bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of m6A Regulator-Associated Methylation Modification Clusters and Immune Profiles in Melanoma
Authors: Du Fengying , Li Han , Li Yan , Liu Yang , Li Xinyu , Dang Ningning , Chu Qingqing , Yan Jianjun , Fang Zhen , Wu Hao , Zhang Zihao , Zhu Xingyu , Li Xiaokang
Published: December 2021

RNA N6-methyladenosine (m6A) modification in tumorigenesis and progression has been highlighted and discovered in recent years. However, the molecular and clinical implications of m6A modification in melanoma tumor microenvironment (TME) and immune infiltration remain largely unknown. Here, we utilized consensus molecular clustering with nonnegative matrix factorization based on the melanoma transcriptomic profiles of 23 m6A regulators to determine the m6A modification clusters and m6A-related gene signature. Three distinct m6A modification patterns (m6A-C1, C2, and C3), which are characterized by specific m6A regulator expression, survival outcomes, and biological pathways, were identified in more than 1,000 melanoma samples. The immune profile analyses showed that these three m6A modification subtypes were highly consistent with the three known immune phenotypes: immune-desert (C1), immune-excluded (C2), and immune-inflamed (C3). Tumor digital cytometry (CIBERSORT, ssGSEA) algorithm revealed an upregulated infiltration of CD8+ T cell and NK cell in m6A-C3 subtype. An m6A scoring scheme calculated by principal component of m6A signatures stratified melanoma patients into high- and low-m6sig score subgroups; a high score was significantly associated with prolonged survival and enhanced immune infiltration. Furthermore, fewer somatic copy number alternations (SCNA) and PD-L1 expression were found in patients with high m6Sig score. In addition, patients with high m6Sig score demonstrated marked immune responses and durable clinical benefits in two independent immunotherapy cohorts. Overall, this study indicated that m6A modification is involved in melanoma tumor microenvironment immune regulation and contributes to formation of tumor immunogenicity. Comprehensive evaluation of the m6A modification pattern of individual tumors will provide more insights into molecular mechanisms of TME characterization and promote more effective personalized biotherapy strategies.
Metabolite Changes in the Aqueous Humor of Patients With Retinal Vein Occlusion Macular Edema: A Metabolomics Analysis
Authors: Xiong Xiaojing , Chen Xu , Ma Huafeng , Zheng Zheng , Yang Yazhu , Chen Zhu , Zhou Zixi , Pu Jiaxin , Chen Qingwei , Zheng Minming
Published: December 2021

Macular edema (ME) is the main cause of visual impairment in patients with retinal vein occlusion (RVO). The degree of ME affects the prognosis of RVO patients, while it lacks objective laboratory biomarkers. We aimed to compare aqueous humor samples from 28 patients with retinal vein occlusion macular edema (RVO-ME) to 27 age- and sex-matched controls by ultra-high-performance liquid chromatography equipped with quadrupole time-of-flight mass spectrometry, so as to identify the key biomarkers and to increase the understanding of the mechanism of RVO-ME at the molecular level. Through univariate and multivariate statistical analyses, we identified 60 metabolites between RVO-ME patients and controls and 40 differential metabolites in mild RVO-ME [300 μm ≤ central retinal thickness (CRT) < 400 μm] patients compared with severe RVO-ME (CRT ≥ 400 μm). Pathway enrichment analysis showed that valine, leucine, and isoleucine biosynthesis; ascorbate and aldarate metabolism; and pantothenate and coenzyme A biosynthesis were significantly altered in RVO-ME in comparison with controls. Compared with mild RVO-ME, degradation and biosynthesis of valine, leucine, and isoleucine; histidine metabolism; beta-alanine metabolism; and pantothenate and coenzyme A biosynthesis were significantly changed in severe RVO-ME. Furthermore, the receiver operating characteristic (ROC) curve analysis revealed that adenosine, threonic acid, pyruvic acid, and pyro-L-glutaminyl-l-glutamine could differentiate RVO-ME from controls with an area under the curve (AUC) of >0.813. Urocanic acid, diethanolamine, 8-butanoylneosolaniol, niacinamide, paraldehyde, phytosphingosine, 4-aminobutyraldehyde, dihydrolipoate, and 1-(beta-D-ribofuranosyl)-1,4-dihydronicotinamide had an AUC of >0.848 for distinguishing mild RVO-ME from severe RVO-ME. Our study expanded the understanding of metabolomic changes in RVO-ME, which could help us to have a good understanding of the pathogenesis of RVO-ME.
Origin and Development of the Adipose Tissue, a Key Organ in Physiology and Disease
Authors: Parra-Peralbo Esmeralda , Talamillo Ana , Barrio Rosa
Published: December 2021

Adipose tissue is a dynamic organ, well known for its function in energy storage and mobilization according to nutrient availability and body needs, in charge of keeping the energetic balance of the organism. During the last decades, adipose tissue has emerged as the largest endocrine organ in the human body, being able to secrete hormones as well as inflammatory molecules and having an important impact in multiple processes such as adipogenesis, metabolism and chronic inflammation. However, the cellular progenitors, development, homeostasis and metabolism of the different types of adipose tissue are not fully known. During the last decade, Drosophila melanogaster has demonstrated to be an excellent model to tackle some of the open questions in the field of metabolism and development of endocrine/metabolic organs. Discoveries ranged from new hormones regulating obesity to subcellular mechanisms that regulate lipogenesis and lipolysis. Here, we review the available evidences on the development, types and functions of adipose tissue in Drosophila and identify some gaps for future research. This may help to understand the cellular and molecular mechanism underlying the pathophysiology of this fascinating key tissue, contributing to establish this organ as a therapeutic target.
Single-Cell Transcriptomics Reveals the Molecular Anatomy of Sheep Hair Follicle Heterogeneity and Wool Curvature
Authors: Wang Shanhe , Wu Tianyi , Sun Jingyi , Li Yue , Yuan Zehu , Sun Wei
Published: December 2021

Wool is the critical textile raw material which is produced by the hair follicle of sheep. Therefore, it has important implications to investigate the molecular mechanism governing hair follicle development. Due to high cellular heterogeneity as well as the insufficient cellular, molecular, and spatial characterization of hair follicles on sheep, the molecular mechanisms involved in hair follicle development and wool curvature of sheep remains largely unknown. Single-cell RNA sequencing (scRNA-seq) technologies have made it possible to comprehensively dissect the cellular composition of complex skin tissues and unveil the differentiation and spatial signatures of epidermal and hair follicle development. However, such studies are lacking so far in sheep. Here, single-cell suspensions from the curly wool and straight wool lambskins were prepared for unbiased scRNA-seq. Based on UAMP dimension reduction analysis, we identified 19 distinct cell populations from 15,830 single-cell transcriptomes and characterized their cellular identity according to specific gene expression profiles. Furthermore, novel marker gene was applied in identifying dermal papilla cells isolated in vitro. By using pseudotime ordering analysis, we constructed the matrix cell lineage differentiation trajectory and revealed the dynamic gene expression profiles of matrix progenitors' commitment to the hair shaft and inner root sheath (IRS) cells. Meanwhile, intercellular communication between mesenchymal and epithelial cells was inferred based on CellChat and the prior knowledge of ligand–receptor pairs. As a result, strong intercellular communication and associated signaling pathways were revealed. Besides, to clarify the molecular mechanism of wool curvature, differentially expressed genes in specific cells between straight wool and curly wool were identified and analyzed. Our findings here provided an unbiased and systematic view of the molecular anatomy of sheep hair follicle comprising 19 clusters; revealed the differentiation, spatial signatures, and intercellular communication underlying sheep hair follicle development; and at the same time revealed the potential molecular mechanism of wool curvature, which will give important new insights into the biology of the sheep hair follicle and has implications for sheep breeding.
Pterostilbene Alleviates Chlorpyrifos-Induced Damage During Porcine Oocyte Maturation
Authors: Guo Lili , Zhao Yongda , Huan Yanjun
Published: December 2021

Chlorpyrifos (CPF), a widely used organophosphate pesticide, is reported to severely impair mammalian reproductive system. Pterostilbene (PTS), an effective free radical scavenger, is considered as beneficial for mammalian reproduction. However, the toxicity of CPF on oocyte maturation and whether PTS can eliminate the detrimental effect of CPF on oocytes remain unclear. Here, porcine oocytes were applied to investigate the potential effect and possible mechanism of CPF and PTS during oocyte maturation. This work demonstrated that CPF significantly delayed the meiotic progression and decreased the polar body extrusion by disturbing spindle assembly and chromosome alignment and causing DNA damage in oocytes (p < 0.05). And, CPF significantly impaired oocyte cytoplasmic maturation by inducing the high level of reactive oxygen species and decreasing glutathione content (p < 0.05). Moreover, CPF significantly triggered embryo apoptosis and reduced the blastocyst rate and cell number following parthenogenetic activation (p < 0.05). Whereas CPF-exposed oocytes were treated with PTS, these defects caused by CPF were obviously rescued, and oocyte maturation and subsequent embryonic development were also significantly ameliorated (p < 0.05). In conclusion, these results revealed that CPF exerted the toxic effect on porcine oocytes, while PTS effectively alleviated CPF-induced damage on oocytes. This work provides a potential strategy to protect oocyte maturation in mammalian species.
The GW Miracle in Many-Body Perturbation Theory for the Ionization Potential of Molecules
Authors: Bruneval Fabien , Dattani Nike , van Setten Michiel J.
Published: December 2021

We use the GW100 benchmark set to systematically judge the quality of several perturbation theories against high-level quantum chemistry methods. First of all, we revisit the reference CCSD(T) ionization potentials for this popular benchmark set and establish a revised set of CCSD(T) results. Then, for all of these 100 molecules, we calculate the HOMO energy within second and third-order perturbation theory (PT2 and PT3), and, GW as post-Hartree-Fock methods. We found GW to be the most accurate of these three approximations for the ionization potential, by far. Going beyond GW by adding more diagrams is a tedious and dangerous activity: We tried to complement GW with second-order exchange (SOX), with second-order screened exchange (SOSEX), with interacting electron-hole pairs (WTDHF), and with a GW density-matrix (γGW). Only the γGW result has a positive impact. Finally using an improved hybrid functional for the non-interacting Green’s function, considering it as a cheap way to approximate self-consistency, the accuracy of the simplest GW approximation improves even more. We conclude that GW is a miracle: Its subtle balance makes GW both accurate and fast.
Towards Predictive Synthesis of Inorganic Materials Using Network Science
Authors: Aziz Alex , Carrasco Javier
Published: December 2021

Accelerating materials discovery is the cornerstone of modern technological competitiveness. Yet, the inorganic synthesis of new compounds is often an important bottleneck in this quest. Well-established quantum chemistry and experimental synthesis methods combined with consolidated network science approaches might provide revolutionary knowledge to tackle this challenge. Recent pioneering studies in this direction have shown that the topological analysis of material networks hold great potential to effectively explore the synthesizability of inorganic compounds. In this Perspective we discuss the most exciting work in this area, in particular emerging new physicochemical insights and general concepts on how network science can significantly help reduce the timescales required to discover new materials and find synthetic routes for their fabrication. We also provide a perspective on outstanding problems, challenges and open questions.
Recent Progresses in the Multicomponent Synthesis of Dihydropyridines by Applying Sustainable Catalysts Under Green Conditions
Authors: Sonali Anantha Immandhi Sai , Kerru Nagaraju , Maddila Suresh , Jonnalagadda Sreekantha B.
Published: December 2021

The synthesis of dihydropyridines, valuable molecules with diverse therapeutic properties, using eco-friendly heterogeneous catalysts as a green alternative received significant consideration. By selecting appropriate precursors, these compounds can be readily modified to induce the desired properties in the target product. This review focused on synthesising diverse dihydropyridine derivatives in single-pot reactions using magnetic, silica, and zirconium-based heterogeneous catalytic systems. The monograph describes preparation techniques for various catalyst materials in detail. It covers facile and benign magnetic, silica, zirconium-based, and ionic liquid catalysts, exhibiting significant efficacy and consistently facilitating excellent yields in short reaction times and in a cost-effective way. Most of the designated protocols employ Hantzsch reactions involving substituted aldehydes, active methylene compounds, and ammonium acetate. These reactions presumably follow Knoevenagel condensation followed by Michael addition and intra-molecular cyclisation. The multicomponent one-pot protocols using green catalysts and solvents have admirably increased the product selectivity and yields while minimising the reaction time. These sustainable catalyst materials retain their viability for several cycles reducing the expenditure are eco-friendly.
Carboxylato-Pillar[6]arene-Based Fluorescent Indicator Displacement Assays for Caffeine Sensing
Authors: Duan Qunpeng , Xing Yibo , Guo Kainan
Published: December 2021

In the present work, we have developed a new indicator displacement system based on pillararene for anionic water-soluble carboxylato pillar [6] arene (WP6) and aromatic fluorescent dye safranine T (ST). A large fluorescence enhancement and colour change of ST were observed after complexation with electron-rich cavity in WP6 because of host-guest twisted intramolecular charge-transfer interactions. The constructed pillararene-indicator displacement system can be applied for caffeine selective detection in water.
Transcriptomic Analysis of Mycobacterium leprae-Stimulated Response in Peripheral Blood Mononuclear Cells Reveal Potential Biomarkers for Early Diagnosis of Leprosy
Authors: Yuan You-Hua , Liu Jian , You Yuan-Gang , Chen Xiao-Hua , Yuan Lian-Chao , Wen Yan , Li Huan Ying , Zhang Ying
Published: December 2021

We aimed to identify an unique host transcriptional signature in peripheral blood mononuclear cells (PBMCs) in response to Mycobacterium leprae antigens to distinguish between patients with leprosy and non-leprosy controls for early diagnosis of the disease. Sixteen individuals were enrolled in the discovery cohort [eight patients with leprosy, comprising four multibacillary (MB) and four paucibacillary (PB); and eight non-leprosy controls, comprising four healthy house contacts (HHCs) and four endemic controls (ECs)]. The differences in the transcriptome response of PBMCs to M. leprae sonicate antigen were evaluated between leprosy patients and non-leprosy controls, and 12 differentially expressed genes (CCL2/MCP-1, IL-8, JAKM, ATP, ND1, SERP, FLJ10489, LINC00659, LOC34487, LOC101928143, MIR22, and NCF1C) were identified. The accuracy of the 12 differentially expressed genes was further validated for the diagnosis of leprosy using real-time quantitative PCR in 82 individuals (13 MB, 10 PB, 37 HHCs, and 22 ECs) in the validation cohort. We found that a 5 gene signature set IL-8, CCL2/MCP-1, SERP, LINC00659 and FLJ10489 had a suitable performance in discriminating leprosy from ECs. In addition, elevated expression of IL-8, CCL2/MCP-1, SERP and LINC00659 was associated with MB diagnosis compared with ECs, whereas increased expression of IL-8, CCL2/MCP-1, SERP and FLJ10489 was found to be useful biomarkers for PB diagnosis from ECs. Moreover, we found decreased expression of NCF1C among leprosy patients could distinguish leprosy from HHCs, whereas higher expression of CCL2 among MB than PB could distinguish different leprosy patients. In conclusion, among the 12 candidate host genes identified, a three gene signature IL-8, CCL2/MCP-1, and SERP showed the best performance in distinguishing leprosy patients from healthy controls. These findings may have implications for developing a rapid blood-based test for early diagnosis of leprosy.
Clinical, Virological, Immunological, and Genomic Characterization of Asymptomatic and Symptomatic Cases With SARS-CoV-2 Infection in India
Authors: Chatterjee Sanchari , Datey Ankita , Sengupta Soumya , Ghosh Arup , Jha Atimukta , Walia Safal , Singh Sharad , Suranjika Sandhya , Bhattacharya Gargee , Laha Eshna , Keshry Supriya Suman , Ray Amrita , Pani Sweta Smita , Suryawanshi Amol Ratnakar , Dash Rupesh , Senapati Shantibhusan , Beuria Tushar K. , Syed Gulam Hussain , Prasad Punit , Raghav Sunil Kumar , Devadas Satish , Swain Rajeeb K. , Chattopadhyay Soma , Parida Ajay
Published: December 2021

Purpose

The current global pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), led to the investigation with clinical, biochemical, immunological, and genomic characterization from patients to understand the pathophysiology of viral infection.

Methods

Samples were collected from six asymptomatic and six symptomatic SARS-CoV-2-confirmed hospitalized patients in Bhubaneswar, Odisha, India. Clinical details, biochemical parameters, and treatment regimen were collected from a hospital; viral load was determined by RT-PCR; and the levels of cytokines and circulating antibodies in plasma were assessed by Bio-Plex and isotyping, respectively. In addition, whole-genome sequencing of viral strains and mutational analysis were carried out.

Results

Analysis of the biochemical parameters highlighted the increased levels of C-reactive protein (CRP), lactate dehydrogenase (LDH), serum SGPT, serum SGOT, and ferritin in symptomatic patients. Symptomatic patients were mostly with one or more comorbidities, especially type 2 diabetes (66.6%). The virological estimation revealed that there was no significant difference in viral load of oropharyngeal (OP) samples between the two groups. On the other hand, viral load was higher in plasma and serum samples of symptomatic patients, and they develop sufficient amounts of antibodies (IgG, IgM, and IgA). The levels of seven cytokines (IL-6, IL-1α, IP-10, IL-8, IL-10, IFN-α2, IL-15) were found to be highly elevated in symptomatic patients, while three cytokines (soluble CD40L, GRO, and MDC) were remarkably higher in asymptomatic patients. The whole-genome sequence analysis revealed that the current isolates were clustered with 19B, 20A, and 20B clades; however, 11 additional changes in Orf1ab, spike, Orf3a, Orf8, and nucleocapsid proteins were acquired. The D614G mutation in spike protein is linked with higher virus replication efficiency and severe SARS-CoV-2 infection as three patients had higher viral load, and among them, two patients with this mutation passed away.

Conclusions

This is the first comprehensive study of SARS-CoV-2 patients from India. This will contribute to a better understanding of the pathophysiology of SARS-CoV-2 infection and thereby advance the implementation of effective disease control strategies.
Flood Susceptibility Modeling in a Subtropical Humid Low-Relief Alluvial Plain Environment: Application of Novel Ensemble Machine Learning Approach
Authors: Pandey Manish , Arora Aman , Arabameri Alireza , Costache Romulus , Kumar Naveen , Mishra Varun Narayan , Nguyen Hoang , Mishra Jagriti , Siddiqui Masood Ahsan , Ray Yogesh , Soni Sangeeta , Shukla UK
Published: December 2021

This study has developed a new ensemble model and tested another ensemble model for flood susceptibility mapping in the Middle Ganga Plain (MGP). The results of these two models have been quantitatively compared for performance analysis in zoning flood susceptible areas of low altitudinal range, humid subtropical fluvial floodplain environment of the Middle Ganga Plain (MGP). This part of the MGP, which is in the central Ganga River Basin (GRB), is experiencing worse floods in the changing climatic scenario causing an increased level of loss of life and property. The MGP experiencing monsoonal subtropical humid climate, active tectonics induced ground subsidence, increasing population, and shifting landuse/landcover trends and pattern, is the best natural laboratory to test all the susceptibility prediction genre of models to achieve the choice of best performing model with the constant number of input parameters for this type of topoclimatic environmental setting. This will help in achieving the goal of model universality, i.e., finding out the best performing susceptibility prediction model for this type of topoclimatic setting with the similar number and type of input variables. Based on the highly accurate flood inventory and using 12 flood predictors (FPs) (selected using field experience of the study area and literature survey), two machine learning (ML) ensemble models developed by bagging frequency ratio (FR) and evidential belief function (EBF) with classification and regression tree (CART), CART-FR and CART-EBF, were applied for flood susceptibility zonation mapping. Flood and non-flood points randomly generated using flood inventory have been apportioned in 70:30 ratio for training and validation of the ensembles. Based on the evaluation performance using threshold-independent evaluation statistic, area under receiver operating characteristic (AUROC) curve, 14 threshold-dependent evaluation metrices, and seed cell area index (SCAI) meant for assessing different aspects of ensembles, the study suggests that CART-EBF (AUCSR= 0.843; AUCPR= 0.819) was a better performant than CART-FR (AUCSR= 0.828; AUCPR= 0.802). The variability in performances of these novel-advanced ensembles and their comparison with results of other published models espouse the need of testing these as well as other genres of susceptibility models in other topoclimatic environments also. Results of this study are important for natural hazard managers and can be used to compute the damages through risk analysis.
Overcoming Gender Gaps in Entrepreneurship Education and Training
Authors: Pimpa Nattavud
Published: December 2021

Entrepreneurship education and training are essential for female entrepreneurs who juggle family expectations, personal life, and new ventures at the same time. Indeed, generic entrepreneurship training may fail to promote understanding in gender literacy and its relationship with creating and managing business entities. To help address gender gaps, this article explores gender issues in the training process for female entrepreneurs, the researcher collected primary data from 28 trainers through personal interviews and secondary data from the 43 training evaluation forms from trainees who participated in the national entrepreneurship training programs in Thailand. The researcher identifies three themes that are related to gender gaps and effectiveness in the entrepreneurship training context. They include (1) gender mainstreaming, (2) gender-sensitive training approaches, and (3) the adoption of proper technology and innovation for female entrepreneurs. Secondary data also confirm that female entrepreneurs in this study address the need for professional development that promotes them to engage in gender competencies, technology, and innovation for new ventures. The opportunity for professional development can be limited by family and social commitments. Engaging with experienced female entrepreneurs and business role models can promote understanding in the three areas among female entrepreneurs. This article outlines a novel approach in synergizing gender issues, training, and entrepreneurship skills. It concludes with some explanations of the relative efficacy of entrepreneurship training that reduces gender gaps for female entrepreneurs.
Social-Emotional Learning Interventions for Students With Special Educational Needs: A Systematic Literature Review
Authors: Hassani Sepideh , Schwab Susanne
Published: December 2021

In the last decades, social-emotional learning interventions have been implemented in schools with the aim of fostering students’ non-academic competences. Evaluations of these interventions are essential to assess their potential effects. However, effects may vary depending on students’ variables. Therefore, the current systematic review had three main objectives: 1) to identify the effectiveness of social-emotional learning interventions with students with special educational needs, 2) to assess and evaluate those intervention conditions leading to effective outcomes in social-emotional competences for this population, and 3) to draw specific conclusions for the population of students with special educational needs. For this purpose, studies were retrieved from the databases Scopus, ERIC, EBSCO and JSTOR, past meta-analysis and (systematic) reviews, as well as from journal hand searches including the years 1994–2020. By applying different inclusion criteria, such as implementation site, students’ age and study design, a total of eleven studies were eligible for the current systematic review. The primary findings indicate that most of the intervention studies were conducted in the United States and confirm some positive, but primarily small, effects for social-emotional learning interventions for students with special educational needs. Suggestions for future research and practice are made to contribute to the improvement of upcoming intervention studies.
Association Between Paternal Separation During Early Childhood and Pubertal Timing Among Girls Using Longitudinal Birth Cohort in Japan
Authors: Katagiri Aomi , Nawa Nobutoshi , Fujiwara Takeo
Published: December 2021

Introduction

Previous studies have shown that paternal absence leads to earlier pubertal timing among girls in high-income countries. Despite the low divorce rate in Japan, paternal separation is commonly seen due to a unique corporation system, tanshin funin, where employees relocate with their spouses and children. We examined paternal separation, including paternal absence (due to divorce or paternal death) and paternal tanshin funin, during early childhood as a predictor of earlier girl’s pubertal development, assessed as age at peak height velocity (PHV).

Methods

This study examined 15 214 girls from a longitudinal survey conducted in Japan from 2001 to 2016 by the Ministry of Health, Labor and Welfare. Paternal separation was determined by the occurrence through annual surveys conducted at ages 0.5 to 4.5 years. Outcome was defined as age at PHV between ages 6 to 15 years. We conducted linear regression, adjusted for potential confounders and other covariates.

Results

Continuous father cohabitation was seen in 88.7% of households, while paternal separation was experienced 1-2, 3-4 and 5 times (always) among 7.4%, 2.8% and 1.1% of households, respectively. Girls who confronted continuous paternal separation (5 times) experienced 0.42 years earlier [95% confidence interval (CI): -0.75, -0.10] age at PHV compared to their peers who always lived with their fathers.

Conclusion

Girls who experienced paternal separation throughout ages 0.5 to 4.5 years experienced PHV earlier.
Association Between Diabetes Mellitus and All-Cause and Cardiovascular Mortality Among Individuals With Ultrasound-Defined Non-Alcoholic Fatty Liver Disease
Authors: Wu Weiti , Xiang Jingjing , Chen Xiaoye
Published: December 2021

Objective

The influence of diabetes on mortality among patients with non-alcoholic fatty liver disease (NAFLD) in the general population has not been extensively studied. This study aimed to determine the relationship between diabetes and all-cause and cardiovascular mortality in patients with hepatic ultrasound-confirmed NAFLD using data from the Third National Health and Nutrition Examination Survey (NHANES III), 1988–1994.

Methods

Data from 4,037 adult individuals with NAFLD from the NHANES III and mortality outcomes linked to National Death Index records through December 31, 2015, were included. Cox proportional hazards models were used to calculate the hazard ratio (HR) and corresponding 95% CI for mortality from all causes and cardiovascular disease after adjusting for multiple variables.

Results

Among 4,037 subjects with NAFLD (55.9% female), 483 had diabetes at baseline. During a median follow-up of 22.1 years, 1,517 (11.5%) died, including 332 (8.22%) from cardiovascular causes. Diabetes was associated with increased all-cause (HR 3.02 [95% CI 2.67–3.41]) and cardiovascular (HR 3.36 [95% CI 2.61–4.32]) mortality in an unadjusted multivariable Cox regression model. The association remained statistically significant after adjusting for a range of potential confounders (HR 2.20 [95% CI 1.90–2.55] for all-cause mortality and HR 2.47 [95% CI 1.81–3.37] for cardiovascular mortality). An additional stratified analysis did not reveal significantly altered results.

Conclusion

Diabetes was associated with all-cause and cardiovascular mortality in patients with NAFLD. This link could be further characterized in future studies assessing the degree of glycemic control and its relationship with mortality in patients with diabetes and NAFLD.
Climate Adaptive Silviculture for the City: Practitioners and Researchers Co-create a Framework for Studying Urban Oak-Dominated Mixed Hardwood Forests
Authors: Piana Max R. , Hallett Richard A. , Johnson Michelle L. , Sonti Nancy F. , Brandt Leslie A. , Aronson Myla F. J. , Ashton Mark , Blaustein Max , Bloniarz David , Bowers Ashley A. , Carr Megan E. , D’Amico Vince , Dewald Laura , Dionne Heather , Doroski Danica A. , Fahey Robert T. , Forgione Helen , Forrest Todd , Hale Jack , Hansen Eric , Hayden Lisa , Hines Sarah , Hoch Jessica M. , Ieataka Taro , Lerman Susannah B. , Murphy Charles , Nagele Eliot , Nislow Keith , Parker Dhan , Pregitzer Clara C. , Rhodes Luke , Schuler Jessica , Sherman Alexander , Trammell Tara , Wienke Brittany M. , Witmer Thomas , Worthley Thomas , Yesilonis Ian
Published: December 2021

Urban forested natural areas are an important component of the forest and tree canopy in northeastern United States urban areas. Although similar to native forests in surrounding regions in structure, composition, and function, these natural areas are threatened by multiple, co-occurring biological and climate stressors that are exacerbated by the urban environment. Furthermore, forests in cities often lack application of formal silvicultural approaches reliant upon evidence-based applied ecological sciences. These include both urban- and climate-adapted silvicultural techniques to increase the resilience and sustainability of native forests in cities. With this in mind, we convened a group of urban forest practitioners and researchers from along a latitudinal gradient in the northeastern United States to participate in a workshop focused on co-developing long-term, replicated ecological studies that will underlie the basis for potential silvicultural applications to urban forests. In this article we review the process and outcomes of the workshop, including an assessment of forest vulnerability, and adaptive capacity across the region, as well as shared management goals and objectives. We discuss the social and ecological challenges of managing urban oak-dominated mixed hardwood forests relative to non-urban forests and identify potential examples of urban- and climate-adapted silviculture strategies created by practitioners and researchers. In doing so, we highlight the challenges and need for basic and long-term applied ecological research relevant to silvicultural applications in cities.
The Genetic Structure and East-West Population Admixture in Northwest China Inferred From Genome-Wide Array Genotyping
Authors: Ma Bin , Chen Jinwen , Yang Xiaomin , Bai Jingya , Ouyang Siwei , Mo Xiaodan , Chen Wangsheng , Wang Chuan-Chao , Hai Xiangjun
Published: December 2021

Northwest China is a contacting region for East and West Eurasia and an important center for investigating the migration and admixture history of human populations. However, the comprehensive genetic structure and admixture history of the Altaic speaking populations and Hui group in Northwest China were still not fully characterized due to insufficient sampling and the lack of genome-wide data. Thus, We genotyped genome-wide SNPs for 140 individuals from five Chinese Mongolic, Turkic speaking groups including Dongxiang, Bonan, Yugur, and Salar, as well as the Hui group. Analysis based on allele-sharing and haplotype-sharing were used to elucidate the population history of Northwest Chinese populations, including PCA, ADMIXTURE, pairwise Fst genetic distance, f-statistics, qpWave/qpAdm and ALDER, fineSTRUCTURE and GLOBETROTTER. We observed Dongxiang, Bonan, Yugur, Salar, and Hui people were admixed populations deriving ancestry from both East and West Eurasians, with the proportions of West Eurasian related contributions ranging from 9 to 15%. The genetic admixture was probably driven by male-biased migration- showing a higher frequency of West Eurasian related Y chromosomal lineages than that of mtDNA detected in Northwest China. ALDER-based admixture and haplotype-based GLOBETROTTER showed this observed West Eurasian admixture signal was introduced into East Eurasia approximately 700 ∼1,000 years ago. Generally, our findings provided supporting evidence that the flourish transcontinental communication between East and West Eurasia played a vital role in the genetic formation of northwest Chinese populations.
Integrative RNA-Seq and ATAC-Seq Analysis Reveals the Migration-Associated Genes Involved in Antitumor Effects of Herbal Medicine Feiyanning on Lung Cancer Cells
Authors: Wang Chenyang , Li Pengxiao , Peng Yonglin , Liu Ruiqi , Wu Xiaoting , Tan Sheng , Zhang Ming , Zhao Xiaodong
Published: December 2021

Lung cancer is one of the leading causes of cancer-associated death in the world. It is of great importance to explore new therapeutic targets. Traditional Chinese medicine formula Feiyanning has been clinically administered in China for more than a decade and raised attention due to its anticancer effect in lung cancer. However, the underlying molecular mechanisms remain to be elucidated. In the present study, we carried out cellular and molecular assays to examine the antitumor activities and understand the mechanism of the Feiyanning formula in lung cancer cells. The cellular viability of Feiyanning-treated lung cancer cells was evaluated by Cell Counting Kit-8. The effect of the Feiyanning formula on cellular migration and invasion of lung cancer cells was examined by wound healing and transwell assays. Transcriptome and chromatin accessibility analysis by RNA-seq and ATAC-seq was performed to investigate the underlying molecular mechanisms. Our results revealed that the Feiyanning formula inhibited the cellular activities of proliferation, migration, and invasion in non-small cell lung cancer cell lines A549, H1975, and 95D. Furthermore, we observed that the transcriptional activity of the migration-associated genes was downregulated upon Feiyanning formula treatment in non-small cell lung cancer cells. The chromatin accessibility of the Feiyanning-treated lung cancer genome tended to decrease, and the regulation of the cellular component movement biological process and PI3K-AKT pathway were enriched among these altered genomic regions. Taken together, the present study suggested that Feiyanning formula exerted the antitumor effects by modulating the expression and chromatin accessibility levels of migration-associated genes.
Meta-QTL Analysis in Rice and Cross-Genome Talk of the Genomic Regions Controlling Nitrogen Use Efficiency in Cereal Crops Revealing Phylogenetic Relationship
Authors: Sandhu Nitika , Pruthi Gomsie , Prakash Raigar Om , Singh Mohini Prabha , Phagna Kanika , Kumar Aman , Sethi Mehak , Singh Jasneet , Ade Pooja Ankush , Saini Dinesh Kumar
Published: December 2021

The phenomenal increase in the use of nitrogenous fertilizers coupled with poor nitrogen use efficiency is among the most important threats to the environment, economic, and social health. During the last 2 decades, a number of genomic regions associated with nitrogen use efficiency (NUE) and related traits have been reported by different research groups, but none of the stable and major effect QTL have been utilized in the marker-assisted introgression/pyramiding program. Compiling the data available in the literature could be very useful in identifying stable and major effect genomic regions associated with the root and NUE-related trait improving the rice grain yield. In the present study, we performed meta-QTL analysis on 1,330 QTL from 29 studies published in the past 2 decades. A total of 76 MQTL with a stable effect over different genetic backgrounds and environments were identified. The significant reduction in the confidence interval of the MQTL compared to the initial QTL resulted in the identification of annotated and putative candidate genes related to the traits considered in the present study. A hot spot region associated with correlated traits on chr 1, 4, and 8 and candidate genes associated with nitrate transporters, nitrogen content, and ammonium uptake on chromosomes 2, 4, 6, and 8 have been identified. The identified MQTL, putative candidate genes, and their orthologues were validated on our previous studies conducted on rice and wheat. The research-based interventions such as improving nitrogen use efficiencyviaidentification of major genomic regions and candidate genes can be a plausible, simple, and low-cost solution to address the challenges of the crop improvement program.
Chromosome-Level Assembly of the Southern Rock Bream (Oplegnathus fasciatus) Genome Using PacBio and Hi-C Technologies
Authors: Bai Yulin , Gong Jie , Zhou Zhixiong , Li Bijun , Zhao Ji , Ke Qiaozhen , Zou Xiaoqing , Pu Fei , Wu Linni , Zheng Weiqiang , Zhou Tao , Xu Peng
Published: December 2021

The Rock Bream (Oplegnathus fasciatus) is an economically important rocky reef fish of the Northwest Pacific Ocean. In recent years, it has been cultivated as an important edible fish in coastal areas of China. Despite its economic importance, genome-wide adaptions of domesticated O. fasciatus are largely unknown. Here we report a chromosome-level reference genome of female O. fasciatus (from the southern population in the subtropical region) using the PacBio single molecule sequencing technique (SMRT) and High-through chromosome conformation capture (Hi-C) technologies. The genome was assembled into 120 contigs with a total length of 732.95 Mb and a contig N50 length of 27.33 Mb. After chromosome-level scaffolding, 24 chromosomes with a total length of 723.22 Mb were constructed. Moreover, a total of 27,015 protein-coding genes and 5,880 ncRNAs were annotated in the reference genome. This reference genome of O. fasciatus will provide an important resource not only for basic ecological and population genetic studies but also for dissect artificial selection mechanisms in marine aquaculture.
A Combination of Deworming and Prime-Boost Vaccination Regimen Restores Efficacy of Vaccination Against Influenza in Helminth-Infected Mice
Authors: Stetter Nadine , Hartmann Wiebke , Brunn Marie-Luise , Stanelle-Bertram Stephanie , Gabriel Gülsah , Breloer Minka
Published: December 2021

Helminths still infect a quarter of the human population. They manage to establish chronic infections by downmodulating the immune system of their hosts. Consequently, the immune response of helminth-infected individuals to vaccinations may be impaired as well. Here we study the impact of helminth-induced immunomodulation on vaccination efficacy in the mouse system. We have previously shown that an underlying Litomosoides sigmodontis infection reduced the antibody (Ab) response to anti-influenza vaccination in the context of a systemic expansion of type 1 regulatory T cells (Tr1). Most important, vaccine-induced protection from a challenge infection with the 2009 pandemic H1N1 influenza A virus (2009 pH1N1) was impaired in vaccinated, L. sigmodontis-infected mice. Here, we aim at the restoration of vaccination efficacy by drug-induced deworming. Treatment of mice with Flubendazole (FBZ) resulted in elimination of viable L. sigmodontis parasites in the thoracic cavity after two weeks. Simultaneous FBZ-treatment and vaccination did not restore Ab responses or protection in L. sigmodontis-infected mice. Likewise, FBZ-treatment two weeks prior to vaccination did not significantly elevate the influenza-specific Ig response and did not protect mice from a challenge infection with 2009 pH1N1. Analysis of the regulatory T cell compartment revealed that L. sigmodontis-infected and FBZ-treated mice still displayed expanded Tr1 cell populations that may contribute to the sustained suppression of vaccination responses in successfully dewormed mice. To outcompete this sustained immunomodulation in formerly helminth-infected mice, we finally combined the drug-induced deworming with an improved vaccination regimen. Two injections with the non-adjuvanted anti-influenza vaccine Begripal conferred 60% protection while MF59-adjuvanted Fluad conferred 100% protection from a 2009 pH1N1 infection in FBZ-treated, formerly L. sigmodontis-infected mice. Of note, applying this improved prime-boost regimen did not restore protection in untreated L. sigmodontis-infected mice. In summary our findings highlight the risk of failed vaccinations due to helminth infection.
Activation and Functional Alteration of Mucosal-Associated Invariant T Cells in Adult Patients With Community-Acquired Pneumonia
Authors: Ouyang Lichen , Wu Mi , Shen Zhijun , Cheng Xue , Wang Wei , Jiang Lang , Zhao Juan , Gong Yeli , Liang Zhihui , Weng Xiufang , Yu Muqing , Wu Xiongwen
Published: December 2021

Community-acquired pneumonia (CAP) remains the significant infectious cause of morbidity and mortality worldwide. Although mucosal-associated invariant T cells (MAIT) play roles in the pathogenesis of children CAP and ICU-associated pneumonia, their roles in adult CAP are largely unexplored. In this study, we investigated the frequency, phenotype, and function of MAIT cells in peripheral blood and bronchoalveolar lavage fluid (BALF) of adult CAP patients. Our data indicate that MAIT-cell frequency is profoundly lower in the peripheral blood of CAP patients compared to that in healthy individuals. Furthermore, the circulatory MAIT cells express higher levels of CD69 and PD-1 compared to those in healthy individuals. In BALF of CAP patients, MAIT-cell frequency is higher and MAIT cells express higher levels of CD69 and PD-1 compared to their matched blood counterparts. Levels of IL-17A and IFN-γ are increased in BALF of CAP patients compared to those in BALF of patients with pulmonary small nodules. The IL-17A/IFN-γ ratio is significantly positively correlated with MAIT frequency in BALF of CAP patients, suggesting a pathogenic role of MAIT-17 cells in CAP. Of note, blood MAIT-cell frequency in CAP patients is strongly negatively correlated with high-sensitivity C-reactive protein (hsCRP) and neutrophil count percentage in blood. The ability of circulating MAIT cells in CAP patients to produce IFN-γ is significantly impaired compared to those in healthy individuals. In summary, our findings suggest the possible involvement of MAIT cells in the immunopathogenesis of adult CAP.
New Evidence of Gut Microbiota Involvement in the Neuropathogenesis of Bipolar Depression by TRANK1 Modulation: Joint Clinical and Animal Data
Authors: Lai Jianbo , Zhang Peifen , Jiang Jiajun , Mou Tingting , Li Yifan , Xi Caixi , Wu Lingling , Gao Xingle , Zhang Danhua , Chen Yiqing , Huang Huimin , Li Huijuan , Cai Xin , Li Ming , Zheng Peng , Hu Shaohua
Published: December 2021

Tetratricopeptide repeat and ankyrin repeat containing 1 (TRANK1) is a robust risk gene of bipolar disorder (BD). However, little is known on the role of TRANK1 in the pathogenesis of BD and whether the gut microbiota is capable of regulating TRANK1 expression. In this study, we first investigated the serum mRNA level of TRANK1 in medication-free patients with a depressive episode of BD, then a mice model was constructed by fecal microbiota transplantation (FMT) to explore the effects of gut microbiota on brain TRANK1 expression and neuroinflammation, which was further verified by in vitro Lipopolysaccharide (LPS) treatment in BV-2 microglial cells and neurons. 22 patients with a depressive episode and 28 healthy individuals were recruited. Serum level of TRANK1 mRNA was higher in depressed patients than that of healthy controls. Mice harboring ‘BD microbiota’ following FMT presented depression-like phenotype. mRNA levels of inflammatory cytokines and TRANK1 were elevated in mice hippocampus and prefrontal cortex. In vitro, LPS treatment activated the secretion of pro-inflammatory factors in BV-2 cells, which was capable of upregulating the neuronal expression of TRANK1 mRNA. Moreover, primary cortical neurons transfected with plasmid Cytomegalovirus DNA (pcDNA3.1(+)) vector encoding human TRANK1 showed decreased dendritic spine density. Together, these findings add new evidence to the microbiota-gut-brain regulation in BD, indicating that microbiota is possibly involved in the neuropathogenesis of BD by modulating the expression of TRANK1.
Peptides Derived From Mismatched Paternal Human Leukocyte Antigen Predicted to Be Presented by HLA-DRB1, -DRB3/4/5, -DQ, and -DP Induce Child-Specific Antibodies in Pregnant Women
Authors: Niemann Matthias , Matern Benedict M. , Spierings Eric , Schaub Stefan , Hönger Gideon
Published: December 2021

Predicted Indirectly ReCognizable Human Leukocyte Antigen (HLA) Epitopes (PIRCHE) are known to be a significant risk factor for the development of donor HLA-specific antibodies after organ transplantation. Most previous studies on PIRCHE limited their analyses on the presentation of the HLA-DRB1 locus, although HLA-DRB3/4/5, -DQ, and -DP are also known for presenting allopeptides to CD4+ T cells. In this study, we analyzed the impact of predicted allopeptides presented by these additional loci on the incidence of HLA-specific antibodies after an immunization event. We considered pregnancy as a model system of an HLA immunization and observed child-specific HLA antibody (CSA) development of 231 mothers during pregnancy by samples being taken at delivery. Our data confirm that PIRCHE presented by HLA-DRB1 along with HLA-DRB3/4/5, -DQ, and -DP are significant predictors for the development of CSA. Although there was limited peptidome overlap observed within the mothers’ presenting HLA proteins, combining multiple presenting loci in a single predictor improved the model only marginally. Prediction performance of PIRCHE further improved when normalizing scores by the respective presenters’ binding promiscuity. Immunogenicity analysis of specific allopeptides could not identify significant drivers of an immune response in this small cohort, suggesting confirmatory studies.