bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circ_0005615 promotes cervical cancer cell growth and metastasis by modulating the miR‐138‐5p/KDM2A axis
Authors: Luo Xiaoning , Liu Jiewen , Wang Xiangcai , Wang Yili , Yuan Jun , Zhang Yu 
Published: July 2023

AbstractCervical cancer (CC) is a highly fatal gynecological malignancy due to its high metastasis and recurrence rate. Circular RNA (circRNA) has been regarded as a regulator of CC. However, the underlying molecular mechanism of circ_0005615 in CC remains unclear. The levels of circ_0005615, miR‐138‐5p, and lysine demethylase 2A (KDM2A) were measured using qRT‐PCR or western blot. Cell proliferation was assessed by Cell Counting Kit‐8, 5‐ethynyl‐2′‐deoxyuridine, and colony formation experiments. Cell invasion and migration were tested by transwell assay and wound healing assay. Flow cytometry and Caspase‐Glo 3/7 Assay kit were used to analyze cell apoptosis. The expression of proliferation‐related and apoptosis‐related markers was detected by western blot. The binding relationships among circ_0005615, miR‐138‐5p, and KDM2A were verified by dual‐luciferase reporter assay or RNA immunoprecipitation assay. Xenograft assay was applied to detect the effect of circ_0005615 in vivo. Circ_0005615 and KDM2A were upregulated, while miR‐138‐5p was downregulated in CC tissues and cells. Circ_0005615 knockdown retarded cell proliferation, migration, and invasion, while promoting apoptosis. Besides, circ_0005615 sponged miR‐138‐5p, and miR‐138‐5p could target KDM2A. miR‐138‐5p inhibitor reversed the regulation of circ_0005615 knockdown on CC cell growth and metastasis, and KDM2A overexpression also abolished the inhibitory effect of miR‐138‐5p on CC cell growth and metastasis. In addition, we also discovered that circ_0005615 silencing inhibited CC tumor growth in vivo. Circ_0005615 acted as a tumor promoter in CC by regulating the miR‐138‐5p/KDM2A pathway.
Saikosaponin‐D induces the pyroptosis of lung cancer by increasing ROS and activating the NF‐κB/NLRP3/caspase‐1/GSDMD pathway
Authors: Chen Mengqing , Hu Chunyan , Yang Lei , Guo Qingxi , Liang Yuling , Wang Wenjun 
Published: July 2023

AbstractSaikosaponin‐D (SSD), an active ingredient in Bupleurum chinense, exerts anticancer effects in various cancers by inhibiting cancer proliferation and inducing apoptosis. However, whether SSD can induce other forms of cell death is unknown. The current study aims to demonstrate that SSD can induce pyroptosis in non‐small‐cell lung cancer. In this study, HCC827 and A549 non‐small‐cell lung cancer cells were treated with different concentrations of SSD for 1.5 h. HE and TUNEL staining were used to verify cell damage caused by SSD. Immunofluorescence and western blotting were performed to verify the effect of SSD on the NF‐κB/NLRP3/caspase‐1/gasdermin D (GSDMD) pathway. Changes in inflammatory factors were detected by ELISAs. Finally, the reactive oxygen species (ROS) scavenger N‐acetylcysteine (NAC) was introduced to verify that SSD induces pyroptosis through the ROS/NF‐κB pathway. The results of the HE and TUNEL staining showed that SSD resulted in balloon‐like swelling of NSCLC cells accompanied by increased DNA damage. Immunofluorescence and western blot assays confirmed that SSD treatment activated the NLRP3/caspase‐1/GSDMD pathway, stimulated an increase in ROS levels and activated NF‐κB in lung cancer cells. The ROS scavenger N‐acetylcysteine significantly attenuated SSD‐induced NF‐κB/NLRP3/caspase‐1/GSDMD pathway activation and inhibited the release of the inflammatory cytokines IL‐1β and IL‐18. In conclusion, SSD induced lung cancer cell pyroptosis by inducing ROS accumulation and activating the NF‐κB/NLRP3/caspase‐1/GSDMD pathway. These experiments lay the foundation for the application of SSD in the treatment of non‐small‐cell lung cancer and regulation of the lung cancer immune microenvironment.
Sinensetin ameliorates high glucose‐induced diabetic nephropathy via enhancing autophagy in vitro and in vivo
Authors: Kong Zili , Lv Wenshan , Wang Yunyang , Huang Yajing , Che Kui , Nan Huiqi , Xin Yu , Wang Jiaxuan , Chen Jintao , Wang Yangang , Chi Jingwei 
Published: July 2023

AbstractDiabetic nephropathy (DN) affects around 40% of people with diabetes, the final outcome of which is end‐stage renal disease. The deficiency of autophagy and excessive oxidative stress have been found to participate in the pathogenesis of DN. Sinensetin (SIN) has been proven to have strong antioxidant capability. However, the effect of SIN on DN has not been studied. We examined the effect of SIN on cell viability and autophagy in the podocyte cell line, MPC5 cells, treated with high glucose (HG). For in vivo studies, DN mice models were established by intraperitoneal injected with streptozotocin (40 mg/kg) for 5 consecutive days and fed with a 60% high‐fat diet, and SIN was given (10, 20, and 40 mg/kg) for 8 weeks via intraperitoneal injection. The results showed that SIN could protect MPC5 cells against HG‐induced damage and significantly improve the renal function of DN mice. Moreover, SIN remarkably restored the autophagy activity of MPC5 cells which was inhibited under HG conditions. Consistent with this, SIN efficiently improved autophagy in the kidney tissue of DN mice. In brief, our findings demonstrated the protective effect of SIN on DN via restoring the autophagic function, which might provide a basis for drug development.
Sanguinarine targets BRD4 to suppress cell proliferation and migration in clear cell renal cell carcinoma
Authors: Wen Yibo , Song Yue , Ma Yuan , Wen Jianguo , Yang Jinghua 
Published: July 2023

AbstractSanguinarine is an alkaloid with diverse biological activities, nevertheless, whether it can target epigenetic modifiers remains unknown. In this study, sanguinarine was characterized as a strong BRD4 inhibitor with IC50 = 361.3 nM against BRD4 (BD1) and IC50 = 302.7 nM against BRD4 (BD2) that can inactivate BRD4 reversibly. Additional cellular assays suggested that sanguinarine can bind BRD4 in human clear cell renal cell carcinoma (ccRCC) cell line 786‐O and inhibit cell growth with IC50 (24 h) = 0.6752 μM and IC50 (48 h) = 0.5959 μM in a BRD4 dependent manner partially. Meanwhile, sanguinarine can inhibit the migration of 786‐O cells in vitro and in vivo, and reverse epithelial−mesenchymal transition. Moreover, it can inhibit 786‐O cells proliferation in vivo in a BRD4 dependent manner partially. In sum, our study identified BRD4 as a new target of sanguinarine, and sanguinarine may serve as a potential therapeutic agent against ccRCC.
PPARγ agonist inhibits c‐Myc‐mediated colorectal cancer tumor immune escape
Authors: Xu Liuqian , Che Suning , Chen Huiqing , Liu Qian , Shi Juanjuan , Jin Jianhua , Hou Yongzhong 
Published: July 2023

AbstractAs a master transcription factor, c‐Myc plays an important role in promoting tumor immune escape. In addition, PPARγ (peroxisome proliferator‐activated receptor γ) regulates cell metabolism, inflammation, and tumor progression, while the effect of PPARγ on c‐Myc‐mediated tumor immune escape is still unclear. Here we found that cells treated with PPARγ agonist pioglitazone (PIOG) reduced c‐Myc protein expression in a PPARγ‐dependent manner. qPCR analysis showed that PIOG had no significant effect on c‐Myc gene levels. Further analysis showed that PIOG decreased c‐Myc protein half‐life. Moreover, PIOG increased the binding of c‐Myc to PPARγ, and induced c‐Myc ubiquitination and degradation. Importantly, c‐Myc increased PD‐L1 and CD47 immune checkpoint protein expression and promoted tumor immune escape, while PIOG inhibited this event. These findings suggest that PPARγ agonist inhibited c‐Myc‐mediated tumor immune escape by inducing its ubiquitination and degradation.
The role of GPLD1 in chronic diseases
Authors: Cao Jing , Zhou Anni , Zhou Zhuoyang , Liu Hui , Jia Shaohui 
Published: July 2023

AbstractGlycosylphosphatidylinositol‐specific phospholipase D (GPLD1) is a specific enzyme for glycosylphosphatidylinositol (GPI) anchors, thereby exerting its biological functions by cleaving membrane‐associated GPI molecules. GPLD1 is abundant in serum, with a concentration of approximately 5−10 µg/mL. Previous studies have demonstrated that GPLD1 plays a crucial role in the pathogenesis of numerous chronic diseases including disorders of lipid and glucose metabolism, cancer, and neurological disorders. In the present study, we reviewed the structure, functions, and localization of GPLD1 in chronic diseases, as well as exercise‐mediated regulation of GPLD1, thus providing a theoretical support to develop GPLD1 as a new therapeutic target for chronic diseases.
Plant anthraquinones: Classification, distribution, biosynthesis, and regulation
Authors: Wang Peng , Wei Jia , Hua Xin , Dong Gangqiang , Dziedzic Krzysztof , Wahab Atia‐tul , Efferth Thomas , Sun Wei , Ma Pengda 
Published: July 2023

AbstractAnthraquinones are polycyclic compounds with an unsaturated diketone structure (quinoid moiety). As important secondary metabolites of plants, anthraquinones play an important role in the response of many biological processes and environmental factors. Anthraquinones are common in the human diet and have a variety of biological activities including anticancer, antibacterial, and antioxidant activities that reduce disease risk. The biological activity of anthraquinones depends on the substitution pattern of their hydroxyl groups on the anthraquinone ring structure. However, there is still a lack of systematic summary on the distribution, classification, and biosynthesis of plant anthraquinones. Therefore, this paper systematically reviews the research progress of the distribution, classification, biosynthesis, and regulation of plant anthraquinones. Additionally, we discuss future opportunities in anthraquinone research, including biotechnology, therapeutic products, and dietary anthraquinones.
Trastuzumab Deruxtecan Dosing in Human Epidermal Growth Factor Receptor 2‐Positive Gastric Cancer: Population Pharmacokinetic Modeling and Exposure–Response Analysis
Authors: Yoshihara Kazutaka , Kobayashi Yoshimasa , Endo Seiko , Fukae Masato , Hennig Stefanie , Kastrissios Helen , Kamiyama Emi , Garimella Tushar , Abutarif Malaz 
Published: July 2023

AbstractThis study evaluated the benefit/risk of trastuzumab deruxtecan (T‐DXd) 6.4 mg/kg in patients with human epidermal growth factor receptor 2 (HER2)‐positive gastric cancer using pharmacometrics. A population pharmacokinetic (PopPK) model was developed using data from patients with gastric cancer, breast cancer, or other tumors in T‐DXd clinical trials, primarily conducted in Asia. Post hoc model‐estimated pharmacokinetic metrics were used in exposure–efficacy (objective response rates, ORRs) and exposure–safety analyses. The PopPK analysis included 808 patients (217 with gastric cancer, 512 with breast cancer, and 79 with other cancers). In gastric cancer, the T‐DXd 6.4 mg/kg steady‐state exposure metrics were lower compared with 6.4 mg/kg in breast cancer, but were similar to 5.4 mg/kg in breast cancer. Tumor type was selected as a significant covariate on T‐DXd clearance. In exposure–efficacy analysis among 160 patients with gastric cancer, the T‐DXd steady‐state minimum concentration was associated with a confirmed ORR in univariate logistic regression analysis (P = .023). The model‐predicted confirmed ORRs in gastric cancer were 36.0% (90%CI 29.3% to 43.7%) with 5.4 mg/kg and 40.0% (90%CI 33.1% to 47.6%) with 6.4 mg/kg. Among 808 patients in the exposure–safety analyses, the model‐predicted estimates for the rates of any‐grade interstitial lung disease (ILD) over a period of 180 days were 10.2% (90%CI 8.7% to 12.8%) with 6.4 mg/kg in gastric cancer and 9.7% (90%CI 8.2% to 11.8%) with 5.4 mg/kg in breast cancer. In gastric cancer, the efficacy of T‐DXd was higher at 6.4 mg/kg than at 5.4 mg/kg. Exposure and ILD rates were comparable between 6.4 mg/kg in gastric cancer and 5.4 mg/kg in breast cancer. This study identified T‐DXd 6.4 mg/kg as the recommended dose in HER2‐positive gastric cancer.
Electronic periodontal tool integration to enrich clinical diagnosis
Authors: Garcia M. Nathalia , Whitener Sara J. , Miley Douglas , Hildebolt Charles F. 
Published: July 2023

AbstractPurpose/objectivesThe objective of this study was to evaluate the effectiveness of an Electronic‐Periodontal‐Diagnosis‐Tool (EPDT) to facilitate the formulation of a correct periodontal diagnosis and analyze students’ perceptions of the use of the EPDT.MethodsFifty Year‐3 students who recently started their clinical training, were randomly assigned to two groups. Two clinical scenarios involving challenging periodontal diagnoses, each one with unique components, variables, and categories were distributed with specific instructions. The cases were analyzed to determine the correct periodontal diagnosis–half without the use of the EPDT and half with the use of the EPDT. A post‐exercise discussion conducted by the faculty explained the answer rationales. The students completed an anonymous/voluntary survey to evaluate their perceptions. Statistical analysis using likelihood ratio chi‐square tests and a generalized linear model evaluated whether the use of the EPDT resulted in higher percentages of correct diagnoses.ResultsEPDT use resulted in a three times higher percentage of correct classifications than no tool use (48% versus 16%), which the investigators considered an important effect of the EPDT. The generalized‐linear‐model assessment confirmed that EPDT resulted in better classifications (p < 0.0001). The feedback about the perceptions of the EPDT was favorable.ConclusionStudents using the EPDT resulted in higher percentages of correct diagnoses. The EPDT provided students with a useful framework to determine the correct periodontal diagnoses, which is essential in providing appropriate treatments.
Skeletal anatomy of the pectoral fin in mudskipper species from terrestrial and aquatic habitats
Authors: Zhou Haodong , Donatelli Cassandra M. , Laneuville Odette , Standen Emily M. 
Published: July 2023

AbstractMudskippers are a group of amphibious fishes in the family Oxudercidae, whose species inhabit a range of habitats from mostly aquatic to mostly terrestrial. Most of our understanding about habitat preference comes from natural history observations, particularly where they are collected (i.e., low intertidal vs. high intertidal regions). Mudskippers have undergone several morphological changes to accommodate a terrestrial life, including major changes to the pectoral and pelvic girdles. These changes result in a novel crutching gait, which mudskippers use to move over land. Though the appendicular morphology and crutching gait of mudskippers have been described in some species, few studies have compared skeletal structures across the family. In our study, we use microcomputed tomography (µCT) scans to compare the skeletal anatomy of 16 species of aquatic and terrestrial mudskippers. Linear discriminant analysis is used to analyze measurements obtained through geometric morphometrics (landmarks). We found bone structures of the pectoral region in the terrestrial group were significantly longer and wider than those in the aquatic group. Furthermore, a significant difference in anatomy is shown between terrestrial and aquatic genera with both axial and appendicular elements contributing to the separation between groups. This work describes the differences in skeletal morphology associated with terrestriality in mudskippers and provides valuable insights into specific anatomical characteristics contributing to their adaptation to novel environments.
A protospacer adjacent motif‐free, multiplexed, and quantitative nucleic acid detection platform with barcode‐based Cas12a activity
Authors: Zhou Miaojin , Zhang Chunhua , Chen Miaomiao , Hu Zhiqing , Li Menglin , Li Zhuo , Wu Lingqian , Liang Desheng 
Published: July 2023

AbstractClustered regularly interspaced short palindromic repeat (CRISPR)‐based biosensors have been developed to facilitate the rapid and sensitive detection of nucleic acids. However, most approaches using CRISPR‐based detection have disadvantages associated with the limitations of CRISPR RNA (crRNA), protospacer adjacent motif (PAM) or protospacer flanking sequence restriction, single channel detection, and difficulty in quantitative detection resulting in only some target sites being detected qualitatively. Here, we aimed to develop a barcode‐based Cas12a‐mediated DNA detection (BCDetection) strategy, which overcomes the aforementioned drawbacks and enables (1) detection with a universal PAM and crRNA without PAM or crRNA restriction, (2) simultaneous detection of multiple targets in a single reaction, and (3) quantitative detection, which can significantly distinguish copy number differences up to as low as a two‐fold limit. We could efficiently and simultaneously detect three β‐thalassemia mutations in a single reaction using BCDetection. Notably, samples from normal individuals, spinal muscular atrophy (SMA) carriers, and SMA patients were significantly and accurately distinguished using the quantitative detection ability of BCDetection, indicating its potential application in β‐thalassemia and SMA carrier screening. Therefore, our findings demonstrate that BCDetection provides a new platform for accurate and efficient quantitative detection using CRISPR/Cas12a, highlighting its bioanalytical applications.
Modulation of the immunity and inflammation by autophagy
Authors: Gan Ting , Qu Shu , Zhang Hong , Zhou Xu‐jie 
Published: July 2023

AbstractAutophagy, a highly conserved cellular self‐degradation pathway, has emerged with novel roles in the realms of immunity and inflammation. Genome‐wide association studies have unveiled a correlation between genetic variations in autophagy‐related genes and heightened susceptibility to autoimmune and inflammatory diseases. Subsequently, substantial progress has been made in unraveling the intricate involvement of autophagy in immunity and inflammation through functional studies. The autophagy pathway plays a crucial role in both innate and adaptive immunity, encompassing various key functions such as pathogen clearance, antigen processing and presentation, cytokine production, and lymphocyte differentiation and survival. Recent research has identified novel approaches in which the autophagy pathway and its associated proteins modulate the immune response, including noncanonical autophagy. This review provides an overview of the latest advancements in understanding the regulation of immunity and inflammation through autophagy. It summarizes the genetic associations between variants in autophagy‐related genes and a range of autoimmune and inflammatory diseases, while also examining studies utilizing transgenic animal models to uncover the in vivo functions of autophagy. Furthermore, the review delves into the mechanisms by which autophagy dysregulation contributes to the development of three common autoimmune and inflammatory diseases and highlights the potential for autophagy‐targeted therapies.
Low‐profile omnidirectional antenna with broad bandwidth and high gain
Authors: Guo Yao , Zhao Jing , Hui Weihua , Xie Kunlun , Hou Quanwen , Zhao Xiaopeng 
Published: July 2023

AbstractIn this study, a novel low profile wideband omnidirectional antenna is proposed. Horizontal dimension is utilized by introducing annular patches and near‐zero‐index metamaterials, instead of enhancing horizontal gain through increasing the profile of antenna. Measured results illustrate that horizontal gain of this antenna is enhanced to more than 2.5 dBi with 9.81% relative bandwidth (4.97−5.49 GHz) and low profile (0.034λ). Compared with other works, this novel antenna has obvious advantages in electromagnetic characteristics and physical structure, which has great potential in vehicular communications.
Impact of undernutrition on the pharmacokinetics of chemotherapy in children with cancer: A systematic review
Authors: Schoon Sterre , Makamo Nthongase , Uittenboogaard Aniek , Bernhardt Melanie B. , Ozuah Nmazuo W. , Kaspers Gertjan J. L. , Huibers Minke H. W. 
Published: July 2023

AbstractObjectivesThis systematic review provides an overview of the effect of undernutrition on the pharmacokinetics of chemotherapy in children with cancer.MethodsPubMed, Embase, and Cochrane were searched to identify eligible studies. This study uses the definition for undernutrition from the World Health Organization and the Gomez classification.ResultsFour studies with a total of 668 children with cancer were included and n = 121 (18%) were undernourished. Significant decreased clearance rates were found for vincristine in undernourished children compared to children with a normal nutritional status.ConclusionPresenting outcomes only show significant changes in the pharmacokinetics of vincristine in undernourished children with cancer. However, data are scarce, groups were small, and none of the studies included severely undernourished children. In order to improve outcomes for (severely) undernourished children with cancer, more pharmacokinetic research is needed. The ultimate goal would be to develop subgroups, and ultimately individualized drug dosing in order to improve outcomes for children with cancer worldwide.
A comparison of high‐ and low‐resolution gas chromatography–mass spectrometry for herbal product classification: A case study with Ocimum essential oils
Authors: Abraham Evelyn J. , Wallace E. Diane , Kellogg Joshua J. 
Published: July 2023

AbstractIntroductionSelection of marker compounds for targeted chemical analysis is complicated when considering varying instrumentation and closely related plant species. High‐resolution gas chromatography–mass spectrometry (GC–MS), via orbitrap detection, has yet to be evaluated for improved marker compound selection.ObjectiveThis study directly compares high‐ and low‐resolution GC–MS for botanical maker compound selection using Ocimum tenuiflorum L. (OT) and Ocimum gratissimum L. (OG) for botanical ingredient authentication.MethodsThe essential oils of OT and OG were collected via hydrodistillation before untargeted chemical analysis with gas chromatography coupled to single‐quadrupole (GC‐SQ) and orbitrap (GC‐Orbitrap) detectors. The Global Natural Products Social Molecular Networking (GNPS) software was used for compound annotation, and a manual search was used to find the 41 most common Ocimum essential oil metabolites.ResultsThe GC‐Orbitrap resulted in 1.7‐fold more metabolite detection and increased dynamic range compared to the GC‐SQ. Spectral matching and manual searching were improved with GC‐Orbitrap data. Each instrument had differing known compound concentrations; however, there was an overlap of six compounds with higher abundance in OG than OT and three compounds with a higher abundance in OT than OG, suggesting consistent detection of the most variable compounds. An unsupervised principal component analysis (PCA) could not discern the two species with either dataset.ConclusionGC‐Orbitrap instrumentation improves compound detection, dynamic range, and feature annotation in essential oil analysis. However, considering both high‐ and low‐resolution data may improve reliable marker compound selection, as GC‐Orbitrap analysis alone did not improve unsupervised separation of two Ocimum species compared to GC‐SQ data.