demonstrated that the gestational intestinal microbiota colonized the intestines of mice, allowing researchers to construct a humanized mouse model of gestational FMT. The main intestinal flora of the gestational period were transplanted into GF mice, with the gestational flora being similar to the flora of GF mice after transplantation. However, antibiotics could not eliminate the original microbial flora in SPF mice, and the flora was complex and variable after FMT with little increase in abundance. Background flora had a significant impact on the outcomes assessment. The results were better in GF mice than in SPF mice, and after microbiota transplantation, a superior effect was observed on day 21 compared to days 7 and 14.
Comparative genomics reveals new insights into the evolution of the IncA and IncC family of plasmids
Authors: Zhang Fengwei , Ye Xianwei , Yin Zhiqiu , Hu Mingda , Wang Boqian , Liu Wenting , Li Beiping , Ren Hongguang , Jin Yuan , Yue Junjie
Published: November 2022

Incompatibility groups IncA and IncC plasmids are of great concern due to their ability to disseminate antibiotic resistance in bacteria via conjugative transfer. A deep understanding of their genomic structures and evolutionary characteristics is of great significance for improving our knowledge about its multidrug-resistance evolution and dissemination. However, current knowledge of their backbone structure, features of core functional modules and the characteristics of variable regions is based on a few plasmids, which highlights the need for a comprehensive systematic study. The present study thoroughly compared and analysed 678 IncA and IncC plasmid genomes. We found that their core functional genes were occasionally deficient and sometimes existed as multiple functional copies/multiple families, which resulted in much diversity. The phylogeny of 13 core functional genes corresponded well to the plasmid subtypes. The conjugative transfer system gained diverse complexity and exhibited many previously unnoticed types with multiple combinations. The insertion of mobile genetic elements (MGEs) in plasmids varied between types and was present in 4 insertion spots in different types of plasmids with certain types of transposons, integrons and insertion sequences. The impact of gene duplication, deletion, the insertion of MGEs, genome rearrangement and recombination resulted in the complex dynamic variable backbone of IncA and IncC plasmids. And IncA and IncC plasmids were more complex than their closest relative SXT/R391 integrative conjugative elements (ICEs), which included nearly all of the diversity of SXT/R391 in key systems. Our work demonstrated a global and systematic view of the IncA and IncC plasmids and provides many new insights into their genome evolution.
Human milk microbial species are associated with infant head-circumference during early and late lactation in Guatemalan mother-infant dyads
Authors: Ajeeb Tamara T. , Gonzalez Emmanuel , Solomons Noel W. , Koski Kristine G.
Published: November 2022

Human milk contains abundant commensal bacteria that colonize and establish the infant’s gut microbiome but the association between the milk microbiome and head circumference during infancy has not been explored. For this cross-sectional study, head-circumference-for-age-z-scores (HCAZ) of vaginally delivered breastfed infants were collected from 62 unrelated Mam-Mayan mothers living in eight remote rural communities in the Western Highlands of Guatemala during two stages of lactation, ‘early’ (6–46 days postpartum, n = 29) or ‘late’ (109–184 days postpartum, n = 33). At each stage of lactation, infants were divided into HCAZ ≥ −1 SD (early: n = 18; late: n = 14) and HCAZ < −1 SD (early: n = 11; late: n = 19). Milk microbiome communities were assessed using 16S ribosomal RNA gene sequencing and DESeq2 was used to compare the differential abundance (DA) of human milk microbiota with infant HCAZ subgroups at both stages of lactations. A total of 503 ESVs annotated 256 putative species across the 64 human milk samples. Alpha-diversity using Chao index uncovered a difference in microbial community richness between HCAZ ≥ −1 SD and HCAZ < −1 SD groups at late lactation (p = 0.045) but not at early lactation. In contrast, Canonical Analysis of Principal Coordinates identified significant differences between HCAZ ≥ −1 SD and HCAZ < −1 SD at both stages of lactation (p = 0.003); moreover, 26 milk microbial taxa differed in relative abundance (FDR < 0.05) between HCAZ ≥ −1 SD and HCAZ < −1 SD, with 13 differentially abundant at each lactation stage. Most species in the HCAZ ≥ −1 SD group were Streptococcus species from the Firmicutes phylum which are considered human colonizers associated with human milk whereas the HCAZ < −1 SD group at late lactation had more differentially abundant taxa associated with environmentally and ‘potentially opportunistic’ species belonging to the Actinobacteria genus. These findings suggest possible associations between brain growth of breastfed infants and the milk microbiome during lactation. Importantly, these data provide the first evidence of cross talk between the human milk microbiome and the infant brain that requires further investigation.
Multimodal medical image fusion using convolutional neural network and extreme learning machine
Authors: Kong Weiwei , Li Chi , Lei Yang
Published: November 2022

The emergence of multimodal medical imaging technology greatly increases the accuracy of clinical diagnosis and etiological analysis. Nevertheless, each medical imaging modal unavoidably has its own limitations, so the fusion of multimodal medical images may become an effective solution. In this paper, a novel fusion method on the multimodal medical images exploiting convolutional neural network (CNN) and extreme learning machine (ELM) is proposed. As a typical representative in deep learning, CNN has been gaining more and more popularity in the field of image processing. However, CNN often suffers from several drawbacks, such as high computational costs and intensive human interventions. To this end, the model of convolutional extreme learning machine (CELM) is constructed by incorporating ELM into the traditional CNN model. CELM serves as an important tool to extract and capture the features of the source images from a variety of different angles. The final fused image can be obtained by integrating the significant features together. Experimental results indicate that, the proposed method is not only helpful to enhance the accuracy of the lesion detection and localization, but also superior to the current state-of-the-art ones in terms of both subjective visual performance and objective criteria.
The role of mesenchymal stem cell transplantation for ischemic stroke and recent research developments
Authors: Zhou Li , Wang Jiani , Huang Jiagui , Song Xiaosong , Wu Youlin , Chen Xia , Tan Yongjun , Yang Qin
Published: November 2022

Ischemic stroke is a common cerebrovascular disease that seriously affects human health. However, most patients do not practice self-care and cannot rely on the current clinical treatment for guaranteed functional recovery. Stem cell transplantation is an emerging treatment studied in various central nervous system diseases. More importantly, animal studies show that transplantation of mesenchymal stem cells (MSCs) can alleviate neurological deficits and bring hope to patients suffering from ischemic stroke. This paper reviews the biological characteristics of MSCs and discusses the mechanism and progression of MSC transplantation to provide new therapeutic directions for ischemic stroke.
How important is the N-terminal acetylation of alpha-synuclein for its function and aggregation into amyloids?
Authors: Iyer Aditya , Sidhu Arshdeep , Subramaniam Vinod
Published: November 2022

N-α-acetylation is a frequently occurring post-translational modification in eukaryotic proteins. It has manifold physiological consequences on the regulation and function of several proteins, with emerging studies suggesting that it is a global regulator of stress responses. For decades, in vitro biochemical investigations into the precise role of the intrinsically disordered protein alpha-synuclein (αS) in the etiology of Parkinson’s disease (PD) were performed using non-acetylated αS. The N-terminus of α-synuclein is now unequivocally known to be acetylated in vivo, however, there are many aspects of this post-translational modifications that are not understood well. Is N-α-acetylation of αS a constitutive modification akin to most cellular proteins, or is it spatio-temporally regulated? Is N-α-acetylation of αS relevant to the as yet elusive function of αS? How does the N-α-acetylation of αS influence the aggregation of αS into amyloids? Here, we provide an overview of the current knowledge and discuss prevailing hypotheses on the impact of N-α-acetylation of αS on its conformational, oligomeric, and fibrillar states. The extent to which N-α-acetylation of αS is vital for its function, membrane binding, and aggregation into amyloids is also explored here. We further discuss the overall significance of N-α-acetylation of αS for its functional and pathogenic implications in Lewy body formation and synucleinopathies.
The anorexic effect of DL-fenfluramine is dependent on animals' habituation to different food types
Authors: Yi Sun Shin , Choi SuJean
Published: November 2022

Background

As rates of obesity and diabetes have increased dramatically over the past few decades, the use of anti-obesity drugs has now become a routine therapeutic measure. However, the pharmacological effects of chronic use of these drugs in humans frequently lead to reduced efficacy in reducing appetite and body weight through as-yet-unidentified mechanisms. An example of this can be found in animal studies where the appetite suppressant DL-fenfluramine (FEN) is chronically administered and its tolerance develops in animals and humans. The appetite effects of FEN are typically measured in several animal studies by the feeding changes in a balanced standard diet. To determine whether FEN differentially altered appetite suppression in animals with long-term expression with different macronutrient diet compositions, its anorexic effects were measured specifically in male rats that had previously been chronically maintained on normal chow (NC) or a high-fat and high-carbohydrate western diet (WD).

Methods

Three experiments were conducted by feeding the animals either NC or WD for 1 month to habituate them with their diet. Animals maintained on either NC or WD were subsequently offered both diet options ad libitum for a 2- or 7-day adaptation period while receiving daily systemic FEN treatment.

Results

The results suggested that long-term habituated food affected the food preference of animals and their appetite even after chronic systemic FEN administration. Therefore, the effectiveness and success or failure of repeated use of chronic anti-obesity drugs may depend on habituated food type.

Conclusion

The appetite suppressant effect was found to be determined by the palatability of a specific macronutrient and the habituated food rather than by a change in the concentration of the administered FEN. This results in a critical analysis of the rationale for taking medication considering the patient's past dietary habits to achieve successful weight loss.
Physicochemical properties and gel-forming ability changes of duck myofibrillar protein induced by hydroxyl radical oxidizing systems
Authors: Zhu Xueshen , Shi Xiandong , Liu Shaohua , Gu Ying , Liu Junya , Fu Qingquan , Wang Renlei
Published: November 2022

This paper focuses on the changes of physicochemical properties and gel-forming ability of duck myofibrillar proteins (DMPs) induced using hydroxyl radical oxidizing systems. DMPs were firstly extracted and then oxidized at various H2O2 concentrations (0, 4, 8, and 12 mmol/L) using Fenton reagent (Fe3+-Vc-H2O2) to generate hydroxyl radicals, and the effects of hydroxyl radical oxidation on the physicochemical changes and heat-induced gel-forming capacity of DMPs were analyzed. We observed obvious increases in the carbonyl content (p < 0.05) and surface hydrophobicity of DMPs with increasing of H2O2 concentrations (0–12 mmol/L). In contrast, the free thiol content (p < 0.05) and water retention ability of DMPs decreased with increasing H2O2 concentrations (0–12 mmol/L). These physicochemical changes suggested that high concentrations of hydroxyl radicals significantly altered the biochemical structure of DMPs, which was not conducive to the formation of a gel mesh structure. Furthermore, the gel properties were reduced based on the significant decrease in the water holding capacity (p < 0.05) and increased transformation of immobilized water of the heat-induced gel to free water (p < 0.05). With the increase of H2O2 concentrations, secondary structure of proteins analysis results indicated α-helix content decreased significantly (p < 0.05), however, random coil content increased (p < 0.05). And more cross-linked myosin heavy chains were detected at higher H2O2 concentrations groups through immunoblot analysis (p < 0.05). Therefore, as H2O2 concentrations increased, the gel mesh structure became loose and porous, and the storage modulus and loss modulus values also decreased during heating. These results demonstrated that excessive oxidation led to explicit cross-linking of DMPs, which negatively affected the gel-forming ability of DMPs. Hence, when processing duck meat products, the oxidation level of meat gel products should be controlled, or suitable antioxidants should be added.
Preparation of highly efficient p-doped porous camellia shell-based activated carbon and its adsorption of carotenoids in camellia oil
Authors: Tian Run , Liu Yang , Cao Danyu , Gai Lili , Du Nan , Yin Jiangyu , Hu Dongbin , Lu Haiqin , Li Wen , Li Kai
Published: November 2022

The vegetable oil industry is limited by the high cost of the refining process, and the camellia shells (CS) are beneficial to the development of the industry as a biomass raw material for camellia oil decolorization. In this study, CS-based p-doped porous activated carbon (CSHAC) obtained after the pyrolysis of H3PO4-laden CS-hydrochar (CSH) was used for the adsorption of carotenoids in camellia oil. The results showed that the adsorption efficiency of CSHAC for carotenoids was 96.5% compared to 67–87% for commercial decolorizers, and exhibited a fast adsorption rate (20 min). The results of adsorption isotherms indicated that the adsorption of carotenoids on CSHAC occurred through a multi-layer process. Furthermore, the analysis of adsorption kinetics showed that the adsorption of carotenoids by CSHAC was a complex process involving physical and chemical reactions, and chemisorption was the dominant kinetic mechanism. This superior performance of CSHAC in adsorbing carotenoids was attributed to its micro-mesoporous structure, hydrophobicity, and numerous active sites.
Tannic acid supplementation in the diet of Holstein bulls: Impacts on production performance, physiological and immunological characteristics, and ruminal microbiota
Authors: Wang Zuo , Zhao Yuan , Lan Xinyi , He Jianhua , Wan Fachun , Shen Weijun , Tang Shaoxun , Zhou Chuanshe , Tan Zhiliang , Yang Yanming
Published: November 2022

This study was conducted to evaluate the influences of supplementing tannic acid (TA) at different doses on the production performance, physiological and immunological characteristics, and rumen bacterial microbiome of cattle. Forty-eight Holstein bulls were randomly allocated to four dietary treatments: the control (CON, basal diet), the low-dose TA treatment [TAL, 0.3% dry matter (DM)], the mid-dose TA treatment (TAM, 0.9% DM), and the high-dose TA treatment (TAH, 2.7% DM). This trial consisted of 7 days for adaptation and 90 days for data and sample collection, and samples of blood and rumen fluid were collected on 37, 67, and 97 d, respectively. The average daily gain was unaffected (P > 0.05), whilst the ruminal NH3-N was significantly decreased (P < 0.01) by TA supplementation. The 0.3% TA addition lowered (P < 0.05) the levels of ruminal isobutyrate, valerate, and tumor necrosis factor alpha (TNF-α), and tended to (P < 0.1) increase the gain to feed ratio. The digestibility of DM, organic matter (OM), and crude protein, and percentages of butyrate, isobutyrate, and valerate were lower (P < 0.05), while the acetate proportion and acetate to propionate ratio in both TAM and TAH were higher (P < 0.05) than the CON. Besides, the 0.9% TA inclusion lessened (P < 0.05) the concentrations of glucagon and TNF-α, but enhanced (P < 0.05) the interferon gamma (IFN-γ) level and Simpson index of ruminal bacteria. The 2.7% TA supplementation reduced (P < 0.05) the intake of DM and OM, and levels of malondialdehyde and thyroxine, while elevated (P < 0.05) the Shannon index of the rumen bacterial populations. Moreover, the relative abundances of the phyla Fibrobacteres and Lentisphaerae, the genera Fibrobacter and Bradyrhizobium, and the species Bradyrhizobium sp., Lachnospiraceae bacterium RM29, and Lachnospiraceae bacterium CG57 were highly significantly (q < 0.01) or significantly (q < 0.05) raised by adding 2.7% TA. Results suggested that the TA addition at 0.3% is more suitable for the cattle, based on the general comparison on the impacts of supplementing TA at different doses on all the measured parameters.
Diagnostic accuracy of the waist-to-height ratio and other anthropometric indices for metabolically healthy obesity in the working population
Authors: Guzmán-García José-Miguel , Romero-Saldaña Manuel , Molina-Recio Guillermo , Álvarez-Fernández Carlos , Raya-Cano Elena , Molina-Luque Rafael
Published: November 2022

Approximately one-third of overweight individuals, and half of those with obesity, do not have cardiometabolic disorders. For this reason, a phenotype called metabolically healthy obese (MHO) has emerged to describe this population group. The early detection of this situation could save costs associated with the development of comorbidities or pharmacological interventions. Therefore, the aim is to know the prevalence of MHO in the working population and propose variables for its detection. Cross-sectional descriptive study of 635 workers of the Cordoba City Council was carried out based on the results of the 2016 health surveillance. The outcome variables were the MHO, established based on the criteria of the IDF, NCEP—ATP III, and Aguilar—Salinas. In addition, the degree of agreement between the different MHO criteria was studied using Cohen's kappa (k), and the predictive capacity of the anthropometric variables was assessed with Receiver Operator Curves. The prevalence of MHO ranged from 6.6 to 9%. The highest agreement was reached between the IDF and NCEP-ATP III definitions (k = 0.811; 95% CI 0.724–0.898; p < 0.001). The waist-to-height ratio (WHtR) showed the highest discriminant capacity for MHO, with its best cut-off point at 0.55 for all criteria used. Sensitivity ranged from 84 to 93%. The prevalence of MHO in the working population differed according to the criteria used for diagnosis. The anthropometric variable with the highest discriminant capacity for MHO was WHtR, presenting the same cut-off point in the three criteria analyzed. Therefore, WHtR is the variable that best detects the presence of MHO.