bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of vitamin D deficiency and insufficiency with uncontrolled type 1 diabetes Mellitus among Saudi pediatric patients; a hospital-based retrospective study
Authors: Almansour Salman , Alsalamah Abdullrahman , Almutlaq Mohammad , Sheikh Ahmed , Hamdan Hamdan Z. , Al-Nafeesah Abdullah , AlEed Ashwaq , Adam Ishag , Al-Wutayd Osama 
Published: January 2025

BackgroundThe association between 25-hydroxy-vitamin D [25(OH)D] levels and glycemic control in pediatric patients with type 1 diabetes mellitus (T1DM) is unclear. In this study, we aimed to investigate the association between 25(OH)D levels and glycemic control in Saudi pediatric patients' with T1DM in a region that is sunny year-round.Materials and methodsA retrospective study was conducted in the Pediatric Department of King Saud Hospital in Unaizah, Saudi Arabia. A total of 218 children with T1DM were enrolled in the study and grouped according to their glycated hemoglobin (HbA1C) levels into the controlled T1DM (HbA1C ≤ 7.5%) and the uncontrolled T1DM (HbA1C &gt; 7.5%). Their 25(OH)D levels and thyroid function were measured using standard methods.ResultsOf the 218 children in this study, 182 (83.5%) had uncontrolled T1DM, while only 36 (16.5%) had controlled T1DM. The median (interquartile range) of 25(OH)D levels was significantly lower in the uncontrolled T1DM group compared with the controlled group [45.4 (31.2–59.7) nmol/L vs. 56.1 (37.5–77.6) nmol/L; p = 0.007], respectively. Vitamin D deficiency (&lt;50.0 nmol/L) and insufficiency (50–74 nmol/L) were detected in 55.0% and 31.1% of all the enrolled children, respectively. Vitamin D deficiency was detected in 86.6% of the uncontrolled T1DM patients and in 16.5% of the controlled T1DM patients (p = 0.012). The multivariable analysis showed that both vitamin D deficiency [adjusted odds ratio (aOR) = 2.92, p = 0.048] and insufficiency [aOR = 3.17, p = 0.042] were risk factors for uncontrolled diabetes.ConclusionVitamin D deficiency was highly prevalent in the studied group. Both vitamin D deficiency and insufficiency are associated with uncontrolled T1DM. Further study is needed.
Vitamin D protects spermatogonia and Sertoli cells from heat stress damage by inhibiting NLRP3
Authors: Chu Han , Deng Qi-Fei , Fang Yuan 
Published: January 2025

IntroductionCryptorchidism can damage cells in the cryptorchid testes due to elevated local temperatures, potentially impacting the fertility of the child in adulthood. Research indicates that vitamin D enhances sperm quality in adult males. This study aimed to explore whether vitamin D inhibits NLRP3 activation, thus helping to mitigate heat stress damage to testicular spermatogenic and Sertoli cells.Materials and methodsFive cases of normal testicular tissue adjacent to a tumor (testis removed due to tumorous growth) and five cases of atrophied cryptorchid testicular tissue (testis removed) were analyzed for immunohistochemistry to determine NLRP3 expression in cryptorchid tissue. In Phase I, spermatogonia (GC-1) and Sertoli cells (TM4) were separated into blank and heat stress groups. Apoptosis, inflammatory factor levels, and the expression of Bcl-2 and NLRP3 genes and proteins were measured at 2, 6, and 10 h after heat stress treatment. In Phase II, the cells were re-cultured and divided into three groups: heat stress, siRNA + heat stress, and VD + heat stress. After 10 h, the apoptosis, inflammatory factor levels, and gene and protein expressions of Bcl-2 and NLRP3 were reassessed in each group.ResultsImmunohistochemistry indicated NLRP3 expression in cryptorchid tissue. Phase I, extending heat stress duration led to increased apoptosis in spermatogonia (GC-1) and testicular Sertoli cells (TM4), heightened levels of inflammatory factors, reduced BCL-2 expression, and elevated NLRP3 expression compared to the control group. Phase II, both the siRNA + heat stress and VD + heat stress groups showed decreased apoptosis in spermatogonia and Sertoli cells, lower inflammatory factor levels, increased BCL-2 expression, and decreased NLRP3 expression compared to the heat stress-only group, with statistically significant differences (P &lt; 0.05).ConclusionsThis is the first time we found the expression of NLRP3 in cryptorchidism. Vitamin D can inhibit the expression of NLRP3 and reduce the damage of heat stress on testicular spermatogenic cells and Sertoli cells, and play a protective role for testicular spermatogenic cells and Sertoli cells. This provides a theoretical basis for preserving testicular function during the “treatment gap” in boys with cryptorchidism who have not received surgical treatment.
Nature’s magic: how natural products work hand in hand with mitochondria to treat stroke
Authors: Cheng Lin , Lv Shangbin , Wei Chengkai , Li Sucheng , Liu Hao , Chen Yong , Luo Zhaoliang , Cui Hongyan 
Published: January 2025

BackgroundMitochondria, as the energy factories of cells, are involved in a wide range of vital activities, including cell differentiation, signal transduction, the cell cycle, and apoptosis, while also regulating cell growth. However, current pharmacological treatments for stroke are challenged by issues such as drug resistance and side effects, necessitating the exploration of new therapeutic strategies.ObjectiveThis review aims to summarize the regulatory effects of natural compounds targeting mitochondria on neuronal mitochondrial function and metabolism, providing new perspectives for stroke treatment.Main findingsNumerous in vitro and in vivo studies have shown that natural products such as berberine, ginsenosides, and baicalein protect neuronal mitochondrial function and reduce stroke-induced damage through multiple mechanisms. These compounds reduce neuronal apoptosis by modulating the expression of mitochondrial-associated apoptotic proteins. They inhibit the activation of the mitochondrial permeability transition pore (mPTP), thereby decreasing ROS production and cytochrome C release, which helps preserve mitochondrial function. Additionally, they regulate ferroptosis, mitochondrial fission, and promote mitochondrial autophagy and trafficking, further enhancing neuronal protection.ConclusionAs multi-target chemical agents, natural products offer high efficacy with fewer side effects and present promising potential for innovative stroke therapies. Future research should further investigate the effectiveness and safety of these natural products in clinical applications, advancing their development as a new therapeutic strategy for stroke.
Disproportionate adverse event signals of selumetinib in neurofibromatosis type I: insights from FAERS
Authors: Li Lin 
Published: January 2025

BackgroundNeurofibromatosis type 1 (NF1) is a rare neurogenetic disorder with limited treatment options. Selumetinib, a MEK1/2 inhibitor, has emerged as a promising therapy for inoperable NF1-related plexiform neurofibromas.MethodsOur retrospective pharmacovigilance study utilized the FDA Adverse Event Reporting System (FAERS) to comprehensively evaluate Selumetinib’s safety profile in real-world settings. Data from the third quarter of 2020 to the fourth quarter of 2023 were analyzed, identifying 498 adverse event reports with Selumetinib as the primary suspect drug.ResultsStatistical analysis revealed disproportionate signals for skin and subcutaneous tissue disorders, eye disorders, and various congenital, familial, and genetic disorders. The most common adverse events were elevated blood creatine phosphokinase, rash, and acneiform dermatitis. Notably, several adverse events, including rhabdomyolysis, were identified but not listed on the Selumetinib product label, based on a comparison with the FDA drug labeling.ConclusionThe study underscores the importance of early detection and management of adverse reactions associated with Selumetinib, particularly within the initial month of treatment. These findings provide valuable insights for clinicians and regulators to ensure the safe and effective use of Selumetinib in NF1 patients.
Current research status and trends of potassium-competitive acid blockers in the treatment of acid-related diseases: a bibliometric analysis
Authors: Zhu Baoqiang , Chen Long , Tao Xue , Zheng Hong , Li Xia , Wu Qingfang , Long Enwu , Lin Haixia 
Published: January 2025

ObjectiveTo explore the current research status and trends of potassium-competitive acid blockers (P-CABs) in the treatment of acid related diseases (ARDs) using bibliometric analysis.Materials and methodsWe collected publications related to P-CAB in the treatment of acid-related diseases in the Web of Science (WOS) Core Collection from the establishment of the database to 30 June 2024. We evaluated the publication volume and citation status over the years using the WOS platform, and visualized the authors, countries, institutions, keywords, and citations of the publications using CiteSpace and VOSviewer.ResultsThis study included a total of 455 articles. The number of publications and citations related to research has been increasing year by year. The results show that the scholars with the highest number of publications mainly come from South Korea and Japan. Scholars such as Geun Seog Song, Bongtae Kim, and Nobuhiro Inatomi produced many works in related fields. The most popular drug in this field was vonoprazan, and research on this drug mainly focused on the effectiveness and safety evaluation of ARDs such as Helicobacter pylori infection, gastroesophageal reflux disease, peptic ulcers, etc. Researchers were concerned about the evaluation of treatment regimens and efficacy comparison between P-CABs and traditional proton pump inhibitors (PPIs) in the treatment of ARDs. At the same time, researchers are also closely monitoring the potential adverse reactions and long-term adverse outcomes of clinical application of P-CABs for ARDs.ConclusionThe clinical application of P-CABs, represented by vonoprazan, in ARDs is receiving widespread attention from researchers. The exploration of the application of this type of drug in ARDs is constantly expanding, and it is a research field with great clinical value and research potential.
Oxyberberine alleviates lipopolysaccharide-induced intestinal barrier disruption and inflammation in human colonic Caco-2 cells in vitro
Authors: Li Cailan , Wang Jiahao , Yang Hongmei , Luo Shuang , Lu Qiang 
Published: January 2025

BackgroundOxyberberine (OBB) is a naturally occurring isoquinoline alkaloid that is believed to possess various health-promoting properties, including anti-fungus, hepatoprotection, anti-inflammation, and anti-intestinal mucositis effects. Despite several studies reporting the health benefits of OBB in treating ulcerative colitis (UC), its specific mechanism of action has yet to be fully elucidated.PurposeThis investigation is designed to explore the potential protective efficacy of OBB and the latent mechanism using an in vitro model of UC-like inflammatory intestinal cells.MethodsCaco-2 cells were pretreated with OBB and subsequently exposed to lipopolysaccharide (LPS). The transepithelial electrical resistance (TEER), paracellular permeability, and the distribution and expression of tight- and adherent junction proteins were determined to assess barrier integrity. The levels of proinflammatory cytokines, reactive oxygen species (ROS), Nrf2, and NF-κB signaling cascade were analyzed via ELISA, qRT-PCR, immunofluorescence, or Western blotting.ResultsOBB was found to mitigate the effects of LPS on Caco-2 cell monolayers, as evidenced by the improvement in TEER and the decrease in FITC-dextran flux. Moreover, OBB ameliorated the LPS-induced decrease in the distribution and expression of several tight junction markers, including ZO-1, occludin, and E-cadherin. In addition, OBB treatment effectively inhibited LPS-induced increases in ROS, apoptosis, and Keap1 and decreases in Nrf2 and HO-1. LPS-induced elevations in nuclear NF-κB p65 and p-IκBα were suppressed by OBB. In addition, ML385, an antagonist of Nrf2, abolished the protective role of OBB.ConclusionOBB has a pronounced beneficial effect on LPS-induced damage to enteral barrier function, and the regulation of the Nrf2/NF-κB pathway is an important mechanism responsible for the protection afforded by OBB.
Ponatinib alleviates non-alcoholic steatohepatitis through TFEB-mediated autophagy
Authors: Lin Zhuomiao , Yang Meiqing , Yu Xihui , Tan Guozhu , Zhong Jiahong 
Published: January 2025

ObjectiveNon-alcoholic steatohepatitis (NASH) is a progressive liver disease with lipid accumulation, inflammation, and liver fibrosis. Ponatinib, a third-generation tyrosine kinase inhibitors for the treatment of chronic myeloid leukemia, was found to improve metabolic disorders in mice. However, the role of ponatinib in liver inflammation and fibrosis remains to be elucidated. Here we aimed to determine the effect of ponatinib in non-alcoholic steatohepatitis.MethodsWe explored the function and mechanism of ponatinib using a mouse model of NASH induced by a methionine and choline deficient (MCD) diet and LO2 cells cultured in MCD mimic medium.ResultsHere, we found that ponatinib reduced liver lipid deposition, fibrosis, and inflammation induced by MCD diet without affecting body weight and blood glucose. Meanwhile, we found that ponatinib attenuated steatohepatitis and inflammation in LO2 cells induced by MCD mimic medium. We further discovered that the expression levels of LC3II and lysosomal associated membrane protein 1 (LAMP1) were reduced and the expression level of p62 was upregulated in both mouse and cell models, suggesting that autophagy was inhibited, which was restored by ponatinib treatment. In addition, transcription factor EB (TFEB) is a major regulator of autophagy and lysosome biogenesis and the transcription and protein expression levels of TFEB were decreased in steatosis hepatocytes, which could be ameliorated by ponatinib treatment.ConclusionThese results revealed that the beneficial effects of ponatinib on NASH via TFEB-mediated autophagy.
Identification of Salvia miltiorrhiza germplasm resources based on metabolomics and DNA barcoding
Authors: He Gaojie , Man Jinhui , Chen Ying , Zhang Xiaoqin , Wang Xin , An Kelu , Amu Laha , Chen Wenqin , Wang Baowei , Shi Yue , Wang Xiaohui , Wei Shengli 
Published: January 2025

IntroductionSalvia miltiorrhiza radix et rhizoma (Danshen) is a crucial medicinal material for treating cardiovascular and cerebrovascular diseases. However, the presence of adulterants and intraspecific variability poses challenges to its clinical safety.MethodsThis study collected samples of S. miltiorrhiza from various regions and commonly encountered adulterants. The composition differences of S. miltiorrhiza radix and its adulterants were analyzed by fingerprint and broad-target metabolomics. Chloroplast genome was used to distinguish intra-genus species and DNA barcoding was used to identify germplasm sources.ResultsThe fingerprinting analysis proved that there is no chemical composition consistency between S. miltiorrhiza radix and its adulterants. Broad-targeted metabolomics can distinguish S. miltiorrhiza radix from Salvia yunnanensis radix, Dipsacus asperoides radix, and Arctium lappa radix. Additionally, comparative chloroplast genome analysis indicated that atpF and rps4-trnT-UGU were the potential DNA barcodes for S. miltiorrhiza. 259 samples from 13 provinces and 21 origins were amplified and sequenced, resulting in the identification of 62 haplotypes. The unique haplotypes found in Shanxi Luoyang, Shandong Qingdao and other places can be used as molecular geographic markers for the identification of the germplasm source of S. miltiorrhiza.DiscussionThis study systematically differentiates S. miltiorrhiza from its adulterants and highlights the potential of unique haplotypes as markers for sourcing. The findings provide strong scientific evidence for the clinical safety of S. miltiorrhiza, emphasizing the importance of proper cultivation, selection, and breeding of varieties.
Effects of aerobic training with blood flow restriction on aerobic capacity, muscle strength, and hypertrophy in young adults: a systematic review and meta-analysis
Authors: Gao Zhendong , Li Yan , Zhang Jinjin , Li Liqiang , Wang Tao , Wang Xiaolin , Wang Hao 
Published: January 2025

Aerobic training with blood flow restriction (AT-BFR) has shown promise in enhancing both aerobic capacity and exercise performance. The aim of this review was to systematically analyze the evidence regarding the effectiveness of this novel training method on aerobic capacity, muscle strength, and hypertrophy in young adults. Studies were identified through a search of databases including PubMed, Scopus, Web of Science, SPORTDiscus, CINAHL, Cochrane Library, and EMBASE. A total of 16 studies, involving 270 subjects, were included in the meta-analysis. The results revealed that AT-BFR induced greater improvements in VO2max (SMD = 0.27, 95%CI: [0.02, 0.52], p &lt; 0.05), and muscle strength (SMD = 0.39, 95%CI: [0.09, 0.69], p &lt; 0.05), compared to aerobic training with no blood flow restriction (AT-noBFR). However, no significant effect was observed on muscle mass (SMD = 0.23, 95%CI: [-0.09, 0.56], p = 0.162). Furthermore, no moderating effects on the outcomes were found for individual characteristics or training factors. In conclusion, AT-BFR is more effective than AT-noBFR in improving aerobic capacity and muscle strength, making it a promising alternative to high-intensity training.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42024559872.
Cross-education: motor unit adaptations mediate the strength increase in non-trained muscles following 8 weeks of unilateral resistance training
Authors: Lecce Edoardo , Conti Alessandra , Del Vecchio Alessandro , Felici Francesco , Scotto di Palumbo Alessandro , Sacchetti Massimo , Bazzucchi Ilenia 
Published: January 2025

IntroductionEarly increases in muscle strength following unilateral resistance training are typically accompanied by strength gains in the contralateral untrained muscles, a phenomenon known as cross-education. However, the specific motor unit adaptations responsible for this gain transfer remain poorly understood. To address this gap, we recorded myoelectrical activity from the biceps brachii using high-density electromyography.MethodsNine participants performed 8-week unilateral resistance training and were compared to nine control individuals who did no intervention. Discharge characteristics of longitudinally tracked motor units were assessed during maximal voluntary contractions and isometric ramp contractions at 35% and 70% of the maximal voluntary force (MVF) at baseline (T0), 4 weeks (T1), and 8 weeks (T2) post-intervention.ResultsMVF increased by 7% in untrained muscles at T1 and 10% at T2 (p &lt; 0.05). These gains were accompanied by significant decreases in motor unit recruitment thresholds (p &lt; 0.01) and higher net discharge rate (i.e., gain in discharge rate from recruitment to peak) following intervention (p &lt; 0.05). Trained muscles presented greater MVF (+11%, T1; +19%, T2) with similar motor unit adaptations, including a lower recruitment threshold (p &lt; 0.01) and a higher net discharge rate (p &lt; 0.01).DiscussionOur findings indicate that higher strength in untrained muscles is associated with a higher net discharge rate, implying a greater spinal motoneuron output to muscles. The present results underscore the role of motor unit adaptations in the transfer of strength gains to non-trained muscles, offering novel insights into the neural mechanisms underlying cross-education.
Controlled-release nitrogen combined with ordinary nitrogen fertilizer improved nitrogen uptake and productivity of winter wheat
Authors: Ali Muhammad Fraz , Han Ruifeng , Lin Xiang , Wang Dong 
Published: January 2025

BackgroundBlending controlled-release nitrogen fertilizer (CRNF) with ordinary nitrogen fertilizer (ONF) is a strategic approach to improve winter wheat nutrient management. This blend provides nitrogen (N) to winter wheat in a balanced and consistent manner, ensuring long-term growth, reducing nutrient loss due to leaching or volatilization, and increasing N use efficiency (NUE).AimsCRNF aims to enhance N application suitability, optimizes soil nutrient dynamics, and its widespread use can boost crop NUE and yield. The study investigates how different CRNF and ONF blending ratios affect soil N content, winter wheat growth, and yield.MethodsThe experiment used two N application rates of 192(N1) and 240(N2) kg ha-1 of ONF, with five different blending ratios CRNF. The proportions of CRNF were 0%(F1), 30%(F2), 50%(F3), 70%(F4), and 100%(F5), respectively. The effects of changes in soil nitrate concentration, dry matter accumulation, N uptake, and transportation at various growth stages and yield were analyzed.ResultsCRNF at the jointing and anthesis stages helps maintain nitrate N levels throughout the growth cycle. Compared to full CRNF application at different N rates, this method also reduces nitrate N leaching in the soil. The 0-60 cm soil layer was primarily influenced by increasing the proportion of CRNF, especially from jointing to maturity. CRNF promotes a higher plant population during the turning green and jointing stages by increasing soil N content, thereby establishing a strong yield foundation for winter wheat. It increases winter wheat N accumulation and correlates positively with soil N content during key growth stages.ConclusionWinter wheat grain yield has increased, with significant yield increases observed at 70% blending with a higher amount of N at 240 kg ha-1 and achieved a 2.8% increase in NUE and a 3.0%-15.3% increase in grain yield. In order to improved winter wheat yields through effective N utilization, N2 application (240 kg ha-1) with the combination of (F4) 30% ONF + 70% CRNF would be recommended for northwest region of Shaanxi province in China. By increasing the amount of N accumulation at the anthesis stage, N transport is significantly increased after anthesis, and N accumulation and distribution ratio in grains are significantly increased at maturity.