bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanistic evaluation of the effect of sodium‐dependent glucose transporter 2 inhibitors on delayed glucose absorption in patients with type 2 diabetes mellitus using a quantitative systems pharmacology model of human systemic glucose dynamics
Authors: Mori‐Anai Kazumi , Tashima Yoshihiko , Nakada Tomohisa , Nakamaru Yoshinobu , Takahata Takayuki , Saito Ryuta 
Published: October 2020

AbstractSodium‐dependent glucose transporter (SGLT) 2 is specifically expressed in the kidney, while SGLT1 is present in the kidneys and small intestine. SGLT2 inhibitors are a class of oral antidiabetic drugs that lower elevated plasma glucose levels by promoting the urinary excretion of excess glucose through the inhibition of renal glucose reuptake. The inhibition selectivity for SGLT2 over SGLT1 (SGLT2/1 selectivity) of marketed SGLT2 inhibitors is diverse, while SGLT2/1 selectivity of canagliflozin is relatively low. Although canagliflozin suppresses postprandial glucose levels, the degree of contribution for SGLT1 inhibition to this effect remains unproven. To analyze the effect of SGLT2 inhibitors on postprandial glucose level, we constructed a novel quantitative systems pharmacology (QSP) model, called human systemic glucose dynamics (HSGD) model, integrating intestinal absorption, metabolism, and renal reabsorption of glucose. This HSGD model reproduced the postprandial plasma glucose concentration–time profiles during a meal tolerance test under different clinical trial conditions. Simulations after canagliflozin administration showed a dose‐dependent delay of time (Tmax,glc) to reach maximum concentration of glucose (Cmax,glc), and the delay of Tmax,glc disappeared when inhibition of SGLT1 was negated. In addition, contribution ratio of intestinal SGLT1 inhibition to the decrease in Cmax,glc was estimated to be 23%–28%, when 100 and 300 mg of canagliflozin are administered. This HSGD model enabled us to provide the partial contribution of intestinal SGLT1 inhibition to the improvement of postprandial hyperglycemia as well as to quantitatively describe the plasma glucose dynamics following SGLT2 inhibitors.
Extracellular vesicles from organoids and 3D culture systems
Authors: Abdollahi Sara 
Published: October 2020

AbstractWhen discovered, extracellular vesicles (EVs) such as exosomes were thought of as junk carriers and a means by which the cell disposed of its waste material. Over the years, the role of EVs in cell communication has become apparent with the discovery that the nano‐scale vesicles also transport RNA, DNA, and other bioactive components to and from the cells. These findings were originally made in EVs from body fluids of organisms and from in vitro two‐dimensional (2D) cell culture models. Recently, organoids and other 3D multicellular in vitro models are being used to study EVs in the context of both physiologic and pathological states. However, standard, reproducible methods are lacking for EV analysis using these models. As a step toward understanding the implications of these platforms, this review provides a comprehensive picture of the progress using 3D in vitro culture models for EV analysis. Translational efforts and regulatory considerations for EV therapeutics are also briefly overviewed to understand what is needed for scale‐up and, ultimately, commercialization.
Effects of psychosocial and socio‐environmental factors on anxiety disorder among adolescents in Bangladesh
Authors: Khan Md. Mostaured Ali , Khan Md. Nuruzzaman 
Published: October 2020

AbstractBackgroundAnxiety is a common psychiatric disorder among adolescents in developing countries. This study aimed to examine the risk factors of anxiety disorder and the adverse consequences of anxiety disorder among adolescents in Bangladesh.MethodsA total of 2,989 adolescent data of the 2014 Global School‐based Student Health Survey (GSHS), Bangladesh, was analyzed WHO. The prevalence of anxiety disorder across psychosocial and socio‐environmental factors was calculated as descriptive statistics, whereas their effects on occurring anxiety disorder were determined using the unadjusted and adjusted multivariable binary logistic regression model. The consequences of anxiety disorder were also determined using the multivariable binary logistic regression model.ResultsThe prevalence of anxiety disorder was 4.7%, which was found higher among female than their male counterparts. The psychosocial factors were found associated with the anxiety disorder are loneliness (AOR: 2.26, 95% CI: 1.08–4.72), being bullied (AOR: 6.00, 95% CI: 3.14–11.47), and physical abuse (AOR: 2.12, 95% CI: 1.07–4.21). Moreover, poor understandings with parents (AOR: 1.75, 95% CI: 1.02–3.01) and lack of peer support (AOR: 2.23, 95% CI: 1.18–4.23) were the socio‐environmental factors that found associated with the anxiety disorder. Subgroup analysis across gender found these associations were consistent for adolescent male and female. Moreover, the likelihood increased with the increasing number of the adverse psychosocial, or socio‐environmental factors.ConclusionsAround 5% of school‐going adolescents in Bangladesh reported anxiety associated with the exposure of single or multiple adverse psychosocial and socio‐environmental factors including bullying and physical abuse. Early screening and interventions are essential, targeted to adolescent at risk, which could reduce the rate of anxiety disorder among adolescent in Bangladesh.
Validation of the 1,4‐butanediolthermoplastic polyurethane as a novel material for3Dbioprinting applications
Authors: Chocarro‐Wrona Carlos , de Vicente Juan , Antich Cristina , Jiménez Gema , Martínez‐Moreno Daniel , Carrillo Esmeralda , Montañez Elvira , Gálvez‐Martín Patricia , Perán Macarena , López‐Ruiz Elena , Marchal Juan Antonio 
Published: October 2020

AbstractTissue engineering (TE) seeks to fabricate implants that mimic the mechanical strength, structure, and composition of native tissues. Cartilage TE requires the development of functional personalized implants with cartilage‐like mechanical properties capable of sustaining high load‐bearing environments to integrate into the surrounding tissue of the cartilage defect. In this study, we evaluated the novel 1,4‐butanediol thermoplastic polyurethane elastomer (b‐TPUe) derivative filament as a 3D bioprinting material with application in cartilage TE. The mechanical behavior of b‐TPUe in terms of friction and elasticity were examined and compared with human articular cartilage, PCL, and PLA. Moreover, infrapatellar fat pad‐derived human mesenchymal stem cells (MSCs) were bioprinted together with scaffolds. in vitro cytotoxicity, proliferative potential, cell viability, and chondrogenic differentiation were analyzed by Alamar blue assay, SEM, confocal microscopy, and RT‐qPCR. Moreover, in vivo biocompatibility and host integration were analyzed. b‐TPUe demonstrated a much closer compression and shear behavior to native cartilage than PCL and PLA, as well as closer tribological properties to cartilage. Moreover, b‐TPUe bioprinted scaffolds were able to maintain proper proliferative potential, cell viability, and supported MSCs chondrogenesis. Finally,in vivostudies revealed no toxic effects 21 days after scaffolds implantation, extracellular matrix deposition and integration within the surrounding tissue. This is the first study that validates the biocompatibility of b‐TPUe for 3D bioprinting. Our findings indicate that this biomaterial can be exploited for the automated biofabrication of artificial tissues with tailorable mechanical properties including the great potential for cartilage TE applications.
An antibody‐drug conjugate targeting a GSTA glycosite‐signature epitope of MUC1 expressed by non‐small cell lung cancer
Authors: Pan Deng , Tang Yubo , Tong Jiao , Xie Chengmei , Chen Jiaxi , Feng Chunchao , Hwu Patrick , Huang Wei , Zhou Dapeng 
Published: October 2020

AbstractAntibodies targeting aberrantly glycosylated proteins are ineffective in treating cancer. Antibody‐drug conjugates have emerged as effective alternatives, facilitating tumor‐specific drug delivery. Previous studies have assessed the aberrantly glycosylated tandem repeat region of MUC1 glycoprotein as three site‐specific glycosylated neoantigen peptide motifs (PDTR, GSTA, and GVTS) for binding with a monoclonal antibody. This study aimed to develop an antibody‐drug conjugate for cancer treatment based on monoclonal antibodies against the aforementioned three neoantigen peptide motifs. Internalization of monoclonal antibodies was assessed via immunofluorescence staining and colocalization with lysosomal markers in live cells. Antibody positivity in tumor and peritumoral tissue samples was assessed via immunohistochemistry. The efficacy of anti‐MUC1 ADCs was evaluated using various cancer cell lines and a mouse tumor xenograft model. An anti‐MUC1 ADC was synthesized by conjugating GSTA neoantigen‐specific 16A with monomethyl auristatin E (MMAE), which displayed potent antitumoral efficacy with an IC50 ranging 0.2–49.4 nM toward various cancer cells. In vivo, 16A‐MMAE inhibited tumor growth in a dose‐dependent manner in a mouse xenograft model established using the NCI‐H838 NSCLC cell line, at a minimum effective dose of 1 mg/kg. At 3 mg/kg, 16A‐MMAE did not cause significant toxicity in a transgenic mouse expressing human MUC1. The high antitumoral efficacy of 16A‐MMAE suggests that aberrant glycosylated MUC1 neoantigen is a potential target for the development of ADCs for treating various cancers. Personalized therapy may be achieved through such glycosite‐specific ADCs.
A qualitative study of service user non‐engagement in psychological therapy groups on acute mental health wards
Authors: Harris Lara , Lechevallier Zina , Buhagiar Kurt 
Published: October 2020

AbstractAims and methodNon‐engagement with psychological therapy groups in mental health settings is a long‐standing problem, with implications on group processes and service delivery. Little is known about service user‐related factors hindering this engagement, especially on inpatient wards. We aimed to investigate the perspectives of service users on barriers to engagement with a therapeutic group facilitated by assistant psychologists. Experiences of therapy groups were explored via focus groups and in‐depth semi‐structured interviews with 16 participants on two acute wards. Data were analysed by means of thematic analysis adopting an inductive approach embedded in a constructivist paradigm.ResultsThe analysis identified three higher‐order themes: ways that facilitators might encourage group attendance; a need for safe therapeutic conditions within the groups; and a need for good applicability of group content to recovery outside of hospital. The results are discussed with reference to psychological approaches, group therapy research and trauma‐informed care.ConclusionFindings bear implications on clinical practice within inpatient mental health settings, specifically: (a) the need to approach service users individually to invite to groups and establish role expectancies; (b) supervision for facilitators focussing on difficult group dynamics and creating robust groups agreements to facilitate containment; (c) working with teams to ensure stable, protected physical spaces for groups on wards, in turn avoiding the re‐traumatising effects of disruption; (d) emphasising that participation does not require sharing difficult personal information, to prevent destabilisation and improve uptake of group offer; and (e) increasing focus on applicability of skills through consideration of potential obstacles to their real‐life application.
Polysaccharide from Lycium arabicum: Structural Features, in Vitro Antioxidant Activities and Protective Effect against Oxidative Damage in Human Erythrocytes
Authors: Fakhfakh Jawhar , Athmouni Khaled , Mallek‐Fakhfakh Hanen , Ayedi Habib , Allouche Noureddine 
Published: October 2020

AbstractIn this research work, a water‐soluble polysaccharide (LAP) isolated from the fruits of Lycium arabicum was investigated. LAP contains carbohydrates (82.45±1.23 %), protein (1.56±0.21 %), and uronic acids (3.56±0.34 %). The analysis of the monosaccharide composition revealed the presence of rhamnose, arabinose, galactose, glucose and mannose in a molar ratio of 4.7 : 1.5 : 1 : 8.7 : 16.4 : 5.6. The extracted polysaccharide (PS) was considered as heterogeneous and highly branched by interpreting its GC/MS, FT‐IR and NMR data. Crystallinity of LAP was inferred from its X‐ray diffractometry (XRD) and Scanning Electron Microscopy (SEM) analysis. LAP exhibited an interesting stability at high temperatures (∼254 °C) and in a wide range of pH (3–9) deduced, respectively, from its DSC and zeta potential analysis. LAP displayed a strong antioxidant activity at low concentrations evaluated by the 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH)‐radical scavenging, ferric reducing activity power (FRAP), free radical scavenging ability, superoxide radical‐scavenging and hydroxyl radical‐scavenging abilities. Inhibition of erythrocyte hemolysis and lipid peroxidation was also assessed. In 5 h, LAP treatment allowed the protection of the damaged erythrocytes caused by AAPH (2,2‐azobis(2‐amidinopropane) dihydrochloride), to reduce the level of malondialdehyde (MDA) as well as to increase the reduced glutathione (GSH) level.
Discovery of Natural Product‐Based Fungicides (II): Semisynthesis and Biological Activity of Sarisan Attached 3‐Phenylisoxazolines as Antifungal Agents
Authors: Liu Zhiyan , Cao Jiangping , Yan Xiaoting , Cheng Wanqing , Wang Xiaoguang , Yang Ruige , Guo Yong 
Published: October 2020

AbstractMany phytopathogenic fungi cause severe damage to crop yields. In continuation of our research aimed at the discovery and development of natural products‐based fungicides, a series of thirty‐one sarisan attached 3‐phenylisoxazolines were synthesized and evaluated for their antifungal activities against five phytopathogenic fungi (B. cinerea, C. lagenarium, A. solani, F. solani, and F. graminearum). Among all title sarisan derivatives, compounds IV2, IV14 and IV23 showed potent antifungal activity against some phytopathogenic fungi. In particular, compound IV2 exhibited a broad‐spectrum and more potent antifungal activity against A. solani, F. solani, and F. graminearum than the commercial fungicide Hymexazol. In addition, compounds IV2, IV14 and IV23 also displayed relative low toxicity on normal NRK‐52E cells. This work will give some insights into the development of sarisan derivatives as new fungicide candidates in plant protection.
Comparing QFR and FFR in small vessels—Expanding the spectrum of use
Authors: Kern Morton J. , Seto Arnold H. 
Published: October 2020

Key Points
Quantitative flow reserve (QFR) estimates fractional flow reserve (FFR) reasonably well but accuracy in small diameter vessels has been challenged.
This study demonstrates excellent performance for QFR across either small (≤2.8 mm) or large (>2.8 mm) vessels.
QFR requires further study in a larger patient cohort with significant lesions (FFR < 0.80) before becoming a standard of care.
Single‐Molecule Interactions between Heme Proteins and Carboxylic Groups in Various Chemical Environments
Authors: Hao Xian , Zhang Jingdong , Yang Yifei , Wang Hongda , Chi Qijin 
Published: October 2020

AbstractNoncovalent chemical interactions, including electrostatic interactions, hydrogen bonding, and hydrophobic interactions, constitute crucial driving forces in the bottom‐up assembly of multifunctional molecular complexes and nanomaterials. Electrostatic interactions in chemical environments are generally considered as non‐specific interactions, which pose notable challenges for the control and direct measurement of electrostatic forces at the single‐molecule level. Here, we report a model system consisting of cytochrome c and molecules containing carboxyl groups, and use electrochemical AFM force spectroscopy to navigate the electrostatic forces of the system under various chemical conditions. The effects of solution pH, ion strength, and redox states of cytochrome c on electrostatic interactions as well as control over these parameters are systematically studied. This work provides a useful approach for investigating intermolecular electrostatic interactions at the single‐molecule level.
CoPd Nanoalloys with Metal–Organic Framework as Template for Both N‐Doped Carbon and Cobalt Precursor: Efficient and Robust Catalysts for Hydrogenation Reactions
Authors: Zhu Jie , Xu Deng , Ding Lu‐jia , Wang Peng‐cheng 
Published: October 2020

AbstractIn this work, a series of metal–organic framework (MOF)‐derived CoPd nanoalloys have been prepared. The nanocatalysts exhibited excellent activities in the hydrogenation of nitroarenes and alkenes in green solvent (ethanol/water) under mild conditions (H2 balloon, room temperature). Using ZIF‐67 as template for both carbon matrix and cobalt precursor coating with a mesoporous SiO2 layer, the catalyst CoPd/NC@SiO2 was smoothly constructed. Catalytic results revealed a synergistic effect between Co and Pd components in the hydrogenation process due to the enhanced electron density. The mesoporous SiO2 shell effectively prevented the sintering of hollow carbon and metal NPs at high temperature, furnishing the well‐dispersed nanoalloy catalysts and better catalytic performance. Moreover, the catalyst was durable and showed negligible activity decay in recycling and scale‐up experiments, providing a mild and highly efficient way to access amines and arenes.
Electrochemical C−H Amidation of Heteroarenes with N‐Alkyl Sulfonamides in Aqueous Medium
Authors: Zhang Yan , Lin Zhipeng , Ackermann Lutz 
Published: October 2020

AbstractThe construction of C−N bonds by free radical reactions represents a powerful synthetic approach for direct C−H amidations of arenes or heteroarenes. Developing efficient and more environmentally friendly synthetic methods for C−H amidation reactions remains highly desirable. Herein, metal‐free electrochemical oxidative dehydrogenative C−H amidations of heteroarenes with N‐alkylsulfonamides have been accomplished. The catalyst‐ and chemical‐oxidant‐free C−H amidation features an ample scope and employs electricity as the green and sole oxidant. A variety of heteroarenes, including indoles, pyrroles, benzofuran and benzothiophene, thereby underwent this C(sp2)−H nitrogenation. Cyclic voltammetry studies and control experiments provided evidence for nitrogen‐centered radicals being directly generated under metal‐free electrocatalysis.
Strong Equatorial Crystal Field Enhances the Axial Anisotropy and Energy Barrier for Spin Reversal Process in Yb2 Single Molecule Magnets
Authors: Mondal Arpan , Konar Sanjit 
Published: October 2020

AbstractThe importance of equatorial crystal fields on magnetic anisotropy of ytterbium single molecule magnets (SMMs) is observed for the first time. Herein, we report three similar dinuclear ytterbium complexes with the formula [Yb2(3‐OMe‐L)2(DMF)2(NO3)2]⋅DMF (1), [Yb2(3‐H‐L)2(DMF)2(NO3)2]⋅DMF⋅H2O (2), and [Yb2(3‐NO3‐L)2(DMF)2(NO3)2] (3), [where 3‐X‐H2L=N′‐(2‐hydroxy‐3‐X‐benzylidene)picolinohydrazide, X=OMe (1), H (2) NO2 (3)]. Detailed magnetic measurements reveal the presence of weak antiferromagnetic interactions between the Yb centers and a field‐induced slow relaxation of magnetization in all complexes. A higher energy barrier for spin reversal was observed for complex 1 (Ueff=50 K) and it decreases in the order of 2 (47 K) to 3 (40 K). Notably, complex 1 shows a remarkable energy barrier within the frequency range of 1–850 Hz reported for Yb‐based SMMs. Further, ab initio calculations show a higher axial anisotropy and lower quantum tunneling of magnetization (QTM) in the ground state for 1 compared to 2 and 3. It was also observed that the presence of a strong crystal field in the equatorial plane (when the ∡ O1−Yb−O3 bond angle is close to 90°) enhances the axial anisotropy and improves the SMM behavior in the studied complexes. Both the experimental and theoretical analysis of relaxation dynamics discloses that Raman and QTM play major role on slow relaxation process for all complexes. To provide more insight into the exchange interactions, broken‐symmetry DFT calculations were performed.
Surface‐enhanced Raman Scattering on 2D Nanomaterials: Recent Developments and Applications†
Authors: Zheng Tingting , Zhou Yan , Feng Enduo , Tian Yang 
Published: October 2020

AbstractSurface enhanced Raman spectroscopy (SERS) has emerged as a highly powerful and sensitive tool for molecular analysis. Of the various factors that affect SERS performance, substrate material is the most critical. Since first observed in 1974, noble metals have been the most common substrates for SERS. However, their increasing defects including low selectivity, weak uniformity, and poor stability are all obstacles to these noble metal‐based SERS substrates. Recently, due to the unique layer‐dependent optical properties and a very large surface‐to‐volume ratio, two‐dimensional (2D) nanomaterials are found to be promising candidates to overcome the shortcomings of a conventional metallic SERS substrate. Herein, we concentrate on the latest development and applications of SERS‐active 2D nanomaterials in our group as well as in other related research studies. The enhancement mechanism of the SERS effect and the development of various SERS‐active 2D nanomaterials have been discussed in detail. Eventually, the latest development in 2D nanomaterial‐SERS‐based analytical applications from trace detection of small organic pollutants and macromolecular biomarkers to in‐situ cytosensing and in‐situ theranostic analysis is introduced.
Novel Phenylmethylenecyclohexenone Derivatives as Potent TrxR Inhibitors Display High Antiproliferative Activity and Induce ROS, Apoptosis, and DNA Damage
Authors: Wang Xiaomei , Qian Jianqiang , Zhu Peng , Hua Rong , Liu Ji , Hang Jiaying , Meng Chi , Shan Wenpei , Miao Jiefei , Ling Yong 
Published: October 2020

AbstractThe natural product piperlonguminine (PL) has been shown to exert potential anticancer activity against several types of cancer via elevation of reactive oxidative species (ROS). However, the application of PL has been limited due to its poor water solubility and moderate activity. To improve PL's potency, we designed and synthesized a series of 17 novel phenylmethylenecyclohexenone derivatives and evaluated their pharmacological properties. Most of them exerted antiproliferative activities against four cancer cell lines with IC50 values lower than PL. Among these, compound 10 e not only showed good water solubility and exerted the most potent antiproliferative activity against HGC27 cells (IC50=0.76 μM), which was 10‐fold lower than PL (IC50=7.53 μM), but also exhibited lower cytotoxicity in human normal gastric epithelial cells GES‐1 compared with HGC27 cells. Mechanistically, compound 10 e inhibited thioredoxin reductase (TrxR) activity, increased ROS levels, and diminished mitochondrial transmembrane potential (MTP) in HGC27 cells. Furthermore, 10 e also induced G2/M cell‐cycle arrest, and triggered cancer cell apoptosis through the regulation of apoptotic proteins. Finally, 10 e promoted DNA damage in HGC27 cells via the activation of the H2AX(S139ph) and p53 signaling. In conclusion, 10 e, with prominent tumor selectivity and water solubility, could be a promising candidate for the treatment of cancer and, as such, warrants further investigation.