bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adaptive remodeling of rat adrenomedullary stimulus-secretion coupling in a chronic hypertensive environment
Authors: Paillé Vincent , Park Joohee , Toutain Bertrand , Bourreau Jennifer , Fontanaud Pierre , De Nardi Frédéric , Gabillard-Lefort Claudie , Bréard Dimitri , Guilet David , Henrion Daniel , Legros Christian , Guérineau Nathalie C. 
Published: November 2024

Abstract

Chronic elevated blood pressure impinges on the functioning of multiple organs and therefore harms body homeostasis. Elucidating the protective mechanisms whereby the organism copes with sustained or repetitive blood pressure rises is therefore a topical challenge. Here we address this issue in the adrenal medulla, the master neuroendocrine tissue involved in the secretion of catecholamines, influential hormones in blood pressure regulation. Combining electrophysiological techniques with catecholamine secretion assays on acute adrenal slices from spontaneously hypertensive rats, we show that chromaffin cell stimulus-secretion coupling is remodeled, resulting in a less efficient secretory function primarily upon sustained cholinergic challenges. The remodeling is supported by revamped both cellular and tissular mechanisms. This first includes a decrease in chromaffin cell excitability in response to sustained electrical stimulation. This hallmark was observed both experimentally and in a computational chromaffin cell model, and occurs with concomitant changes in voltage-gated ion channel expression. The cholinergic transmission at the splanchnic nerve-chromaffin cell synapses and the gap junctional communication between chromaffin cells are also weakened. As such, by disabling its competence to release catecholamines in response sustained stimulations, the hypertensive medulla has elaborated an adaptive shielding mechanism against damaging effects of redundant elevated catecholamine secretion and associated blood pressure.
A “Plug-n-Play” permeable brick-based microfluidic pump
Authors: Chen Zhihao , Liu Jiahao , Min Shuqiang , Zhan Tonghuan , Huang Yange , Wu Xianchang , Xu Bing , Chen Jianfeng 
Published: November 2024

Abstract

Inexpensive, autonomous, easy to fabricate and portable self-powered microfluidic pumps are urgently required especially in rapid point-of-care testing (POCT). Here, we propose a “Plug-n-Play” permeable brick-based (PB) micropump for autonomous and continuous liquid flow without any external power sources. The key advantage of this pump is that its operation only requires the user to place the PB pump on the outlet of microfluidic devices. The PB pumps are fabricated by simply slicing permeable bricks into predetermined shapes. The microcosmic morphology investigations unveil that their unique porous structures and uneven surface provide outstanding capillary force. For instance, a typical cuboid PB pump (2 × 2 × 2 cm3) can produce an average flow rate of more than 100 µL min− 1, a working time of 10 minutes and a maximum liquid absorption volume of ~ 1200 µL. Also, the flow rate and absorption volume can be programmed by using the PB pumps with different shapes. Finally, we apply hydrophobic reagents (Glaco) treatment on the PB pumps to achieve the control over the liquid flow rates. Based on its advantages of low cost, long service life, and adjustable flow rates, brick pump can be easily integrated into microfluidic systems and has great potential for microfluidic applications, especially in developing regions or in resource-limited settings.
The mechanism of the phosphine-catalyzed oxa-Michael reaction: A DFT investigation
Authors: Suthar Priyanka , Singh Ruchi , Bansal R. K. 
Published: November 2024

Abstract

The model reactions of phenol and methanol with acrolein catalyzed by trimethylphosphine were computed in the gas phase at the B3LYP/6–31 + G(d) level. The reaction is found to occur in four steps. It is initiated by the combination of the oxa-compound with trimethylphosphine to generate successively the reactant complex and the phenoxide/methoxide anion. The latter reacts with acrolein to produce the enolate anion, which accepts a proton from the protonated trimethylphosphonium cation to generate enol intermediate. Finally, 1,3-prototropic shift occurs via trimethylphosphine molecule to afford the final product. Acetonitrile is found to lower activation energies in all the four steps.
Unveiling Green Entrepreneurial Intentions and Behaviour Among Saudi Arabian Youth: Insights and Implications
Authors: Mabkhot Hashed , Semlali Yahdih , Gelaidan Hamid Mahmood , Abdelwahed Nadia A Abdelmegeed , Shaari Hasnizam 
Published: November 2024

Abstract

This study investigates green entrepreneurial intention and behaviour among youth, aiming to provide insights into the factors influencing these phenomena. A survey was conducted with 441 students from the Universities in the Kingdom of Saudi Arabia, and the data were analysed using SmartPLS-3.3.2. Several hypotheses were tested. Firstly, a positive and significant relationship was found between commitment to environmental causes (CTE) and green entrepreneurial intention (GEI), aligning with prior research. This underscores the influence of personal beliefs and values on driving individuals towards green entrepreneurial activities. Secondly, entrepreneurial motivation (EM) demonstrated a positive and significant relationship with GEI, emphasizing the importance of individual motivation in fostering intentions toward green entrepreneurship. Thirdly, university entrepreneurship support (UES) showed insufficient evidence to establish a significant relationship with GEI, suggesting a potential gap in university support for green entrepreneurship initiatives. Similarly, entrepreneurship education (EE) did not exhibit a statistically significant impact on GEI, highlighting the need for enhanced incorporation of environmental issues in educational programs to inspire GEI. Furthermore, the study emphasizes the significance of promoting green consumption among university students, who possess significant potential to drive positive change in consumption habits. Lastly, a strong and highly significant relationship was observed between GEI and green entrepreneurial behaviour (GEB), emphasizing the pivotal role of intentions in translating into concrete actions. Overall, the findings contribute to understanding the dynamics of GEI and behaviour among Saudi Arabian youth, suggesting avenues for policy interventions and future research directions in fostering sustainable entrepreneurship.
Bonding Super Translucent Multilayered Monolithic Zirconia to Different Foundation Materials: An Invitro Study
Authors: Essam Noha , Ahmed Shaimaa , Attia Ahmed 
Published: November 2024

Abstract

Background: The purpose of the current study was to assess the impact of bonded substrate, zirconia surface conditioning and the interaction between them on the shear bond strength of monolithic zirconia.
Methods: A total of 48 monolithic zirconia discs were fabricated and divided into two groups according to surface treatment either as milled and Monobond N (P) or sandblasting then Monobond N (SP). Each main group was further divided into 3 subgroups according to the bonded substrate: dentin (DSP, DP), composite (CSP, CP) or resin modified glass ionomer (RMGI) (GSP, GP). Multilinik automix (Ivoclar-Vivadent) adhesive resin cement was used for bonding according to the manufacturer instructions. One hour after bonding, specimens were stored in water bath for six months followed by thermal cycling for 10000 cycles to simulate clinical situation. Finally, specimens underwent shear bond strength test using a universal testing machine. Two and one-way ANOVA and Bonferroni Post Hoc tests were used for statistical analysis.
Results: The means±SD (MPa) shear bond strength for each group were calculated. DSP group showed the highest mean shear bond strength (22.65±2.0) followed by DP group (18.61±2.55). Meanwhile, GSP and GP groups showed the lowest mean shear bond strength (4.77±0.09, 4.57±0.73 respectively).
Conclusion: Sandblasting with priming is recommended as a monolithic zirconia surface treatment method. Dentin is the most reliable substrate followed by composite.
An herbal formula Ruji decoction combined with 5-fluorouracil inhibits triple negative breast cancer growth by regulating the PTEN/PI3K/AKT signaling pathway
Authors: Lei Xiaochun , Chen Xikang , Wang Panpan , Gao Lanwen , Madni Asadullah , Oliveira Ralph Santos , Bai Li , Xie Mengjie , Zhang Kewei , Cao Ye , Li Detang , Cai Yu , Tian Huaqin 
Published: November 2024

Abstract

Objective: The purpose of the current research was to assess the inhibitory effect and potential mechanism of Ruji decoction (RJF) combined with 5-fluorouracil (5-FU) on TNBC growth through network pharmacology and in vivo experiments.
Methods: Compounds in RJF aqueous extracts were identified and their contents were determined by high performance liquid chromatography. Network pharmacology was used to screen potential targets for RJF in breast cancer. Subsequently, the inhibitory effect and mechanism of action of RJF in combination with 5-FU on tumour growth were evaluated in mouse experiments.
Results: The study showed that the herbal formula RJF contains Lobetyolin and screened 87 compounds and 226 related targets. The intersection of 2,644 targets related to bladder cancer yielded 147 targets related to RJF, with the main functions focusing on transcriptional regulation, hormonal responses and cancer pathways. Animal experiments showed that the combination of RJF and 5-FU increased tumour suppression, reduced 5-FU toxicity, inhibited metastasis, increased PTEN expression in tumour tissues, and decreased PI3K/AKT signalling pathway activity.
Conclusion: The combination of RJF and 5-FU could inhibit TNBC growth and reduce the toxic side effects of 5-FU by regulating the PTEN/PI3K/AKT signaling pathway.
Utility of ctDNA assessment after six weeks of immunotherapy to predict radiological response in advanced oesophageal cancer
Authors: Pacey Simon , Linossi Constanza , Azizi Alexander , Dayimu Alimu , Machin Andrea , Demiris Nikos , Miremadi Ahmad , O'Donovan Maria , Mennea Paulius , Zhou Ze , An Angela , Smyth Elizabeth , Dovedi Simon , Fitzgerald Rebecca , Roshan Amit , Godfrey Edmund , Faull Iris 
Published: November 2024

Abstract

The prospective, single-arm CALIBRATION trial (NCT03653052) assessed liquid biopsies for early response concordance compared with CT scan assessment in patients with advanced oesophageal cancer given durvalumab (PD-L1 inhibitor) after at least one prior systemic therapy.
19 participants received 1500mg of durvalumab every four weeks. ctDNA was analysed retrospectively with Guardant 360® CDx at baseline, weeks 4 and 7. Response at week 26 was assessed by RECIST v1.1. Tumour samples underwent 30X Whole Genome Sequencing.
Concordance between ctDNA and CT results was pre-defined as either ≥50% increase in ctDNA mean variant allele frequency (VAF) with progressive disease, or ≥50% decrease in VAF correlating with radiological response or stable disease. At week four, 4/17 patients (23.5%) showed concordance; at week seven, this rose to 6/12 patients (50.0%). We reduced ctDNA VAF thresholds sequentially from ±50% to ±1% and identified that with any change in ctDNA at week 7, 75% of cases (9/12) showed concordance. 14/18 (77.7%) of patients progressed in the cohort at 6 months. All patients with ctDNA increases progressed.
Our data supports assessing ctDNA at week seven rather than week four for immunotherapy response prediction. ctDNA VAF increases, especially, could aid decision-making in early-phase clinical trials to cease non-beneficial interventions.
Therapeutic Drug Monitoring of Nirmatrelvir/Ritonavirin Patients with COVID-19
Authors: ping xu , lijun zhang , qingguo wu 
Published: November 2024

Abstract

Background
The aim of this study is to retrospectively analyze the factors that lead to the drug concentration of Nirmatrelvir/Ritonavir (NMV/RTV) not reaching the standard.
Methods
In this study, the NMV/RTV drug concentration(Cnmv/rtv)data (n = 114) of COVID-19 patients over 18 years old were collected from May 2022 to October 2022, and the results of the patients were retrospectively compared. According to the analysis of the early study of NMV/RTV, combined with the research results at home and abroad, according to whether the measured drug concentration > 987ng/ml, the patients were divided into target group and non-target group ,The non-target group was defined as not reaching the trough concentration level.
Results
Serum NMV/RTV concentration in adult patients was correlated with prognostic nutritional index [PNI,(P < 0.05)], height (P < 0.05), weight (P < 0.05) and creatinine clearance [Crcl ,(P < 0.05)]. Multivariate analysis showed that height, weight, PNI, lymphocyte (LYM) and CrCl were independent influencing factors of NMV/RTV trough concentration. However, after the correction of BMI calculation, there was no correlation between NMV/RTV and BMI, so in the clinical medication plan, the drug was not adjusted according to the height and weight.
Conclusions
The serum NMV/RTV concentration of adult patients gradually decreased with the increase of CrCl. For patients with high and low CrCl, the trough concentration of NMV/RTV should be continuously monitored and the dosing regimen should be adjusted to achieve the target trough concentration in these patients to reduce the effect of CrCl. PNI is also a key factor affecting drug concentration. For poor nutritional status, drug concentration should be closely monitored and the dose should be adjusted.
Prescription Patterns and Trends of Antiparkinsonian Drugs in Korean Patients With Parkinson’s Disease: A Real-World Data Analysis
Authors: Yoon Bora , Kim Hwa Jung 
Published: November 2024

Abstract

While guidelines exist for Parkinson's disease (PD) treatment, variations in real-world patient management highlight the need for understanding prescription practices, yet real-world data (RWD) are limited. We aimed to analyze prescribing trends in patients with PD using RWD. We used the Korean National Health Insurance Service database to identify 160,476 patients with PD from 2002 to 2019. We analyzed initial drug prescriptions, dosage patterns, combination therapies, and dosage adjustments. Group-based trajectory modeling identified distinct levodopa prescription trajectories. Most patients initiated monotherapy (66.3%), with levodopa being the predominant across all ages. The dopamine agonist (DA)/levodopa ratio decreased with age. The average initial levodopa dose in the monotherapy group was 300 mg, irrespective of age. In the polytherapy group (33.7%), over 90% of patients started with levodopa or DA combinations; 73.4% started with two drugs, 21.8% with three, and 4.8% with four or more. In the initial levodopa monotherapy group, levodopa dosage increases and add-on therapies were most common within the first year. Trajectory analysis revealed four distinct levodopa prescription patterns. This RWD analysis provides valuable insights into age-dependent prescription variations and the timing of medication changes or dosage increases in PD management, aiding clinicians in making informed, patient-centered treatment decisions.
Comparative Study of Femtosecond and Conventional Optical Tweezers
Authors: SINGH AJITESH , SINGH KRISHNA KANT , KUMAR DEEPAK , GOSWAMI DEBABRATA 
Published: November 2024

Abstract

We present a comparative study of continuous-wave (CW) and pulsed optical tweezers for trapping polystyrene beads with radii of 250 nm, 500 nm, and 1 µm, using five different laser power settings. A Ti:Sapphire (MIRA 900F) laser, capable of seamlessly switching between CW and pulsed modes, was used to ensure identical experimental conditions for both cases. The trap strength in each mode was determined by fitting the power spectrum to a Lorentzian curve. Our results show that pulsed tweezers are more effective for smaller particles, while for larger particles, both CW and pulsed tweezers perform similarly at lower laser powers. However, as the power increases, pulsed tweezers provide more stable trapping.
Modulating Tumor-Associated Macrophages through CSF1R Inhibition: A Potential Therapeutic Strategy for HNSCC
Authors: Chen Kaiting , Li Xiaochen , Dong Shuyi , Guo Yu , Luo Ziyin , Zhuang Shi-Min , Liu Jie , Liu Tianrun , Liao Jing , Wen WeiPing 
Published: November 2024

Abstract

Purpose: Tumor-associated macrophages (TAMs) are pivotal immune cells within the tumor microenvironment (TME), exhibiting dual roles across various cancer types. Depending on the context, TAMs can either suppress tumor progression and weaken drug sensitivity or facilitate tumor growth and drive therapeutic resistance. This study explores whether targeting TAMs can suppress the progression of head and neck squamous cell carcinoma (HNSCC) and improve the efficacy of chemotherapy.
Methods: Bioinformatics analyses were performed to evaluate TAMs infiltration levels in HNSCC tumor tissues and examine their associations with patients’ clinicopathological characteristics and prognosis. Flow cytometry was utilized to measure the expression of key macrophage markers and assess apoptosis following treatment with colony stimulating factor 1 receptor (CSF1R) inhibitors (BLZ945, PLX3397). Additionally, immunohistochemistry was employed to detect CD68 and CD8 expression. In vivo, the antitumor efficacy of CSF1R inhibitors was tested in mouse HNSCC tumor model, both as monotherapy and in combination with cisplatin, to evaluate potential synergistic effects.
Results: Bioinformatic analysis identified TAMs as the predominant infiltrating immune cells in the TME of HNSCC, with significantly higher infiltration levels in tumor tissues compared to adjacent non-tumor tissues. High TAMs infiltration was associated with poorer overall survival (OS), disease-free survival (DFS), human papillomavirus (HPV) infection status, and advanced disease staging. The TAMs-related genes prediction model demonstrated high prognostic accuracy. CSF1R is primarily expressed in TAMs, where high CSF1R expression may suppress antigen binding and activation. In vitro experiments showed that CSF1R inhibitors induce TAMs apoptosis, enhance their phagocytic activity, and reduce CD206 expression and IL-10 secretion, thereby diminishing their immunosuppressive function. In vivo experiments revealed that while CSF1R inhibitors alone had limited efficacy in suppressing tumor growth, their combination with cisplatin significantly enhanced therapeutic efficacy, as evidenced by increased CD8+ T cell infiltration within the TME.
Conclusion: Regulating TAMs by targeting CSF1R to diminish immunosuppressive functions and enhance anti-tumor immunity represents a promising therapeutic strategy for HNSCC.
Energy supply of comprehensive energy system in the park considering load density and efficiency zoning
Authors: ZHONG Jiaqing , LI Yunzhuo , SUN Xinying , ZHANG Xiaohui 
Published: November 2024

Abstract

In order to make a reasonable energy supply zoning plan for the comprehensive energy system in the park and realize the efficient utilization of energy, this paper puts forward an energy supply zoning strategy for the comprehensive energy system in the park based on the load density of each functional area in the park, and considers the cascade utilization of energy, and puts forward a multi-objective planning model for the park with the optimization goal of economy and efficiency. Firstly, the principle of energy cascade utilization of comprehensive energy system is studied, and the energy efficiency evaluation method of comprehensive energy system in park based on efficiency is put forward. Secondly, according to the land use characteristics and building structure characteristics of various functional areas in the park, the comprehensive load density of functional areas is calculated, the energy supply zoning strategy of the comprehensive energy system in the park is put forward, and the multi-objective planning model of the park is established. Finally, taking a park as an example, the effectiveness of the model and its solution is verified by numerical simulation. The results show that the proposed method can realize the complementarity of energy grades among loads, effectively realize the reasonable energy supply zoning of the park, and consider the influencing factors of load density, so as to improve the economy of the planning scheme and effectively realize the efficient use of energy.
Study on the bond-slip degradation mechanism of lightweight steel and foam concrete interface under freeze-thaw cycle
Authors: Yang Minghao , Yuan Hai , Yang Shuwang , Xu Qiang , Jiang Yongbiao , Zhang Chen , Xu Yingdong , Su Chenhao , Zhang Zhiyuan 
Published: November 2024

Abstract

In the overall mechanical properties of lightweight steel-foam concrete composite structures, the bonding properties of the interface play a crucial role. However, freeze-thaw cycles significantly affect the pore structure of foam concrete, which has an irreversible impact on the interfacial bonding properties of the composite structure, seriously affecting the overall performance and mechanical properties. Therefore, in this paper, the interfacial bond performance of the composite specimens of foam concrete and cold-formed thin-walled galvanized C-type steel under a freeze-thaw environment is analyzed by using the test method combining microscopic and macroscopic tests. Foam concrete was subjected to 0, 50, 100, and 150 freeze-thaw cycles, and the internal and surface microscopic pore structure of foam concrete was observed and analyzed under different densities and different freeze-thaw cycles using SEM and optical microscope. The test results show that the freeze-thaw cycle makes the pore structure of foam concrete deteriorate obviously, and the degree of pore damage is inversely proportional to the density of foam concrete. The internal porosity of the foam concrete increased with the increase in the number of freezing and thawing. Push-out tests were also conducted on 23 composite specimens. The results show that with the increase in freeze-thaw cycles, the maximum peak bond stress and residual bond stress of foam concrete of the same density decrease, and the slip corresponding to the maximum peak bond stress increases; the strain at the loading end decreases gradually. The maximum peak bond stress, the slip corresponding to the maximum peak bond stress, and the residual bond strength at the same number of freeze-thaw cycles increased with the increase of foam concrete density. For the analysis of bond-slip behavior, a three-stage model of bond-slip considering the change of porosity and compressive strength under ambient temperature environment was established, and the relative bond strength and slip calculation formulas based on the freeze-thaw damage of porosity and initial porosity under freeze-thaw environment were proposed.