bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thioredoxin Reductase 3 Suppression Promotes Colitis and Carcinogenesis via Activating Pyroptosis and Necrosis
Authors: Liu Qi , Du Pengyue , Zhu Yue , Zhang Xintong , Cai Jingzeng , Zhang Ziwei 
Published: September 2021

Abstract
Background
Txnrd3 as selenoprotein play key roles in antioxidant process and sperm maturation. Inflammatory bowel diseases, such as ulcerative colitis and Crohn's disease are becoming significantly increasing disease worldwide in recent years which are proved relative to diet especially selenium intake.
Methods
In the present study, 8-week-old C57BL/6N male Txnrd3-/-, Txnrd3-/+, Txnrd3+/+ mice weight 25-30g were randomly chosen and each group 30 mice. Feed 3.5% DSS drinking water and normal water continuously for 7 days. Mouse colon cancer cells (CT26) were cultured in vitro to establish Txnrd3 overexpressed/knocked-down model by cell transfection technology. Morphology and ultrastructure, calcium levels, ROS level, cell death were observed and detected in vivo and vitro.
Results
Ulcerative colitis was more severe, morphological and ultrastructural lesions were extremely significant in Txnrd3-/- mice based on the fact that expression of NLRP3, Caspase1, RIPK3, MLKL related to pyroptosis and necrosis pathway was significantly increased. Overexpression of Txnrd3 could lead to increased oxidative stress through intracellular calcium outflow induced oxidative stress increase. Followed by necrosis and pyroptosis pathway activation and further inhibit the growth and proliferation of colon cancer cells.
Conclusion
Txnrd3 overexpression leads to intracellular calcium outflow, endoplasmic reticulum stress, and increased ROS, which eventually leads to necrosis and focal death of colon cancer cells, while Txnrd3-/- mice depth of the crypt deeper, weakened intestinal secretion and immune function. And aggravate the occurrence of ulcerative colitis. The present study lays a foundation for the prevention and treatment of ulcerative colitis and colon carcinoma in clinic treatment.
Administration of Mucuna Beans (Mucuna Pruriences (L.) DC. Var. Utilis) Improves Cognition and Neuropathology of 3×Tg-AD Mice
Authors: Konishi Fumiko , Furusho Tadasu , Soeda Yoshiyuki , Yamauchi Jun , Kobayashi Shoko , Ito Masatoshi , Araki Takuma , Kogore Sarasa , Takashima Akihiko , Takekoshi Susumu 
Published: September 2021

Abstract
Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by the accumulation of extracellular amyloid-beta peptides (Aβ) resulting in senile plaques and intracellular hyperphosphorylated tau protein resulting in neurofibrillary tangles (NFTs). Mucuna beans (Mucuna pruriences (L.) DC. var. utilis) are unique plants containing 3%–9% L-3,4-dihydroxyphenylalanine (L-DOPA). Here we investigated the effect of the administration of Mucuna beans on AD prevention by feeding triple-transgenic mice (3×Tg-AD mice) with a diet containing Mucuna beans for 13 months. The levels of Aβ oligomers and detergent-insoluble phosphorylated tau decreased in the brain of mice fed with Mucuna beans (Mucuna group) compared to those of the Control group. Aβ accumulation and phosphorylated tau accumulation in the brain in the Mucuna group were also reduced. In addition, administration of Mucuna beans improved cognitive function. These results suggest that administration of Mucuna beans may have a preventive effect on AD development in 3×Tg-AD mice.
Sex Differences In Impact of Sarcopenia On Falls In Community-Dwelling Older Adults
Authors: Won Chang Won , Soh Yunsoo 
Published: September 2021

Abstract
Background: Falls are one of the most serious health problems among older adults. Sarcopenia is characterized by a decrease in muscle mass, strength, and physical function. Due to potentially age-related conditions, both falls and sarcopenia have common risk factors. However, the association between sarcopenia and falls is controversial.Methods: In this cross-sectional study, we used data from the Korean Frailty and Aging Cohort Study; 2,323 community-dwelling older adults (1,111 men and 1,212 women) aged 70–84 years were recruited in this cross-sectional study. To evaluate sarcopenia, the Asian Working Group for Sarcopenia (AWGS) diagnostic algorithm was used. We compared the faller and non-faller groups. Unadjusted and fully adjusted logistic regression analyses were performed to evaluate the relationship between sarcopenia and falls.Results: A total of 239 (24.1%) women in the faller group had a history of falls in the past year, which was statistically higher than that in men (176, 15.8%). In the fully adjusted model, handgrip strength (odds ratio [OR]=1.508, 95% confidence interval [CI]=1.028–2.211), short physical performance battery (OR=2.068, 95% CI=1.308–3.271), and 4-m walking speed (OR=3.499, 95% CI=2.044–5.991) were significantly lower in the male faller group. However, the female faller group only showed a significantly low appendicular skeletal muscle mass index (OR=1.419, 95% CI=1.058–1.903) in the fully adjusted model.Conclusions: This large cohort study aimed to identify the incidence of sarcopenia in older Korean population using the AWGS diagnostic algorithm and its correlation with falls. The incidence of falls did not increase in the sarcopenia group. Among the sarcopenia components, sex differences affect the a history of falls. Therefore, when studying the risk of falls in old age, sex differences should be considered.
Plectin Promotes Melanoma Tumor Formation by Regulation of Src Activity
Authors: Mizuta Kana , Matsubara Takuma , Goto Akino , Addison William N. , Nakatomi Mitsushiro , Matsuo Kou , Tada-Shigeyama Yukiyo , Honda Hiromi , Yoshioka Izumi , Kokabu Shoichiro 
Published: September 2021

Abstract
Melanoma is malignant cancer characterized by high proliferation and aggressive metastasis. To address efficient treatment for melanoma, we should understand the molecular mechanisms for a proto-oncogene Src, which is highly activated and promotes cell proliferation, migration, adhesion, and metastasis in melanoma. We recently identified plectin as the Src binding protein and regulates Src activity in osteoclasts. Plectin, a cytoskeleton regulatory protein, is focused as the candidates of biomarker of certain tumors because of higher expression and the candidate of anti-tumor reagents such as ruthenium pyridinecarbothioamide although the molecular mechanisms how plectin works in melanoma is unclear. In this study, we examined the pathological role in melanoma tumor formation. Depletion of plectin induced low density and sparce tumor formation by melanoma cells in vivo. In vitro experiment revealed that plectin deficient melanomas reduced cell proliferation and suppressed cell-to-cell adhesion. Because Src activity was reduced in plectin deficient melanomas, we examined the relationship between plectin and Src signaling. Src overexpression that restored Src activity rescued cell proliferation and cell-to-cell adhesion of plectin deficient melanomas. These results suggest that plectin is required for tumor formation by promoting cell proliferation and cell-to-cell adhesion via Src signaling activity in melanoma.
Effective Suppression of Hypoxia Induced Angiogenesis by Synergism of Simvastatin and Metformin via Inhibiting ET-1-ETBR-Hif1α Signaling Axis
Authors: Liu Jie , Wang Huxia , Zhang Miao , Li Yazhao , Wang Ruiqi , Chen He , Wang Bo , Gao Xiaoqian , Song Shaoran , Wang Jichang , Wang Yaochun , Li Juan , Liu Peijun 
Published: September 2021

Abstract
Background: Hypoxic stress accelerates metabolic reprogramming to promote malignant progression, which contains huge and interesting drug targets for cancer therapy. According to recently reports and our previously researches, simvastatin (SVA) or metformin (MET), two metabolic relevant drugs, play an important role in inhibiting tumor growth, angiogenesis, improvement hypoxic microenvironment. However, the signal networks of hypoxia induced metabolic reprogramming is enormous and intricacy, blocking a signal target can’t play an effective role in antitumor, whether combination of SVA and MET could exert a more effective antitumor effect is not clear.Methods: The antitumor effect of synergism of SVA and MET were detected in mouse models, breast cancer patient-derived organoid (PDO) and multiple tumor cell lines compared with untreated, SVA or MET alone. Transcriptome sequencing were performed for exploring the possible mechanisms. Inhibition of endothelin 1 (ET-1) induced Hif1α by synergism of SVA and MET were contrasted with bosentan, an ETBR antagonist.Results: Our results show that synergism of SVA and MET can inhibit tumor cell proliferation and promote apoptosis, alleviate hypoxia, decrease angiogenesis and increase vessel normalization within tumor than use of SVA or MET alone. RNA-sequencing result implies that just synergism of SVA and MET can inhibit EDN1 expression, which encodes endothelin 1, an important regulator of angiogenesis and hypoxia-related pathway, but not in use of SVA or MET alone. More specifically, synergism of SVA and MET suppresses the ET-1 induced Hif1α expression by inhibiting ET-1-ETBR signaling pathway and increasing PHD2 expression. In addition, the antitumor effect of synergism of SVA and MET is more efficient than bosentan in tumor cells and breast cancer PDO by inhibiting ET-1-ETBR-Hif1α signaling axis.Conclusions: Thus, our data show that synergism of SVA and MET can be a viable therapy for antitumor.
Involvement of lncRNA IL21-AS1 in Interleukin-2 and T Follicular Regulatory Cell Activation in Systemic Lupus Erythematosus
Authors: Hao He , Nakayamada Shingo , Ohkubo Naoaki , Yamagata Kaoru , Zhang Mingzeng , Shan Yu , Iwata Shigeru , Zhang Tong , Tanaka Yoshiya 
Published: September 2021

Abstract
Background
The single nucleotide polymorphism (SNP) rs62324212, located in IL21 antisense RNA 1 (IL21-AS1), has been identified as a genetic risk variant associated with systemic lupus erythematosus (SLE). We aimed to probe the characteristics of IL21-AS1 and explore its clinical relevance focusing T helper subsets and disease activity in patients with SLE.
Methods
rs62324212 genotyping was determined using allelic discrimination by quantitative PCR. Gene expression in peripheral blood mononuclear cells and cell surface markers in CD4+ T cells were analyzed using PCR and flow cytometry. The association among IL21-AS1, CD4+ T cell subsets and SLE disease activity were accessed.
Results
Ensembl Genome Browser analysis revealed that rs62324212 (C > A) was located in the predicting enhancer region of IL21-AS1. IL21-AS1 was expressed in the nucleus of CD4+ T and B cells, but its expression was decreased in patients with SLE. IL21-AS1 expression was positively correlated with mRNA levels of IL-2 but not IL-21, and it was associated with the proportion of activated T follicular regulatory (Tfr) cells. Furthermore, we observed a significant negative correlation between IL21-AS1 expression and disease activity in patients with SLE (n = 53, p < 0.05).
Conclusion
IL21-AS1 has an effect on disease activity through an impairment of IL-2-mediated activation of Tfr cell in SLE. Thus, targeting the IL21-AS1 may provide therapeutic approaches for SLE.
Prevalence of Resistance Genes to Biocides in Antibiotic-Resistant Pseudomonas Aeruginosa Clinical Isolates
Authors: Khademi Farzad , Habibzadeh Shahram , Vaez Hamid , Arzanlou Mohsen , Safarirad Somayeh , Bazghandi Seyed Ali , Sahebkar Amirhossein 
Published: September 2021

Abstract
Background: Biocides are frequently used as preservative, disinfectant and sterilizer against many microorganisms in hospitals, industry and home. However, the resistance rate of Pseudomonas aeruginosa (P. aeruginosa) strains to biocides is increasing. The aim of this study was to evaluate the antimicrobial activity of four frequently used biocides against P. aeruginosa and to determine the prevalence of genes involved in biocide resistance. Methods: A total of 76 clinical isolates of P. aeruginosa strains were used in the present study. The minimum inhibitory concentrations (MICs) of four biocides, i.e. chlorhexidine digluconate, benzalkonium chloride, triclosan and formaldehyde, against P. aeruginosa strains were determined using agar dilution method. In addition, the prevalence of biocide resistance genes was determined using the polymerase chain reaction (PCR) method.Results: In the present study, the highest MIC90 value was observed for benzalkonium chloride (MIC90=1024 μg/mL), followed by formaldehyde (MIC90=512 μg/mL), triclosan (MIC90=512 μg/mL) and chlorhexidine digluconate (MIC90=64 μg/mL). Furthermore, the prevalence of qacEΔ1, qacE, qacG, fabV, cepA and fabI genes were 73.7% (n=56), 26.3% (n=20), 11.8% (n=9), 84.2% (n=64), 81.5% (n=62) and 0% (n=0), respectively. A significant association was observed between the presence of biocide resistance genes and MICs (p<0.05). Furthermore, there was no significant association between the presence of biocide resistance genes and antibiotic resistance (p>0.05), except for levofloxacin and norfloxacin antibiotics and qacE and qacG genes (p<0.05). Conclusion: Our results revealed that chlorhexidine digluconate is the most effective biocide against P. aeruginosa isolates in Ardabil hospitals. However, we recommend continuous monitoring of the antimicrobial activity of biocides and the prevalence of biocide-associated resistance genes for a better prevention of microorganism dissemination and infection control in hospitals.
A 12-chemokine Gene Signature Is Associated With an Enhanced Cancer-immunity Cycle and Is Relevant for Precision Immunotherapy
Authors: Li Xingchen , Wan Zhiyi , Liu Xiu , Ou Kai , Yang Lin 
Published: September 2021

Abstract
Background: Advances in the understanding of checkpoint blockade immunotherapy have suggested that boosting the cancer-immunity cycle (CIC) can help induce regression of tumors. However, good efficacy only occurs in a subset of patients. Predictive biomarkers that can reflect the tumor microenvironment (TME) and CIC may have great potential. More recently, the presence of intratumoral tertiary lymphoid structures (TLSs) has also been correlated with clinical benefit in patients.Methods: In this study, we comprehensively measured the immunogram scores (IGSs) for the CIC and explored the associations between immunological and mutational features and a 12-chemokine metagene TLS signature in data from The Cancer Genome Atlas (TCGA). Three immunotherapy datasets were further applied for validation.Results: In the TCGA dataset, we observed that the 12-chemokine TLS signature score was positively associated with a boosted CIC, as represented by increased tumor mutational burden (TMB) and neoantigen burden (TNB), enriched immune cell infiltration, and elevated cytolytic activity and checkpoint expression. Specifically, in bladder cancer and melanoma, a high 12-chemokine TLS signature score was found to potentially reflect an expanded CIC phenotype characterized by high TNB and an immune-inflamed feature. The predictive and prognostic value of the 12-chemokine TLS signature was further validated in several immunotherapy datasets.Conclusion: The score of a 12-chemokine metagene signature may serve as a pancancer marker of the immune-active phenotype. The 12-chemokine TLS signature showed promise as a predictive and prognostic biomarker for ICB efficacy, especially in melanoma and bladder cancer.
Application of Rapid Rehabilitation Concept in Enhanced Recovery After Cesarean Section in Patients With Gestational Diabetes Mellitus: a Systematic Review
Authors: Jian Aiwen , Yang Qiuhong 
Published: September 2021

Abstract
Background: Gestational diabetes mellitus (GDM) is defined as all cases of diabetes observed during gestation, including pre-gestational diabetes and true GDM with its first onset during pregnancy. A rising number of parturient are diagnosed with GDM due to increased maternal weight, creating a serious global health concern. In order to improve maternal health and reduce childhood mortality, rapid rehabilitation approaches for postpartum recovery are of significant importance. However, most guidelines regarding this area remains extremely limited with poor quality, Methods: All the references included in this work were either in English or in Chinese, enrolled via systematic selection from database PubMed, Web of Science (WOS) and CNKI. “Gestational diabetes mellitus”, “rehabilitation”, “cesarean”, “neonatal diabetes mellitus” etc. were selected as keywords during the search. No restriction was placed on publish date, quality or the setting of the studies.Results: A total of 666 literatures were found in the initial selection. After sorting out 130 duplications, 536 articles had titles and abstracts read, among which 70 were thoroughly read. The contents of the articles include maternal-neonatal complications of GDM, maternal health managements in antenatal period, during labor and postpartum period, providing descriptions of maternal and neonatal outcomes after GDM patients receiving the interventions.Conclusions: The application of rapid rehabilitation concept in enhanced recovery of cesarean section in pregnant women with GDM during perioperative period can significantly reduce the risk of multiple maternal-neonatal complications. However, the studies focusing on the discovery of new rapid rehabilitation approaches are still inadequate.
The Associations of Serum Valine with Mild Cognitive Impairment and Alzheimer’s Disease
Authors: Xiong Yong-lan , Therriault Joseph , Ren Shu-jiang , Jing Xiao-jun , Zhang Hua 
Published: September 2021

Abstract
The introduction of metabolomics makes it possible to study the characteristic changes of peripheral metabolism in Alzheimer’s disease (AD). Recent studies have found that the levels of valine are related to mild cognitive impairment (MCI) and AD, but its characteristics in MCI and AD need to be further clarified. A total of 786 participants from the Alzheimer’s Disease Neuroimaging Initiative-1 (ADNI-1) cohort were selected to evaluate the relationships between serum valine and cerebrospinal fluid (CSF) biomarkers, brain structure (magnetic resonance imaging, MRI), cerebral glucose metabolism (18F-fluorodeoxyglucose-positron emission tomography, FDG-PET), and cognitive declines, through different cognitive subgroups. We found that (1) serum valine was decreased in patients with AD compared with cognitive normal (CN) and stable MCI (sMCI), and in progressive MCI (pMCI) compared with CN; (2) serum valine was negatively correlated with CSF total tau (t-tau) and phosphorylated tau (p-tau) in pMCI; (3) serum valine significantly predicted conversion from MCI to AD; (4) serum valine was related to the rate of change of cerebral glucose metabolism during the follow-up period in pMCI. We speculated serum valine may be a peripheral biomarker of pMCI and AD, and its level predicts the progression of MCI to AD. Our study may help to reveal the metabolic changes during AD disease trajectory and its relationship to clinical phenotype.
The Optimal Allocation Policy Via Multi-Label Tagging for Translation Tasks of China’s Imperial Maritime Customs Archives
Authors: CHEN LILAN , Chen Yongsheng 
Published: September 2021

Abstract
How to recruit, test and train the adaptive archive allocation system users, and how to assign the archive translation tasks to all available system users according to the optimal matching principle are still a problem that needs to be solved. With the help of proper names and terms in China’s Imperial Maritime Customs archives, this paper aims to solve the problem. When the corresponding translation, domain or attributes of a proper name or term is known, it will be easier for some archive translation tasks to be completed, and the adaptive archive allocation system will also improve the efficiency of archive translation task allocation and the quality of archive translation tasks. These related domains or attributes are different labels of these archives. To put it simply, multi-label classification means that the same instance can have multiple labels or be labeled into multiple categories, which is called multi-label classification. With the multi-label classification, archives can be classified into different categories, such as the trade archives, preventive archives, personnel archives, etc. The system users are divided into different professional domains by some tests, for instance, system users who are good at economic knowledge and users who have higher language skills. With these labels, the adaptive archive allocation system can make the optimal match between the archives and system users, so as to improve the efficiency and quality of archive translation tasks. In this paper, through multi-label classification, the adaptive archive allocation system can realize the optimal allocation of archive translation tasks to the system users. The optimal allocation is realized through the construction of optimization control model, and verifies that the adaptive archive allocation system can improve the performance of task allocation over time without the participation of task issuers.
Does Good National Governance Boost COVID-19 Vaccination? Cross-Country Evidence
Authors: Aida Takeshi , Shoji Masahiro 
Published: September 2021

Abstract
BackgroundAs herd immunity by universal vaccination is essential to end the COVID-19 pandemic, the COVID-19 Vaccine Global Access (COVAX) facility has been established to provide developing countries with subsidized vaccines. However, a critical issue is that the developing countries also need to effectively deploy vaccines to citizens. Although this argument suggests positive effects of good national governance on vaccination coverage, to the best of our knowledge, there is no such evidence. The goal of this study was to examine the association between the national governance index and vaccination coverage, particularly among developing countries.MethodsUsing cross-country data, an ordinary least squares regression was conducted to examine the association between the national governance index and two outcome variables on vaccination—the number of days until the administration of the first dose in the country since December 2019 and the number of doses per 100 citizens as of the end of July 2021. The results were compared between the model including all countries and the model including only non-OECD countries. We also examined the influence of governance on the selection of vaccine manufacturers.ResultsA one standard deviation increase in the national governance index was associated with 9.1 days (95%CI: -15.76, -2.43) earlier administration of vaccines in the country, and a 12.1 dose increase (95%CI: 4.76, 19.34) per 100 citizens. Results also showed that these associations were larger in the non-OECD sample and indicated the role of governance in the type of vaccine that is predominantly administered in the country.ConclusionThe provision of subsidized vaccines alone is not sufficient to control the spread of infection in developing countries; logistical and administrative support should also be offered, especially in countries with low governance indices.Trial registrationNot applicable.