bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic profiling of human bone marrow mesenchymal stromal cells after in vitro expansion in clinical grade human platelet lysate
Authors: De Becker Ann , Heestermans Robbe , De Brouwer Wouter , Bockstaele Kara , Maes Ken , Van Riet Ivan
Published: October 2022

Mesenchymal stromal cells (MSCs) are non-hematopoietic cells that have a broad therapeutic potential. To obtain sufficient cells for clinical application, they must be expanded ex vivo. In the initial expansion protocols described, fetal calf serum (FCS) was used as the reference growth supplement, but more recently different groups started to replace FCS with platelet lysate (PL). We investigated in this study the impact of the culture supplement on gene expression of MSCs. Human bone marrow derived MSCs were expanded in vitro in FCS and PL supplemented medium. We found that MSCs expanded in PL-containing medium (PL-MSCs) express typical MSC immunomorphological features and can migrate, as their counterparts expanded in FCS-containing medium, through a layer of endothelial cells in vitro. Additionally, they show an increased proliferation rate compared to MSCs expanded in FCS medium (FCS-MSCs). RNA sequencing performed for MSCs cultured in both types of expansion medium revealed a large impact of the choice of growth supplement on gene expression: 1974 genes were at least twofold up- or downregulated. We focused on impact of genes involved in apoptosis and senescence. Our data showed that PL-MSCs express more anti-apoptotic genes and FCS-MSCs more pro-apoptotic genes. FCS-MSCs showed upregulation of senescence-related genes after four passages whereas this was rarer in PL-MSCs at the same timepoint. Since PL-MSCs show higher proliferation rates and anti-apoptotic gene expression, they might acquire features that predispose them to malignant transformation. We screened 10 MSC samples expanded in PL-based medium for the presence of tumor-associated genetic variants using a 165 gene panel and detected only 21 different genetic variants. According to our analysis, none of these were established pathogenic mutations. Our data show that differences in culture conditions such as growth supplement have a significant impact on the gene expression profile of MSCs and favor the use of PL over FCS for expansion of MSCs.
Predicting OCT images of short-term response to anti-VEGF treatment for retinal vein occlusion using generative adversarial network
Authors: Xu Fabao , Yu Xuechen , Gao Yang , Ning Xiaolin , Huang Ziyuan , Wei Min , Zhai Weibin , Zhang Rui , Wang Shaopeng , Li Jianqiao
Published: October 2022

To generate and evaluate post-therapeutic optical coherence tomography (OCT) images based on pre-therapeutic images with generative adversarial network (GAN) to predict the short-term response of patients with retinal vein occlusion (RVO) to anti-vascular endothelial growth factor (anti-VEGF) therapy. Real-world imaging data were retrospectively collected from 1 May 2017, to 1 June 2021. A total of 515 pairs of pre-and post-therapeutic OCT images of patients with RVO were included in the training set, while 68 pre-and post-therapeutic OCT images were included in the validation set. A pix2pixHD method was adopted to predict post-therapeutic OCT images in RVO patients after anti-VEGF therapy. The quality and similarity of synthetic OCT images were evaluated by screening and evaluation experiments. We quantitatively and qualitatively assessed the prognostic accuracy of the synthetic post-therapeutic OCT images. The post-therapeutic OCT images generated by the pix2pixHD algorithm were comparable to the actual images in edema resorption response. Retinal specialists found most synthetic images (62/68) difficult to differentiate from the real ones. The mean absolute error (MAE) of the central macular thickness (CMT) between the synthetic and real OCT images was 26.33 ± 15.81 μm. There was no statistical difference in CMT between the synthetic and the real images. In this retrospective study, the application of the pix2pixHD algorithm objectively predicted the short-term response of each patient to anti-VEGF therapy based on OCT images with high accuracy, suggestive of its clinical value, especially for screening patients with relatively poor prognosis and potentially guiding clinical treatment. Importantly, our artificial intelligence-based prediction approach’s non-invasiveness, repeatability, and cost-effectiveness can improve compliance and follow-up management of this patient population.
Digging into primary financial market: The issues of primary financial market issuance and investigations from the perspective of blockchain
Authors: Liu Ji , Xu Zheng , Zhang Yanmei , Dai Wei , Wu Hao , Chen Shiping
Published: October 2022

With the characteristics of anonymity, trust, tamper-proof, etc., blockchain technology can effectively solve some problems faced by the financial market, such as trust issues and information asymmetry issues. To deeply understand the application scenarios of blockchain in the financial market, the issue of securities issuance and trading in the primary market is studied. The authors conducted an empirical study to investigate the main difficulties faced by primary market participants in their business practices and the potential challenges of the deepening adoption of blockchain technology in the primary market. The authors adopted a hybrid method by combing interviews (qualitative methods) and surveys (quantitative methods) to conduct this research in two stages. In the first stage, authors interview 15 major primary market participants with different backgrounds and expertise. In the second phase, authors conducted a verification survey of 54 primary market practitioners to confirm various insights from the interviews, including challenges and desired improvements. The interviews and survey results reveal several significant challenges facing blockchain applications in the primary market: complex due diligence, mismatching, and difficult monitoring. The research shows that primary market participants have a positive attitude towards the application of blockchain technology to the primary market and are ready to adopt blockchain technology to solve some of the current issues.
High-resolution atomic force microscopy as a tool for topographical mapping of surface budding
Authors: Sbarigia C. , Tacconi S. , Mura F. , Rossi M. , Dinarelli S. , Dini L.
Published: October 2022

Extracellular vesicles (EVs) are membranous nanoparticles secreted by almost all cell types. Reflecting the physiopathological state of the parental cell, EVs circulate in all body fluids, reaching distant cell targets and delivering different bioactive cargoes. As biological carriers, EVs influence their microenvironment altering cellular responses, being considered promising biomarkers for both physiological and pathological conditions. EVs are heterogeneous in terms of size and composition, depending on cell type and exposure to stimuli, and different methods have been developed to characterize their morphological, biophysical, and biochemical features. Among them, electron microscopy (EM) is the main technique used, however, the lack of standardized protocols makes it difficult to characterize EVs with a good reproducibility, thus using multiple approaches may represent a way to obtain more precise information. Furthermore, the relationship between architecture and function, not only in a molecular, but also in a cellular level, is gaining growing emphasis, characterizing morphometric parameters may represent a distinct, but effective approach to study the physiopathological state of the cell. Atomic force microscopy (AFM), may represent a promising method to study in detail EVs dynamics throughout the cell surface and its variations related to the physiological state, overcoming the limits of EM, and providing more reliable information. In this study, human neuroblastoma SH-SY5Y cell line, a cellular model to investigate neurodegeneration and oxidative stress, has been used to perform a comparative morphological and quantitative analysis of membrane budding and isolated large vesicles-enriched (microvesicles-like vesicles; MVs) fraction from control or oxidative stressed cells. Our main goal was to build up a methodology to characterize EVs morphology and spatial distribution over the cell surface in different physiological conditions, and to evaluate the efficacy of AFM against conventional EM. Interestingly, both microscopy techniques were effective for this analysis, but AFM allowed to reveal a differential profiling of plasma membrane budding between the physiological and the stress condition, indicating a potential relationship between mechanical characteristics and functional role. The results obtained may provide interesting perspectives for the use of AFM to study EVs, validating a morphometric approach to understand the pathophysiological state of the cell related to EVs trafficking.
A comparative analysis of molecular genotypes of Mycobacterium tuberculosis isolates from HIV-positive and HIV-negative patients
Authors: Singh Jitendra , Singh Niti , Suresh Gayatri , Srivastava Rahul , Aggarwal Upasna , Behera Digamber , Munisamy Murali , Malhotra Anvita Gupta , Singh Sarman
Published: October 2022

Setting

Tuberculosis Research Laboratory, Division of Clinical Microbiology and Molecular Medicine, Department of Laboratory Medicine, All India Institute of Medical Sciences, and the National Institute of Tuberculosis and Respiratory Diseases (NITRD), both situated in New Delhi.

Objectives

We aimed to identify the distribution of various genotypes of M. tuberculosis among HIV-positive and HIV-negative patients suspected of having Tuberculosis, seen at the National Institute of Tuberculosis and Respiratory Diseases, New Delhi, which is a tertiary care dedicated TB hospital.

Patients and methods

Genotyping by Spoligotyping and 24 loci MIRU-VNTR was performed and analyzed using SITVITWEB and MIRU-VNTRplus. Drug susceptibility patterns were also analyzed.

Results

A total of 503 subjects who were PTB/EPTB suspected were recruited and 287 were culture positive. Among them, 276 had growth of Mycobacterium tuberculosis (MTB) and in 11 patients non-tuberculous mycobacteria (NTM) were grown. The isolation rate of NTM was predominantly from HIV positive [10 of 130 (7.6%)] patients. Of the total isolates of MTB, 156 (56.5%) were from HIV negative patients and 120 (43.5%) were from HIV positive patients. All 276 M. tuberculosis isolates were genotyped and tested for drug susceptibility patterns. The CAS genotype was most predominant [153 (55.4%)], followed by Beijing lineage [44 (15.9%)], East African India [25 (9.1%)] and others [54 (19.6%)]. Beijing genotype was significantly more common in HIV positive patients (22.5%) than in HIV negative patients (10.9%). In MIRU-VNTR analysis, clustering was found to be more frequent in CAS strains irrespective of HIV status. In the HIV positive group, spoligotyping could differentiate various genotypes in 90% of isolates and MIRU-VNTR analysis in 84.2% of isolates. The clustering of various MTB strains was more associated with drug resistance.

Conclusion

The Beijing lineage was predominant in HIV-TB coinfected cases, even though the Central Asian Strain (CAS) was overall more predominant in the region.
Bacterial DNA involvement in carcinogenesis
Authors: Yangyanqiu Wang , Shuwen Han
Published: October 2022

The incidence of cancer is high worldwide, and biological factors such as viruses and bacteria play an important role in the occurrence of cancer. Helicobacter pylori, human papillomavirus, hepatitis B viruses and other organisms have been identified as carcinogens. Cancer is a disease driven by the accumulation of genome changes. Viruses can directly cause cancer by changing the genetic composition of the human body, such as cervical cancer caused by human papillomavirus DNA integration and liver cancer caused by hepatitis B virus DNA integration. Recently, bacterial DNA has been found around cancers such as pancreatic cancer, breast cancer and colorectal cancer, and the idea that bacterial genes can also be integrated into the human genome has become a hot topic. In the present paper, we reviewed the latest phenomenon and specific integration mechanism of bacterial DNA into the human genome. Based on these findings, we also suggest three sources of bacterial DNA in cancers: bacterial DNA around human tissues, free bacterial DNA in bacteremia or sepsis, and endogenous bacterial DNA in the human genome. Clarifying the theory that bacterial DNA integrates into the human genome can provide a new perspective for cancer prevention and treatment.
RED, PEF, and EPD: Conflicting rules for determining the carbon footprint of biofuels give unclear signals to fuel producers and customers
Authors: Brandão Miguel , Ekvall Tomas , Poulikidou Sofia , Johansson Kristin , Nilsson Johan , Nojpanya Pavinee , Wikström Anna , Rydberg Tomas
Published: October 2022

Biofuel producers and other commodity suppliers are increasingly affected by conflicting rules for life cycle assessment (LCA). They may get multiple requests for LCAs to be used in various contexts, which require the application of different methodological approaches that vary in scope, system boundaries, data demand, and more. This results in increased cost and competence requirements for producers, as well as confusion among other actors including their customers. Differences in methodologies might also lead to various outcomes, conclusions and conflicting guidance regarding which fuels to prioritize or develop. We have analyzed the actual differences when applying three different frameworks: the EU Renewable Energy Directive (RED), the EU framework for Product Environmental Footprints (PEF), and the framework of Environmental Product Declarations (EPD), which have different modeling requirements. We analyzed the methods from a conceptual point of view and also applied the methods to estimate the carbon footprint on a wide range of biofuel production pathways: (i) ethanol from corn, (ii) fatty acid methyl ester (FAME) from rapeseed oil, (iii) biogas from food waste, (iv) hydrogenated vegetable oil (HVO) from rapeseed oil, and (v) HVO from used cooking oil. Results obtained for a specific fuel could differ substantially depending on the framework applied and the assumptions and interpretations made when applying the different frameworks. Particularly, the results are very sensitive to the modeling of waste management when biofuel is produced from waste. Our results indicate a much higher climate impact for, e.g., biogas and HVO produced from used cooking oil when assessed with the PEF framework compared to the other frameworks. This is because PEF assigns at least part of the production of primary materials and energy to the use of recycled material and recovered energy. Developing Category Rules for biofuels for PEF and EPD ought to help clarifying remaining ambiguities.
DPP3: From biomarker to therapeutic target of cardiovascular diseases
Authors: Ye Peng , Duan Wei , Leng Yue-Qi , Wang Yang-Kai , Tan Xing , Wang Wei-Zhong
Published: October 2022

Cardiovascular disease is the leading cause of death globally among non-communicable diseases, which imposes a serious socioeconomic burden on patients and the healthcare system. Therefore, finding new strategies for preventing and treating cardiovascular diseases is of great significance in reducing the number of deaths and disabilities worldwide. Dipeptidyl peptidase 3 (DPP3) is the first zinc-dependent peptidase found among DPPs, mainly distributes within the cytoplasm. With the unique HEXXGH catalytic sequence, it is associated with the degradation of oligopeptides with 4 to 10 amino acids residues. Accumulating evidences have demonstrated that DPP3 plays a significant role in almost all cellular activities and pathophysiological mechanisms. Regarding the role of DPP3 in cardiovascular diseases, it is currently mainly used as a biomarker for poor prognosis in patients with cardiovascular diseases, suggesting that the level of DPP3 concentration in plasma is closely linked to the mortality of diseases such as cardiogenic shock and heart failure. Interestingly, it has been reported recently that DPP3 regulates blood pressure by interacting with the renin-angiotensin system. In addition, DPP3 also participates in the processes of pain signaling, inflammation, and oxidative stress. But the exact mechanism by which DPP3 affects cardiovascular function is not clear. Hence, this review summarizes the recent advances in the structure and catalytic activity of DPP3 and its extensive biological functions, especially its role as a therapeutic target in cardiovascular diseases. It will provide a theoretical basis for exploring the potential value of DPP3 as a therapeutic target for cardiovascular diseases.
Case report: Dual atrioventricular nodal non-reentrant tachycardia with six types of ECG patterns leading to tachycardia-induced cardiomyopathy in a 51-year-old man
Authors: Ren Man-Yi , Zhang Yong , Zhang Yu-Jiao , Gao Mei , Sang Cai-Hua , Cha Yong-Mei , Hou Ying-Long
Published: October 2022

More than three types of ECG manifestations in one patient with dual atrioventricular nodal non-reentrant tachycardia (DAVNNT) are rare. We report a 51-year-old male patient with DAVNNT consisting of six types of ECG patterns leading to tachycardia-induced cardiomyopathy. After radiofrequency ablation of the slow pathway, DAVNNT was eliminated and cardiac function was restored.
Current and potential therapeutic strategies for transthyretin cardiac amyloidosis
Authors: Williams Marcus A. C. , Shankar Bairavi , Vaishnav Joban , Ranek Mark J.
Published: October 2022

Cardiac amyloidosis is a progressive disorder caused by the deposition of amyloid, abnormal proteins that aggregate to form insoluble plaques in the myocardium resulting in restrictive cardiomyopathy. The two most common subtypes of cardiac amyloidosis are immunoglobulin light chain (AL) and transthyretin (TTR) amyloid cardiomyopathy (ATTR-CM). ATTR-CM can further be subdivided into two main categories, wild-type or hereditary TTR. TTR is a homotetrameric protein complex that is synthesized in the liver and is secreted into the circulation for retinol and vitamin A transfer. Genetic mutations in the TTR gene can disrupt the thermodynamic stability of the homotetrameric complex causing dissociation into monomers that, when taken up by the myocardium, will aggregate to form insoluble fibers. Though the mechanism of wild-type TTR is not fully elucidated, it is thought to be an age-related process. Myocardial uptake and aggregation of TTR monomeric subunits result in cytotoxicity, impaired cardiac function, and eventually heart failure. Historically, ATTR-CM had a poor prognosis, with no therapeutics available to specifically target ATTR-CM and treatment focused on managing symptoms and disease-related complications. In 2019, the FDA approved the first-in-class TTR stabilizer for ATTR-CM, which has led to improved outcomes. In recent years, several promising novel therapies have emerged which aim to target various points of the ATTR-CM amyloidogenic cascade. In this review, we discuss the mechanistic underpinnings of ATTR-CM, review current FDA-approved strategies for treatment, and highlight ongoing research efforts as potential therapeutic options in the future.
Chemically induced phenotypes during the blood stage development of Plasmodium falciparum as indicators of the drug mode of action
Authors: Reghunandanan Keerthy , Chandramohanadas Rajesh
Published: October 2022

Malaria remains a health and economic burden, particularly in marginalized populations worldwide. The current strategies for combating malaria rely on eliminating the mosquito vector, using insecticide-treated nets, and other management policies or through the administration of small molecule drugs to perturb the intra-erythrocytic development of the parasite. However, resistance against commonly used drugs such as artemisinin has recently become a concern necessitating the identification of novel pharmacophores with unique mechanisms of action. This review summarizes the various life-stage events of the malaria parasite, Plasmodium falciparum, during the in vitro development, which can be targeted by different classes of small molecules. We also describe various chemically induced phenotypes and methods to ascertain and validate drug-induced changes to derive early insights into which cellular mechanisms are affected.
Therapeutic applications of transcutaneous auricular vagus nerve stimulation with potential for application in neurodevelopmental or other pediatric disorders
Authors: Zhu Siyu , Zhang Xiaolu , Zhou Menghan , Kendrick Keith M. , Zhao Weihua
Published: October 2022

Non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) as a newly developed technique involves stimulating the cutaneous receptive field formed by the auricular branch of the vagus nerve in the outer ear, with resulting activation of vagal connections to central and peripheral nervous systems. Increasing evidence indicates that maladaptive neural plasticity may underlie the pathology of several pediatric neurodevelopmental and psychiatric disorders, such as autism spectrum disorder, attention deficit hyperactivity disorder, disruptive behavioral disorder and stress-related disorder. Vagal stimulation may therefore provide a useful intervention for treating maladaptive neural plasticity. In the current review we summarize the current literature primarily on therapeutic use in adults and discuss the prospects of applying taVNS as a therapeutic intervention in specific pediatric neurodevelopmental and other psychiatric disorders. Furthermore, we also briefly discuss factors that would help optimize taVNS protocols in future clinical applications. We conclude from these initial findings that taVNS may be a promising alternative treatment for pediatric disorders which do not respond to other interventions.
Myocardial protection of S-nitroso-L-cysteine in diabetic cardiomyopathy mice
Authors: Peng Lulu , Zhu Mengying , Huo Shengqi , Shi Wei , Jiang Tao , Peng Dewei , Wang Moran , Jiang Yue , Guo Junyi , Men Lintong , Huang Bingyu , Wang Qian , Lv Jiagao , Lin Li , Li Sheng
Published: October 2022

Diabetic cardiomyopathy (DCM) is a severe complication of diabetes mellitus that is characterized by aberrant myocardial structure and function and is the primary cause of heart failure and death in diabetic patients. Endothelial dysfunction plays an essential role in diabetes and is associated with an increased risk of cardiovascular events, but its role in DCM is unclear. Previously, we showed that S-nitroso-L-cysteine(CSNO), an endogenous S-nitrosothiol derived from eNOS, inhibited the activity of protein tyrosine phosphatase 1B (PTP1B), a critical negative modulator of insulin signaling. In this study, we reported that CSNO treatment induced cellular insulin-dependent and insulin-independent glucose uptake. In addition, CSNO activated insulin signaling pathway and promoted GLUT4 membrane translocation. CSNO protected cardiomyocytes against high glucose-induced injury by ameliorating excessive autophagy activation, mitochondrial impairment and oxidative stress. Furthermore, nebulized CSNO improved cardiac function and myocardial fibrosis in diabetic mice. These results suggested a potential site for endothelial modulation of insulin sensitivity and energy metabolism in the development of DCM. Data from these studies will not only help us understand the mechanisms of DCM, but also provide new therapeutic options for treatment.
Relationship between triglyceride–glucose index and carotid plaques in a high-stroke-risk population in southeast china: A population-based cross-sectional survey
Authors: Tang Xiang , Zhang Lulu , Li Yidan , Zhou Yun , Cai Xiuying , Yao Ye , Fang Qi
Published: October 2022

Background

Cervical arterial atherosclerosis (CAA) is an important risk factor of stroke in China. The triglyceride–glucose (TyG) index is a simple and low-cost marker for ischemic stroke. Whether the TyG index predicts cervical arterial atherosclerosis remains uncertain. This study aimed to investigate the relationship between the TyG index and cervical arterial atherosclerosis.

Methods

This cross-sectional study was conducted in residents aged ≥40 years in the general population of southeast China. All participants completed a detailed questionnaire and provided blood samples. The high-stroke-risk groups further completed cervical artery ultrasonography. The TyG index was calculated using a well-established formula and analyzed in quartiles (Q1–Q4). Multivariate logistic regression was used to investigate the relationship between the TyG index and cervical arterial atherosclerosis.

Results

A total of 4,499 participants aged ≥40 years were finally included, with 23.47% comprising the high-stroke-risk population. The prevalence rates of increased intima–media thickness (IMT), carotid plaque, and cervical artery stenosis (CAS) in the high-stroke-risk population were 21.97%, 39.3%, and 6.1%, respectively. Subjects with higher TyG were still more likely to have carotid plaque. After adjusting for several established risk factors, compared with the TyG-Q1 group, the TyG-Q2, TyG-Q3, and TyG-Q4 groups were more likely to have carotid plaque (OR = 1.85, 95%CI = 1.28–2.67; OR = 1.51, 95%CI = 1.05–2.18; and OR = 1.29, 95%CI = 0.90–1.84). TyG was an independent predictor of the presence of plaque in the carotid artery of the high-stroke-risk population.

Conclusions

An elevated TyG index is a potential predictor of carotid plaques in the high-stroke-risk population older than 40 years.
Implementation of corneal confocal microscopy for screening and early detection of diabetic neuropathy in primary care alongside retinopathy screening: Results from a feasibility study
Authors: Carmichael Josie , Fadavi Hassan , Ishibashi Fukashi , Howard Susan , Boulton Andrew J. M. , Shore Angela C. , Tavakoli Mitra
Published: October 2022

Objective

Screening for diabetic peripheral neuropathy (DPN) is essential for early detection and timely intervention. Quantitative assessment of small nerve fiber damage is key to the early diagnosis and assessment of its progression. Corneal confocal microscopy (CCM) is a non-invasive, in-vivo diagnostic technique that provides an accurate surrogate biomarker for small-fiber neuropathy. In this novel study for the first time, we introduced CCM to primary care as a screening tool for DPN alongside retinopathy screening to assess the level of neuropathy in this novel cohort.

Research design and methods

450 consecutive subjects with type 1 or type 2 diabetes attending for annual eye screening in primary care optometry settings underwent assessment with CCM to establish the prevalence of sub-clinical diabetic peripheral neuropathy. Subjects underwent assessment for neurological and ocular symptoms of diabetes and a history of diabetic foot disease, neuropathy and diabetic retinopathy (DR).

Results

CCM examination was completed successfully in 427 (94.9%) subjects, 22% of whom had neuropathy according to Diabetic Neuropathy Symptom (DNS) score. The prevalence of sub-clinical neuropathy as defined by abnormal corneal nerve fiber length (CNFL) was 12.9%. In the subjects with a short duration of type 2 diabetes, 9.2% had abnormal CNFL. CCM showed significant abnormalities in corneal nerve parameters in this cohort of subjects with reduction of corneal nerve fiber density (CNFD, p<0.001), CNFL (p<0.001) and corneal nerve branch density (CNBD, p<0.001) compared to healthy subjects. In subjects who had no evidence of DR (67% of all subjects), 12.0% had abnormal CNFL.

Conclusions

CCM may be a sensitive biomarker for early detection and screening of DPN in primary care alongside retinopathy screening.
Contribution of mitochondrial gene variants in diabetes and diabetic kidney disease
Authors: Li Meng , Gong Siqian , Han Xueyao , Zhou Lingli , Zhang Simin , Ren Qian , Cai Xiaoling , Luo Yingying , Liu Wei , Zhu Yu , Zhou Xianghai , Li Yufeng , Ji Linong
Published: October 2022

Objectives

Mitochondrial DNA (mtDNA) plays an important role in the pathogenesis of diabetes. Variants in mtDNA have been reported in diabetes, but studies on the whole mtDNA variants were limited. Our study aims to explore the association of whole mtDNA variants with diabetes and diabetic kidney disease (DKD).

Methods

The whole mitochondrial genome was screened by next-generation sequencing in cohort 1 consisting of 50 early-onset diabetes (EOD) patients with a maternally inherited diabetes (MID) family history. A total of 42 variants possibly associated with mitochondrial diseases were identified according to the filtering strategy. These variants were sequenced in cohort 2 consisting of 90 EOD patients with MID. The association between the clinical phenotype and these variants was analyzed. Then, these variants were genotyped in cohort 3 consisting of 1,571 type 2 diabetes mellitus patients and 496 subjects with normal glucose tolerance (NGT) to analyze the association between variants with diabetes and DKD.

Results

Patients with variants in the non-coding region had a higher percentage of obesity and levels of fasting insulin (62.1% vs. 24.6%, P = 0.001; 80.0% vs. 26.5% P < 0.001). The patients with the variants in rRNA had a higher prevalence of obesity (71.4% vs. 30.3%, P = 0.007), and the patients with the variants in mitochondrial complex I had a higher percentage of the upper tertile of FINS (64.3% vs. 34.3%, P = 0.049). Among 20 homogeneous variants successfully captured, two known variants (m.A3943G, m.A10005G) associated with other mitochondrial diseases were only in the diabetic group, but not in the NGT group, which perhaps indicated its possible association with diabetes. The prevalence of DKD was significantly higher in the group with the 20 variants than those without these variants (18.7% vs. 14.6%, P = 0.049) in the participants with diabetes of cohort 3.

Conclusion

MtDNA variants are associated with MID and DKD, and our findings advance our understanding of mtDNA in diabetes and DKD. It will have important implications for the individual therapy of mitochondrial diabetes.
Effects of seawater and freshwater challenges on the Gh/Igf system in the saline-tolerant blackchin tilapia (Sarotherodon melanotheron)
Authors: Link Karl , Shved Natallia , Serrano Nabil , Akgül Gülfirde , Caelers Antje , Faass Oliver , Mouttet Farouhar , Raabe Oksana , D’Cotta Helena , Baroiller Jean-François , Eppler Elisabeth
Published: October 2022

Prolactin (Prl) and growth hormone (Gh) as well as insulin-like growth factor 1 (Igf1) are involved in the physiological adaptation of fish to varying salinities. The Igfs have been also ascribed other physiological roles during development, growth, reproduction and immune regulation. However, the main emphasis in the investigation of osmoregulatory responses has been the endocrine, liver-derived Igf1 route and local regulation within the liver and osmoregulatory organs. Few studies have focused on the impact of salinity alterations on the Gh/Igf-system within the neuroendocrine and immune systems and particularly in a salinity-tolerant species, such as the blackchin tilapia Sarotherodon melanotheron. This species is tolerant to hypersalinity and saline variations, but it is confronted by severe climate changes in the Saloum inverse estuary. Here we investigated bidirectional effects of increased salinity followed by its decrease on the gene regulation of prl, gh, igf1, igf2, Gh receptor and the tumor-necrosis factor a. A mixed population of sexually mature 14-month old blackchin tilapia adapted to freshwater were first exposed to seawater for one week and then to fresh water for another week. Brain, pituitary, head kidney and spleen were excised at 4 h, 1, 2, 3 and 7 days after both exposures and revealed differential expression patterns. This investigation should give us a better understanding of the role of the Gh/Igf system within the neuroendocrine and immune organs and the impact of bidirectional saline challenges on fish osmoregulation in non-osmoregulatory organs, notably the complex orchestration of growth factors and cytokines.
Weight gain in type 1 diabetes during the SARS-CoV-2 pandemic. Does lockdown affect the metabolic control of pediatric patients?
Authors: Zubkiewicz-Kucharska Agnieszka , Wikiera Beata , Noczyńska Anna
Published: October 2022

Background and aims

Due to the severe acute respiratory syndrome coronavirus 2 pandemic, governments of many countries decided to implement lockdowns, which included school closures. This major lifestyle change also applied to people with diabetes. The aim of this paper was to analyze how the COVID-19 pandemic and related restrictions influenced the metabolic compensation of diabetes in the pediatric population.

Methods

Patients with type 1 diabetes (T1D), treated by one therapeutic team, who in 2020 and 2021 paid at least two in-person visits in the outpatient clinic, were included in the study. The time in range (TIR) and HbA1c, as well as the total daily dose (TDD) of insulin and BMI from the visit before the announcement of the pandemic restrictions (March 2020) and during the lockdown (second visit after 6 months) and within the period of loosened restrictions (two visits in 2021) were analyzed.

Results

A total of 185 patients with T1D were included in the study (96 boys), aged 2–18 years (11.5 ± 3.5); 135 of them (72.9%) use CSII and 142 (76.8%) use CGM or FGM. During the first months of the studied period, despite comparable (p>0.05) TIR (57.5 ± 21.4% vs. 59.9 ± 20.5%), improvement of HbA1c was noticed (7.9 ± 1.6% vs. 7.5 ± 1.4%, p=0.0336), whereas in the following months, both HbA1c and TIR were comparable. Also, the TDD increased significantly (from 37.3 ± 18.9 units/day on the first visit up to 46.8 ± 22.7 units/day on the last visit, p=0.0003); however, TDD/kg remained constant (p>0.05) (0.8 ± 0.2 units/kg/day vs. 0.8 ± 0.3 units/kg/day) possibly due to an increased BMI (19.1 ± 3.7 kg/m2vs. 20.9 ± 4.1 kg/m2, p=0.0001). The percentage of basal insulin in the TDD remained stable (p>0.05) (39.7 ± 11.3% vs. 39.3 ± 13.6%). Furthermore, a significant (p=0.0001) change in the BMI percentile was noticed [from 58.9 ± 26.2 percentiles (%iles) before lockdown vs. 64.6 ± 26.0%iles on the second visit]. However, the BMI percentile returned to baseline (58.1 ± 28.4%iles) at the visit at the end of the observation period.

Conclusions

The parameters of metabolic control in pediatric patients with T1D during the pandemic period remained stable; however, weight gain and an increase in daily insulin dose have been observed, possibly due to reduced physical activity.
The factors influencing the supply of rural elderly services in China based on CHARLS data: Evidence from rural land use and management
Authors: Zhao Yan
Published: October 2022

The problem of elderly service supply is a important issue that must be solved for the development of an aging society. This study uses microdata from the China Health and Retirement Longitudinal Study that were published in 2017 and from a regression analysis using a dichotomous logistic model. Finally, the article examines the factors that affect the supply of elderly services and land use in rural China. The results show that 1) the health level is the most direct influencing factor on whether rural elderly people in rural land can obtain elderly services; 2) the family characteristics that affects the supply of elderly services in rural land is the relationship of living with children rather than the number of children; 3) socio-economic status has an impact on the supply of elderly services, but this impact is limited; and 4) the factors affecting the supply of family elderly services and social elderly services for the rural elderly are basically the same, with the fundamental difference between the two being that the service targets are different, which reflects typological characteristics.
Air pollution in China: Spatial patterns and spatial coupling with population and economy
Authors: Yan Dachuan , Zhou Meichun , Diao Yiwei , Yang Meng
Published: October 2022

This paper analyzes the daily data of China’s air quality index (AQI) from 2015 to 2020 using kriging, spatial autocorrelation, and gravity center method. The results confirm that China’s air pollution is gradually controlled. From 2015 to 2020, the AQI, the proportion of air pollution days and the city air quality exceedance rate decreased by about 29%, 44%, and 49% respectively. The spatial distribution of air pollution changes with seasons. The heavily polluted area (AQI > 200) is largest in spring, which accounts for 0.48% of the total area, while the polluted area (AQI > 100) is largest in winter due to large area pollution in the North China Plain. The air pollution has strong spatial autocorrelation with a global Moran’s Index larger than 0.7. The Beijing-Tianjin-Hebei region and southern Xinjiang are high-pollution clustering areas. The former is dominated by PM2.5 pollution caused by anthropogenic activities, while the latter is dominated by PM10 pollution from natural sources. Using gravity center method, it works out the air pollution gravity center (APGC), economic gravity center (EGC), the secondary industry gravity center (SIGC), the tertiary industry gravity center (TIGC) and the population gravity center (PGC) in the Beijing-Tianjin-Hebei region and its surrounding areas. Results show that the spatial overlapping indicator of the APGC with the PGC is the highest, and the APGC and the SIGC has the highest shifting consistency indicator. When combining the two indicators, it is obtained that air pollution has the highest degree of spatial coupling with the secondary industry, but low coupling with economic volume. It is indicated that the driving factors of air pollution is the secondary industry. Therefore, it is suggested that the regulation of air pollution should start from optimizing the industrial structure in China.
The effect of land fragmentation on farmers’ rotation behavior in rural China
Authors: Yang Boqiong , Duan Yuxin , Zhao Qiran
Published: October 2022

Background: Arable land protection is the key to guaranteeing food security in China, as well as protecting the ecological environment and ensuring the continuous increase of farmers’ income. Crop rotation is one of the many forms of arable land protection.

Objectives: In this paper, we aim to estimate the possible influence of land fragmentation, famers’ willingness to rotate, and farmers’ rotation behavior in China. Combining farmers’ willingness to rotate and farmers’ rotation behavior using the theory of intermediary effect, we determine whether the degree of land fragmentation will affect farmers’ willingness to rotate or not, thereby affecting farmers’ rotation behavior.

Methodology: This study based on the field survey conducted in Heilongjiang Province in 2018, focused on the impact of land fragmentation on farmers’ rotation behavior through OLS and Probit model. Specifically, the degree of land fragmentation and farmers’ willingness to rotate are 0.187 and 0.463, respectively. Further, by taking the farmers’ willingness to rotate as the mediator, this paper discusses the mechanism on the effect of land fragmentation on farmers’ rotation behavior. Finally, the farmers are divided into large and small farmers—according to acreage for heterogeneity analysis.

Main findings: This study found that the degree of land fragmentation affects farmers’ willingness to rotate, thereby having some mediating effects on farmers’ rotation behavior.

Conclusion: The indirect impact accounts for only 39.86% of the total impact, and more comes from the direct impact. Thus, policy makers should strengthen the guidance for farmers to stimulate their behavior and willingness to implement rotation. Furthermore, it is vital to improve the popularization of arable land protection knowledge and increase crop rotation subsidies.
Release behavior of uranium from a uranium tailing in Jiangxi Province
Authors: Xue Shiqi , Wang Zili , Ouyang Jinbo , Zhou Limin , Liu Zhirong
Published: October 2022

In this study, nine soils at different depths in a decommissioned uranium tailing pond in Jiangxi Province are selected as the research objects to study their mineralogical properties and reveal the leaching law of radioactive element uranium under natural rainfall conditions. The research results are as follows: 1) The distribution characteristics of uranium are affected by the mineral composition, microscopic morphology and physical and chemical properties of uranium tailings. 2) In static leaching experiments, acidic solutions, small particles, and high solid-to-liquid ratios all promote the release of uranium. 3) In the dynamic leaching experiment, the lower the pH of simulated rainfall, the more uranium is released. According to Fick theory, the migration mechanism of uranium is mainly surface dissolution, and the release of uranium is related to the content of migratory uranium.
Distinctive metabolite profiles in migrating Amur ide (Leuciscus waleckii) reveal changes in osmotic pressure, gonadal development, and energy allocation strategies
Authors: Wang Shuangyi , Huang Jing , Liang Liqun , Su Baofeng , Zhang Yu , Liew Hon Jung , Sun Bo , Zhang Limin , Chang Yumei
Published: October 2022

Amur ide (Leuciscus waleckii) lives in alkali-saline water (pH = 9.6) in the Lake Dali and spawns in freshwater rivers after migration annually. During spawning migrations, Amur ide not only experience osmoregulation modification from alkali-saline water to freshwater but also deal with energy prioritization for basal metabolism and gonadal development. To achieve an optimal cost-benefit balance, a series of metabolism modifications are needed. This study investigated the changing metabolite profiles that contribute to maintaining a balance of osmotic pressure and energy allocation for gonadal maturation. We applied ultra-performance liquid chromatography together with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS), combined with chemometrics, for identifying metabolic changes regarding spawning broodstocks of Amur ide during migration. According to findings, there were 11,333 metabolites in Amur ide serum and 3,159 metabolites were found to change significantly during migration. Differentially expressed metabolites mainly affected the steroid hormone biosynthesis, the arachidonic acid metabolism, the biosynthesis of phenylalanine, tyrosine, and tryptophan, pyruvate metabolism, citrate cycle, as well as glycerophospholipid metabolism. Based on the enrichment analysis regarding metabolic pathways, biosynthesis of steroid hormone and arachidonic acid metabolism are two representative pathways, which are crucial for osmoregulation and gonadal maturation. The perturbation of some metabolites during migration was highlighted, which involves sexual maturation and reproduction, nitrogenous waste excretion, and energy allocation. The study assists in understanding the physiological plasticity exhibited by Amur ide during migratory spawning from a new perspective, which is useful as a scientific basis for the artificial breeding of Amur ide.
Genome-wide identification of Aux/IAA gene family and their expression analysis in Prunus mume
Authors: Cheng Wenhui , Zhang Man , Cheng Tangren , Wang Jia , Zhang Qixiang
Published: October 2022

AUXIN/INDOLE ACETIC ACIDs (Aux/IAAs), an early auxin-responsive gene family, is important for plant growth and development. To fully comprehend the character of Aux/IAA genes in woody plants, we identified 19 PmIAA genes in Prunus mume and dissected their protein domains, phylogenetic relationship, gene structure, promoter, and expression patterns during floral bud flushing, auxin response, and abiotic stress response. The study showed that PmIAA proteins shared conserved Aux/IAA domain, but differed in protein motif composition. 19 PmIAA genes were divided into six groups (Groups Ⅰ to Ⅵ) based on phylogenetic analysis. The gene duplication analysis showed that segmental and dispersed duplication greatly influenced the expansion of PmIAA genes. Moreover, we identified and classified the cis-elements of PmIAA gene promoters and detected elements that are related to phytohormone responses and abiotic stress responses. With expression pattern analysis, we observed the auxin-responsive expression of PmIAA5, PmIAA17, and PmIAA18 in flower bud, stem, and leaf tissues. PmIAA5, PmIAA13, PmIAA14, and PmIAA18 were possibly involved in abiotic stress responses in P. mume. In general, these results laid the theoretical foundation for elaborating the functions of Aux/IAA genes in perennial woody plant development.
Rethinking benefit sharing in collaborative human genetic research from an Afrocommunitarian perspective
Authors: Ewuoso Cornelius , Sudoi Allan , Kamuya Dorcas
Published: October 2022

This article draws on reflections about humanness, friendliness and partiality, in the writings of Afro-communitarians to develop principles for thinking critically about why benefit sharing, what may count as benefits within the context of human research in Africa and the limits of the obligation of benefit sharing. Suppose the thinking about humanness, friendliness, and partiality in Afro-communitarianism were the foundation of human genetic research in Africa, then, individuals who have contributed to research or borne its burden would benefit from its rewards. This is even more important if participants have pressing needs that researchers and/or research institutions can help ease. A failure to aid sample contributors and data providers in need when researchers and research institutions can—as well as an indifference to the serious needs of contributors—are failures to exhibit friendliness in the relevant ways. Finally, though providing benefits to contributors can be an important way of showing humanity to them, nonetheless, this obligation is not absolute and may be limited by the stronger obligation of shared experience—to advance science. Studies are still required to inquire how well these norms will work in practice and inform regulatory and legal frameworks.