bluuebunny/crossref_metadata_2025_split huggingface dataset:
The protective effects of trelagliptin on high‐fat diet‐induced nonalcoholic fatty liver disease in mice
Authors: Wang Guang , Wu Bing , Zhang Lening , Jin Xuefei , Wang Kun , Xu Wenzhou , Zhang Bo , Wang Heyuan 
Published: January 2021

AbstractNonalcoholic fatty liver disease (NAFLD) occurs in patients with type 2 diabetes mellitus (T2DM). Trelagliptin is an important member of the Gliptins family, which has been recently licensed for the treatment of T2DM. However, the pharmacological function of trelagliptin in NAFLD has not been previously reported. In this study, we aimed to investigate the roles of trelagliptin in the development of NAFLD in a mouse model. To induce NAFLD disease, C57BL/6 mice were fed a high‐fat diet for 10 weeks. Our results indicate that trelagliptin reduced plasma lipid levels in NAFLD mice by reducing triglycerides, total cholesterol, low‐density lipoprotein cholesterol, and high‐density lipoprotein cholesterol. Treatment with trelagliptin exhibited an improvement in insulin resistance. More important, trelagliptin improved liver function by reducing alanine transaminase, aspartate transaminase, lactate dehydrogenase, and total bile acid. In addition, trelagliptin ameliorated oxidative stress in the liver of NAFLD mice by reducing malondialdehyde and increasing the levels of reduced glutathione and superoxide dismutase activity. Also, the enzyme‐linked immunosorbent assay results indicate that trelagliptin‐treated mice displayed anti‐inflammatory properties by reducing the levels of interleukin 1β (IL‐1β), IL‐6, and tumor necrosis factor‐α. Hematoxylin and eosin and Oil red O staining show that trelagliptin treatment ameliorates liver tissue damage and hepatic lipid deposition. Mechanistically, we found that the administration of trelagliptin reduced the activity of hepatic nuclear factor‐κB but increased the activity of AMP‐activated protein kinase. These findings suggest that trelagliptin might become a promising therapeutic agent for the treatment of NAFLD.
The existence of r‐golf designs
Authors: Li Xiangqian , Chang Yanxun , Zhou Junling 
Published: January 2021

AbstractAn r‐golf design of order , briefly by r‐G(v), is a large set of idempotent Latin squares of order (ILSs) which contains symmetric ILSs and transposed pairs of ILSs. In this paper, we mainly consider the existence problem of r‐G(v)s. We present several recursive constructions and also display some direct constructions. As an application, several infinite classes of r‐G(v)s are determined, including the existence of 0‐G(v)s for more than half of admissible parameters and the existence of r‐G(v)s where and is any admissible integer ( odd and ).
Clinical evaluation of a laboratory‐developed test using clone E1L3N for the detection of PD‐L1 expression status in non‐small cell lung cancer
Authors: Xu Hanyan , Dong Xidan , Zhao Hanxin , Hou Tongtong , Chen Chengshui , Chen Guorong , Ye Junru , Li Yuping 
Published: January 2021

AbstractBackgroundProgrammed death ligand 1 (PD‐L1) has been used as a diagnostic marker to identify patients that will benefit from immune checkpoint inhibitors in non‐small cell lung cancer (NSCLC). Immunohistochemistry with E1L3N clone is one of the most widely used and inexpensive laboratory‐developed tests for PD‐L1, but still need to be compared and validated with standard methods for clinical application.MethodsWe investigated the performance of E1L3N clone for PD‐L1 testing in 299 tumor tissues of NSCLC patients and its comparability with FDA‐approved 22C3 clone.ResultsThe results show that the negative coincidence rate, weak positive coincidence rate, and positive coincidence rate were 97.4%, 92.2%, and 97.6% using the E1L3N assay relative to the 22C3 assay, respectively. An overall agreement of 96.3% was achieved between these two assays. We also found that the overall concordances were 97.8% and 93.9% for PD‐L1 detection in large and small specimens, respectively, and no significant difference was obtained between these two assays (p = 0.076). In addition, the expression of PD‐L1 was not detected in tumor tissues of benign lung disease using both the E1L3N and 22C3 assays.ConclusionE1L3N can be used as a reliable alternative antibody clone to evaluate PD‐L1 expression status for NSCLC patients.
Overexpression of GLUT3 promotes metastasis of triple‐negative breast cancer by modulating the inflammatory tumor microenvironment
Authors: Tsai Tai‐Hua , Yang Ching‐Chieh , Kou Tai‐Chih , Yang Chang‐En , Dai Jia‐Zih , Chen Chia‐Ling , Lin Cheng‐Wei 
Published: January 2021

AbstractTriple‐negative breast cancer (TNBC) exhibits a higher level of glycolytic capacity and are commonly associated with an inflammatory microenvironment, but the regulatory mechanism and metabolic crosstalk between the tumor and tumor microenvironment (TME) are largely unresolved. Here, we show that glucose transporter 3 (GLUT3) is particularly elevated in TNBC and associated with metastatic progression and poor prognosis in breast cancer patients. Expression of GLUT3 is crucial for promoting the epithelial‐to‐mesenchymal transition and enhancing invasiveness and distant metastasis of TNBC cells. Notably, GLUT3 is correlated with inflammatory gene expressions and is associated with M1 tumor‐associated macrophages (TAMs), at least in part by C‐X‐C Motif Chemokine Ligand 8 (CXCL8). We found that expression of GLUT3 regulates CXCL8 production in TNBC cells. Secretion of CXCL8 participates in GLUT3‐overexpressing TNBC cells‐elicited activation of inflammatory TAMs, which further enhances GLUT3 expression and mobility of TNBC cells. Our findings demonstrate that aerobic glycolysis in TNBC not only promotes aggressiveness of tumor cells but also initiates a positive regulatory loop for enhancing tumor progression by modulating the inflammatory TME.
The antithetic role of ceramide and sphingosine‐1‐phosphate in cardiac dysfunction
Authors: Cirillo Federica , Piccoli Marco , Ghiroldi Andrea , Monasky Michelle M. , Rota Paola , La Rocca Paolo , Tarantino Adriana , D'Imperio Sara , Signorelli Paola , Pappone Carlo , Anastasia Luigi 
Published: January 2021

AbstractCardiovascular diseases (CVDs) are the leading cause of death globally and the number of cardiovascular patients, which is estimated to be over 30 million in 2018, represent a challenging issue for the healthcare systems worldwide. Therefore, the identification of novel molecular targets to develop new treatments is an ongoing challenge for the scientific community. In this context, sphingolipids (SLs) have been progressively recognized as potent bioactive compounds that play crucial roles in the modulation of several key biological processes, such as proliferation, differentiation, and apoptosis. Furthermore, SLs involvement in cardiac physiology and pathophysiology attracted much attention, since these molecules could be crucial in the development of CVDs. Among SLs, ceramide and sphingosine‐1‐phosphate (S1P) represent the most studied bioactive lipid mediators, which are characterized by opposing activities in the regulation of the fate of cardiac cells. In particular, maintaining the balance of the so‐called ceramide/S1P rheostat emerged as an important novel therapeutical target to counteract CVDs. Thus, this review aims at critically summarizing the current knowledge about the antithetic roles of ceramide and S1P in cardiomyocytes dysfunctions, highlighting how the modulation of their metabolism through specific molecules, such as myriocin and FTY720, could represent a novel and interesting therapeutic approach to improve the management of CVDs.
Development and functional characterization of novel fully human anti‐CD19 chimeric antigen receptors for T‐cell therapy
Authors: Dai Zhenyu , Hu Xuelian , Jia Xiangyin , Liu Jianwei , Yang Yongkun , Niu Panpan , Hu Guang , Tan Taochao , Zhou Jianfeng 
Published: January 2021

AbstractImpressive outcomes have been achieved by chimeric antigen receptor (CAR)‐T cell therapy using murine‐derived single‐chain variable fragment (scFv) FMC63 specific for CD19 in patients with B cell malignancies. However, evidence suggests that human anti‐mouse immune responses might be responsible for poor persistence and dysfunction of CAR‐T cells, leading to poor outcomes or early tumor recurrence. Substituting a fully human scFv for murine‐derived scFv may address this clinically relevant concern. In this study, we discovered two human anti‐CD19 scFv candidates through an optimized protein/cell alternative panning strategy and evaluated their function in CAR‐T cells and CD19/CD3 bispecific antibody formats. The two clones exhibited excellent cytotoxicity in CAR‐T cells and bispecific antibodies in vitro compared with the benchmarks FMC63 CAR‐T cells and blinatumomab. Furthermore, Clone 78‐BBz CAR‐T cells exhibited similar in vivo antitumor activity to FMC63‐BBz CAR‐T cells. Our results indicate that Clone 78‐BBz CAR has excellent efficacy and safety profile and is a good candidate for clinical development.
Melatonin maintains inner blood‐retinal barrier via inhibition of p38/TXNIP/NF‐κB pathway in diabetic retinopathy
Authors: Tang Lei , Zhang Chaoyang , Yang Qian , Xie Hai , Liu Dandan , Tian Haibin , Lu Lixia , Xu Jing‐Ying , Li Weiye , Xu Guoxu , Qiu Qinghua , Liu Kun , Luo Dawei , Xu Guo‐Tong , Zhang Jingfa 
Published: January 2021

AbstractThe pathophysiology of diabetic retinopathy (DR) was complex. Under hyperglycemic conditions, the release of proinflammatory cytokines and the adhesion of leukocytes to retinal capillaries contribute to endothelial damage and the subsequent increase in vascular permeability resulting in macular edema. Melatonin, produced in the retina to regulate redox reactions and dopamine metabolism, plays protective roles against inflammation and oxidative stress. Considering its anti‐inflammatory and antioxidative properties, melatonin was speculated to exert beneficial effects in DR. In this study, we characterized the protective effects of melatonin on the inner blood–retinal barrier (iBRB), as well as the possible mechanisms in experimental DR. Results showed that in diabetic rat retinas, the leakage of iBRB and the expression of inflammatory factors (VEGF, TNF‐α, IL‐1β, ICAM‐1, and MMP9) increased dramatically, while the expression of tight junction proteins (ZO‐1, occludin, JAM‐A, and claudin‐5) decreased significantly. The above changes were largely ameliorated by melatonin. The in vivo data were confirmed in vitro. In addition, the protein expressions of p38 MAPK, NF‐κB, and TXNIP were upregulated significantly in diabetes and were downregulated following melatonin treatment. Melatonin could maintain the iBRB integrity by upregulating the expression of tight junction proteins via inhibiting p38/TXNIP/NF‐κB pathway, thus decreasing the production of inflammatory factors. This study may shed light on the development of melatonin‐based DR therapy.
Advanced purification platform using circularly permuted caspase‐2 for affinity fusion‐tag removal to produce native fibroblast growth factor 2
Authors: Lingg Nico , Cserjan‐Puschmann Monika , Fischer Andreas , Engele Petra , Kröß Christina , Schneider Rainer , Brocard Cécile , Berkemeyer Matthias , Striedner Gerald , Jungbauer Alois 
Published: January 2021

AbstractBACKGROUNDRecombinant proteins produced for use as biopharmaceuticals need to harbor their native N‐terminus. A drawback in expression of recombinant proteins as fusion proteins with an affinity fusion‐tag is that enzymatic or chemical processing is required to trim the artificial tag and release the true protein of interest. In many cases, however, this processing step generates an incorrect N‐terminus.RESULTSHuman fibroblast growth factor 2 (FGF2) was expressed as a fusion protein in Escherichia coli fed‐batch cultivations. The protein of interest (POI) carried an N‐terminal affinity fusion‐tag which enabled purification via affinity chromatography. After enzymatic removal of the affinity fusion‐tag with a circularly permuted human caspase‐2 (cpCasp2), the POI was further purified using subtractive affinity chromatography. Mass spectrometric analysis confirmed the authentic N‐terminus of the POI. The generated POI was highly pure with 42 ppm host cell protein, 3.7 μg mL−1 dsDNA and ~ 1000 EU mL−1 endotoxin. Only a small number of E. coli host cell proteins were co‐purified with the POI. Because of the high specificity of the novel protease cpCasp2, no off‐target cleavage could be observed.CONCLUSIONOur findings demonstrate that cpCasp2 can be used for the production of native proteins using a fusion‐protein process. This represents a first case study at large laboratory scale for the production of an industrially relevant protein. This technology constitutes the basis of a highly scalable cpCasp2‐based platform fusion protein process (CASPON technology) purification platform. © 2021 The Authors. Journal of Chemical Technology & Biotechnology published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Fe doped CeO2 nanocubes with the exposure of active (100) facets for photocatalytic ozonation of 4‐chlorophenol under solar irradiation
Authors: Xu Shiting , Chen Xixi , Zhan Shujuan , Tian Shuanghong , Xiong Ya 
Published: January 2021

AbstractBACKGROUNDTo strengthen the treatment efficiency of photocatalytic ozonation, it is necessary to develop a stable bifunctional catalyst active in both processes of photocatalysis and catalytic ozonation.RESULTSA series of Fe doped CeO2 nanocubes with the main exposure of active (100) crystal facets were simply synthesized by a one‐pot hydrothermal method and applied in photocatalytic ozonation for the first time. It was found that doping did not change the morphology of nanocubes but it decreased the crystal size, induced abundant defects of oxygen vacancies and Ce3+, and shifted the optical absorption edge to the visible region. Due to these structure modifications, Fe doped CeO2 nanocubes enhanced the mineralization rate of 4‐chlorophenol by 55.4–74.7% and reduced the formation of carcinogenic bromate by 60.2–85.4%, depending on the doping content. Due to the simultaneous occurrence of photocatalysis, catalytic ozonation, and their synergy in 5%Fe‐CeO2 mediated photocatalytic ozonation under solar irradiation, 4‐chlorophenol almost completely degraded within 9 min, 74.7% of mineralization rate was achieved within 45 min, and the first order kinetics reaction constant reached 2.97 × 10−2·min−1, about 4.1 times that of photo ozonation without any catalysts. Moreover, the introduction of 5%Fe‐CeO2 to the ozonation, photolysis, and photo ozonation decreased the corresponding energy consumption by 60.2%, 84.2%, and 62.5%, respectively.CONCLUSIONIn this study, an efficient and economical Fe doped CeO2 nanocubes‐mediated photocatalytic ozonation process was successfully developed for the refractory organics‐containing wastewater treatment under solar light irradiation. © 2021 Society of Chemical Industry
Cell cycle during neuronal migration and neocortical lamination
Authors: Wu Shanshan , Wei Tingting , Fan Wenjuan , Wang Yanli , Li Chaojie , Deng Jinbo 
Published: January 2021

AbstractObjectivesIn order to understand the relationships between neocortical lamination and cell cycle, various cells, such as neural stem cell, migrating postmitotic neuron, Cajal‐Retzius (CR) cell, and mature pyramidal cell in various cell phases were investigated in mouse cortices.MethodsWith mouse neocortex and hippocampus, the immunofluorescent labeling, BrdU assay, and DiI tracing technique were implemented in the study.Results(1) During mouse development, the neocortex expressed different proteins, such as FOXP2, CDP, and Nestin, which could be used as the markers for cortical lamination. (2) The neural stem cells were mainly located in the subventricular zone, with the expressions of Nestin, Cyclin A2, Cyclin E1, and CDT1, suggesting that they were in the repeated cell cycle. Furthermore, the migrating neurons in the neocortex were Cyclin D1‐ (G1 phase‐specific marker) positive, suggesting that they were in the G1 phase. However, Pyramidal cells that developed from postmitotic migrating neurons and settled in the cortical plate were Cyclin D1‐ negative, suggesting that they were in the G0 phase. (3) Reelin positive CR cells appeared in the molecular layer of the neocortex in early embryonic day (E10), which could express Cyclin A2, Cyclin E1, and CDT1 as pyramidal cells, but not Cyclin D1, suggesting that they may have exited the cell cycle and entered the G0 phase.ConclusionThe neural migration, neural proliferation, and cell cycle alterations play an important role during cortical lamination. During the cortical development and lamination, the neural stem cells and migrating postmitotic neurons are in different cell cycle phases, but pyramidal cells and CR cells have exited the cell cycle.
Ultra‐structural and physico‐chemical characterization of eggs and egg hairs (setae) of the new invasive pest, fall armyworm,Spodoptera frugiperda(J. E. Smith) in India: A first report
Authors: Kannan Malaichamy , Elango Kolanthasamy , Kalyanasundaram Manickavasagam , Govindaraju Kasivelu 
Published: January 2021

AbstractIn this study, we report first time in India on the morphology, ultra‐architectural pattern of the chorion in the egg and egg hair (setae). Further, physico‐chemical characterizations of egg hairs (setae) were studied in the new invasive pest, fall armyworm,Spodoptera frugiperda. The egg is dome shaped with flattened base and curves upward to a broadly rounded point at the apex. HR‐SEM micrographs revealed the surface ultrastructure of eggs chorion and shows structural elements of a marked rosette of petals surround the micropyle followed by micropylar rosette region around the micropyle plate. There was a small single micropylar opening along with 9 micropylar rosette cells and 13 micropylar rosette zones present near to the micropylar pit. In the egg the first order ribs were absent, but around 58–60 numbers of second order ribs were present. All the ventral and lateral cells of the eggs are connected by 19–22 cross striae and not forming a grid pattern, but joints with the longitudinal ribs at several of angles and totally 1,277–1,495 convex cells present at the egg's surface. The physico‐chemical characteristics of egg hairs were studied using Fourier transform infrared (FT‐IR) and thermogravimetric analysis (TGA) analysis. TGA results show that three weight losses occurred at 142, 418, and 880°C, respectively. FT‐IR confirms the presence of amides, sulfoxide, and nitro compounds in egg hairs (setae).
Comprehensive evaluation of methods for small extracellular vesicles separation from human plasma, urine and cell culture medium
Authors: Dong Liang , Zieren Richard C. , Horie Kengo , Kim Chi‐Ju , Mallick Emily , Jing Yuezhou , Feng Mingxiao , Kuczler Morgan D. , Green Jordan , Amend Sarah R. , Witwer Kenneth W. , de Reijke Theo M. , Cho Yoon‐Kyoung , Pienta Kenneth J. , Xue Wei 
Published: January 2021

AbstractOne of the challenges that restricts the evolving extracellular vesicle (EV) research field is the lack of a consensus method for EV separation. This may also explain the diversity of the experimental results, as co‐separated soluble proteins and lipoproteins may impede the interpretation of experimental findings. In this study, we comprehensively evaluated the EV yields and sample purities of three most popular EV separation methods, ultracentrifugation, precipitation and size exclusion chromatography combined with ultrafiltration, along with a microfluidic tangential flow filtration device, Exodisc, in three commonly used biological samples, cell culture medium, human urine and plasma. Single EV phenotyping and density‐gradient ultracentrifugation were used to understand the proportion of true EVs in particle separations. Our findings suggest Exodisc has the best EV yield though it may co‐separate contaminants when the non‐EV particle levels are high in input materials. We found no 100% pure EV preparations due to the overlap of their size and density with many non‐EV particles in biofluids. Precipitation has the lowest sample purity, regardless of sample type. The purities of the other techniques may vary in different sample types and are largely dependent on their working principles and the intrinsic composition of the input sample. Researchers should choose the proper separation method according to the sample type, downstream analysis and their working scenarios.
The impact of oral diseases in cirrhosis on complications and mortality
Authors: Ladegaard Grønkjær Lea , Holmstrup Palle , Jepsen Peter , Vilstrup Hendrik 
Published: January 2021

AbstractBackground and AimThe aims of this study were to describe the prevalence of various oral diseases and to examine the association of the oral diseases with complications and mortality of cirrhosis.MethodsA total of 184 cirrhosis patients were enrolled and were followed up for 2 years. They underwent oral clinical and radiographic examination. At study entry, the associations between oral diseases with nutrition, inflammation, and cirrhosis complication status were examined. Then, the associations of oral diseases with all‐cause and cirrhosis‐related mortality were examined using Cox regression to adjust for confounding by age, gender, smoking, alcohol use, alcoholic cirrhosis, cirrhosis complications, comorbidity, Child‐Pugh, and Model of End‐Stage Liver Disease (MELD) score.ResultsAt entry, 26% of the patients had gross caries, 46% periapical lesions, 27% oral mucosal lesions, and 68% periodontitis. Having one or more oral diseases was associated with a higher prevalence of cirrhosis complications (46.7 vs 20.5%), higher C‐reactive protein (28.5 mg/L vs 10.4 mg/L), and higher nutritional risk score (4 vs 3). Two‐thirds of the patients died during follow‐up. The patients with more than one oral disease had an increasingly higher all‐cause mortality (two diseases: hazard ratio [HR] 1.55, 95% confidence interval [CI] 1.02–1.98; three and four diseases: HR 1.75, 95% CI 1.05–3.24) and even higher cirrhosis‐related mortality (two diseases: HR 1.60, 95% CI 1.01–2.40; three and four diseases: HR 2.04, 95% CI 1.05–8.83) compared to those with no oral disease.ConclusionIn cirrhosis, having more than one oral disease was associated with more complications and with higher mortality.
Domestic revenue mobilisation in developing countries: An exploratory analysis of sub‐Saharan Africa and Latin America
Authors: Gwaindepi Abel 
Published: January 2021

AbstractThis study compares taxation trends, volatility and tax effort between sub‐Saharan Africa (SSA) and Latin American and the Caribbean (LAC) countries since 1980. It finds that the LAC countries lead on revenue collection and revenue stability, but richer SSA countries outperform their LAC counterparts. Since 2010, there has been a divergence on personal income taxes, which have grown in SSA but declined in the LAC. The panel analysis shows that tax determinants are sensitive to income levels. The study shows the importance of exploring diversity and cross‐regional variations on income levels. Additionally, it shows that room exists for peer‐to‐peer lessons on tax reforms.