bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vitro and in silico characterization of the inhibition of Kir4.1 channels by aminoglycoside antibiotics
Authors: Morán‐Zendejas Rita , Delgado‐Ramírez Mayra , Xu Jie , Valdés‐Abadía Belkis , Aréchiga‐Figueroa Iván A. , Cui Meng , Rodríguez‐Menchaca Aldo A. 
Published: July 2020

Background and PurposeAminoglycoside antibiotics are positively charged molecules that are known to inhibit several ion channels. In this study, we have shown that aminoglycosides also inhibit the activity of Kir4.1 channels. Aminoglycosides inhibit Kir4.1 channels by a pore‐blocking mechanism, plugging the central vestibule of the channel.Experimental ApproachPatch‐clamp recordings were made in HEK‐293 cells transiently expressing Kir4.1 channels to analyse the effects of gentamicin, neomycin and kanamycin. In silico modelling followed by mutagenesis were realized to identify the residues critical for aminoglycosides binding to Kir4.1.Key ResultsAminoglycoside antibiotics block Kir4.1 channels in a concentration‐ and voltage‐dependent manner, getting access to the protein from the intracellular side of the plasma membrane. Aminoglycosides block Ki4.1 with a rank order of potency as follows: gentamicin ˃ neomycin ˃ kanamycin. The residues T128 and principally E158, facing the central cavity of Kir4.1, are important structural determinants for aminoglycosides binding to the channel, as determined by our in silico modelling and confirmed by mutagenesis experiments.Conclusion and ImplicationsKir4.1 channels are also target of aminoglycoside antibiotics, which could affect potassium transport in several tissues.
Bromo‐ and extraterminal domain protein inhibition improves immunotherapy efficacy in hepatocellular carcinoma
Authors: Liu Chen , Miao Xiaolong , Wang Yao , Wen Liang , Cheng Xiawei , Kong Deqiang , Zhao Pengwei , Song Dandan , Wang Xinyi , Ding Xianfeng , Xia Hongguang , Wang Weilin , Sun Qiming , Gong Weihua 
Published: July 2020

AbstractHepatocellular carcinoma (HCC) represents the majority of liver cancer and is the fourth most common cause of cancer‐related death. Although advances in molecular targeted therapy have shown promise, none of these agents has yet demonstrated significant clinical benefit. Bromo‐ and extraterminal domain (BET) protein inhibitors have been considered potential therapeutic drugs for HCC but the biological activity remains unclear. This study found that BET protein inhibition did not effectively suppress the progression of HCC, using a transgenic HCC mouse model. Mechanistically, the BET protein inhibitor JQ1 upregulated the expression of programmed cell death‐ligand 1 (PD‐L1) on the plasma membrane in vivo and in vitro. Moreover, JQ1 enhanced the expression of Rab8A, which upregulated the expression of PD‐L1 on the plasma membrane. This study also showed that JQ1 combined with anti‐PD‐L1 Ab effectively suppressed HCC progression, and this benefit was obtained by enhancing the activation and cytotoxic capabilities of CD8 T cells. These results revealed the crucial role and regulation of BET protein inhibition on the expression of PD‐L1 in HCC. Thus, combining BET protein inhibition with immune checkpoint blockade offers an efficient therapeutic approach for HCC.
Hypoxia‐inhibited miR‐338‐3p suppresses breast cancer progression by directly targeting ZEB2
Authors: He Juanjuan , Wang Jing , Li Songchao , Li Teng , Chen Kunlun , Zhang Shaojin 
Published: July 2020

AbstractHypoxia plays an essential role in the development of various cancers. The biological function and underlying mechanism of microRNA‐338‐3p (miR‐338‐3p) under hypoxia remain unclarified in breast cancer (BC). Herein, we performed bioinformatics, gain and loss of function of miR‐338‐3p, a luciferase reporter assay, and chromatin immunoprecipitation (ChIP) in vitro and in a tumor xenograft model. We also explored the potential signaling pathways of miR‐338‐3p in BC. We detected the expression levels and prognostic significance of miR‐338‐3p in BC by qRT‐PCR and in situ hybridization. MiR‐338‐3p was lowly expressed in BC tissues and cell lines, and BC patients with underexpression of miR‐338‐3p tend to have a dismal overall survival. Functional experiments showed that miR‐338‐3p overexpression inhibited BC cell proliferation, invasion, migration, and epithelial‐mesenchymal transition (EMT) process, whereas miR‐338‐3p silencing abolished these biological behaviors. Zinc finger E‐box‐binding homeobox 2 (ZEB2) was validated as a direct target of miR‐338‐3p. ZEB2 overexpression promoted while ZEB2 knockdown abolished the promoted effects of miR‐338‐3p knockdown on cell biological behaviors through the NF‐ĸB and PI3K/Akt signal pathways. HIF1A can transcriptionally downregulate miR‐338‐3p under hypoxia. In total, miR‐338‐3p counteracts hypoxia‐induced BC cells growth, migration, invasion, and EMT via the ZEB2 and NF‐ĸB/PI3K signal pathways, implicating miR‐338‐3p may be a promising target to treat patients with BC.
Design, synthesis, and biological evaluation of piperidinyl‐substituted [1,2,4]triazolo[1,5‐a]pyrimidine derivatives as potential anti‐HIV‐1 agents with reduced cytotoxicity
Authors: Huang Boshi , Kang Dongwei , Tian Ye , Daelemans Dirk , De Clercq Erik , Pannecouque Christophe , Zhan Peng , Liu Xinyong 
Published: July 2020

AbstractTaking the previously reported compound BH‐7d as the lead, we designed and synthesized a series of piperidinyl‐substituted [1,2,4]triazolo[1,5‐a]pyrimidines, and their anti‐HIV activities as well as cytotoxicities were evaluated. Several compounds exhibited moderate anti‐HIV (IIIB) potency, among which 2b was the most active one (EC50 = 4.29 μM). Structure–activity relationships derived from the antiretroviral results were analyzed. Additionally, most compounds demonstrated reduced cytotoxicity (CC50 > 200 μM) compared with those of BH‐7d and etravirine. Molecular docking study further revealed the binding conformation of 2b in the binding pocket of HIV‐1 reverse transcriptase.
Children Hold Leaders Primarily Responsible, Not Entitled
Authors: Stavans Maayan , Diesendruck Gil 
Published: July 2020

Do children construe leaders as individuals whose position of power entails primarily more responsibility or more entitlement, compared with nonleaders? To address this question, 5‐year‐old children (n = 128) heard a story involving a hierarchical dyad (a leader and a nonleader) and an egalitarian dyad (two nonleaders), and then assessed protagonists’ relative contributions to a collaborative endeavor (Experiments 1 and 2) or relative withdrawals from a common resource pool earned jointly (Experiment 3). Children expected a leader to contribute more toward a joint goal than its nonleader partner, and to withdraw an equal share (not more) from a common pool. Children thus gave evidence that they construed leaders as more responsible, rather than more entitled, relative to nonleaders.
The stability of initial tacrolimus concentration following allogeneic hematopoietic stem cell transplantation reduces the risk of acute GVHD
Authors: Okabe Motohito , Morishita Takanobu , Ichiki Tomoe , Kawaguchi Yuka , Lee Yoonha , Ohbiki Marie , Goto Miyo , Osaki Masahide , Araie Hiroaki , Goto Tatsunori , Ozawa Yukiyasu , Miyamura Koichi 
Published: July 2020

AbstractBackgroundEarly tacrolimus (TAC) concentrations correlate with the risk of acute graft‐versus‐host disease (aGVHD); however, whether the variability of early TAC concentrations after allo‐HSCT governs the occurrence of aGVHD remains unknown. Here, we evaluate the correlation between the intrapatient variability (IPV) of initial TAC concentrations and the development of aGVHD.MethodsWe retrospectively assessed 202 patients who underwent allo‐HSCT and received standard GVHD prophylaxis by continuous intravenous (iv) infusion of TAC and iv methotrexate. IPV was calculated by using the % coefficient of variation in the initial 4 weeks.ResultsWith median follow‐up duration of 20.7 months, 24 patients were diagnosed with grades II‐IV aGVHD. Overall survival (OS) and relapse at 12 months after allo‐HSCT were 70.6% (95% confidence interval [CI], 63.7%‐76.4%) and 18.9% (95% CI, 13.0%‐24.4%), respectively. When IPV was categorized into two groups (high: ≥9.5%; low: <9.5%), the cumulative incidence of grades II‐IV aGVHD was greater in the IPV‐high group at week 3 (odds ratio: 4.15; 95% CI, 1.37%‐12.6%, P = .01). No significant differences were observed in OS and relapse between the two groups.ConclusionWe concluded that adjusting early TAC concentration stable may reduce aGVHD after allo‐HSCT without affecting the relapse rate.
Contrasting effects of exotic plant invasions and managed honeybees on plant–flower visitor interactions
Authors: Corcos Daria , Cappellari Andree , Mei Maurizio , Paniccia Dino , Cerretti Pierfilippo , Marini Lorenzo 
Published: July 2020

AbstractAimTo explore how a highly invasive plant species (Buddleja davidii Franch.), managed honeybees and flower diversity affected plant–flower visitor interactions over the whole elevational range distribution of the exotic plant.LocationItalian Alps.MethodsWe selected nine pairs of sites (one invaded and one non‐invaded by B. davidii) across gradients in honeybee abundance and diversity of flower resources. We observed plant–flower visitor interactions every three weeks, for a total of five surveys covering the full flowering season of B. davidii (June–August). We tested how B. davidii, honeybee abundance and flowering plant diversity affected network robustness, overlap in flower resource use of wild flower visitors with honeybees and flower visitor specialization. We also tested for an interaction between B. davidii presence and honeybee abundance, and tested whether the effects of the two variables changed among insect orders.ResultsBuddleja davidii and honeybees had contrasting effects on network robustness and on several species‐level metrics. Network robustness increased with increasing honeybee abundance and flower diversity. Increasing honeybee abundance generally increased specialization of lepidopterans and dipterans that tended to switch to less visited plant species, possibly in order to avoid competition. Specialization of flower visitors declined in sites invaded by B. davidii, indicating that the invasive plant attracted pollinators, which in turn also visited co‐occurring species in the neighbourhood.Main conclusionsAlthough increasing honeybee abundance was associated with higher network stability, it also modified plant–flower visitor interactions by forcing species to shift their diet irrespective of floral diversity. The effect was particularly strong for non‐bee flower visitors. The consequences of these changes in plant–flower visitor interactions for the reproductive success of flowering plants are still largely unknown.
Focused echocardiography in cardio‐oncology
Authors: Keramida Kalliopi , Farmakis Dimitrios , López Fernández Teresa , Lancellotti Patrizio 
Published: July 2020

AbstractTransthoracic echocardiography (TTE) is the cornerstone of imaging in patients with a malignancy in all stages of their treatment—before, during, and after the completion of it—to identify most of the cardiotoxic complications. However, the restricted time and resources of cardio‐oncology services and the high volume of oncological patients and survivors on the other hand limit the access of this population to this modality. Focused Echo in Cardio‐Oncology (FECO) in proportion to other focused cardiac protocols is proposed as a valuable tool after the initial standard complete TTE to: (a) identify the potential toxicity expected by the specific cancer therapy applied; (b) assess sequentially the pre‐existing abnormality, if any, in relation to therapy; (c) assess the effect of any cardio‐protective intervention; (d) identify any cardiac origin of patient complaints during or after therapy; (e) assess cardiac function in asymptomatic patients who develop significant changes in cardiac biomarkers during cancer therapy. Four different protocols of FECO are proposed according to the type of cardiotoxicity anticipated: FECOm (in patients on chemotherapeutics that cause myocardial dysfunction), FECOv (in patients at risk of valvular heart disease), FECOpd (in patients at risk of pericardial disease), and FECOph (in patients at risk of pulmonary hypertension). The application of FECO protocols is aimed to ensure accuracy, reliability, and effectiveness in the early identification of cardiovascular complications, improving quality of life, and being at the same time cost‐effective.
Organic cation transporter 3 and the dopamine transporter differentially regulate catecholamine uptake in the basolateral amygdala and nucleus accumbens
Authors: Holleran Katherine M. , Rose Jamie H. , Fordahl Steven C. , Benton Kelsey C. , Rohr Kayla E. , Gasser Paul J. , Jones Sara R. 
Published: July 2020

AbstractRegional alterations in kinetics of catecholamine uptake are due in part to variations in clearance mechanisms. The rate of clearance is a critical determinant of the strength of catecholamine signaling. Catecholamine transmission in the nucleus accumbens core (NAcc) and basolateral amygdala (BLA) is of particular interest due to involvement of these regions in cognition and motivation. Previous work has shown that catecholamine clearance in the NAcc is largely mediated by the dopamine transporter (DAT), but clearance in the BLA is less DAT‐dependent. A growing body of literature suggests that organic cation transporter 3 (OCT3) also contributes to catecholamine clearance in both regions. Consistent with different clearance mechanisms between regions, catecholamine clearance is more rapid in the NAcc than in the BLA, though mechanisms underlying this have not been resolved. We compared the expression of DAT and OCT3 and their contributions to catecholamine clearance in the NAcc and BLA. We found DAT protein levels were ~ 4‐fold higher in the NAcc than in the BLA, while OCT3 protein expression was similar between the two regions. Immunofluorescent labeling of the two transporters in brain sections confirmed these findings. Ex vivo voltammetry demonstrated that the magnitude of catecholamine release was greater, and the clearance rate was faster in the NAcc than in the BLA. Additionally, catecholamine clearance in the BLA was more sensitive to the OCT3 inhibitor corticosterone, while clearance in the NAcc was more cocaine sensitive. These distinctions in catecholamine clearance may underlie differential effects of catecholamines on behavioral outputs mediated by these regions.
Microstructural‐based strain accumulation during cyclic loading of Ni‐based superalloys: The role of neighboring grains on interconnected slip bands
Authors: Rotella John , Sangid Michael D. 
Published: July 2020

AbstractCyclic loading of polycrystalline materials results in the localization of strain relative to microstructural features. In this work, strains characterized from digital image correlation were used to calculate a value for the incremental slip on the active slip systems and identify cases of slip transmission. Interconnected slip bands, between neighboring grains, were shown to accumulate more incremental slip (and associated strain) compared with slip bands confined to a single grain, where slip transmission did not occur. These results rationalize the role of grain clusters leading to intense strain accumulation and thus serving as potential sites for fatigue crack initiation.
Using structured eradication feasibility assessment to prioritize the management of new and emerging invasive alien species in Europe
Authors: Booy Olaf , Robertson Pete A. , Moore Niall , Ward Jess , Roy Helen E. , Adriaens Tim , Shaw Richard , Van Valkenburg Johan , Wyn Gabrielle , Bertolino Sandro , Blight Olivier , Branquart Etienne , Brundu Giuseppe , Caffrey Joe , Capizzi Dario , Casaer Jim , De Clerck Olivier , Coughlan Neil E. , Davis Eithne , Dick Jaimie T. A. , Essl Franz , Fried Guillaume , Genovesi Piero , González‐Moreno Pablo , Huysentruyt Frank , Jenkins Stuart R. , Kerckhof Francis , Lucy Frances E. , Nentwig Wolfgang , Newman Jonathan , Rabitsch Wolfgang , Roy Sugoto , Starfinger Uwe , Stebbing Paul D. , Stuyck Jan , Sutton‐Croft Mike , Tricarico Elena , Vanderhoeven Sonia , Verreycken Hugo , Mill Aileen C. 
Published: July 2020

AbstractPrioritizing the management of invasive alien species (IAS) is of global importance and within Europe integral to the EU IAS regulation. To prioritize management effectively, the risks posed by IAS need to be assessed, but so too does the feasibility of their management. While the risk of IAS to the EU has been assessed, the feasibility of management has not. We assessed the feasibility of eradicating 60 new (not yet established) and 35 emerging (established with limited distribution) species that pose a threat to the EU, as identified by horizon scanning. The assessment was carried out by 34 experts in invasion management from across Europe, applying the Non‐Native Risk Management scheme to defined invasion scenarios and eradication strategies for each species, assessing the feasibility of eradication using seven key risk management criteria. Management priorities were identified by combining scores for risk (derived from horizon scanning) and feasibility of eradication. The results show eradication feasibility score and risk score were not correlated, indicating that risk management criteria evaluate different information than risk assessment. In all, 17 new species were identified as particularly high priorities for eradication should they establish in the future, whereas 14 emerging species were identified as priorities for eradication now. A number of species considered highest priority for eradication were terrestrial vertebrates, a group that has been the focus of a number of eradication attempts in Europe. However, eradication priorities also included a diverse range of other taxa (plants, invertebrates and fish) suggesting there is scope to broaden the taxonomic range of attempted eradication in Europe. We demonstrate that broad scale structured assessments of management feasibility can help prioritize IAS for management. Such frameworks are needed to support evidence‐based decision‐making.
Inulin added electrospun composite nanofibres by electrospinning for the encapsulation of probiotics: characterisation and assessment of viability during storage and simulated gastrointestinal digestion
Authors: Duman Dilan , Karadag Ayse 
Published: July 2020

SummaryThe probiotic Lactobacillus fermentum was encapsulated in the electrospun nanofibres composed of polyvinyl alcohol, sodium alginate and three different inulin. The addition of inulin did not have a significant effect on electrical conductivity and surface tension of electrospinning solutions. Nanofibres showed uniform morphology with an average diameter between 200 and 400 nm. The encapsulation efficiency of probiotics was between 74.26% and 80.63%. FTIR analysis confirmed the presence of bacteria in the nanofibres. The addition of inulin improved the tensile strength and elongation at break values. Compared to free cells, encapsulated bacteria showed higher viability during the storage at 25, 4 and −18 °C up to 8 weeks. The survivability of cells especially encapsulated into inulin added composite nanofibres showed higher viability against simulated gastric and intestinal fluids. This study suggested that obtained composite nanofibres present a great delivery system to improve the viability of encapsulated cells against adverse conditions.
Labour Market Integration of Refugee Health Professionals in Germany: Challenges and Strategies
Authors: Khan‐Gökkaya Sidra , Mösko Mike 
Published: July 2020

AbstractRefugee health professionals are a vulnerable group in a host country’s labour market as they experience several barriers on their path to labour market integration. This study aims to identify challenges refugee health professionals and their supervisors experience at their workplaces and strategies they have developed to overcome these barriers. Semi‐structured interviews were conducted with refugee health professionals who have been living in Germany for an average of four years and their supervisors (n = 24). The interviews were analysed using qualitative content analysis. Nine themes were identified: (1) recognition of qualifications, (2) language competencies, (3) differing healthcare systems, (4) working culture, (5) challenges with patients, (6) challenges with team members, (7) emotional challenges, (8) discrimination and (9) exploitation. Results indicate the need to implement structural changes in order to improve the labour market experiences of refugee health professionals.
Nanocrystallization of lead‐free Cs3Sb2Br9 perovskites in chalcogenide glass
Authors: Long Nengbing , Lin Changgui , Chen Feifei , Jiao Qing , Liu Xueyun , Nie Qiuhua 
Published: July 2020

AbstractLead‐free halide perovskite nanocrystals (HPNCs) are an emergent alternative of lead‐based halide perovskites owing to their environmentally benign nature. In this work, lead‐free Cs3Sb2Br9 HPNCs were precipitated firstly in chalcogenide glass through an elaborated composition design and appropriate crystallization process. The microstructural evolution and nanocrystallization behavior of the Cs3Sb2Br9 crystallized glass‐ceramics were analyzed by employing advanced characterization techniques. It is revealed that the crystallization process is temperature‐dependent and can be described as two stages. At the first crystallization stage, the nucleation and crystal growth of Cs3Sb2Br9 HPNCs occur due to the presence of structural similarity of [Sb2Br9]3− dioctahedral clusters in the precursor glass. And then the second crystalline phase of GeS2 is successively separated from the residual glassy matrix under high‐temperature treatment. This work should be of great guiding significance for developing novel glass‐ceramic materials embedded with lead‐free HPNCs.
Sintering behavior of a nanostructured thermal barrier coating deposited using electro‐sprayed particles
Authors: Xing Chen , Yi Meiyu , Shan Xiao , Wang Xin , Zhao Xiaofeng , Guo Fangwei 
Published: July 2020

AbstractDuring high temperature service, a series of microstructure and phase evolutions occur in thermal barrier coatings (TBCs), which result in degradation of thermal insulation and durability. In this study, the sintering behavior of an air plasma sprayed 8 wt% YSZ coating deposited using electro‐sprayed nanostructured particles (ESP) as feedstock powder was investigated and compared with conventional YSZ coating deposited using hollow spherical powders (HOSP). Due to the distinct asymmetric porous structure formed by nanosized YSZ particles, the ESP powder was partially melted in the plasma jet during the deposition, which resulted in the formation of a nanostructured coating that consisted of porous nanozones and dense zones. The ESP coating not only shows a significantly lower initial thermal conductivity of 0.70 W/mK, but also exhibits a stronger sintering resistance in terms of phase stability and thermal insulation compared to the conventional coating. When subjected to prolonged sintering at 1400°C for 128 hours, the thermal conductivity of the ESP coating would gradually increase to about half that of the HOSP coating at 1.29 W/mK. These differences are ascribed to the interaction among different sintering behavior between nanozones and dense zones.