bluuebunny/crossref_metadata_2025 huggingface dataset:
Proteomic profiling and correlations with clinical features reveal biomarkers indicative of diabetic retinopathy with diabetic kidney disease
Authors: Fan Xiao’e , Xu Manhong , Chen Xin , Ren Qianfeng , Fan Yan , Wang Ranran , Chen Jiaqi , Cui Li , Wang Zhengmin , Sun Xiaoyan , Guo Nannan
Published: October 2022

Diabetic retinopathy (DR) and diabetic kidney disease (DKD) are complications of diabetes and place serious health and economic burdens on society. However, the identification and characterization of early biomarkers for DKD, especially for nonproliferative DR (NPDR) patients with DKD, are still needed. This study aimed to demonstrate the plasma proteomic profiles of NPDR+DKD and NPDR patients and identify potential biomarkers for early diagnosis of DKD. Fifteen plasma samples from the NPDR group and nine from the NPDR+DKD group were analyzed by LC−MS/MS to identify the differentially expressed proteins between the two groups. Functional enrichment, protein−protein interaction and clinical feature correlation analyses revealed the target protein candidates, which were verified using ELISA and receiver operating characteristic (ROC) analysis. In total, 410 proteins were detected in plasma; 15 were significantly upregulated and 7 were downregulated in the NPDR+DKD group. Bioinformatics analysis suggested that DKD is closely related to cell adhesion and immunity pathways. β-2-Microglobulin (B2M) and vimentin (VIM) were upregulated in NPDR+DKD, enriched as hub proteins and strongly correlated with clinical features. ELISA showed that B2M (p<0.001) and VIM (p<0.0001) were significantly upregulated in NPDR+DKD compared with NPDR. In ROC analysis, B2M and VIM could distinguish DKD from NPDR with area under the curve values of 0.9000 (p < 0.0001) and 0.9950. Our proteomic study revealed alterations in the proteomic profile and identified VIM and B2M as early biomarkers of DKD, laying the foundation for the prevention, diagnosis and treatment of DKD.
Influence of arginine vasopressin on the ultradian dynamics of Hypothalamic-Pituitary-Adrenal axis
Authors: Stojiljković Aleksandra S. , Čupić Željko , Maćešić Stevan , Ivanović-Šašić Ana , Kolar-Anić Ljiljana
Published: October 2022

Numerous studies on humans and animals have indicated that the corticotrophin-releasing hormone (CRH) and arginine vasopressin (AVP) stimulate both individually and synergistically secretion of adrenocorticotropic hormone (ACTH) by corticotropic cells in anterior pituitary. With aim to characterize and better comprehend the mechanisms underlying the effects of AVP on Hypothalamic-Pituitary-Adrenal (HPA) axis ultradian dynamics, AVP is here incorporated into our previously proposed stoichiometric model of HPA axis in humans. This extended nonlinear network reaction model took into account AVP by: reaction steps associated with two separate inflows of AVP into pituitary portal system, that is synthesized and released from hypothalamic parvocellular and magnocellular neuronal populations, as well as summarized reaction steps related to its individual and synergistic action with CRH on corticotropic cells. To explore the properties of extended model and its capacity to emulate the effects of AVP, nonlinear dynamical systems theory and bifurcation analyses based on numerical simulations were utilized to determine the dependence of ultradian oscillations on rate constants of the inflows of CRH and AVP from parvocellular neuronal populations, the conditions under which dynamical transitions occur due to their synergistic action and, moreover, the types of these transitions. The results show that under certain conditions, HPA system could enter into oscillatory dynamic states from stable steady state and vice versa under the influence of synergy reaction rate constant. Transitions between these dynamical states were always through supercritical Andronov-Hopf bifurcation point. Also, results revealed the conditions under which amplitudes of ultradian oscillations could increase several-fold due to CRH and AVP synergistic stimulation of ACTH secretion in accordance with results reported in the literature. Moreover, results showed experimentally observed superiority of CRH as a stimulator of ACTH secretion compared to AVP in humans. The proposed model can be very useful in studies related to the role of AVP and its synergistic action with CRH in life-threatening circumstances such as acute homeostasis dynamic crisis, autoimmune inflammations or severe hypovolemia requiring instant or several-days sustained corticosteroid excess levels. Moreover, the model can be helpful for investigations of indirect AVP-induced HPA activity by exogenously administered AVP used in therapeutic treatment.
Effect of COVID-19 pandemic on diagnosis and treatment of thyroid cancer in Brazil
Authors: Silveira Vitor Bock , Schwengber Wallace Klein , Hetzel Guilherme Moreira , Zanella André B. , Scheffel Rafael Selbach , Maia Ana Luiza , Dora Jose Miguel
Published: October 2022

Introduction

The COVID-19 pandemic delayed the diagnosis, treatment, and follow-up visits of patients with thyroid cancer. However, the magnitude with which these restrictions affected the Brazilian health care is still unknown.

Methods

Retrospective analysis of thyroid cancer-related procedures performed in the Brazilian public health system from 2019 to 2021. Data were retrieved from the Department of Informatics of the Unified Health System (DATASUS). The following procedures were evaluated: fine-needle aspiration biopsies (FNABs), oncologic thyroidectomies, and radioiodine (RAI) therapies for thyroid cancer. The year of 2019 served as baseline control.

Results

Compared with 2019, FNABs, oncologic thyroidectomies, and RAI therapies performed in 2020 decreased by 29%, 17% and 28%, respectively. In 2021, compared with 2019, FNABs increased by 2%, and oncologic thyroidectomies and RAI therapies decreased by 5% and 25%, respectively. Most pronounced reductions were observed in the first months of the pandemic. In April 2020, FNABs decreased by 67%, oncologic thyroidectomies by 45%, and RAI therapies by 75%. In 2021, RAI therapies were the only procedure with a statistically significant decrease.

Conclusion

The restrictions to public health care during the COVID-19 pandemic resulted in a significant reduction in diagnostic and treatment procedures for thyroid cancer in Brazil. The effects of these transitory gaps in thyroid cancer care, due to COVID-19, are still unclear.
Why do consumers buy recycled shoes? An amalgamation of the theory of reasoned action and the theory of planned behaviour
Authors: Yadav Sher Singh , Kar Sanjay Kumar , Rai Prashant Kumar
Published: October 2022

The footwear industry’s transition to a circular economy is a essential for sustainable development. The emerging recycled shoe production may lead to sustainable consumption in the footwear industry. Consumers are now more cognizant of the negative effects of their shopping choices. We studied the factors influencing consumers’ intentions of buying recycled shoes. We applied the theory of reasoned action (TRA) and the theory of planned behaviour (TPB). As this is an emerging trend, there is a dearth of sufficient literature regarding sustainable recycled shoe purchase behaviour. We aimed to fill this broad gap with this empirical research. We found that perceived environmental knowledge, subjective norms, sustainable label awareness, and shoe choice motives influenced attitude, and attitude, word of mouth, and environmental consciousness shaped purchase intentions. Sustainable label awareness, shoe surplus, and purchase intentions affected purchase behaviour. The study is beneficial for policymakers and managers of companies for making decisions related to footwear product positioning and targeting.
Spatially varying impacts of the built environment on physical activity from a human-scale view: Using street view data
Authors: Luo Pinyang , Yu Bingjie , Li Pengfei , Liang Pengpeng
Published: October 2022

Developing evidence-based planning interventions for promoting physical activity (PA) is considered an effective way to address urban public health issues. However, previous studies exploring how the built environment affects PA over-relied on small-sample survey data, lacked human-centered measurements of the built environment, and overlooked spatially-varying relationships. To fill these gaps, we use cycling and running activity trajectories derived from the Strava crowdsourcing data to comprehensively measure PA in the central city area of Chengdu, China. Meanwhile, we introduce a set of human-scale, eye-level built environment factors such as green, sky, and road view indexes by extracting streetscape characteristics from the Baidu street-view map using the fully Convolutional Neural Network (CNN). Based on these data, we utilize the geographically weighted regression (GWR) model to scrutinize the spatially heterogeneous impact of the built environment on PA. The results are summarized as follows: First, model comparisons show that GWR models outperform global models in terms of the goodness-of-fit, and most built environment factors have spatially varying impacts on cycling and running activities. Second, the green view index restrains cycling activities in general. In contrast, it has a wide-ranging and positive impact on running activities while hampers them in the PA-unfriendly old town. Third, the sky view index stimulates cycling activities in most areas. However, it has a mixed influence on running activities. Fourth, the road view index widely promotes cycling and running activities but hinders them in some areas of the old town dominated by automobiles and under construction. Finally, according to these empirical findings, we propose several recommendations for PA-informed planning initiatives.
Investment merger efficiency evaluation of energy enterprises: From a perspective of energy internet
Authors: Deng Yirui , Cao Guiling , Wei Zhifei , Xu Xiaofeng , Ma Li , Gao Guowei
Published: October 2022

Evaluating the efficiency of energy enterprises’ investment merger in the energy Internet sector can be a visual measure of the effectiveness of their investment merger in this sector. It is crucial for energy enterprises to achieve strategic transformation and expand their market share. To this end, this study aims to investigate the efficiency of energy enterprises’ investment merger in the energy Internet sector by constructing an efficiency evaluation index system and evaluation model with the characteristics of the sector. Based on which the TOPSIS model is used to distinguish the differences in the efficiency of the same enterprises’ investment merger in different years. The results of the validation on international power enterprises show that the size of the enterprise has an important influence on its investment merger efficiency in this field. In addition, the evaluation index system and method constructed prove to be effective in evaluating and differentiating the annual investment merger efficiency of energy enterprises in the energy Internet field.
Iron-copper interaction in soil spectra and its effect on the estimation of copper content
Authors: Feng Zhijun , Zhang Shiwen , Yang Bin , Zhou Tao , Rui Tingting
Published: October 2022

It is important to clarify the iron-copper interaction pattern to effectively extract the characteristic bands and improve the inversion accuracy of copper content in soil. In this study, based on experimental samples, spectral feature analysis and analysis of variance (ANOVA) were used to deeply uncover the iron-copper interaction pattern. And used natural samples to build a random forest model to analyze the effect of interaction patterns on inversion accuracy. The results of the study showed that the effect of iron content in soil on spectral reflectance varied with copper content in soil, and similarly, the effect of copper content in soil on spectral reflectance varied with iron content in soil. The effect of iron, copper and their interaction on the spectral reflectance of soil varied with the wavelength. In the wavelength from 400 to 2,500 nm, the effect of iron on the spectral features was more than copper, and in the characteristic wavelength of iron (600–700 nm), even more than 5 times that of copper, the effect of iron on the spectral reflectance played a major role, and the iron content in soil must be considered in the inversion of copper content in soil. The Pearson correlation coefficient method was used as the selected characteristic wavelength, the selected wavelength was used as the independent variable, and the copper content in the soil was the dependent variable. Inversion model was built by the random forest algorithm, and the determination coefficient was 0.73. Under the condition of considering the interaction, the coefficient of determination was 0.87. It was shown that the characteristic wavelength was selected by considering the iron-copper interaction, which can better characterize the response signal of copper in soil. This paper provided a new idea for the accurate inversion of copper content in soil, which can provide technical support for the rapid detection of copper content in soil.
An empirical mediation analysis of technological innovation based on artificial intelligence in the relationship between economic development and corporate governance mechanism
Authors: Khan Muhammad Anees , Mazliham M. S. , Alam Muhammad Mansoor , Aman Nida , Malik Sakshi , Urooj Syeda Faiza , Taj Tanveer
Published: October 2022

Although strong recommendations and steps have been developed and taken to adopt the latest technological trend through corporate governance reforms for improving the economic development, however, the trend toward adopting the latest technology has not been adopted and thus has remained a big issue in the non-financial sector for the last two decades around the globe. The study used GLS (random effect) regression estimator to a sample composed of 1600 firm-year observations from 2017 to 2021. The findings indicated that the majority of the firms were involved in an income-decreasing economic situation. Moreover, the findings evidenced that compliance with some specific CG attributes welcomed the technological innovation and significantly had an impact on the economic development. However, some CG attributes of the models did not play any significant role in technological innovation and economic development which needs improvement. Moreover, this study also evidenced that the impact of CG attributes is not directly affecting economic development but is mediated by the technological innovation, which is of importance to managers of a firm, who hold responsibility for investing and financing activities. In addition, this study revealed a fully significant mediating role of technological innovation in the relationship of BOD meetings, audit committee size, managerial ownership, and foreign ownership with economic development. However, no significant mediating role of technological innovation was observed in the relationship of independent BOD and economic development. All in all, the results of this study have significance for regulatory bodies, researchers, academic researchers, practitioners, publicly listed companies in Malaysia, the Bursa Malaysia and the security commission to uplift their financial performance and curb EM activities through the effective use of CG mechanisms.
Ethnic density and area-deprivation effects on central obesity among ethnic minority people in England—A cross-sectional, multi-level analysis
Authors: Higgins Vanessa
Published: October 2022

Background

Central obesity is a risk factor for many health conditions, and it disproportionately affects some ethnic minority groups. Research has shown that there is an association between area environments and obesity, but no studies have explored the association between co-ethnic density and central obesity in the UK (United Kingdom). This paper addresses the following research question: Does the relationship between co-ethnic density/area deprivation and waist circumference differ by ethnic group in England?

Methods

Data come from 4 years of the cross-sectional Health Survey for England (1998, 1999, 2003, 2004) and linked area-level data from the 2001 Census. More recent data on objectively measured central obesity for a nationally representative sample of ethnic minorities does not exist. Multi-level modeling methods account for individual-level and area-level factors. Interaction models test the effect of area deprivation and co-ethnic density for each ethnic group compared with the White reference group.

Results

For women, the relationship between area deprivation and waist circumference does not vary by ethnic group. For Indian and Bangladeshi men there is a decrease in waist circumference as area deprivation increases. There is an increase in waist circumference as co-ethnic density increases for Black Caribbean women. For Indian men there is a decrease in waist circumference as co-ethnic density increases.

Conclusions

Further research is needed to understand the mechanisms through which (1) increasing area-deprivation is protective for Indian and Bangladeshi men and (2) increasing co-ethnic density is associated with an increase in waist circumference for Black Caribbean women but a decrease in waist circumference among Indian men. Each of these results are important because (1) Indian and Bangladeshi men have an increased risk of the metabolic syndrome, which is linked to central obesity, and (2) Black Caribbean women have a higher risk of central obesity than the general population in England.
The many definitions of multiplicity of infection
Authors: Schneider Kristan Alexander , Tsoungui Obama Henri Christian Junior , Kamanga George , Kayanula Loyce , Adil Mahmoud Yousif Nessma
Published: October 2022

The presence of multiple genetically different pathogenic variants within the same individual host is common in infectious diseases. Although this is neglected in some diseases, it is well recognized in others like malaria, where it is typically referred to as multiplicity of infection (MOI) or complexity of infection (COI). In malaria, with the advent of molecular surveillance, data is increasingly being available with enough resolution to capture MOI and integrate it into molecular surveillance strategies. The distribution of MOI on the population level scales with transmission intensities, while MOI on the individual level is a confounding factor when monitoring haplotypes of particular interests, e.g., those associated with drug-resistance. Particularly, in high-transmission areas, MOI leads to a discrepancy between the likelihood of a haplotype being observed in an infection (prevalence) and its abundance in the pathogen population (frequency). Despite its importance, MOI is not universally defined. Competing definitions vary from verbal ones to those based on concise statistical frameworks. Heuristic approaches to MOI are popular, although they do not mine the full potential of available data and are typically biased, potentially leading to misinferences. We introduce a formal statistical framework and suggest a concise definition of MOI and its distribution on the host-population level. We show how it relates to alternative definitions such as the number of distinct haplotypes within an infection or the maximum number of alleles detectable across a set of genetic markers. It is shown how alternatives can be derived from the general framework. Different statistical methods to estimate the distribution of MOI and pathogenic variants at the population level are discussed. The estimates can be used as plug-ins to reconstruct the most probable MOI of an infection and set of infecting haplotypes in individual infections. Furthermore, the relation between prevalence of pathogenic variants and their frequency (relative abundance) in the pathogen population in the context of MOI is clarified, with particular regard to seasonality in transmission intensities. The framework introduced here helps to guide the correct interpretation of results emerging from different definitions of MOI. Especially, it excels comparisons between studies based on different analytical methods.
Cuproptosis-related immune checkpoint gene signature: Prediction of prognosis and immune response for hepatocellular carcinoma
Authors: Cong Tianhao , Luo Yingen , Liu Yu , Yang Chao , Yang Hongcai , Li Yujie , Li Jingui , Li Xiao
Published: October 2022

Immune checkpoint genes (ICGs), the foundation of immunotherapy, are involved in the incidence and progression of hepatocellular carcinoma (HCC). Cuproptosis is characterized by copper-induced cell death, and this novel cell death pathway has piqued the interest of researchers in recent years. It is worth noting that there is little information available in the literature to determine the relationship between cuproptosis and anti-tumor immunity. We identified 39 cuproptosis-related ICGs using ICGs co-expressed with cuproptosis-related genes. A prognostic risk signature was constructed using the Cox regression and the least absolute shrinkage and selection operator analysis methods. The signature was built using the Cancer Genome Atlas (TCGA)-Liver Hepatocellular Carcinoma database. The TCGA and International Cancer Genome Consortium cohorts were classified into two groups; the low- and high-risk groups were determined using a prognostic signature comprised of five genes. The multivariate Cox regression analysis revealed that the signature could independently predict overall survival. Furthermore, the level of immune infiltration analysis revealed the robustness of the prognostic signature-immune cell infiltration relationship observed for Tregs, macrophages, helper T cells, and naive B cells. Both groups showed significant differences in immune checkpoint expression levels. The gene enrichment analysis was used for characterization, and the results revealed that enriching various pathways such as PI3K-AKT-mTOR signaling, glycolysis, Wnt/beta-catenin signaling, and unfolded protein response could potentially influence the prognosis of patients with HCC and the level of immune infiltration. The sensitivity of the two groups of patients to various drug-targeted therapy methods and immunotherapy was analyzed. In conclusion, the findings presented here lay the foundation for developing individualized treatment methods for HCC patients. The findings also revealed that studying the cuproptosis-based pathway can aid in the prognosis of HCC patients. It is also possible that cuproptosis contributes to developing anti-tumor immunity in patients.
GAHP: An integrated software package on genetic analysis with bi-parental immortalized heterozygous populations
Authors: Zhang Luyan , Wang Xinhui , Wang Kaiyi , Wang Jiankang
Published: October 2022

GAHP is a freely available software package for genetic analysis with bi-parental immortalized heterozygous and pure-line populations. The package is project-based and integrated with multiple functions. All operations and running results are properly saved in a project, which can be recovered when the project is re-open by the package. Four functionalities have been implemented in the current version of GAHP, i.e., 1) MHP: visualization of genetic linkage maps; 2) VHP: analysis of variance (ANOVA) and estimation of heritability on phenotypic data; 3) QHP: quantitative trait locus (QTL) mapping on both genotypic and phenotypic data; 4) SHP: simulation of bi-parental immortalized heterozygous and pure-line populations, and power analysis of QTL mapping. VHP and QHP can be conducted in individual populations, as well as in multiple populations by the combined analysis. Input files are arranged either in the plain text format with an extension name same as the functionality or in the MS Excel formats. Output files have the same prefix name as the input file, but with different extensions to indicate their contents. Three characters before the extension names stand for the types of populations used in analysis. In the interface of the software package, input files are grouped by functionality, and output files are grouped by individual or combined mapping populations. In addition to the text-format outputs, the constructed linkage map can be visualized per chromosome or for a number of selected chromosomes; line plots and bi-plots can be drawn from QTL mapping results and phenotypic data. Functionalities and analysis methods available in GAHP help the investigation of genetic architectures of complex traits and the mechanism of heterosis in plants.
Effect of ribose-glycated BSA on histone demethylation
Authors: Xi Mengqi , Zhang Lingyun , Wei Yan , Li Ting , Qu Meihua , Hua Qian , He Rongqiao , Liu Ying
Published: October 2022

A reducing sugar reacts with the protein, resulting in advanced glycation end-products (AGEs), which have been implicated in diabetes-related complications. Recently, it has been found that both type 1 and type 2 diabetic patients suffer from not only glucose but also ribose dysmetabolism. Here, we compared the effects of ribose and glucose glycation on epigenetics, such as histone methylation and demethylation. To prepare ribose-glycated (riboglycated) proteins, we incubated 150 μM bovine serum albumin (BSA) with 1 M ribose at different time periods, and we evaluated the samples by ELISAs, Western blot analysis, and cellular experiments. Riboglycated BSA, which was incubated with ribose for approximately 7 days, showed the strongest cytotoxicity, leading to a significant decrease in the viability of SH-SY5Y cells cultured for 24 h (IC50 = 1.5 μM). A global demethylation of histone 3 (H3K4) was observed in SH-SY5Y cells accompanied with significant increases in lysine-specific demethylase-1 (LSD1) and plant homeodomain finger protein 8 (PHF8) after treatment with riboglycated BSA (1.5 μM), but demethylation did not occur after treatment with glucose-glycated (glucoglycated) proteins or the ribose, glucose, BSA, and Tris–HCl controls. Moreover, a significant demethylation of H3K4, H3K4me3, and H3K4me2, but not H3K4me1, occurred in the presence of riboglycated proteins. A significant increase of formaldehyde was also detected in the medium of SH-SY5Y cells cultured with riboglycated BSA, further indicating the occurrence of histone demethylation. The present study provides a new insight into understanding an epigenetic mechanism of diabetes mellitus (DM) related to ribose metabolic disorders.
Whole-transcriptome sequencing and ceRNA interaction network of temporomandibular joint osteoarthritis
Authors: Wu Fan , An Yanxin , Zhou Libo , Zhao Yuqing , Chen Lei , Wang Jing , Wu Gaoyi
Published: October 2022

Purpose: The aim of this study was to conduct a comprehensive transcriptomic analysis to explore the potential biological functions of noncoding RNA (ncRNAs) in temporomandibular joint osteoarthritis (TMJOA).

Methods: Whole transcriptome sequencing was performed to identify differentially expressed genes (DEGs) profiles between the TMJOA and normal groups. The functions and pathways of the DEGs were analyzed using Metascape, and a competitive endogenous RNA (ceRNA) network was constructed using Cytoscape software.

Results: A total of 137 DEmRNAs, 65 DEmiRNAs, 132 DElncRNAs, and 29 DEcircRNAs were identified between the TMJOA and normal groups. Functional annotation of the DEmRNAs revealed that immune response and apoptosis are closely related to TMJOA and also suggested key signaling pathways related to TMJOA, including chronic depression and PPAR signaling pathways. We identified vital mRNAs, including Klrk1, Adipoq, Cryab, and Hspa1b. Notably, Adipoq expression in cartilage was significantly upregulated in TMJOA compared with normal groups (10-fold, p < 0.001). According to the functional analysis of DEmRNAs regulated by the ceRNA network, we found that ncRNAs are involved in the regulation of autophagy and apoptosis. In addition, significantly DEncRNAs (lncRNA-COX7A1, lncRNA-CHTOP, lncRNA-UFM1, ciRNA166 and circRNA1531) were verified, and among these, circRNA1531 (14.5-fold, p < 0.001) and lncRNA-CHTOP (14.8-fold, p < 0.001) were the most significantly downregulated ncRNAs.

Conclusion: This study showed the potential of lncRNAs, circRNAs, miRNAs, and mRNAs may as clinical biomarkers and provides transcriptomic insights into their functional roles in TMJOA. This study identified the transcriptomic signatures of mRNAs associated with immunity and apoptosis and the signatures of ncRNAs associated with autophagy and apoptosis and provides insight into ncRNAs in TMJOA.
A sequence-based 163plex microhaplotype assay for forensic DNA analysis
Authors: Tao Ruiyang , Yang Qi , Xia Ruocheng , Zhang Xiaochun , Chen Anqi , Li Chengtao , Zhang Suhua
Published: October 2022

Novel genetic marker microhaplotype has led to an upsurge in forensic genetic research. This study established a 163 microhaplotype (MH) multiplex assay based on next-generation sequencing (NGS) and evaluated the assay’s performance and applicability. Our results showed that the 163 MH assay was accurate, repeatable and reliable, and could distinguish between African, European-American, Southern Asia and Eastern Asia populations. Among the 163 MH makers, 48 MHs with Ae > 3.0 in China Eastern Han were selected and confirmed to be highly polymorphic, with a combined power of discrimination of 1–8.26 × 10–44 and the combined power of exclusion in duos and trios of 1–1.26 × 10–8 and 1–8.27 × 10–16, respectively. Moreover, the mixture study demonstrated the realizability of the MHs in deconvoluting mixtures with different proportions of two to five-person. In conclusion, our findings support the use of this MH assay for ancestry inference, human identification, paternity testing and mixture deconvolution in forensic research.
Signals of adaptation to agricultural stress in the genomes of two European bumblebees
Authors: Hart Alex F. , Verbeeck Jaro , Ariza Daniel , Cejas Diego , Ghisbain Guillaume , Honchar Hanna , Radchenko Vladimir G. , Straka Jakub , Ljubomirov Toshko , Lecocq Thomas , Dániel-Ferreira Juliana , Flaminio Simone , Bortolotti Laura , Karise Reet , Meeus Ivan , Smagghe Guy , Vereecken Nicolas , Vandamme Peter , Michez Denis , Maebe Kevin
Published: October 2022

Human-induced environmental impacts on wildlife are widespread, causing major biodiversity losses. One major threat is agricultural intensification, typically characterised by large areas of monoculture, mechanical tillage, and the use of agrochemicals. Intensification leads to the fragmentation and loss of natural habitats, native vegetation, and nesting and breeding sites. Understanding the adaptability of insects to these changing environmental conditions is critical to predicting their survival. Bumblebees, key pollinators of wild and cultivated plants, are used as model species to assess insect adaptation to anthropogenic stressors. We investigated the effects of agricultural pressures on two common European bumblebees, Bombus pascuorum and B. lapidarius. Restriction-site Associated DNA Sequencing was used to identify loci under selective pressure across agricultural-natural gradients over 97 locations in Europe. 191 unique loci in B. pascuorum and 260 in B. lapidarius were identified as under selective pressure, and associated with agricultural stressors. Further investigation suggested several candidate proteins including several neurodevelopment, muscle, and detoxification proteins, but these have yet to be validated. These results provide insights into agriculture as a stressor for bumblebees, and signal for conservation action in light of ongoing anthropogenic changes.
Matrix metalloproteinase 7 contributes to intestinal barrier dysfunction by degrading tight junction protein Claudin-7
Authors: Xiao Ying , Lian Haifeng , Zhong Xiaoying S. , Krishnachaitanya Srikruthi S. , Cong Yingzi , Dashwood Roderick H. , Savidge Tor C. , Powell Don W. , Liu Xiaowei , Li Qingjie
Published: October 2022

Background

Previous studies implicated matrix metalloproteinases (MMPs), such as MMP-7, in inflammatory bowel diseases (IBD) by showing increased activity during inflammation of the gut. However, the pathophysiological roles of MMP-7 have not been clearly elucidated.

Methods

The expression of MMP-7 was assessed in colonic biopsies of patients with ulcerative colitis (UC), in rodents with experimental colitis, and in cell-based assays with cytokines. Wild-type and MMP-7-null mice treated with dextran sulfate sodium (DSS) or trinitrobenzene sulfonic acid were used for determining the pro-inflammatory function(s) of MMP-7 in vivo.

Results

MMP-7 was highly expressed in patients with UC and in rodents with experimental colitis. IL-1β, IL-4, IL-13, TNFα, or lipopolysaccharide enhanced MMP-7 expression in human colonic epithelial cells, rat colonic smooth muscle cells, and THP-1-derived macrophages. Active MMP-7 degraded tight junction protein Claudin-7 in epithelial cells, cleaved recombinant Claudin-7 in cell-free system, and increased Caco-2 monolayer permeability. Immunostaining of colon biopsies revealed up-regulation of MMP-7 and reduction of Claudin-7 in UC patients. Compared to wild-type mice, Mmp7-/- mice had significantly less inflammation in the colon upon DSS insult. DSS-induced alterations in junction proteins were mitigated in Mmp7-/- mice, suggesting that MMP-7 disrupts the intestinal barrier. MMP-7 antibody significantly ameliorated colonic inflammation and Claudin-7 reduction in 2 different rodent models of colitis.

MMP-7 impairs intestinal epithelial barrier by cleavage of Claudin-7, and thus aggravating inflammation. These studies uncovered Claudin-7 as a novel substrate of MMP-7 in the intestinal epithelium and reinforced MMP-7 as a potential therapeutic target for IBD.
System-wide identification of myeloid markers of TB disease and HIV-induced reactivation in the macaque model of Mtb infection and Mtb/SIV co-infection
Authors: Gough Maya , Singh Dhiraj K. , Singh Bindu , Kaushal Deepak , Mehra Smriti
Published: October 2022

Mycobacterium tuberculosis (Mtb) has developed specialized mechanisms to parasitize its host cell, the macrophage. These mechanisms allow it to overcome killing by oxidative burst and persist in the wake of an inflammatory response. Mtb infection in the majority of those exposed is controlled in an asymptomatic form referred to as latent tuberculosis infection (LTBI). HIV is a well-known catalyst of reactivation of LTBI to active TB infection (ATB). Through the use of nonhuman primates (NHPs) co-infected with Mtb and Simian Immunodeficiency Virus (Mtb/SIV), we are able to simulate human progression of TB/AIDS comorbidity. The advantage of NHP models is that they recapitulate the breadth of human TB outcomes, including immune control of infection, and loss of this control due to SIV co-infection. Identifying correlates of immune control of infection is important for both vaccine and therapeutics development. Using macaques infected with Mtb or Mtb/SIV and with different clinical outcomes we attempted to identify signatures between those that progress to active infection after SIV challenge (reactivators) and those that control the infection (non-reactivators). We particularly focused on pathways relevant to myeloid origin cells such as macrophages, as these innate immunocytes have an important contribution to the initial control or the lack thereof, following Mtb infection. Using bacterial burden, C-reactive protein (CRP), and other clinical indicators of disease severity as a guide, we were able to establish gene signatures of host disease state and progression. In addition to gene signatures, clustering algorithms were used to differentiate between host disease states and identify relationships between genes. This allowed us to identify clusters of genes which exhibited differential expression profiles between the three groups of macaques: ATB, LTBI and Mtb/SIV. The gene signatures were associated with pathways relevant to apoptosis, ATP production, phagocytosis, cell migration, and Type I interferon (IFN), which are related to macrophage function. Our results suggest novel macrophage functions that may play roles in the control of Mtb infection with and without co-infection with SIV. These results particularly point towards an interplay between Type I IFN signaling and IFN-γ signaling, and the resulting impact on lung macrophages as an important determinant of progression to TB.
Prognostic impact of the controlling nutritional status score in patients with hematologic malignancies: A systematic review and meta-analysis
Authors: Lu Chuanyang , Chen Qiuni , Fei Linrong , Wang Junhui , Wang Chunling , Yu Liang
Published: October 2022

Background

An increasing number of studies have validated the prognostic significance of the controlling nutritional status (CONUT) score in patients with solid tumors. However, the extent of the correlation between the CONUT score and clinical outcomes of patients with hematologic malignancies is unclear.

Objective

This study aimed to investigate the prognostic role of the CONUT score in patients with hematologic malignancies.

Methods

All relevant articles published up to November 15, 2021, were identified by systematically searching PubMed, Embase, Web of Science, and Cochrane Library. Pooled hazard ratios (HRs) and 95% confidence intervals were used to quantitatively analyze the association between the CONUT scores and clinical outcomes of patients with hematologic malignancies. Subgroup and sensitivity analyses were performed. Funnel plots as well as Begg’s and Egger’s tests were used to assess publication bias.

Results

Six studies with 1811 patients were included in the meta-analysis. The results showed that a high CONUT score was associated with worse overall survival (OS) (HR=1.34, 95%CI 1.14-1.59, P < 0.001) and progression-free survival (PFS) (HR=1.20, 95%CI 1.10-1.32, P < 0.001).

Conclusions

The CONUT score is an independent prognostic factor in patients with hematologic malignancies.

Systematic review registration

http://www.crd.york.ac.uk/prospero/, identifier CRD42021292621.
Pulmonary hypertension: Linking inflammation and pulmonary arterial stiffening
Authors: Liu Shao-Fei , Nambiar Veetil Netra , Li Qiuhua , Kucherenko Mariya M. , Knosalla Christoph , Kuebler Wolfgang M.
Published: October 2022

Pulmonary hypertension (PH) is a progressive disease that arises from multiple etiologies and ultimately leads to right heart failure as the predominant cause of morbidity and mortality. In patients, distinct inflammatory responses are a prominent feature in different types of PH, and various immunomodulatory interventions have been shown to modulate disease development and progression in animal models. Specifically, PH-associated inflammation comprises infiltration of both innate and adaptive immune cells into the vascular wall of the pulmonary vasculature—specifically in pulmonary vascular lesions—as well as increased levels of cytokines and chemokines in circulating blood and in the perivascular tissue of pulmonary arteries (PAs). Previous studies suggest that altered hemodynamic forces cause lung endothelial dysfunction and, in turn, adherence of immune cells and release of inflammatory mediators, while the resulting perivascular inflammation, in turn, promotes vascular remodeling and the progression of PH. As such, a vicious cycle of endothelial activation, inflammation, and vascular remodeling may develop and drive the disease process. PA stiffening constitutes an emerging research area in PH, with relevance in PH diagnostics, prognostics, and as a therapeutic target. With respect to its prognostic value, PA stiffness rivals the well-established measurement of pulmonary vascular resistance as a predictor of disease outcome. Vascular remodeling of the arterial extracellular matrix (ECM) as well as vascular calcification, smooth muscle cell stiffening, vascular wall thickening, and tissue fibrosis contribute to PA stiffening. While associations between inflammation and vascular stiffening are well-established in systemic vascular diseases such as atherosclerosis or the vascular manifestations of systemic sclerosis, a similar connection between inflammatory processes and PA stiffening has so far not been addressed in the context of PH. In this review, we discuss potential links between inflammation and PA stiffening with a specific focus on vascular calcification and ECM remodeling in PH.
Revealing the novel autophagy-related genes for ligamentum flavum hypertrophy in patients and mice model
Authors: Li Peng , Fei Cheng-shuo , Chen Yan-lin , Chen Ze-sen , Lai Zhong-ming , Tan Rui-qian , Yu Yong-peng , Xiang Xin , Dong Jia-le , Zhang Jun-xiong , Wang Liang , Zhang Zhong-min
Published: October 2022

Background

Fibrosis is a core pathological factor of ligamentum flavum hypertrophy (LFH) resulting in degenerative lumbar spinal stenosis. Autophagy plays a vital role in multi-organ fibrosis. However, autophagy has not been reported to be involved in the pathogenesis of LFH.

Methods

The LFH microarray data set GSE113212, derived from Gene Expression Omnibus, was analyzed to obtain differentially expressed genes (DEGs). Potential autophagy-related genes (ARGs) were obtained with the human autophagy regulator database. Functional analyses including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, Gene Set Enrichment Analysis (GSEA), and Gene Set Variation Analysis (GSVA) were conducted to elucidate the underlying biological pathways of autophagy regulating LFH. Protein-protein interaction (PPI) network analyses was used to obtain hub ARGs. Using transmission electron microscopy, quantitative RT-PCR, Western blotting, and immunohistochemistry, we identified six hub ARGs in clinical specimens and bipedal standing (BS) mouse model.

Results

A total of 70 potential differentially expressed ARGs were screened, including 50 up-regulated and 20 down-regulated genes. According to GO enrichment and KEGG analyses, differentially expressed ARGs were mainly enriched in autophagy-related enrichment terms and signaling pathways related to autophagy. GSEA and GSVA results revealed the potential mechanisms by demonstrating the signaling pathways and biological processes closely related to LFH. Based on PPI network analysis, 14 hub ARGs were identified. Using transmission electron microscopy, we observed the autophagy process in LF tissues for the first time. Quantitative RT-PCR, Western blotting, and immunohistochemistry results indicated that the mRNA and protein expression levels of FN1, TGFβ1, NGF, and HMOX1 significantly higher both in human and mouse with LFH, while the mRNA and protein expression levels of CAT and SIRT1 were significantly decreased.

Conclusion

Based on bioinformatics analysis and further experimental validation in clinical specimens and the BS mouse model, six potential ARGs including FN1, TGFβ1, NGF, HMOX1, CAT, and SIRT1 were found to participate in the fibrosis process of LFH through autophagy and play an essential role in its molecular mechanism. These potential genes may serve as specific therapeutic molecular targets in the treatment of LFH.
Association between immunosuppressants and poor antibody responses to SARS-CoV-2 vaccines in patients with autoimmune liver diseases
Authors: Li Hu , Wang Yuting , Ao Ling , Ke Mingxia , Chen Zhiwei , Chen Min , Peng Mingli , Ling Ning , Hu Peng , Cai Dachuan , Zhang Dazhi , Ren Hong
Published: October 2022

The antibody and B cell responses after inactivated SARS-CoV-2 vaccination have not been well documented in patients with autoimmune liver disease (AILD). Therefore, we conducted a prospective observational study that included AILD patients and healthy participants as controls between July 1, 2021, and September 30, 2021, at the Second Affiliated Hospital of Chongqing Medical University. All adverse events (AEs) after the COVID-19 vaccination were recorded and graded. Immunoglobulin (Ig)-G antibodies against the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein (anti-RBD-IgG) and neutralizicadng antibodies (NAbs) were tested following full-course vaccination (BBIBP-CorV or CoronaVac). In addition, SARS-CoV-2-specific B cells were detected by flow cytometry. In total, 76 AILD patients and 136 healthy controls (HCs) were included. All AEs were mild and self-limiting, and the incidences were similar between the AILD and HCs. The seropositivity rates of anti-RBD-IgG and NAbs in AILD were 97.4% (100% in HCs, p = 0.13) and 63.2% (84.6% in HCs, p < 0.001), respectively. The titers of anti-RBD-IgG and NAbs were significantly lower in AILD patients than those in HCs. After adjusting for confounders, immunosuppressive therapy was an independent risk factor for low-level anti-RBD-IgG (adjusted odds ratio [aOR]: 4.7; 95% confidence interval [CI], 1.5-15.2; p = 0.01) and a reduced probability of NAbs seropositivity (aOR, 3.0; 95% CI, 1.0-8.9; p = 0.04) in AILD patients. However, regardless of immunosuppressants, the SARS-CoV-2-specific memory B cells responses were comparable between the AILD and HC groups. Our results suggest that inactivated SARS-CoV-2 vaccines (BBIBP-CorV and CoronaVac) are safe, but their immunogenicity is compromised in patients with AILD. Moreover, immunosuppressants are significantly associated with poor antibody responses to the SARS-CoV-2 vaccines. These results could inform physicians and policymakers about decisions on screening the populations at higher risk of poor antibody responses to SARS-CoV-2 vaccines and providing additional vaccinations in patients with AILD.
Immune checkpoint inhibitors as mediators for immunosuppression by cancer-associated fibroblasts: A comprehensive review
Authors: Eskandari-Malayeri Fatemeh , Rezaei Marzieh
Published: October 2022

The tumor microenvironment (TME) is a significant contributor to cancer progression containing complex connections between cellular and chemical components and provides a suitable substrate for tumor growth and development. Growing evidence shows targeting tumor cells while ignoring the surrounding TME is not effective enough to overcome the cancer disease. Fibroblasts are essential sentinels of the stroma that due to certain conditions in TME, such as oxidative stress and local hypoxia, become activated, and play the prominent role in the physical support of tumor cells and the enhancement of tumorigenesis. Activated fibroblasts in TME, defined as cancer-associated fibroblasts (CAFs), play a crucial role in regulating the biological behavior of tumors, such as tumor metastasis and drug resistance. CAFs are highly heterogeneous populations that have different origins and, in addition to their role in supporting stromal cells, have multiple immunosuppressive functions via a membrane and secretory patterns. The secretion of different cytokines/chemokines, interactions that mediate the recruitment of regulatory immune cells and the reprogramming of an immunosuppressive function in immature myeloid cells are just a few examples of how CAFs contribute to the immune escape of tumors through various direct and indirect mechanisms on specific immune cell populations. Moreover, CAFs directly abolish the role of cytotoxic lymphocytes. The activation and overexpression of inhibitory immune checkpoints (iICPs) or their ligands in TME compartments are one of the main regulatory mechanisms that inactivate tumor-infiltrating lymphocytes in cancer lesions. CAFs are also essential players in the induction or expression of iICPs and the suppression of immune response in TME. Based on available studies, CAF subsets could modulate immune cell function in TME through iICPs in two ways; direct expression of iICPs by activated CAFs and indirect induction by production soluble and then upregulation of iICPs in TME. With a focus on CAFs’ direct and indirect roles in the induction of iICPs in TME as well as their use in immunotherapy and diagnostics, we present the evolving understanding of the immunosuppressive mechanism of CAFs in TME in this review. Understanding the complete picture of CAFs will help develop new strategies to improve precision cancer therapy.