bluuebunny/crossref_metadata_2025_split huggingface dataset:
Computer classification and construction of a novel prognostic signature based on moonlighting genes in prostate cancer
Authors: Mei Wangli , Jin Liang , Zhang Bihui , Sun Xianchao , Yang Guosheng , Li Sheng , Ye Lin 
Published: October 2022

Advanced prostate cancer (PRAD) patients have poor prognosis and rising morbidity despite the ongoing iteration of molecular therapeutic agents. As newly discovered proteins with several functions, Moonlighting proteins have showed an important role in tumor progression but has not been extensively investigated in PRAD. Our study aimed to identify moonlighting-related prognostic biomarkers and prospective PRAD therapy targets. 103 moonlighting genes were gathered from previous literatures. A PRAD classification and multivariate Cox prognostic signature were constructed using dataset from The Cancer Genome Atlas (TCGA). Subsequently, we tested our signature’s potential to predict biochemical failure-free survival (BFFS) using GSE21032, a prostate cancer dataset from Gene Expression Omnibus (GEO). The performance of this signature was demonstrated by Kaplan-Meier (KM), receiver operator characteristic (ROC), areas under ROC curve (AUC), and calibration curves. Additionally, immune infiltration investigation was conducted to determine the impact of these genes on immune system. This signature’s influence on drug susceptibility was examined using CellMiner’s drug database. Both training and validation cohorts demonstrated well predictive capacity of this 9-gene signature for PRAD. The 3-year AUCs for TCGA-PRAD and GSE21032 were 0.802 and 0.60 respectively. It can effectively classify patients into various biochemical recurrence risk groups. These genes were also assessed to be connected with tumor mutation burden (TMB), immune infiltration and therapy. This work created and validated a moonlighting gene signature, revealing fresh perspectives on moonlighting proteins in predicting prognosis and improving treatment of PRAD.
Role of the TSPO–NOX4 axis in angiogenesis in glioblastoma
Authors: Jiang Hongxiang , Li Fei , Cai Linzhi , Chen Qianxue 
Published: October 2022

Objective: Angiogenesis is a pathological feature of glioblastoma. Nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) is a vital source of reactive oxygen species (ROS) related to angiogenesis. However, signaling pathways correlated with the isoform oxidase are unknown. The aim of this study was to elucidate the detailed mechanism of the role of NOX4 in angiogenesis in glioblastoma.Methods: Public datasets were searched for studies on immunohistochemistry and western blotting to evaluate NOX4 expression in glioma. The location of NOX4 expression was detected by immunofluorescence. We conducted conditional deletion of the translocator protein (TSPO) targeting the protein with the synthetic ligand XBD173 in the glioblastoma mouse model. NOX4 downregulation was conducted with the NOX4 inhibitor GLX351322, and ROS production and angiogenesis were detected in glioma tissues.Results: Clinical samples and public datasets showed that NOX4 was upregulated and associated with the prognosis. NOX4 is mainly expressed in endothelial cells of glioblastoma. Both TSPO and NOX4 promoted angiogenesis in an ROS-dependent manner, suggesting that TSPO triggered ROS production in glioblastoma via NOX4.Conclusion: These results showed that TSPO is an upstream target of NOX4-derived mitochondrial ROS, which is indispensable for NOX4-derived mitochondrial ROS-induced angiogenesis in glioblastoma. TSPO–NOX4 signaling could serve as a molecular target for therapeutic strategies for glioblastoma.
Ganfule capsule alleviates bile duct ligation-induced liver fibrosis in mice by inhibiting glutamine metabolism
Authors: Ke Chang , Gao Jianlong , Tu Jiyuan , Wang Yan , Xiao Yangxin , Wu Yuan , Liu Yanju , Zhou Zhongshi 
Published: October 2022

Background: Liver fibrosis is a pathological outcome of a variety of liver diseases, and it can also progress into liver cirrhosis and liver cancer. Specific liver antifibrotic drugs have not been clinically approved yet. Studies have demonstrated the protective effects of Ganfule capsule (GFL) on the liver and its therapeutic potential in hepatic cancer. However, the mechanism of GFL is not clear in the treatment of liver fibrosis.Objective: This article aims to study the protective effect of GFL on liver fibrosis and its possible mechanism.Methods: The cholestatic liver fibrosis model was prepared by subjecting C57BL/6 mice to bile duct ligation (BDL). The GFL groups were treated with different concentrations of GFL for 14 days. Pathological analysis, serum biochemical index detection, metabonomic analysis, immunohistochemistry, Western blot, and real-time PCR were carried out.Results: GFL could alleviate liver injury and liver fibrosis caused by BDL in mice. Metabonomic analysis of mice serum showed postoperative metabolic disorder, which could be alleviated by GFL through glutamine metabolism; valine, leucine, and isoleucine biosynthesis; aminoacyl-tRNA biosynthesis; and other metabolic pathways. GFL affected glutamine metabolism by inhibiting the activity of glutaminase 1 (GLS1). The activation of GLS1 is regulated by the NF-κB pathway, and experiments showed that GFL could inhibit IκB-α and NF-κB p65 phosphorylation.Conclusion: This study confirms the protective effect of GFL on liver injury and shows that GFL inhibits glutamine metabolism, which was correlated with the NF-κB pathway, and eventually alleviates liver fibrosis. These results are conducive to the development of new therapeutic drugs for liver fibrosis.
Brazilian organic propolis for prevention and treatment of radiation-related oral acute toxicities in head and neck cancer patients: A double-blind randomized clinical trial
Authors: Fernandes Patrícia Maria , Rosalen Pedro Luiz , Fernandes Diego Tetzner , Dias-Neto Emmanuel , Alencar Severino Matias , Bueno-Silva Bruno , Alves Fábio de Abreu , Lopes Márcio Ajudarte 
Published: October 2022

Background: Oral mucositis (OM) is one of the most important acute toxicities from radiotherapy (RT) in head and neck cancer patients and can impair oncologic treatment. Dysphagia, dysgeusia, pain, and oral candidiasis are other common toxicities. Brazilian Organic Propolis (BOP) is a recently described propolis variant and BOP types 4 and 6 have shown important antioxidant, anti-inflammatory, and antifungal properties.Purpose: To investigate the use of BOP as a preventive and/or complementary therapeutic option for radiotherapy-induced oral mucositis, dysphagia, dysgeusia, pain, and oral candidiasis. Additionally, proinflammatory cytokines were assessed to investigate their anti-inflammatory role.Methods: Sixty patients were included in this randomized, double-blind, controlled clinical trial. Patients were randomized to receive either aqueous suspension of a BOP or placebo throughout RT. Also, all patients underwent low-level laser therapy as routine oral care. OM, dysphagia, and dysgeusia were assessed weekly according to WHO and NCI scales. Pain-related to OM was assessed according to a Visual Analog Scale and the presence or absence of oral candidiasis was checked by intraoral examination. Protein levels of TNF-α and IL-1β from oral mucosa were assessed by ELISA.Results: Patients in the propolis group had a lower mean score of OM, dysphagia, dysgeusia, and most patients reported moderate pain. Fewer patients developed oral candidiasis in the propolis group, and the number of episodes was lower among patients that used BOP (p &lt; 0.05). In addition, the BOP group presented significantly lower levels of IL-1β since the beginning of treatment when compared with placebo patients (p &lt; 0.05) and a lower level of TNF-α at the end of treatment (p &lt; 0.001).Conclusion: Topic use of BOP reduced TNF-α and IL-1β levels, oral candidiasis episodes, and seems to be a useful complementary option for the prevention and treatment of the main acute oral toxicities of RT.Clinical Trial Registration:http://www.ensaiosclinicos.gov.br/rg/RBR-9f8c78/, identifier RBR-9f8c78
SeDeM tool-driven full factorial design for osmotic drug delivery of tramadol HCl: Formulation development, physicochemical evaluation, and in-silico PBPK modeling for predictive pharmacokinetic evaluation using GastroPlus™
Authors: Saleem Muhammad Talha , Shoaib Muhammad Harris , Yousuf Rabia Ismail , Ahmed Farrukh Rafiq , Ahmed Kamran , Siddiqui Fahad , Mahmood Zafar Alam , Sikandar Muhammad , Imtiaz Muhammad Suleman 
Published: October 2022

The study is based on using SeDeM expert system in developing controlled-release tramadol HCl osmotic tablets and its in-silico physiologically based pharmacokinetic (PBPK) modeling for in-vivo pharmacokinetic evaluation. A Quality by Design (QbD) based approach in developing SeDEM-driven full factorial osmotic drug delivery was applied. A 24 Full-factorial design was used to make the trial formulations of tramadol HCl osmotic tablets using NaCl as osmogen, Methocel K4M as rate controlling polymer, and avicel pH 101 as diluent. The preformulation characteristics of formulations (F1-F16) were determined by applying SeDeM Expert Tool. The formulation was optimized followed by in-vivo predictive pharmacokinetic assessment using PBPK “ACAT” model of GastroPlus™. The FTIR results showed no interaction among the ingredients. The index of good compressibility (ICG) values of all trial formulation blends were ≥5, suggesting direct compression is the best-suited method. Formulation F3 and F4 were optimized based on drug release at 2, 10, and 16 h with a zero-order kinetic release (r2 = 0.992 and 0.994). The SEM images confirmed micropores formation on the surface of the osmotic tablet after complete drug release. F3 and F4 were also stable (shelf life 29.41 and 23.46 months). The in vivo simulation of the pharmacokinetics of the PBPK in-silico model revealed excellent relative bioavailability of F3 and F4 with reference to tramadol HCl 50 mg IR formulations. The SeDeM expert tool was best utilized to evaluate the compression characteristics of selected formulation excipients and their blends for direct compression method in designing once-daily osmotically controlled-release tramadol HCl tablets. The in-silico GastroPlus™ PBPK modeling provided a thorough pharmacokinetic assessment of the optimized formulation as an alternative to tramadol HCl in vivo studies.
Healthcare professionals’ knowledge, attitude and practice towards National Centralized Drug Procurement policy in central China: A cross-sectional study
Authors: Huang Anqi , Wang Xuanxuan , Tao Yun , Lin Likai , Cheng Hong 
Published: October 2022

Background: National Centralized Drug Procurement (NCDP), an ongoing government-led policy starting in 2019 in China, aimed at reducing drug costs. During the implementation of NCDP, healthcare professionals (HCPs) still have a certain degree of concern about the policy, which affects the clinical use of related drugs.Objective: This study aims to assess the level of knowledge, attitude and practice (KAP) of HCPs towards NCDP policy, together with the associated factors that determine their KAP.Methods: A cross-sectional study was conducted between September and November of 2021 in 30 hospitals in Hubei province in Central China. A self-designed online questionnaire including KAP towards NCDP policy was administered to HCPs. Logistic regression analysis was adopted to identify the factors associated with KAP.Results: A Total of, 742 HCPs completed the questionnaires. 43.4% of HCPs had good knowledge, 24.7% had a positive attitude, and 23.7% held good practice. Through multivariate logistic regression analysis, HCPs who are males, pharmacists, with senior professional titles and 6–10 years of professional working experience contributed to a higher knowledge level. Pharmacists and HCPs with good knowledge were more likely to have positive attitudes, while HCPs with higher education were less likely to have positive attitudes. Pharmacists, HCPs who had 11–20 years of professional working experience, worked in medium-size urban areas or had good knowledge were more likely to have good practice. Good practice is also associated with the positive attitude towards the efficacy of centralized-purchased medicines and impacts of NCDP policy.Conclusion: Only a small percentage of HCPs had good KAP towards NCDP policy. Pharmacists showed better KAP than physicians. The positive attitude towards the efficacy of centralized-purchased medicines and impacts of NCDP policy contributed to better practice. High-quality clinical evidence on the therapeutic effects and safety of the centralized-purchased drugs is needed.
Inefficient intramolecular vibrational energy redistribution for the H + HO2 reaction and negative internal energy dependence for its rate constant
Authors: Jasper Ahren W. , Moberg Daniel R. , Tao Yujie , Klippenstein Stephen J. , Sivaramakrishnan Raghu 
Published: October 2022

Quasiclassical trajectories (QCT) and newly constructed global potential energy surfaces are used to compute thermal and nonthermal rate constants for the H + HO2 reaction. The thermal QCTs rate constants are up to 50% smaller than transition state theory (TST) rate constants based on the same level of electronic structure theory. This reduction is demonstrated to result from inefficient intramolecular vibrational energy redistribution (IVR) in the transient H2O2 well, with a significant fraction of trajectories that reach the H2O2 well promptly dissociating back to reactants instead of via the heavily statistically favored 2OH channel. The nonstatistical reduction factor, κIVR, that quantifies this effect is shown to increase in importance with temperature, with κIVR = 0.81 at 300 K and 0.47 at 2500 K. Finally, we show that inefficient IVR causes H + HO2 rate constants mediated by H2O2 to depend inversely on the initial vibrational excitation of HO2.
Generation of h–Shaped pulse in a mode–Locked erbium-doped fiber laser
Authors: Liu Chao , Li Guoru , Su Xiancui , Wang Yiran , Gao Feilong , Xie Yiyan , Kumar Santosh , Zhang Bingyuan 
Published: October 2022

In this paper, the generation of h-shaped pulse is demonstrated in a nonlinear polarization rotation mode-locked erbium-doped fiber laser (MLEDFL). The length of the entire cavity is about 2506 m to enhance the nonlinear effect in the cavity. The multi-pulse state is obtained firstly under the certain pump power and polarization state. By further adjusting the polarization controller the h-shaped pulse with sharp top and flat bottom is generated under the pump power of ∼100 mW. And the duration of pulse is tuned with a range of 54.63–470 ns. The width and intensity of pulse trailing part vary differently during the process of increasing pulse width. The results indicate that the peak power clamping effect and weak birefringence effect dominate in different h-shaped pulse forming process.
Polydatin attenuates tubulointerstitial fibrosis in diabetic kidney disease by inhibiting YAP expression and nuclear translocation
Authors: He Manlin , Feng Lan , Chen Yang , Gao Bin , Du Yiwei , Zhou Lu , Li Fei , Liu Hongbao 
Published: October 2022

The activation of Yes-associated protein (YAP) pathway is mutually causal with the increase of extracellular matrix (ECM) stiffness. Polydatin (PD) has been proved to have anti-fibrosis effect in diabetic kidney disease (DKD), but it is still a mystery whether PD participates in YAP-related mechano-transduction. Therefore, this study intends to solve the following two problems: 1) To construct an in vitro system of polyacrylamide hydrogels (PA gels) based on the true stiffness of kidneys in healthy and DKD rats, and observe the effect of PD on pathological matrix stiffness-induced YAP expression in renal fibroblasts; 2) Compared with verteporfin (VP), a pharmacological inhibitor of YAP, to explore whether the therapeutic effect of PD on DKD in vivo model is related to the regulation of YAP. In this study, the in vitro system of PA gels with 3 kPa, 12 kPa and 30 kPa stiffness was constructed and determined for the first time to simulate the kidney stiffness of healthy rats, rats with DKD for 8 weeks and 16 weeks, respectively. Compared with the PA gels with 3 kPa stiffness, the PA gels with 12 kPa and 30 kPa stiffness significantly increased the expression of YAP, α-smooth muscle actin (α-SMA) and collagen I, and the production of reactive oxygen species (ROS) in renal fibroblasts, and the PA gels with 30 kPa stiffness were the highest. PD significantly inhibited the above-mentioned changes of fibroblasts induced by pathological matrix stiffness, suggesting that the inhibition of PD on fibroblast-to-myofibroblast transformation and ECM production was at least partially associated with regulating YAP-related mechano-transduction pathway. Importantly, the inhibitory effect of PD on YAP expression and nuclear translocation in kidneys of DKD rats is similar to that of VP, but PD is superior to VP in reducing urinary protein, blood glucose, blood urea nitrogen and serum creatinine, as well as decreasing the expression of α-SMA and collagen I, ROS overproduction and renal fibrosis. Our results prove for the first time from the biomechanical point of view that PD is a potential therapeutic strategy for delaying the progression of renal fibrosis by inhibiting YAP expression and nuclear translocation.
Crop yield and water use efficiency in response to long-term diversified crop rotations
Authors: Cui Zhengjun , Yan Bin , Gao Yuhong , Wu Bing , Wang Yifan , Xie Yaping , Xu Peng , Wang Haidi , Wen Ming , Wang Yingze , Ma Xingkang 
Published: October 2022

Crop production and water productivity may be impacted by diverse crop rotation and management practices. A field study was conducted from 2017-2020 in the Loess Plateau to evaluate the effects of crop rotation sequences on pre-planting and post-harvest soil water storage (SWS), annualized crop yield, water use, and water productivity. Crops in rotation included oil flax (Linum usitatissimum L.) (F), wheat (Triticum aestivum L.) (W), potato (Solanum tuberosum L.) (P). Twelve 4-year-cycle crop rotation treatments, along with a continuous oil flax treatment as a baseline, were included. The results showed that the average soil water content under the 0-150 cm soil layer in all treatments was increased after one rotation cycle, and the PWFW treatment achieved the highest SWC (17.1%). The average soil water storage (winter fallow season) and evapotranspiration (ETa) (growing season) under different crop rotation sequences were lower than those under continuous oil flax cropping. The ETa of FFFF increased by 28.9, 2.7, 15.3, and 28.4%, compared to average crop rotations in 2017, 2018, 2019, and 2020, respectively. Crop rotation had a significant effect on average annual yield and water use efficiency (WUE), which varied by year and rotation sequence. The crop rotations with the highest grain yield of oil flax were FFWP (2017), WFWP (2018),WPFF (2019) and FWPF (2020); the grain yield of wheat was highest when the two pre-crops (previously cultivated crops) were F-F, and potato yield was highest when the two pre-crops were W-F (except 2018). On average, the WUE of oil flax was 8.6, 38.7, 22.7, and 42.1% lower with FFFF than other diversity crop rotations in 2017, 2018, 2019, and 2020. We found that the WUE was not the largest when the grain yield of oil flax and wheat was highest. The treatments with maximum grain yield and WUE were not consistent. Our findings also revealed that wheat-potato-oil flax or potato-wheat-oil flax rotation could increase oil flax grain yields while wheat-oil flax-potato-oil flax markedly improved oil flax WUE.
FORMATION OF ENVIRONMENTAL COMPETENCE OF FUTURE BIOLOGY TEACHERS
Authors: BIDA O. , CHYCHUK A. , KUCHAI O. , GONCHARUK V. , KUCHAI T. 
Published: October 2022

The article reveals the essence of the concept of "ecological competence" and substantiates the structural components of the formation of ecological competence of future biology teachers.
Three levels of formation of environmental competence of future science teachers are defined: low – unconscious involuntary incompetence, medium – conscious voluntary incompetence, high – conscious voluntary competence.
The concept of the formation of ecological competence of future biology teachers is revealed, which covers the purpose, tasks, principles, methodological approaches, content, pedagogical conditions for the development and implementation of the studied ability in the process of professional training. The purpose of the concept is methodological substantiation, theoretical and methodical provision of professional training of future biology teachers as a system-integrating basis for the formation of environmental competence. The leading idea of ​​the concept is the justification and development of such a system for the formation of ecological competence of future biology teachers, the basis of which is the creation and functioning of an ecologically oriented environment, the implementation of which in the educational process at the strategic level rationalizes, modernizes and modifies the educational content of professional training and is a system-integrating basis the formation of a pedagogical phenomenon. The concept of forming the ecological competence of future biology teachers is implemented at the methodological, theoretical, methodical and practical levels.
DIDACTIC POTENTIAL OF FORMATIVE ASSESSMENT AS A TOOL FOR PROFESSIONAL TRAINING OF FUTURE PHYSICAL CULTURE TEACHERS IN CONDITIONS OF BLENDED LEARNING
Authors: DANYSKO O. 
Published: October 2022

The formation of digital pedagogy in conditions of global digitalization leads to a rethinking of educational paradigm and development and implementation of new methods of educational process organizing. These changes primarily concern higher pedagogical education, as the development of digital technologies changes the approaches to the training of future teachers and improving its quality. Blended learning, which has become a traditional way of organizing the educational process in higher educational institutions during the pandemic, has highlighted the problem of finding effective tools to motivate students to learn, the formation of academic self-regulation in combined educational environments. One of such innovative tools that changes the approaches to the organization of mixed courses is formative assessment.
The research defines the essence and empirically generalizes the didactic potential of formative assessment as a tool of professional training of future physical culture teachers in conditions of blended learning. It is emphasized that formative assessment is an interactive and informal assessment of the level of academic achievements of students. The purpose of using formative assessment in professional education is to ensure scientific and reflexive independence of students, prevention and elimination of gaps in their mastering of knowledge, skills and abilities.
The characteristics of modelling and designing the educational and professional experience of future physical culture teachers in conditions of blended learning through the algorithms of planning, monitoring and reflection are generalized. The didactic potential of formative evaluation in the process of professional training of future physical culture teachers in conditions of blended learning is determined: constructive and automated feedback (both for the teacher and for the student); timely and accurate description of the student's strengths and weaknesses, as well as suggestions for further activities that will support student development; differentiation and adaptation of the educational process to the needs of students, the development of their reflexive and evaluative skills of self-control, self-evaluation and mutual evaluation; increasing of cognitive activity, formation of academic independence, the ability to make informed educational choices and ways of professional development; formation of communicative competencies and skills of interpersonal communication.