bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficient strategies based on behavioral and electrophysiological methods for epilepsy-related gene screening in the Drosophila model
Authors: Liu Chu-Qiao , Qu Xiao-Chong , He Ming-Feng , Liang De-Hai , Xie Shi-Ming , Zhang Xi-Xing , Lin Yong-Miao , Zhang Wen-Jun , Wu Ka-Chun , Qiao Jing-Da 
Published: April 2023

IntroductionWith the advent of trio-based whole-exome sequencing, the identification of epilepsy candidate genes has become easier, resulting in a large number of potential genes that need to be validated in a whole-organism context. However, conducting animal experiments systematically and efficiently remains a challenge due to their laborious and time-consuming nature. This study aims to develop optimized strategies for validating epilepsy candidate genes using theDrosophilamodel.MethodsThis study incorporate behavior, morphology, and electrophysiology for genetic manipulation and phenotypic examination. We utilized the Gal4/UAS system in combination with RNAi techniques to generate loss-of-function models. We performed a range of behavioral tests, including two previously unreported seizure phenotypes, to evaluate the seizure behavior of mutant and wild-type flies. We used Gal4/UAS-mGFP flies to observe the morphological alterations in the brain under a confocal microscope. We also implemented patch-clamp recordings, including a novel electrophysiological method for studying synapse function and improved methods for recording action potential currents and spontaneous EPSCs on targeted neurons.ResultsWe applied different techniques or methods mentioned above to investigate four epilepsy-associated genes, namelyTango14,Klp3A,Cac, andSbf, based on their genotype-phenotype correlation. Our findings showcase the feasibility and efficiency of our screening system for confirming epilepsy candidate genes in the Drosophila model.DiscussionThis efficient screening system holds the potential to significantly accelerate and optimize the process of identifying epilepsy candidate genes, particularly in conjunction with trio-based whole-exome sequencing.
Quercetin activates vitamin D receptor and ameliorates breast cancer induced hepatic inflammation and fibrosis
Authors: Sannappa Gowda Nirmala G. , Shiragannavar Varsha D. , Puttahanumantharayappa Lakshana D. , Shivakumar Ashwini Tumkur , Dallavalasa Siva , Basavaraju Chaithanya G. , Bhat Smitha S. , Prasad Shashanka K. , Vamadevaiah Ravishankar M. , Madhunapantula SubbaRao V. , Santhekadur Prasanna K. 
Published: April 2023

AimsTo explore the hepatoprotective role of quercetin and its novel molecular mechanism of action on breast cancer associated hepatic inflammation and fibrosis via Vitamin D receptor (VDR).Main methodsWe used Ehrlich Ascites Carcinoma (mouse mammary carcinoma) model for our in-vivo experiments and human breast cancer cell lines for in-vitro assays. We inoculated 1.5 × 106 Ehrlich ascites carcinoma cells into female Swiss albino mice. Quercetin (50 mg/kg) was administered intraperitoneally for 15 days. Liver enzymes activity was determined using a spectrophotometric assay. The hallmarks of inflammation and fibrosis were determined using Immunohistochemistry. The effect of quercetin on tumor formation was elucidated using human breast cancer cell lines and chick chorioallantoic membrane assay. Docking study was performed to explore the binding mode of quercetin with VDR.Key findingsIn EAC tumor-bearing mice, cell numbers, tumor volume, body weight and liver weight were dramatically increased, while they significantly decreased in mice treated with quercetin. Additionally, the peritoneal neo-angiogenesis was also significantly suppressed in the quercetin-treated mice, compared to the control. In addition, quercetin treated EAC tumor bearing mice had lower levels of liver enzymes, decreased hepatic inflammation and fibrosis compared with EAC tumor bearing mice. Docking study confirmed VDR-quercetin interaction. Furthermore, in-vitro assays and chick chorioallantoic membrane assay revealed the Vitamin D mimicking effect of quercetin.SignificanceDietary flavonoid, quercetin could act as a promising therapeutic drug to suppress the breast cancer induced tumor angiogenesis, hepatic inflammation, and fibrosis possibly via activation of VDR.
A novel 25-ferroptosis-related gene signature for the prognosis of gliomas
Authors: Peng Xiaojiang , Liu Chun , Li Jing , Bao Zeqing , Huang Tao , Zeng Lingfeng , He Qixiong , Xue Daojin 
Published: April 2023

BackgroundFerroptosis is closely associated with cancer and is of great importance in the immune evasion of cancer. However, the relationship between ferroptosis and glioma is unclear.MethodsWe downloaded the expression profiles and clinical data of glioma from the GlioVis database and obtained the expression profiles of ferroptosis genes. A ferroptosis-related gene signature was developed for the prognosis of gliomas.ResultsWe screened out prognostic ferroptosis genes, named ferroptosis-related genes, by the Cox regression method. Based on these genes, we used unsupervised clustering to obtain two different clusters; the principal component analysis algorithm was applied to determine the gene score of each patient, and then all the patients were classified into two subgroups. Results showed that there exist obvious differences in survival between different clusters and different gene score subgroups. The prognostic model constructed by the 25 ferroptosis-related genes was then evaluated to predict the clinicopathological features of immune activity in gliomas.ConclusionThe ferroptosis-related genes play an important role in the malignant process of gliomas, potentially contributing to the development of prognostic stratification and treatment strategies.
Machine learning-based construction of a ferroptosis and necroptosis associated lncRNA signature for predicting prognosis and immunotherapy response in hepatocellular cancer
Authors: Zhao Lei , You Zhixuan , Bai Zhixun , Xie Jian 
Published: April 2023

IntroductionLiver hepatocellular carcinoma (LIHC), one of the most common malignancies worldwide, occurs with high incidence and mortality. Ferroptosis and necroptosis are critically associated with LIHC prognosis. Some long non-coding RNAs (lncRNAs) have been found to induce ferroptosis and necroptosis in hepatocellular carcinoma cells.MethodsCox regression analysis was used to construct a risk model for LIHC based on differentially expressed ferroptosis and necroptosis related lncRNAs (F-NLRs), and their expression in SMMC7721, HepG2 and WRL68 cells was detected by qPCR.ResultsFive F-NLRs were associated with LIHC prognosis, including KDM4A-AS1, ZFPM2-AS1, AC099850.3, MKLN1-AS, and BACE1-AS. Kaplan-Meier survival analysis indicated that patients with LIHC in the high-risk group were associated with poor prognosis. The combined F-NLR signature model demonstrated a prognostic AUC value of 0.789 and was more accurate than standard clinical variables for predicting LIHC prognosis. T cell functions and immunotherapy responses differed significantly between patients in the low- and high-risk groups. Additionally, immune checkpoints and m6A-related genes were differentially expressed between patients in the two risk groups. Furthermore, proteins encoded by the five F-NLRs were overexpressed in four liver cancer cell lines compared to that in human liver cell line WRL68. Pan-cancer examination revealed that expression levels of the five F-NLRs differed between most common tumor types and normal tissues.ConclusionF-NLRs identified in this study provide a predictive signature representing ferroptosis and necroptosis in LIHC, which correlated well with patient prognosis, clinicopathological characteristics, and immunotherapy responses. The study findings help to elucidate the mechanisms of F-NLRs in LIHC and provide further guidance for the selection and development of immunotherapeutic agents for LIHC.
Deflux® Endoscopic Treatment of Vesicoureteral Reflux (VUR) in Japan
Authors:   The Japanese Deflux Injection Therapy Study Group
Published: April 2023

IntroductionThe aim of this study is to present the results of a multi-institutional outcome analysis conducted to determine the extent of endoscopic Deflux® injection for treating primary vesicoureteral reflux in Japan.MethodsA 22-question survey was distributed to 174 certified pediatric urologists (Ninteii in Japanese) and councilors of the Japanese Society of Pediatric Urology working at 140 centers to determine the usage and clinical efficacy of Deflux® for treating primary vesicoureteral reflux in Japan.ResultsForty-three of 140 (30.7%) centers participated, which exceeded participation rates of 27.9 and 18.0% for similar surveys conducted in America in 2006 and 2014, respectively. Deflux® was administered at 43 centers using subureteral transurethral injection (n = 19; 44.2%), hydrodistention implantation (n = 5; 11.6%), or double hydrodistention implantation (n = 19; 44.2%) and was the first-line treatment for primary vesicoureteral reflux at 39 (90.7%) centers. Overall, 1,563 ureters were treated in 1,076 patients. The male:female ratio was 527:549; mean follow-up was 5.1 years (range: 3.2–8 years); mean age at diagnosis of primary vesicoureteral reflux was 4.2 years, and mean age at first Deflux® treatment was 6.2 years. Overall cure rates were 65.3% after one Deflux® treatment, 75.3% after two, and 77.3% after three.ConclusionTo the best of our knowledge, this is the first multi-institutional outcome analysis of Deflux® usage for primary vesicoureteral reflux in Japan.
Metformin acts as a dual glucose regulator in mouse brain
Authors: Jin Bo-Yeong , Kim Hyun-Ju , Oh Mi-Jeong , Ha Na-Hee , Jeong Yong Taek , Choi Sang-Hyun , Lee Jun-Seok , Kim Nam Hoon , Kim Dong-Hoon 
Published: April 2023

Aims: Metformin improves glucose regulation through various mechanisms in the periphery. Our previous study revealed that oral intake of metformin activates several brain regions, including the hypothalamus, and directly activates hypothalamic S6 kinase in mice. In this study, we aimed to identify the direct effects of metformin on glucose regulation in the brain.Materials and methods: We investigated the role of metformin in peripheral glucose regulation by directly administering metformin intracerebroventricularly in mice. The effect of centrally administered metformin (central metformin) on peripheral glucose regulation was evaluated by oral or intraperitoneal glucose, insulin, and pyruvate tolerance tests. Hepatic gluconeogenesis and gastric emptying were assessed to elucidate the underlying mechanisms. Liver-specific and systemic sympathetic denervation were performed.Results: Central metformin improved the glycemic response to oral glucose load in mice compared to that in the control group, and worsened the response to intraperitoneal glucose load, indicating its dual role in peripheral glucose regulation. It lowered the ability of insulin to decrease serum glucose levels and worsened the glycemic response to pyruvate load relative to the control group. Furthermore, it increased the expression of hepatic G6pc and decreased the phosphorylation of STAT3, suggesting that central metformin increased hepatic glucose production. The effect was mediated by sympathetic nervous system activation. In contrast, it induced a significant delay in gastric emptying in mice, suggesting its potent role in suppressing intestinal glucose absorption.Conclusion: Central metformin improves glucose tolerance by delaying gastric emptying through the brain-gut axis, but at the same time worsens it by increasing hepatic glucose production via the brain-liver axis. However, with its ordinary intake, central metformin may effectively enhance its glucose-lowering effect through the brain-gut axis, which could surpass its effect on glucose regulation via the brain-liver axis.
Combination therapy for high-volume versus low-volume metastatic hormone-sensitive prostate cancer: A systematic review and network meta-analysis
Authors: Jian Tengteng , Zhan Yang , Yu Ying , Yu Kai , Hu Rui , Wang Jixue , Lu Ji 
Published: April 2023

Purpose: To conduct a systematic review and network meta-analysis (NMA) to compare the efficacy of currently available combination therapies in patients with metastatic hormone-sensitive prostate cancer (mHSPC).Methods: Qualified publications were searched in the PubMed, Embase, and Cochrane CENTRAL databases. Overall survival (OS) and radiographic progression-free survival (rPFS) were indirectly compared and assessed using NMA and the surface under the cumulative ranking curve, respectively. Adverse events (AEs) were also compared.Results: Eighteen publications from 12 trials were analyzed in the NMA. In the overall population, triplet therapy was ranked first for OS (hazard ratio [HR]: 0.57, 95% credible interval [CrI]: 0.48–0.67) and rPFS (HR: 0.33, 95% CrI:0.26–0.41) compared with androgen deprivation therapy (ADT) with or without standard non-steroidal antiandrogen. In high-volume mHSPC, triplet therapy was also ranked first in OS (HR, 0.57; 95% CrI:0.44–0.75) and rPFS(HR, 0.29; 95% CrI: 0.23–0.37). Specifically, abiraterone triplet therapy was ranked first in OS (HR, 0.52; 95% CrI:0.38–0.72) and rPFS (HR, 0.28; 95% CrI:0.21–0.38) among all therapies. ADT plus rezvilutamide was ranked first among doublet therapies (OS: HR, 0.58; 95% CrI:0.44–0.77; rPFS: HR, 0.44; 95% CrI:0.33–0.58). In low-volume mHSPC, doublet and triplet therapies were ranked first in OS (HR:0.68, 95% CrI:0.58–0.80) and rPFS (HR:0.37, 95% CrI:0.25–0.55), respectively. ADT plus apalutamide was ranked first in OS among all therapies (HR:0.53, 95% CrI:0.35–0.79), whereas enzalutamide triplet therapy was ranked first in rPFS (HR:0.27, 95% CrI:0.15–0.51). ADT plus rezvilutamide showed a relatively lower incidence of AE among all therapies (OR:1.00, 95% CrI:0.31–3.15), and a lower risk of specific AEs among doublet therapies, particularly regarding seizure (OR, 0.29; 95% CrI:0.01–8.18) and fatigue (OR, 0.96; 95% CrI:0.63–1.46). Docetaxel-based doublet or triplet therapies significantly increased the risk of any AEs or grade ≥3 AEs.Conclusion: Triplet therapy was the best treatment option for the overall population. In high-volume mHSPC, triplet therapy and ADT plus rezvilutamide had the greatest potential to benefit patients. Patients with low-volume mHSPC were most likely to benefit from ADT plus androgen receptor-targeted agents. Triplet therapy was associated with a higher risk of AEs than the other therapies.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022375347, identifier PROSPERO:CRD42022375347.
The mushroom body development and learning ability of adult honeybees are influenced by cold exposure during their early pupal stage
Authors: Zhu Chenyu , Li Han , Xu Xinjian , Zhou Shujing , Zhou Bingfeng , Li Xiang , Xu Hongzhi , Tian Yuanmingyue , Wang Yanxin , Chu Yu , Zhang Xianlan , Zhu Xiangjie 
Published: April 2023

The honeybees are the most important pollinator in the production of crops and fresh produce. Temperature affects the survival of honeybees, and determines the quality of their development, which is of great significance for beekeeping production. Yet, little was known about how does low temperature stress during development stage cause bee death and any sub-lethal effect on subsequent. Early pupal stage is the most sensitive stage to low temperature in pupal stage. In this study, early pupal broods were exposed to 20°C for 12, 16, 24, and 48 h, followed by incubation at 35°C until emergence. We found that 48 h of low temperature duration cause 70% of individual bees to die. Although the mortality at 12 and 16 h seems not very high, the association learning ability of the surviving individuals was greatly affected. The brain slices of honeybees showed that low temperature treatment could cause the brain development of honeybees to almost stop. Gene expression profiles between low temperature treatment groups (T24, T48) and the control revealed that 1,267 and 1,174 genes were differentially expressed respectively. Functional enrichment analysis of differentially expressed genes showed that the differential expression of Map3k9, Dhrs4, and Sod-2 genes on MAPK and peroxisome signaling pathway caused oxidative damage to the honeybee head. On the FoxO signal pathway, InsR and FoxO were upregulated, and JNK, Akt, and Bsk were downregulated; and on the insect hormone synthesis signal pathway, Phm and Spo genes were downregulated. Therefore, we speculate that low temperature stress affects hormone regulation. It was detected that the pathways related to the nervous system were Cholinergic synapse, Dopaminergic synapse, GABAergic synapse, Glutamatergic synapse, Serotonergic synapse, Neurotrophin signaling pathway, and Synaptic vesicle cycle. This implies that the synaptic development of honeybees is quite possibly greatly affected by low temperature stress. Understanding how low temperature stress affects the physiology of bee brain development and how it affects bee behavior provide a theoretical foundation for a deeper comprehension of the temperature adaptation mechanism that underlies the “stenothermic” development of social insects, and help to improve honeybee management strategies to ensure the healthy of colony.
Insight into the phytochemical profile and antimicrobial activities of Amomum subulatum and Amomum xanthioides: an in vitro and in silico study
Authors: Alruhaili Mohammed H. , Almuhayawi Mohammed S. , Gattan Hattan S. , Alharbi Mohanned Talal , Nagshabandi Mohammed K. , Jaouni Soad K. Al , Selim Samy , AbdElgawad Hamada 
Published: April 2023

IntroductionMedicinal plants have been considered as potential source of therapeutics or as starting materials in drugs formulation.MethodsThe current study aims to shed light on the therapeutic potential of the Amomum subulatom and Amomum xanthioides Fruits by analyzing the phytochemical composition of their seeds and fruits using gas chromatography-mass spectrometry (GC-MS) and high-performance liquid chromatography (HPLC) techniques to determine the presence of bioactive components such as flavonoids, phenols, vitamins, steroids, and essential oils.Results and DiscussionThe protein content is usually higher than the total lipids in both species except the fruit of A. subulatum which contain more lipids than proteins. The total protein contents for A. subulatum were 235.03 ± 21.49 and 227.49 ± 25.82 mg/g dry weight while for A. xanthioides were 201.9 ± 37.79 and 294.99 ± 37.93 mg/g dry weight for seeds and fruit, respectively. The Carvacrol levels in A. subulatum is 20 times higher than that in A. xanthioides. Lower levels of α-Thujene, Phyllanderenes, Ascaridole, and Pinocarvone were also observed in both species. According to DPPH (2,2-diphenylpicrylhydrazyl) assay, seed the extract of A. subulatum exhibited the highest antioxidant activity (78.26±9.27 %) followed by the seed extract of A. xanthioides (68.21±2.56 %). Similarly, FRAP (Ferric Reducing Antioxidant Power) assay showed that the highest antioxidant activity was exhibited by the seed extract of the two species; 20.14±1.11 and 21.18±1.04 µmol trolox g−1 DW for A. subulatum and A. xanthioides, respectively. In terms of anti-lipid peroxidation, relatively higher values were obtained for the fruit extract of A. subulatum (6.08±0.35) and the seed extract of A. xanthioides (6.11±0.55). Ethanolic seed extracts of A. subulatum had the highest efficiency against four Gram-negative bacterial species which causes serious human diseases, namely Pseudomonas aeruginosa, Proteus vulgaris, Enterobacter aerogenes, and Salmonella typhimurium. In addition, P. aeruginosa was also inhibited by the fruit extract of both A. subulatum and A. xanthioides. For the seed extract of A. xanthioides, large inhibition zones were formed against P. vulgaris and the fungus Candida albicans. Finally, we have in silico explored the mode of action of these plants by performing detailed molecular modeling studies and showed that the antimicrobial activities of these plants could be attributed to the high binding affinity of their bioactive compounds to bind to the active sites of the sterol 14-alpha demethylase and the transcriptional regulator MvfR.ConclusionThese findings demonstrate the two species extracts possess high biological activities and therapeutical values, which increases their potential value in a number of therapeutic applications.
Effects of inorganic and compost tea fertilizers application on the taxonomic and functional microbial diversity of the purslane rhizosphere
Authors: Carrascosa Angel , Pascual Jose Antonio , López-García Álvaro , Romo-Vaquero María , De Santiago Ana , Ros Margarita , Petropoulos Spyridon A. , Alguacil Maria Del Mar 
Published: April 2023

IntroductionSoil fertility is a major determinant of plant-microbial interactions, thus, directly and indirectly affecting crop productivity and ecosystem functions. In this study, we analysed for the first time the effects of fertilizer addition on the cropping of purslane (Portulaca oleracea) with particular attention to the taxonomic and functional characteristics of their associated soil microbiota.MethodsWe tested the effects of different doses of inorganic fertilization differing in the amount of N:P:K namely IT1 (300:100:100); IT2 (300:200:100); IT3 (300:200:200); and IT4 (600:100:100) (ppm N:P:K ratio) and organic fertilization (compost tea) which reached at the end of the assay the dose of 300 ppm N.Results and discussionPurslane growth and soil quality parameters and their microbial community structure, abundance of fungal functional groups and prevailing bacterial metabolic functions were monitored. The application of compost tea and inorganic fertilizers significantly increased the purslane shoot biomass, and some soil chemical properties such as pH and soil enzymatic activities related to C, N and P biogeochemical cycles. The bacterial and fungal community compositions were significantly affected by the organic and chemical fertilizers input. The majority of inorganic fertilization treatments decreased the fungal and bacterial diversity as well as some predictive bacterial functional pathways.ConclusionsThese findings suggest that the inorganic fertilization might lead to a change of microbial functioning. However, in order to get stronger evidence that supports the found pattern, longer time-frame experiments that ideally include sampling across different seasons are needed. Thus, further research is still needed to investigate the effects of fertilizations on purslane productivity under commercial field conditions.