bluuebunny/crossref_metadata_2025 huggingface dataset:
Global research trends in immunotherapy for non-small cell lung cancer patients with KRAS mutations: a bibliometric analysis
Authors: Shen Hanyu , Li Chunxiao
Published: May 2024

Background

Immunotherapy, frequently combined with conventional chemotherapy, is crucial for treating NSCLC. Kirsten rat sarcoma virus (KRAS) is a poor prognostic factor in patients with NSCLC, particularly lung adenocarcinoma, where binding of conventional inhibitors to mutated KRAS proteins is challenging. Field profiles, research hotspots, and prospects for immunotherapy for patients with NSCLC-carrying KRAS mutations were uncovered in this study.

Methods

Microsoft Excel 2019, Bibliometrix, VOSviewer software, and Citespace were utilized to conduct a comprehensive scientometric analysis and understand a specific research field's knowledge base and frontiers aided by bibliometrics.

Results

Between 2014 and 2023, 398 eligible documents in the English language were acquired using the WoSCC database, of which 113 and 285 were reviews and articles, respectively. The growth rate per year was 34.25 %. The most cited articles were from the United States, and China published the highest number of articles. Cancers was the journal, with increased publications in recent years. The keywords with the strongest citation bursts were analyzed using Citespace. "Immune checkpoint inhibitors," "co-occurring genomic alterations," and "KRAS" are among the research hotspots in this field.

Conclusion

Using bibliometric and visual analyses, we examined immunotherapy for patients with KRAS-mutant NSCLC over the previous decade. The whole analysis showed a steady, quick increase in yearly publications in this area. Our findings will provide a roadmap for future research on the mechanisms of immunotherapy and immune checkpoint inhibitor action in treating KRAS-mutant NSCLC.
Exploring the therapeutic potential of “Xiaochaihu Decoction”: a systematic review and meta-analysis on the clinical effectiveness and safety in managing cancer-related fever
Authors: Bu Zhijun , Xu Yaoyu , Zhou Xian , Wang Xuefeng , Liu Shuyuan , Wang Linyan , Yang Bei , Zhou Xiaodie , Lu Guanhang , Liu Jianping , Liu Zhaolan
Published: May 2024

Objective: This study aimed to conduct the first meta-analysis to comprehensively evaluate the clinical effectiveness and safety of Xiaochaihu Decoction in treating Cancer-related Fever (CRF).

Methods: Eight databases were systematically searched in September 2023. The risk of bias (ROB) 2.0 tool recommended by Cochrane Handbook was applied to evaluate the ROB of the included randomized controlled trials (RCTs). Additionally, the quality of evidence was assessed using the Grading of recommendations assessment, development and evaluation (GRADE) tool.

Results: We included 18 RCTs involving 1,424 patients. Compared to Western medicine or Xinhuang Tablets, Xiaochaihu Decoction significantly improved clinical effectiveness in CRF patients (risk ratio [RR] = 1.24, 95% confidence interval [CI]: 1.17, 1.32) and expedited the normalization of body temperature (mean difference [MD] = −5.29, 95%CI: −5.59, −4.99). It also demonstrated a reduction in tumor necrosis factor-α (TNF-α) levels (MD = −0.63, 95%CI: −0.84, −0.41) and an increase in IL-2 levels (MD = 1.42, 95%CI: −1.09, 1.74). Analysis of Karnofsky Performance Status (KPS) scores showed that the use of Xiaochaihu Decoction improved the quality of life in CRF patients (RR = 1.57, 95%CI: 1.11, 2.22) and reduced the incidence of adverse events. However, it is important to note that the majority of included studies showed “some concerns” in risk of bias based on ROB 2.0, and the evidence quality assessed by GRADE method was rated as “low”.

Conclusion: While this study suggests the clinical effectiveness and safety of Xiaochaihu Decoction in treating patients with CRF, confirming these findings will necessitate additional high-quality, large-scale RCTs in future research.

Systematic Review Registration:https://www.crd.york.ac.uk/prospero/, identifier CRD42023484068.
Selective and brain-penetrant ACSS2 inhibitors target breast cancer brain metastatic cells
Authors: Esquea Emily M. , Ciraku Lorela , Young Riley G. , Merzy Jessica , Talarico Alexandra N. , Ahmed Nusaiba N. , Karuppiah Mangalam , Ramesh Anna , Chatoff Adam , Crispim Claudia V. , Rashad Adel A. , Cocklin Simon , Snyder Nathaniel W. , Beld Joris , Simone Nicole L. , Reginato Mauricio J. , Dick Alexej
Published: May 2024

Breast cancer brain metastasis (BCBM) typically results in an end-stage diagnosis and is hindered by a lack of brain-penetrant drugs. Tumors in the brain rely on the conversion of acetate to acetyl-CoA by the enzyme acetyl-CoA synthetase 2 (ACSS2), a key regulator of fatty acid synthesis and protein acetylation. Here, we used a computational pipeline to identify novel brain-penetrant ACSS2 inhibitors combining pharmacophore-based shape screen methodology with absorption, distribution, metabolism, and excretion (ADME) property predictions. We identified compounds AD-5584 and AD-8007 that were validated for specific binding affinity to ACSS2. Treatment of BCBM cells with AD-5584 and AD-8007 leads to a significant reduction in colony formation, lipid storage, acetyl-CoA levels and cell survival in vitro. In an ex vivo brain-tumor slice model, treatment with AD-8007 and AD-5584 reduced pre-formed tumors and synergized with irradiation in blocking BCBM tumor growth. Treatment with AD-8007 reduced tumor burden and extended survival in vivo. This study identifies selective brain-penetrant ACSS2 inhibitors with efficacy towards breast cancer brain metastasis.
Protein disulfide isomerase-9 interacts with the lumenal region of the transmembrane endoplasmic reticulum stress sensor kinase, IRE1, to modulate the unfolded protein response in Arabidopsis
Authors: Carrillo Rina , Iwai Kaela , Albertson Alena , Dang Gabrielle , Christopher David A.
Published: May 2024

Environmental stressors disrupt secretory protein folding and proteostasis in the endoplasmic reticulum (ER), leading to ER stress. The unfolded protein response (UPR) senses ER stress and restores proteostasis by increasing the expression of ER-resident protein folding chaperones, such as protein disulfide isomerases (PDIs). In plants, the transmembrane ER stress sensor kinase, IRE1, activates the UPR by unconventionally splicing the mRNA encoding the bZIP60 transcription factor, triggering UPR gene transcription. The induced PDIs catalyze disulfide-based polypeptide folding to restore the folding capacity in the ER; however, the substrates with which PDIs interact are largely unknown. Here, we demonstrate that the Arabidopsis PDI-M subfamily member, PDI9, modulates the UPR through interaction with IRE1. This PDI9–IRE1 interaction was largely dependent on Cys63 in the first dithiol redox active domain of PDI9, and Cys233 and Cys107 in the ER lumenal domain of IRE1A and IRE1B, respectively. In vitro and in vivo, PDI9 coimmunoprecipitated with IRE1A and IRE1B. Moreover, the PDI9:RFP and Green Fluorescence Protein (GFP):IRE1 fusions exhibited strong interactions as measured by fluorescence lifetime imaging microscopy-fluorescence resonance energy transfer (FLIM-FRET) when coexpressed in mesophyll protoplasts. The UPR-responsive PDI9 promoter:mCherry reporter and the UPR-dependent splicing of the bZIP60 intron from the mRNA of the 35S::bZIP60-intron:GFP reporter were both significantly induced in the pdi9 mutants, indicating a derepression and hyperactivation of UPR. The inductions of both reporters were substantially attenuated in the ire1a–ire1b mutant. We propose a model in which PDI9 modulates the UPR through two competing activities: secretory protein folding and via interaction with IRE1 to maintain proteostasis in plants.
Inhomogeneous energy transfer dynamics from iron-stress-induced protein A to photosystem I
Authors: Akhtar Parveen , Jana Sanjib , Lambrev Petar H. , Tan Howe-Siang
Published: May 2024

Cyanobacteria respond to iron limitation by producing the pigment-protein complex IsiA, forming rings associated with photosystem I (PSI). Initially considered a chlorophyll-storage protein, IsiA is known to act as an auxiliary light-harvesting antenna of PSI, increasing its absorption cross-section and reducing the need for iron-rich PSI core complexes. Spectroscopic studies have demonstrated efficient energy transfer from IsiA to PSI. Here we investigate the room-temperature excitation dynamics in isolated PSI–IsiA, PSI, IsiA monomer complexes and IsiA aggregates using two-dimensional electronic spectroscopy. Cross analyses of the data from these three samples allow us to resolve components of energy transfer between IsiA and PSI with lifetimes of 2—3 ps and around 20 ps. Structure-based Förster theory calculations predict a single major timescale of IsiA-PSI equilibration, that depends on multiple energy transfer routes between different IsiA subunits in the ring. Despite the experimentally observed lifetime heterogeneity, which is attributed to structural heterogeneity of the supercomplexes, IsiA is found to be a unique, highly efficient, membrane antenna complex in cyanobacteria.
The impact of social participation on Subjective Wellbeing in the older adult: the mediating role of anxiety and the moderating role of education
Authors: Qing Zaihua , Wu Caihong , Gao Tao
Published: May 2024

Introduction

The study aims to examine the mediating role of anxiety in the relationship between social participation and Subjective Wellbeing among Chinese older adults. Additionally, it investigates the moderating ed of education in this relationship.

Methods

The data came from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) published by peking University, with a sample size of 10,626 individuals aged 60 years and above. SPSS 21.0 was used for the statistical analysis of the data, and Mplus 8.0 was used for the statistical processing of the mediating and moderating effects analysis.

Results

(1) The social participation significantly and positively predicated Subjective Wellbeing; (2) Anxiety partially mediated the eect between social participation and Subjective Wellbeing. The mediating eect value was 0.103; (3) Education plays a moderating role in the impact of social participation on subjective Wellbeing.

Discussion

In summary, social participation can reduce the anxiety and enhance their Subjective Wellbeing. Meanwhile, the eet of social participation on Subjective Wellbeing was the greatest for the older adult with high education. The findings suggest that community-led activities can be initiated to improve social participation in the older adult. Furthermore, educational courses could be to support the healthy aging of older adults in China.
What are the important factors influencing the physical activity level of junior high school students: a cross-sectional survey
Authors: Ma Huijun , Li Xuefeng , Ma Chengliang , Teng Da
Published: May 2024

Background

Engaging in regular physical activity has been consistently linked to improved physical health and academic performance. Despite its known benefits, there is a concerning trend of decreased physical activity among children globally. The study primarily aims to investigate the level of physical activity among junior high school students in Taiyuan and analyse the main affecting factors from a socio-ecological perspective.

Methods

A cross-sectional study was conducted, involving 650 junior high school students from 7 schools in Taiyuan, and 648 valid questionnaires were ultimately collected. The data on students’ physical activity levels were collected through the Children’s Leisure Activities Study Survey Questionnaire, and the data on factors affecting students’ physical activity were collected through the Student Perceived Factors Affecting Physical Activity Questionnaire.

Results

In this study, students from the 7th, 8th, and 9th grades participated in physical activities, averaging 214.500 min per week in moderate-intensity and 25.000 min in high-intensity activities, cumulatively averaging 280.000 min weekly. Notably, a significant disparity (p = 0.012) was observed in the combined duration of moderate and high-intensity activities, with male students engaging more time compared to their female counterparts (307.500 vs. 255.000 min). This variance extended across different grades, particularly evident in 8th graders who recorded the highest weekly high-intensity activity duration (31.000 min) and overall physical activity time (320.500 min), surpassing the 7th graders(p = 0.007 for high-intensity activities). Furthermore, an exploratory factor analysis of a 32-item questionnaire, designed to identify determinants of physical activity, revealed six principal components. These components were found to positively correlate with both moderate and high-intensity physical activities.

Conclusion

Results emphasize that educational institutions and community programs should collaborate to offer engaging weekend physical activity programs. Schools should develop and implement tailored physical education curricula addressing gender and grade differences. Furthermore, schools and local governments should invest in high-quality sports equipment and facilities.
PIF transcription factors-versatile plant epigenome landscapers
Authors: Ammari Moonia , Maseh Kashif , Zander Mark
Published: May 2024

Plants are exquisitely responsive to their local light and temperature environment utilizing these environmental cues to modulate their developmental pathways and adjust growth patterns. This responsiveness is primarily achieved by the intricate interplay between the photoreceptor phyB (phytochrome B) and PIF (PHYTOCHROME INTERACTING FACTORs) transcription factors (TFs), forming a pivotal signaling nexus. phyB and PIFs co-associate in photobodies (PBs) and depending on environmental conditions, PIFs can dissociate from PBs to orchestrate gene expression. Until recently, the mechanisms governing epigenome modifications subsequent to PIF binding to target genes remained elusive. This mini review sheds light on the emerging role of PIFs in mediating epigenome reprogramming by recruiting chromatin regulators (CRs). The formation of numerous different PIF-CR complexes enables precise temporal and spatial control over the gene regulatory networks (GRNs) governing plant-environment interactions. We refer to PIFs as epigenome landscapers, as while they do not directly reprogram the epigenome, they act as critical sequence-specific recruitment platforms for CRs. Intriguingly, in the absence of PIFs, the efficacy of epigenome reprogramming is largely compromised in light and temperature-controlled processes. We have thoroughly examined the composition and function of known PIF-CR complexes and will explore also unanswered questions regarding the precise of locations PIF-mediated epigenome reprogramming within genes, nuclei, and plants.
Dechloranes and chlorinated paraffins in sediments and biota of two subarctic lakes
Authors: Arriola Aline , Al Saify Insam , Warner Nicholas A. , Herzke Dorte , Harju Mikael , Amundsen Per-Arne , Evenset Anita , Möckel Claudia , Krogseth Ingjerd S.
Published: May 2024

Our understanding of the environmental behavior, bioaccumulation and concentrations of chlorinated paraffins (CPs) and Dechloranes (Dec) in the Arctic environment is still limited, particularly in freshwater ecosystems. In this descriptive study, short chain (SCCPs) and medium chain (MCCPs) CPs, Dechlorane Plus (DP) and analogues, and polychlorinated biphenyls (PCBs) were measured in sediments, benthic organisms, three-spined stickleback (Gasterosteus aculeatus), Arctic char (Salvelinus alpinus) and brown trout (Salmo trutta) in two Sub-Arctic lakes in Northern Norway. Takvannet (TA) is a remote lake, with no known local sources for organic contaminants, while Storvannet (ST) is situated in a populated area. SCCPs and MCCPs were detected in all sediment samples from ST with concentration of 42.26–115.29 ng/g dw and 66.18–136.69 ng/g dw for SCCPs and MCCPs, respectively. Only SCCPs were detected in TA sediments (0.4–5.28 ng/g dw). In biota samples, sticklebacks and benthic organisms showed the highest concentrations of CPs, while concentrations were low or below detection limits in both char and trout. The congener group patterns observed in both lakes showed SCCP profiles dominated by higher chlorinated congener groups while the MCCPs showed consistency in their profiles, with C14 being the most prevalent carbon chain length. Anti- and syn-DP isomers were detected in all sediment, benthic and stickleback samples with higher concentrations in ST than in TA. However, they were only present in a few char and trout samples from ST. Dec 601 and 604 were below detection limits in all samples in both lakes. Dec 603 was detected only in ST sediments, sticklebacks and 2 trout samples, while Dec 602 was the only DP analogue found in all samples from both lakes. While there were clear differences in sediment concentrations of DP and Dec 602 between ST and TA, differences between lakes decreased with increasing δ15N. This pattern was similar to the PCB behavior, suggesting the lake characteristics in ST are playing an important role in the lack of biomagnification of pollutants in this lake. Our results suggest that ST receives pollutants from local sources in addition to atmospheric transport.
West Nile virus surveillance using sentinel birds: results of eleven years of testing in corvids in a region of northern Italy
Authors: Tamba Marco , Bonilauri Paolo , Galletti Giorgio , Casadei Gabriele , Santi Annalisa , Rossi Arianna , Calzolari Mattia
Published: May 2024

The natural transmission cycle of West Nile virus (WNV) involves birds as primary hosts and mosquitoes as vectors, but this virus can spread to mammals, human beings included. Asymptomatic infected donors pose a risk to the safety of blood transfusions and organ transplants, as WNV can be transmitted through these medical procedures. Since 2009, the region of Emilia-Romagna in northern Italy has been implementing an integrated surveillance system in order to detect WNV circulation in the environment at an early stage. Here we report the results of the two components of the surveillance system, the active testing of corvids and humans, and demonstrate that bird surveillance alone improves a surveillance system based solely on human case detection. As WNV risk reduction measures are applied on a provincial basis, we assessed the ability of this surveillance system component to detect virus circulation prior to the notification of the first human case for each province. Overall, 99 epidemic seasons were evaluated as a result of 11 years (2013–2023) of surveillance in the nine provinces of the region. In this period, 22,314 corvids were tested for WNV and 642 (2.9%) were found to be infected. WNV was generally first detected in birds in July, with sample prevalence peaks occurring between August and September. During the same period, 469 autochthonous human cases were notified, about 60% of which were reported in August. WNV was detected 79 times out of the 99 seasons considered. The virus was notified in birds 73 times (92.4%) and 60 times (75.9%) in humans. WNV was first or only notified in birds in 57 seasons (72.1%), while it was first or only notified in humans in 22 seasons (27.8%). Active surveillance in corvids generally allows the detection of WNV before the onset of human cases. Failure of virus detection occurred mainly in seasons where the number of birds tested was low. Our results show that active testing of a minimum of 3.8 corvids per 100 km2 provides a satisfactory timeliness in the virus detection, but for early detection of WNV it is crucial to test birds between mid-June and mid-August.
Retrofitting Battery Electric Machinery with Unchanged Hydraulic System and Enhanced Control Strategies
Authors: Ferrari Marco , Beltrami Daniele , Uberti Stefano
Published: May 2024

The push for environmental sustainability has accelerated the acceptance of electric vehicles, as well as the exploration of electrified Non-Road Mobile Machinery. This study emphasizes the challenges of electrifying off-highway machinery, which include the many machinery layouts and the presence of Small- and Medium-sized Enterprises in the market. Recognizing the barriers faced by these companies, this paper shows how modeling and simulation can be effective tools for system integration and control optimization, even when lacking extensive expertise in the topic. However, it emphasizes the need for user-friendly modeling tools and methods adaptable to the operational needs of Small- and Medium-sized Enterprises. This study presents a case study of a retrofitted battery-electric hydraulic material handler. The machinery is simulated using Simscape, and the accuracy of the model is confirmed through experimental validation. By simulating a rational duty cycle, this study proposes two solutions for performance enhancement while maintaining the integrity of the hydraulic system. These solutions offer a balanced compromise between energy consumption and productivity and a novel control algorithm to minimize energy consumption. Most importantly, the two proposed solutions can be easily switched by the operator, which can decide to favor productivity over energy saving based on driving needs.
Study on Soil Selenium-Induced Copper Deficiency in Yudong Black Goats
Authors: Liu Guangyang , Shen Xiaoyun
Published: May 2024

Due to the degradation of pasture and strict restrictions on grazing ranges in recent years, copper (Cu) deficiency in Yudong black goats has been occurring, mainly manifested as emaciation, anemia, loss of appetite and lack of spirit. To explore the main causes of Cu deficiency in Yudong black goats, 40 black goats (1 year old, 25.11 ± 0.52 kg) were selected for this experiment; among them, 20 Yudong black goats with Cu deficiency from the experimental pasture were used as the experimental group, and 20 healthy Yudong black goats from the control pasture were used as the control group. In the pre-experiment, the mineral contents of the soil, forage, blood, and liver of black goats in both groups were determined, and in formal experiments, blood hematological, biochemical, antioxidant, and hemorheological parameters were analyzed. An experiment on the treatment of Cu deficiency in black goats was also conducted. This study showed that selenium (Se) levels in the soil, forage, blood, and liver from the experimental group were significantly lower than those from the control group (p < 0.01). The content of sulfur (S) in the forage was considerably higher than that of the control group (p < 0.01). The contents of Cu in the blood and liver from the experimental group were significantly lower than that from the control group (p < 0.01), and the content of S was considerably higher than that from the control group (p < 0.01). The blood hematology of the experimental group was affected, as evidenced by a decrease in hemoglobin, hematocrit value, mean corpuscular volume and mean corpuscular hemoglobin. The immunity and antioxidant capacity of black goats in the experiment group were impaired to varying degrees, with significant decreases in ceruloplasmin, immunoglobulin M, immunoglobulin G, glutathione peroxidase, and superoxide dismutase, and substantial increases in malondialdehyde. In addition, the experimental group showed a decrease in blood viscosity as evidenced by the rise in high shear viscosity, low shear viscosity, erythrocyte rigidity index, erythrocyte aggregation index, and erythrocyte deformation index, and a decrease in plasma viscosity. In the treatment experiment, oral administration of copper sulfate solution was carried out on 10 black goats with Cu deficiency. All the Cu deficiency goats were cured, and the Cu content in their bodies rebounded. In summary, low Se soil caused an increase in S content in the forage, and Yudong black goats feeding on high S forage resulted in a decrease in Cu absorption, which led to a secondary Cu deficiency.
Identification and Optimization Study of Cavitation in High Power Torque Converter
Authors: Wang Kaifeng , Xu Xiangyang , Zhao Weiwei , Wang Zhongshan , Lei Yulong , Ma Wenxing
Published: May 2024

Aiming at the phenomenon that a high-power torque converter is susceptible to cavitation, which leads to performance degradation, first, a transient flow field model of the torque converter is established, and CFD simulation and experimental research on the torque converter are carried out to find out the speed ratio region where cavitation occurs in the torque converter as well as the rule of occurrence of cavitation, and then the cavitation identification method based on the difference between the inlet and outlet flow of the torque converter is proposed. Then, the transient flow process inside the torque converter is analyzed, and it is pointed out that the angle between the inlet angle of the stator and the outlet angle of the turbine of the torque converter, i.e., the fluid inflow injection deviation angle is an important factor affecting the cavitation phenomenon. By adjusting the key parameters of the stator blade bone line, the fluid inflow deviation angle of the torque converter stator is optimized, so that the speed ratio range of cavitation under large load conditions is greatly reduced from the original 0–0.5 (50%) to 0–0.15 (15%). Meanwhile, in terms of test performance, the nominal torque of the torque converter is greatly improved under the premise of ensuring that the performance is basically unchanged, in which the nominal torque of the test zero speed is increased by 28.7%, and the cavitation of the torque converter has been greatly improved.
Perspectives on Resolving Diagnostic Challenges between Myocardial Infarction and Takotsubo Cardiomyopathy Leveraging Artificial Intelligence
Authors: Moideen Sheriff Serin , Sethi Aaftab , Sood Divyanshi , Bansal Sourav , Goudel Aastha , Murlidhar Manish , Damani Devanshi N. , Kulkarni Kanchan , Arunachalam Shivaram P.
Published: May 2024

Background: cardiovascular diseases, including acute myocardial infarction (AMI) and takotsubo cardiomyopathy (TTC), are significant causes of morbidity and mortality worldwide. Timely differentiation of these conditions is essential for effective patient management and improved outcomes. Methods: We conducted a review focusing on studies that applied artificial intelligence (AI) techniques to differentiate between acute myocardial infarction (AMI) and takotsubo cardiomyopathy (TTC). Inclusion criteria comprised studies utilizing various AI modalities, such as deep learning, ensemble methods, or other machine learning techniques, for discrimination between AMI and TTC. Additionally, studies employing imaging techniques, including echocardiography, cardiac magnetic resonance imaging, and coronary angiography, for cardiac disease diagnosis were considered. Publications included were limited to those available in peer-reviewed journals. Exclusion criteria were applied to studies not relevant to the discrimination between AMI and TTC, lacking detailed methodology or results pertinent to the AI application in cardiac disease diagnosis, not utilizing AI modalities or relying solely on invasive techniques for differentiation between AMI and TTC, and non-English publications. Results: The strengths and limitations of AI-based approaches are critically evaluated, including factors affecting performance, such as reliability and generalizability. The review delves into challenges associated with model interpretability, ethical implications, patient perspectives, and inconsistent image quality due to manual dependency, highlighting the need for further research. Conclusions: This review article highlights the promising advantages of AI technologies in distinguishing AMI from TTC, enabling early diagnosis and personalized treatments. However, extensive validation and real-world implementation are necessary before integrating AI tools into routine clinical practice. It is vital to emphasize that while AI can efficiently assist, it cannot entirely replace physicians. Collaborative efforts among clinicians, researchers, and AI experts are essential to unlock the potential of these transformative technologies fully.
Bay Laurel of Northern Morocco: A Comprehensive Analysis of Its Phytochemical Profile, Mineralogical Composition, and Antioxidant Potential
Authors: Mrabet Amena , Abdelfattah Bahia , El Mansouri Fouad , Simou Ayoub , Khaddor Mohamed
Published: May 2024

Laurus nobilis, sometimes referred to as laurel, has been used for medicinal and culinary purposes for a very long time. The main subjects of this study are the phytochemical composition, mineralogical profile, and potential antioxidant properties of Laurus nobilis in Tangier, Northern Morocco. For phytochemical analysis of methanolic extracts, high-performance liquid chromatography (HPLC-UV-MS) was used, and Fourier transformation infrared spectroscopy (FT-IR) was used to identify each individual component. Minerals were studied by inductively coupled plasma atomic emission spectroscopy (ICP-AES) and wavelength dispersive X-ray fluorescence (WD-XRF). Total tannin, flavonoid, and phenolic amounts were quantified using aqueous and methanolic extracts. The antioxidant properties were assessed using 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azino-bis (3ethylbenzothiazoline-6-sulfonic acid) (ABTS), ferric reducing antioxidant power (FRAP), and oxygen radical absorbance capacity (ORAC) assays. Research has revealed a complex array of phytochemicals, including tannins, flavonoids, and phenolic acids. Mineral analysis has revealed the existence of vital components that are beneficial to health. Comparing the methanolic extract to the water extract, it demonstrated higher levels of phenols, flavonoids, and tannins as well as stronger antioxidant activity, indicating greater health benefits. This comprehensive study highlights the importance of Laurus nobilis from Northern Morocco as a reliable botanic resource with potential pharmaceutical, nutritional, and cosmetic uses.
Numerical Simulation Study on the Impact of Excavation on Existing Subway Stations Based on BIM-FEM Framework
Authors: Qiu Yi , Wang Junwei , Zhang Chao , Hua Lingxiao , Zhou Zhenglong
Published: May 2024

Building information modeling (BIM) and finite element method (FEM) models have a wide range of applications in underground engineering design, construction, and operation and maintenance. This study employs a BIM-FEM framework to numerically simulate the impact of excavation on existing subway stations, using the Yanjiang New City Station TOD project as a case study. This framework simplifies the smooth integration of BIM and FEM models, automating functions such as assigning material properties, conducting construction simulations, and generating high-quality meshes. Simulation results reveal significant horizontal and vertical displacements in diaphragm walls, support structures, and subway station structures, with the greatest impacts occurring closest to the excavation site. The BIM-FEM framework is validated as an effective tool for designing foundation pit support structures, enhancing numerical modeling accuracy and efficiency in underground engineering. The findings contribute to a better understanding of the dynamic interactions between excavation and underground structures, informing the development of construction strategies and protective measures to ensure structural safety.
“Oh, Dear We Are in Tribble”: An Overview of the Oncogenic Functions of Tribbles 1
Authors: Singh Karnika , Showalter Christian A. , Manring Heather R. , Haque Saikh Jaharul , Chakravarti Arnab
Published: May 2024

Pseudokinases are catalytically inactive proteins in the human genome that lack the ability to transfer phosphate from ATP to their substrates. The Tribbles family of pseudokinases contains three members: Tribbles 1, 2, and 3. Tribbles 1 has recently gained importance because of its involvement in various diseases, including cancer. It acts as a scaffolding protein that brings about the degradation of its substrate proteins, such as C/EBPα/β, MLXIPL, and RAR/RXRα, among others, via the ubiquitin proteasome system. It also serves as an adapter protein, which sequesters different protein molecules and activates their downstream signaling, leading to processes, such as cell survival, cell proliferation, and lipid metabolism. It has been implicated in cancers such as AML, prostate cancer, breast cancer, CRC, HCC, and glioma, where it activates oncogenic signaling pathways such as PI3K-AKT and MAPK and inhibits the anti-tumor function of p53. TRIB1 also causes treatment resistance in cancers such as NSCLC, breast cancer, glioma, and promyelocytic leukemia. All these effects make TRIB1 a potential drug target. However, the lack of a catalytic domain renders TRIB1 “undruggable”, but knowledge about its structure, conformational changes during substrate binding, and substrate binding sites provides an opportunity to design small-molecule inhibitors against specific TRIB1 interactions.
In Vitro Investigation of Therapy-Induced Senescence and Senescence Escape in Breast Cancer Cells Using Novel Flow Cytometry-Based Methods
Authors: Tóth Fanni , Moftakhar Zahra , Sotgia Federica , Lisanti Michael P.
Published: May 2024

Although cellular senescence was originally defined as an irreversible form of cell cycle arrest, in therapy-induced senescence models, the emergence of proliferative senescence-escaped cancer cells has been reported by several groups, challenging the definition of senescence. Indeed, senescence-escaped cancer cells may contribute to resistance to cancer treatment. Here, to study senescence escape and isolate senescence-escaped cells, we developed novel flow cytometry-based methods using the proliferation marker Ki-67 and CellTrace CFSE live-staining. We investigated the role of a novel senescence marker (DPP4/CD26) and a senolytic drug (azithromycin) on the senescence-escaping ability of MCF-7 and MDA-MB-231 breast cancer cells. Our results show that the expression of DPP4/CD26 is significantly increased in both senescent MCF-7 and MDA-MB-231 cells. While not essential for senescence induction, DPP4/CD26 contributed to promoting senescence escape in MCF-7 cells but not in MDA-MB-231 cells. Our results also confirmed the potential senolytic effect of azithromycin in senescent cancer cells. Importantly, the combination of azithromycin and a DPP4 inhibitor (sitagliptin) demonstrated a synergistic effect in senescent MCF-7 cells and reduced the number of senescence-escaped cells. Although further research is needed, our results and novel methods could contribute to the investigation of the mechanisms of senescence escape and the identification of potential therapeutic targets. Indeed, DPP4/CD26 could be a promising marker and a novel target to potentially decrease senescence escape in cancer.
Evaluation of Human Platelet Lysate as an Alternative to Fetal Bovine Serum for Potential Clinical Applications of Stem Cells from Human Exfoliated Deciduous Teeth
Authors: Yoon Ji-Young , Vu Huong Thu , Lee Jun Hee , Shin Ji-Sun , Kim Hae-Won , Lee Hae-Hyoung , Kim Jong-Bin , Lee Jung-Hwan
Published: May 2024

In recent years, there has been a surge in demand for and research focus on cell therapy, driven by the tissue-regenerative and disease-treating potentials of stem cells. Among the candidates, dental pulp stem cells (DPSCs) or human exfoliated deciduous teeth (SHED) have garnered significant attention due to their easy accessibility (non-invasive), multi-lineage differentiation capability (especially neurogenesis), and low immunogenicity. Utilizing these stem cells for clinical purposes requires careful culture techniques such as excluding animal-derived supplements. Human platelet lysate (hPL) has emerged as a safer alternative to fetal bovine serum (FBS) for cell culture. In our study, we assessed the impact of hPL as a growth factor supplement for culture medium, also conducting a characterization of SHED cultured in hPL-supplemented medium (hPL-SHED). The results showed that hPL has effects in enhancing cell proliferation and migration and increasing cell survivability in oxidative stress conditions induced by H2O2. The morphology of hPL-SHED exhibited reduced size and elongation, with a differentiation capacity comparable to or even exceeding that of SHED cultured in a medium supplemented with fetal bovine serum (FBS-SHED). Moreover, no evidence of chromosome abnormalities or tumor formation was detected. In conclusion, hPL-SHED emerges as a promising candidate for cell therapy, exhibiting considerable potential for clinical investigation.
Current and Future Therapeutics for Treating Patients with Sickle Cell Disease
Authors: Barak Mariam , Hu Christopher , Matthews Alicia , Fortenberry Yolanda M.
Published: May 2024

Sickle cell disease (SCD) is the most common genetic blood disorder in the United States, with over 100,000 people suffering from this debilitating disease. SCD is caused by abnormal hemoglobin (Hb) variants that interfere with normal red blood cell (RBC) function. Research on SCD has led to the development and approval of several new SCD therapies in recent years. The recent FDA-approved novel gene therapies are potentially curative, giving patients an additional option besides a hematopoietic bone marrow transplant. Despite the promise of existing therapies, questions remain regarding their long-term pharmacological effects on adults and children. These questions, along with the exorbitant cost of the new gene therapies, justify additional research into more effective therapeutic options. Continual research in this field focuses on not only developing cheaper, more effective cures/treatments but also investigating the physiological effects of the current therapies on SCD patients, particularly on the brain and kidneys. In this article, we undertake a comprehensive review of ongoing clinical trials with completion dates in 2024 or later. Our exploration provides insights into the landscape of current therapeutics and emerging novel therapies designed to combat and potentially eradicate SCD, including the latest FDA-approved gene therapies.
Induced Pluripotent Stem Cell-Derived Fibroblasts Efficiently Engage Senescence Pathways but Show Increased Sensitivity to Stress Inducers
Authors: Goyer Marie-Lyn , Desaulniers-Langevin Cynthia , Sonn Anthony , Mansour Nehmo Georgio , Lisi Véronique , Benabdallah Basma , Raynal Noël J.-M. , Beauséjour Christian
Published: May 2024

The risk of aberrant growth of induced pluripotent stem cell (iPSC)-derived cells in response to DNA damage is a potential concern as the tumor suppressor genes TP53 and CDKN2A are transiently inactivated during reprogramming. Herein, we evaluate the integrity of cellular senescence pathways and DNA double-strand break (DSB) repair in Sendai virus reprogrammed iPSC-derived human fibroblasts (i-HF) compared to their parental skin fibroblasts (HF). Using transcriptomics analysis and a variety of functional assays, we show that the capacity of i-HF to enter senescence and repair DSB is not compromised after damage induced by ionizing radiation (IR) or the overexpression of H-RASV12. Still, i-HF lines are transcriptionally different from their parental lines, showing enhanced metabolic activity and higher expression of p53-related effector genes. As a result, i-HF lines generally exhibit increased sensitivity to various stresses, have an elevated senescence-associated secretory phenotype (SASP), and cannot be immortalized unless p53 expression is knocked down. In conclusion, while our results suggest that i-HF are not at a greater risk of transformation, their overall hyperactivation of senescence pathways may impede their function as a cell therapy product.
Interaction between Chromodomain Y-like Protein and Androgen Receptor Signaling in Sertoli Cells Accounts for Spermatogenesis
Authors: Lan Kuo-Chung , Cheng Yin-Hua , Chang Yun-Chiao , Wei Kuo-Ting , Weng Pei-Ling , Kang Hong-Yo
Published: May 2024

Spermatogenesis is a highly regulated process dependent on androgen receptor (AR) signaling in Sertoli cells. However, the pathogenic mechanisms of spermatogenic failure, by which loss of AR impairs downstream target genes to affect Sertoli cell function, remain incompletely understood. By using microarray analysis, we identified several AR-regulated genes involved in the maturation of spermatogenesis, including chromodomain Y-like protein (CDYL) and transition proteins 1 (TNP-1), that were significantly decreased in ARKO mouse testes. AR and CDYL were found to co-localize and interact in Sertoli cells. The AR–CDYL complex bound to the promoter regions of TNP1 and modulated their transcriptional activity. CDYL acts as a co-regulator of AR transactivation, and its expression is decreased in the Sertoli cells of human testes from patients with azoospermia. The androgen receptor–chromodomain Y-like protein axis plays a crucial role in regulating a network of genes essential for spermatogenesis in Sertoli cells. Disruption of this AR–CDYL regulatory axis may contribute to spermatogenic failure. These findings provide insights into novel molecular mechanisms targeting the AR–CDYL signaling pathway, which may have implications for developing new therapeutic strategies for male infertility.
Dysregulation of Glypicans and Notum in Osteoarthritis: Plasma Levels, Bone Marrow Mesenchymal Stromal Cells and Osteoblasts
Authors: González-Guede Irene , López-Ramos María , Rodríguez-Rodríguez Luis , Abasolo Lydia , Mucientes Arkaitz , Fernández-Gutiérrez Benjamín
Published: May 2024

In this study of the alterations of Glypicans 1 to 6 (GPCs) and Notum in plasma, bone marrow mesenchymal stromal cells (BM-MSCs) and osteoblasts in Osteoarthritis (OA), the levels of GPCs and Notum in the plasma of 25 patients and 24 healthy subjects were measured. In addition, BM-MSCs from eight OA patients and eight healthy donors were cultured over a period of 21 days using both a culture medium and an osteogenic medium. Protein and gene expression levels of GPCs and Notum were determined using ELISA and qPCR at 0, 7, 14 and 21 days. GPC5 and Notum levels decreased in the plasma of OA patients, while the BM-MSCs of OA patients showed downexpression of GPC6 and upregulation of Notum. A decrease in GPC5 and Notum proteins and an increase in GPC3 were found. During osteogenic differentiation, elevated GPCs 2, 4, 5, 6 and Notum mRNA levels and decreased GPC3 were observed in patients with OA. Furthermore, the protein levels of GPC2, GPC5 and Notum decreased, while the levels of GPC3 increased. Glypicans and Notum were altered in BM-MSCs and during osteogenic differentiation from patients with OA. The alterations found point to GPC5 and Notum as new candidate biomarkers of OA pathology.
Influence of pH on Room-Temperature Synthesis of Zinc Oxide Nanoparticles for Flexible Gas Sensor Applications
Authors: Mechai Fazia , Al Shboul Ahmad , Bensidhoum Mohand Outahar , Anabestani Hossein , Ketabi Mohsen , Izquierdo Ricardo
Published: May 2024

This research contributes to work on synthesizing zinc oxide nanoparticles (ZnO NPs) at room temperature (RT) and their utilization in flexible gas sensors. RT ZnO NP synthesis with a basicity solution (pH ≈ 13) demonstrates an efficient method for synthesizing well-crystalline ZnO NPs (RT.pH13) comparable to those synthesized by the hydrothermal method (hyd.C). The RT.pH13 achieved a high thermal stability with minimal organic reside impurities (~4.2 wt%), 30–80 nm particle size distribution, and a specific surface area (14 m2 g−1). The synthesized pre- and post-calcinated RT.pH13 NPs were then incorporated into flexible sensors for gas sensing applications at ambient conditions (RT and relative humidity of 30–50%). The pre-calcinated ZnO-based sensor (RT.pH13) demonstrated superior sensitivity to styrene and acetic acid and lower sensitivity to dimethyl-6-octenal. The calcinated ZnO-based sensor (RT.pH13.C) exhibited lower sensitivity to styrene and acetic acid, but heightened sensitivity to benzene, acetone, and ethanol. This suggests a correlation between sensitivity and structural transformations following calcination. The investigation of the sensing mechanisms highlighted the role of surface properties in the sensors’ affinity for specific gas molecules and temperature and humidity variations. The study further explored the sensors’ mechanical flexibility, which is crucial for flexible Internet of Things (IoT) applications.
Hydrothermally Synthesized Cerium Phosphate with Functionalized Carbon Nanofiber Nanocomposite for Enhanced Electrochemical Detection of Hypoxanthine
Authors: Kasare Prashant K. , Wang Sea-Fue
Published: May 2024

This work presents the detection of hypoxanthine (HXA), a purine derivative that is similar to nucleic acids who overconsumption can cause health issues, by using hydrothermally synthesized cerium phosphate (CePO4) followed by a sonochemical approach for CePO4 decorated with a functionalized carbon nanofiber (CePO4@f-CNF) nanocomposite. The formation of the nanocomposite was confirmed with X-ray powder diffraction (XRD), scanning electron microscopy (SEM), and energy-dispersive spectroscopy (EDS). A CePO4@f-CNF nanocomposite is used to modify a glassy carbon electrode (GCE) to analyze the electrochemical detection of HXA. Cyclic voltammetry (CV), Electrochemical impedance spectroscopy (EIS), and Differential pulse voltammetry (DPV) were used to examine the electrochemical properties of the composite. As a result, the modified electrode exhibits a larger active surface area (A = 1.39 cm2), a low limit of detection (LOD) at 0.23 µM, a wide linear range (2.05–629 µM), and significant sensitivity. Therefore, the CePO4@f-CNF nanocomposite was used to study the real-time detection in chicken and fish samples, and it depicted significant results.
Lower Urinary Tract Dysfunction in Pediatric Patients with Multiple Sclerosis: Diagnostic and Management Concerns
Authors: Sollini Maria Laura , Pellegrino Chiara , Barone Giulia , Capitanucci Maria Luisa , Zaccara Antonio Maria , Crescentini Leonardo , Castelli Enrico , Della Bella Gessica , Scorletti Federico , Papetti Laura , Monte Gabriele , Ferilli Michela Ada Noris , Valeriani Massimiliano , Mosiello Giovanni
Published: May 2024

Background: Multiple sclerosis (MS) is increasing in the pediatric population and, as in adults, symptoms vary among patients. In children the first manifestations can sometimes overlap with acute neurological symptoms. Urological symptoms have not been much studied in childhood. We shared our experience with MS urological manifestation in children. Methods: This article is a retrospective evaluation of all children with MS, according to the Krupp criteria, who also present with urological symptoms. We collected demographic and clinical history, the MR localization of demyelinating lesions, urological symptoms, and exams. Results: We report on six MS pediatric cases with urological manifestation. Urinary symptoms, characterized by urinary incontinence in five patients and urinary retention in one patient, appeared in a different time frame from MS diagnosis. Urodynamic exams showed both overactive and underactive bladder patterns. Treatment was defined according to lower urinary tract dysfunction, using clean intermittent catheterization, oxybutynin, and intradetrusor Onabotulinum Toxin-A injection. A low acceptance rate of invasive evaluation and urological management was observed. Conclusions: The MS diagnosis was traumatic for all our patients. We believe it is important to address urological care in young people from the time of diagnosis for prompt management; it could be useful to include a pediatric urologist in multidisciplinary teams.