bluuebunny/crossref_metadata_2025_split huggingface dataset:
Esterase‐Responsive Self‐Immolative Prodrugs for the Sustained Delivery of the Anticancer Drug 5‐Fluorouracil with Turn‐On Fluorescence
Authors: Badirujjaman Md , Thummer Rajkumar P. , Bhabak Krishna P. 
Published: November 2024

AbstractStimuli‐responsive prodrugs of anticancer drugs are advantageous for the selective delivery of drugs to cancer cells with minimized off‐target side effects. In the present study, esterase‐activatable fluorogenic prodrugs of the chemotherapeutic drug 5‐fluorouracil (5‐FU) have been rationally designed and synthesized using multi‐step organic synthesis. While 5‐FU was connected directly with the fluorophore via a C−N bond in the prodrug BJ‐50, an additional self‐immolative benzylic spacer with a carbonate linker was incorporated in the prodrug BJ‐92. Although absorption and emission spectroscopic studies revealed the activation of both the prodrugs by porcine liver esterase (PLE), reverse‐phase HPLC studies confirmed the inability of BJ‐50 to release the active drug 5‐FU. In contrast, a sustained release of 5‐FU and Cou‐OH was observed from BJ‐92 in the presence of PLE. The endogenous esterase‐mediated activation of the prodrug BJ‐92 was validated by the turn‐on fluorescence in A549 cells and the anti‐proliferative activities in A549, and HEK‐293 cells. Modulation of the expression of a few cancer marker proteins by BJ‐92 and 5‐FU was studied to evaluate their anticancer activities. As esterases are overexpressed in cancer cells, the prodrug in the present study would be helpful in selectively delivering 5‐FU to cancer cells with reduced off‐target side‐effects.
Immobilization and characterization of β‐galactosidase from Aspergillus oryzae in polyvinyl alcohol hydrogels
Authors: Akdoğan Doruk , Peksel Ayşegül 
Published: November 2024

AbstractOne of the main goals of contemporary biotechnology has been the development of novel immobilized enzyme formulations. In the present study, the industrially important β‐galactosidase was trapped in a polyvinyl alcohol (PVA) gel to immobilize it. The optimization of immobilization method and characterization of the immobilized enzyme were studied. The results were compared with free enzymes. The results indicate that the optimal temperature range for the enzyme to be at following immobilization is between 40°C and 50°C. At pH 7, the optimal pH, the activity increased, the Vmax value increased from 1.936 to 2.495 U mg‒1, and the Km value decreased from 4.861 to 0.982 mM. Depending on how stable the immobilized enzyme when stored, β‐galactosidases immobilized on PVA gels showed 52.87% activity at the end of the seventh week and 58.86% activity at the end of the fifth week. Their initial activity subsided after three reuses. The final result was 66%. Therefore, one may argue that it increases the catalytic effect of the enzyme. As a result, it has been found that immobilized β‐galactosidase has more potent enzymatic properties than free β‐galactosidase, which may make it more advantageous for industrial processes. Further studies could delve deeper into the mechanistic aspects of the immobilization process in an effort to improve optimization and tailor the immobilized enzyme to specific industrial needs.
Carboplatin‐loaded zeolitic imidazolate framework‐8: Induction of antiproliferative activity and apoptosis in breast cancer cell
Authors: Ganapathy Saravanan , Bharathi Muruganantham , Hirad Abdurahman Hajinur , Alarfaj Abdullah A. , Thangavelu Indumathi , Arulselvan Palanisamy , Jaganathan Ravindran , Ravindran Rajeswari , Suriyaprakash Jagadeesh , Boopathi Thalakulam Shanmugam 
Published: November 2024

AbstractThe challenge with breast cancer is its ongoing high prevalence and difficulties in early detection and access to effective care. A solution lies in creating tailored metal–organic frameworks to encapsulate anticancer drugs, enabling precise and targeted treatment with less adverse effects and improved effectiveness. Zeolitic imidazolate framework‐8 (ZIF‐8) and carboplatin (CP)‐loaded ZIF‐8 were synthesized and characterized using various analytical techniques. High Resolution‐transmission electron microscopy of ZIF‐8 and CP@ZIF‐8 indicates that the particles had a spherical shape and were nanosized. The drug release rate of CP is 98% under an acidic medium (pH 5.5) because of the dissolution of ZIF‐8 into its coordinating ions, whereas 35% in a physiological medium (pH 7.4) with the addition of CP, the high porosity, and pore diameter of ZIF‐8 decrease from 1243 to 1041 m2/g. Breast cancer MCF‐7 cells were shown greater IC50 in CP@ZIF‐8 (15.01 ± 3.03 µg/mL) than free CP (34.98 ± 4.25 µg/mL) in an in vitro cytotoxicity assessment. The cytotoxicity of the CP@ZIF‐8 against MCF‐7 cells was studied using the methylthiazolyldiphenyl‐tetrazolium bromide method. The morphological changes were examined using fluorescent staining (acridine orange–ethidium bromide and Hoechst 33258) methods. The comet assay assessed the DNA fragmentation (single‐cell gel electrophoresis). The results from the study revealed that CP@ZIF‐8 can be used in the treatment of breast cancer.
Investigation of resveratrol as a xanthine oxidase inhibitor: Mechanistic insights and therapeutic implications for gout and hyperuricemia
Authors: Chen Jianmin , Chen Juan , Feng Baozhu , Ning Meilian , Wu Wanhui , Zou Shiqi 
Published: November 2024

AbstractGout predominantly stems from hyperuricemia, precipitating the accumulation of urate crystals and consequent joint inflammation, swelling, and pain, thereby compromising the quality of life and presenting a formidable medical dilemma. Although conventional treatments like allopurinol and febuxostat target uric acid reduction via xanthine oxidase (XO) inhibition, they often entail adverse effects, prompting the exploration of safer alternatives. Resveratrol, a polyphenolic compound abundant in fruits and vegetables, has emerged as a potential XO inhibitor. However, its precise inhibitory mechanisms remain poorly understood. This study aims to comprehensively investigate resveratrol's XO inhibition through mechanistic insights, molecular docking simulations, animal model experiments, and biochemical analysis, contributing valuable insights to the development of novel therapeutics for hyperuricemia and gout.
Do financial constraints lead to environmental, social and governance controversies? The role of country context
Authors: Vargas‐Santander Karen Gloria , Álvarez‐Diez Susana , Baixauli‐Soler Samuel , Belda‐Ruiz María 
Published: November 2024

AbstractThe term sustainability and environmental, social and governance (ESG) criteria has gained greater importance globally in recent decades. As social and environmental issues increase, firms are advocating the need to be more sustainable. However, in this scenario, corporate controversies still persist, and an analysis of their causes is required. This study focuses on establishing the relationship between financial constraints (FC) and ESG controversies and on determining whether the country context might modify the controversial behaviours of financially constrained firms. Through a Tobit analysis for panel data—and using a sample of firms with headquarters in 47 countries—our results show a positive and significant influence of FC on ESG controversies. In addition, our evidence confirms that country context impacts relationships within the firm, and that opting for controversial activities is increasingly less viable for firms located in countries where there is institutionalized sustainability.
Whether Primary Bone‐Only Oligometastatic Nasopharyngeal Carcinoma Patients Benefit From Radiotherapy to the Bones on the Basis of Palliative Chemotherapy Plus Locoregional Radiotherapy?—A Large‐Cohort Retrospective Study
Authors: Guo Wan‐Ping , Jia Guo‐Dong , Xie Si‐Yi , Yu Xuan , Meng Xiao‐Han , Tang Lin‐Quan , Li Xiao‐Yun , Luo Dong‐Hua 
Published: November 2024

ABSTRACTObjectivesWhether to perform local radiotherapy on metastatic bone for primary bone‐only oligometastatic nasopharyngeal carcinoma (NPC) patients remains unclear. Therefore, we analyzed the treatment methods and their survival and developed a prognostic model to predict outcomes and guide personalized treatment.Materials and MethodsWe studied 308 primary bone‐only oligometastatic NPC patients who were treated with either palliative chemotherapy (PCT) alone, PCT combined with locoregional radiotherapy (LRRT), or PCT, LRRT, and radiotherapy to metastatic bones (bRT). The primary endpoint was overall survival (OS). Cox regression was utilized to identify independent prognostic factors, leading to the construction of a nomogram model. Patients were stratified into two risk groups based on median prognostic scores, and treatment modalities were compared using log‐rank test while employing the inverse probability of treatment weighting (IPTW) to balance baseline characteristics and adjust for sample size differences between risk groups.ResultsThe best OS was observed in the group treated with PCT, LRRT, and bRT (HR = 0.60, 95% CI: 0.45–0.81, p = 0.002). Multivariable analysis revealed that age, N stage, pre‐treatment levels of LDH, and EBV DNA were independent prognostic factors for OS. In total, 155 patients were in low‐risk group while 153 were in high‐risk group. Before and after IPTW, the high‐risk group benefited from the PCT, LRRT, and bRT regimen (adjusted HR = 0.53, 95% CI: 0.42–0.67, p < 0.001; unadjusted HR = 0.59, 95% CI: 0.42–0.83, p = 0.007), while the low‐risk group did not (adjusted HR = 0.79, 95% CI: 0.56–1.11, p = 0.345; unadjusted HR = 0.65, 95% CI: 0.37–1.14, p = 0.309).ConclusionBest outcomes of the whole cohort were seen with PCT + LRRT + bRT. Our study identified age, N stage, pre‐treatment LDH levels, and EBV DNA levels as independent prognostic factors for OS. The high‐risk group demonstrated a longer OS when treated with PCT + LRRT + bRT, whereas the low‐risk group did not benefit from the combinatorial treatment.
Experience with reduced‐nicotine cigarettes and whether this decreases smoking and substitution for full‐nicotine cigarettes
Authors: Naudé Gideon P. , Strickland Justin C. , Berry Meredith S. , Dolan Sean B. , Cox David J. , Johnson Matthew W. 
Published: November 2024

AbstractStudies suggest that reduced‐nicotine cigarettes decrease nicotine intake and dependence. However, questions remain about reduced‐nicotine cigarette abuse liability, whether reduced‐nicotine cigarette exposure lowers reduced‐ and full‐nicotine cigarette use, and whether reduced‐nicotine cigarettes substitute for full‐nicotine cigarettes. This randomized, double‐blind laboratory study used operant behavioral economics to examine abuse liability of cigarettes with varying nicotine content. Non‐treatment‐seeking smokers (N = 43) self‐administered reduced‐ (5.2, 2.4, or 1.3 mg/g) and full‐nicotine (15.8 mg/g) cigarettes before and after 3 weeks of at‐home exposure. Participants were randomized to full‐nicotine or one of the reduced‐nicotine cigarettes to determine the effect of exposure on abuse liability and substitutability. Abuse liability was assessed in single‐commodity sessions, and substitutability was measured in concurrent‐commodity sessions. In the self‐administration sessions, concurrently available reduced‐nicotine cigarettes attenuated full‐nicotine cigarette demand and rendered reduced‐nicotine cigarettes partial substitutes for full‐nicotine cigarettes. Exposure to study cigarettes for 3 weeks marginally reduced demand for reduced‐ and full‐nicotine cigarettes irrespective of nicotine content. Results suggest a limited influence of nicotine content on smoking behavior in established smokers and highlight the role of nonpharmacological factors (e.g., taste/smell) on the maintenance of smoking. These results should be considered in determining whether a nicotine‐reduction standard is a feasible path for reducing cigarette demand.
Longitudinal Evolution of the Brain Microstructure in Cirrhotic Patients on Diffusion Kurtosis Imaging
Authors: Chen Yuan‐Yuan , Lu Zi‐Ning , Zhang Qi , Zhang Yi‐Ning , Ma Wen‐Ting , Zhang XiaoDi , Zhang Xiao‐Dong , Ni Hong‐Yan , Cheng Yue 
Published: November 2024

BackgroundAlthough improvement of cognitive function after liver transplantation has been demonstrated in several neuropsychological studies, there is limited research on longitudinal changes in the cirrhotic patients' brain structure before and after transplantation.PurposeTo investigate longitudinal changes of brain microstructure in cirrhotic patients using diffusion kurtosis imaging (DKI).Study TypeProspective.SubjectsA total of 153 cirrhosis patients, comprising 60 hepatic encephalopathy (HE) patients (16 females/44 males) and 93 no‐HE patients (35 females/58 males), along with 93 healthy controls (HCs) (53 females/40 males) were enrolled. Subsequently, 58 recipients completed 1‐month postoperative follow‐up, 29 patients completed 1‐, 3‐months, and 17 patients completed 1‐, 3‐, 6‐month follow‐up.SequenceSpin‐echo single‐shot echo‐planar sequence using a 3.0 T scanner.AssessmentDiffusion kurtosis estimator software was used to estimate the DKI parameter maps by a MR imaging physicist (Y.‐Y.C. with 12 years of experience).Statistical TestsThe diffusion metrics (eg, radial kurtosis [RK], mean kurtosis, fractional anisotropy, mean diffusivity) of the patients before transplantation were compared with those of the HCs using voxel‐wise analysis of variance (ANOVA), along with t tests for post hoc analysis. Linear mixed‐effects models were applied to the longitudinal data. We imposed a cluster level Family Wise Error (FWE) correction rate of PFWE = 0.05 with voxel‐wise cutoff of P = 0.001 together with a cluster‐size cutoff of N ≥ 56, and generated smoothness estimates from the preprocessed data using the mixed‐model autocorrelation function.ResultsThe RK metrics of the patients decreased significantly in the anterior cingulate cortex (HE/no‐HE < HC, ANOVA‐F = 21.91). After transplantation, the RK of the pallidum showed a continuous upward trend (time effect T = 11.26); whereas the RK of the right postcentral gyrus showed a continuous downward trend (time effect T = −9.56). In addition, the RK in superior longitudinal fasciculus showed new‐onset decrease after transplantation.Data ConclusionLongitudinal changes in DKI metrics reveal the course of brain microstructural changes before and after transplantation in cirrhotic patients, potentially associated with cognitive alterations after surgery.Level of Evidence1Technical EfficacyStage 4
Berberine safeguards sepsis‐triggered acute gastric damage and inhibits pyroptosis in gastric epithelial cells via suppressing the ubiquitination and degradation of Nrf2
Authors: Xie Shu‐Rui , Liu Yan‐Jun , Chen Fen‐Qiao , Pan Zhao 
Published: November 2024

AbstractBerberine (BBR), a widely recognized traditional Chinese medicine, has attracted considerable attention for its promising anti‐inflammatory effects. The activation of nuclear factor erythroid 2‐related factor 2 (Nrf2) effectively safeguards against organ damage stemming from sepsis‐induced oxidative stress and inflammatory responses. This study examined the potential of BBR in alleviating sepsis‐induced acute gastric injury, with a particular focus on elucidating whether its mechanism of action involves the activation of the Nrf2 signaling pathway. Following intraperitoneal injection of BBR, mice were subjected to the cecal ligation and puncture (CLP) method to induce sepsis. In vitro experiments involved pre‐treating the normal gastric epithelial cells (GES‐1) with BBR, followed by treatment with lipopolysaccharide (LPS). Functional assays were then performed to assess cell proliferation and apoptosis. To validate the role of Nrf2 in pyroptosis and inflammation, siRNA targeting Nrf2 (si‐Nrf2) was transfected into LPS‐treated GES‐1 cells. Additionally, mice were administered the Nrf2 inhibitor ML385 to confirm the protective effects of BBR in vivo. BBR displayed a dose‐dependent effect in mitigating gastric tissue damage, suppressing the release of inflammatory cytokines, and reducing the expression of NLRP3, ASC, and GSDMD‐N. In vitro, BBR fostered GES‐1 cell proliferation, hindered apoptosis, and suppressed the levels of TNF‐α, IL‐18, IL‐1β, NLRP3, ASC, and GSDMD‐N. Further analysis revealed that knocking down Nrf2 reversed BBR's inhibitory effect on pyroptosis in LPS‐treated GES‐1 cells. Through binding to Keap1, BBR efficiently prevented the ubiquitination and degradation of Nrf2, ultimately promoting its nuclear translocation. In vivo experiments confirmed that ML385 reversed the protective effect of BBR on pyroptosis and inflammation. Our research reveals that BBR interacts with Keap1 to activate the Keap1/Nrf2 signaling pathway in gastric epithelial cells, thereby suppressing pyroptosis and inflammation in sepsis‐induced acute gastric injury.
Skin Biopsy Detection of Phosphorylated α‐Synuclein in Patients of Bullous Pemphigoid with or without Parkinson's Disease
Authors: Cao Shan , Fang Xiang , Wang Jianwen , Sun Yonghu , Zhang Furen 
Published: November 2024

AbstractBackgroundHigh positivity rate of skin phosphorylated α‐synuclein (P‐SYN) was observed in Parkinson's disease (PD). Bullous pemphigoid (BP) is one of the most common autoimmune skin diseases associated with PD.ObjectivesOur aim was to investigate whether BP patients might be a targeted risk population for the screening of skin P‐SYN.MethodsSkin P‐SYN expression was evaluated by immunohistochemistry in BP patients with/without PD.ResultsTwenty‐two BP patients with PD, 24 BP patients without PD, and seven healthy donors were enrolled. Colocalization of P‐SYN and PGP9.5 was found in all BP patients, but only one healthy control, whereas BP patients with PD showed higher expression than BP patients without PD (mean ± standard deviation, 10.7 ± 6.7 vs. 7.3 ± 3.2; P = 0.027). Positive expression was mainly observed in basement membrane zone and dermis.ConclusionThese results indicated BP patients might be a targeted risk population for the screening of skin P‐SYN, which was helpful for the detection of PD early. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Screening and Predictive Biomarkers for Down Syndrome Through Amniotic Fluid Metabolomics
Authors: Zhang Li‐Chao , Yang Xiang‐Chun , Jiang Yong‐Hong , Yang Zhen , Yan Lu‐Lu , Zhang Yu‐Xin , Li Qiong , Tian Li‐Yun , Cao Juan , Zhou Ying , Wu Shan‐Shan , Zhuang Dan‐Yan , Chen Chang‐Shui , Li Hai‐Bo 
Published: November 2024

ABSTRACTBackgroundDown syndrome (DS) is a congenital disorder caused by the presence of an extra copy of all or part of chromosome 21. It is characterized by significant intellectual disability, distinct facial features, and growth and developmental challenges. The utilization of metabolomics to analyze specific metabolic markers in maternal amniotic fluid may provide innovative tools and screening methods for investigating the early pathophysiology of trisomy 21 at the functional level.MethodsAmniotic fluid samples were obtained via amniocentesis from 57 pregnancies with DS and 55 control pregnancies between 173/7 and 240/7 weeks of gestation. The targeted metabolomics focused on 34 organic acids, 17 amino acids, and 5 acylcarnitine metabolites. The untargeted metabolomics analysis concentrated on lipid profiles and included 602 metabolites that met quality control standards. Principal Component Analysis, Orthogonal Partial Least Squares Discriminant Analysis (OPLS‐DA), and false discovery rate (FDR) adjustments were applied. MetaboAnalystR 5.0 was used to perform the metabolic pathway analysis on the identified differential metabolites.ResultsFifty differential metabolites, including L‐glutamine, eight organic acids, and 41 lipids, were significantly altered in DS based on three criteria: VIP > 1 in the OPLS‐DA model, FDR‐adjusted p‐value < 0.05, and |log2FC| > log2(1.5) from a volcano plot of all detected metabolites. An analysis of 212 differential metabolites, selected from both targeted and untargeted approaches (VIP > 1 in the OPLS‐DA model and FDR‐adjusted p‐value < 0.05), revealed significant changes in nine metabolic pathways. Fourteen key metabolites were identified to establish a screening model for DS, achieving an area under the curve of 1.00.ConclusionsOur results underscore the potential of metabolomics approaches in identifying concise and reliable biomarker combinations that demonstrate promising screening performance in DS.
Racial disparities in prosthesis use, satisfaction, and physical function in upper limb amputation and the impact of veteran status
Authors: Resnik Linda , Roberts Anthony I. , Borgia Matthew 
Published: November 2024

AbstractBackgroundPrior research found that Black veterans with upper limb amputation (ULA) reported greater disability and need for assistance compared to White veterans. The extent to which racial disparities in outcomes exist outside of the Department of Veterans Affairs has not been explored.ObjectiveTo examine racial disparities in physical function and prosthesis satisfaction among individuals with ULA and assess the potential moderating role of veteran status.DesignCross‐sectional survey.SettingCommunity‐dwelling participants.ParticipantsU.S. veterans and civilians with ULA.InterventionsNot applicable.Main Outcome MeasuresPhysical function measures included Patient‐Reported Outcomes Measurement Information System–Upper Extremity Amputation‐specific (PROMIS‐UE AMP), and Upper Extremity Functional Scale for Prosthesis Users (UEFS‐P) for one‐handed and two‐handed tasks. Prosthesis satisfaction measures included the modified Client Satisfaction with Device (CSD) Comfort, Appearance, and Utility scales, the CSD‐8, and the Trinity Amputation and Prosthesis Experience Satisfaction (TAPES) scale.ResultsOf 713 participants, 79% were male, with mean age of 61.3 years. The racial composition was 83.6% White, 9.1% Black, and 7.3% other, with 75.4% identifying as veterans. Multivariable linear regression found that Black participants (compared to White) had lower PROMIS 13‐UE AMP (β: −5.1, 95% CI: −7.7 to −2.5) and UEFS‐P Two‐Handed Task Scale (β: −4.0, 95% CI: −7.3 to −2.1) scores. Satisfaction scores were lower for Black participants as measured by modified CSD Comfort (β: −3.9, 95% CI: −7.2 to −0.6), Appearance (β: −4.4, 95% CI: −7.5 to −1.2), Utility (β: −3.9, 95% CI: −7.2 to −0.6), and CSD‐8 (β: −3.9, 95% CI: −7.2 to −0.6) scales. Veteran status moderated the impact of Black race on the UEFS‐P Two‐Handed Task Scale and the TAPES.ConclusionsBlack individuals with ULA had worse physical function and prosthesis satisfaction than White individuals. Although veteran status moderated these disparities, the reasons for these disparities remain unclear. Further research is essential to understand the causes of these disparities.