bluuebunny/crossref_metadata_2025_split huggingface dataset:
NUAK family kinase 2 is a novel therapeutic target for prostate cancer
Authors: Fu Weiwei , Zhao Megan T. , Driver Lucy M. , Schirmer Amelia U. , Yin Qi , You Sungyong , Freedland Stephen J. , DiGiovanni John , Drewry David H. , Macias Everardo 
Published: November 2021

AbstractCurrent advancements in prostate cancer (PC) therapies have been successful in slowing PC progression and increasing life expectancy; however, there is still no curative treatment for advanced metastatic castration resistant PC (mCRPC). Most treatment options target the androgen receptor, to which many PCs eventually develop resistance. Thus, there is a dire need to identify and validate new molecular targets for treating PC. We found NUAK family kinase 2 (NUAK2) expression is elevated in PC and mCRPC versus normal tissue, and expression correlates with an increased risk of metastasis. Given this observation and because NUAK2, as a kinase, is actionable, we evaluated the potential of NUAK2 as a molecular target for PC. NUAK2 is a stress response kinase that also plays a role in activation of the YAP cotranscriptional oncogene. Combining pharmacological and genetic methods for modulating NUAK2, we found that targeting NUAK2 in vitro leads to reduction in proliferation, three‐dimensional tumor spheroid growth, and matrigel invasion of PC cells. Differential gene expression analysis of PC cells treated NUAK2 small molecule inhibitor HTH‐02‐006 demonstrated that NUAK2 inhibition results in downregulation of E2F, EMT, and MYC hallmark gene sets after NUAK2 inhibition. In a syngeneic allograft model and in radical prostatectomy patient derived explants, NUAK2 inhibition slowed tumor growth and proliferation rates. Mechanistically, HTH‐02‐006 treatment led to inactivation of YAP and the downregulation of NUAK2 and MYC protein levels. Our results suggest that NUAK2 represents a novel actionable molecular target for PC that warrants further exploration.
Organic Cation Transporter I and Na+/taurocholate Co‐Transporting Polypeptide are Involved in Retrorsine‐ and Senecionine‐Induced Hepatotoxicity in HepaRG cells
Authors: Enge Anne‐Margarethe , Kaltner Florian , Gottschalk Christoph , Kin Angelina , Kirstgen Michael , Geyer Joachim , These Anja , Hammer Helen , Pötz Oliver , Braeuning Albert , Hessel‐Pras Stefanie 
Published: November 2021

Scope1,2‐unsaturated pyrrolizidine alkaloids (PAs) are secondary plant metabolites that are found in many plant species throughout the world. They are of concern for risk assessment as consumption of contaminated foodstuff can cause severe liver damage. Of late, transporter‐mediated uptake and transport has advanced as a vital determinant of PA toxicity. In this study, the authors investigate a transporter‐mediated uptake of PAs and its implications in PA toxicity.Methods and ResultsWe show that transporter expression levels are significantly affected by treatment with the PAs senecionine (Sc) and retrorsine (Re) in the human hepatoma cell line HepaRG. Furthermore, the specific contribution to PA uptake of the two transporters Na+/taurocholate co‐transporting polypeptide (SLC10A1) and organic cation transporter I (SLC22A1), both belonging to the heterogeneous solute carrier super family, is investigated by means of a siRNA‐mediated knockdown approach. Knockdown of both uptake transporters result in reduced uptake of Re and Sc in a time‐dependent manner and attenuated PA‐mediated cytotoxic effects in HepaRG cells.ConclusionOur results confirm previous findings of active transport mechanisms of PAs into hepatocytes and highlight the importance of toxicokinetic studies for the risk assessment of PAs.
Circular cross‐coupling dielectric waveguide filter based on 90‐degree sectoral resonators
Authors: Huang Zhengwei , Cheng Yong , Zhang Yerong 
Published: November 2021

AbstractIn this study, a circular cross‐coupled dielectric waveguide (DW) filter was realized based on 90‐degree sectoral resonators. The filter is formed by splicing four 90‐degree sectoral DW resonators (SDWRs). A shallow blind hole (BH) was set at the center of each 90‐degree SDWR to adjust the resonant frequency. The magnetic coupling between the resonators was realized through the rectangular wall and shallow BH. Electrical coupling between the resonators was achieved through deep BHs. The overall structure was designed, simulated, and fabricated. The measured results demonstrate that the designed filter has a center frequency of 3.6 GHz, bandwidth of 200 MHz, insertion loss less than 1 dB, in‐band return loss greater than 15 dB, and two out‐of‐band transmission zeros at 3.38 and 3.82 GHz.
Correlates of mental health problems among students in Texas alternative high schools and school‐level efforts to address mental health
Authors: Johnson Karen E. , Hoskote Ashwini R. , Rolin Donna G. , Kesler Shelli R. 
Published: November 2021

AbstractStudents in alternative high schools (AHSs) are an understudied population who experience disproportionate levels of risk factors that contribute to mental health problems. Using logistic regression, we explored associations between mental health problems and risk and protective factors among students in Texas AHSs (n = 515; mean age 17.1 years; 51% female, 78% youth of color, 64% eligible for free/reduced lunch). Principals (n = 14) and lead health educators (n = 14) reported on school‐level efforts to address mental health. Students reported, on average, 1.55 of 4 mental health problems in the past year. Logistic regression indicated that greater number of adverse childhood experiences, lower self‐esteem, female gender, and sleep disruption (getting <8 h of sleep per night) were common contributors to symptoms of depression, anxiety, suicidal ideation, and PTSD with models showing medium‐to‐large effects (AUC: 0.73–0.81). We assessed school‐level efforts to address mental health using descriptive statistics. At the school level, most (>50%) principals reported having policies and services to support student mental health, with the exception of having mental health/social services staff represented on school health councils (36%) and having Gay‐Straight Alliances (21%). Most lead health educators (86%) reported educating AHS students about mental health, and many (57%) reported receiving professional development in mental health. Future research with a larger number of schools is needed to analyze whether school policies are statistically associated with student‐level mental health outcomes. Such multi‐level research can inform policies and practices for AHS student mental health.
Combining a β3 adrenergic receptor agonist with alpha‐lipoic acid reduces inflammation in male mice with diet‐induced obesity
Authors: Abdul Sater Zahraa , Cero Cheryl , Pierce Anne E. , Lea Hannah J. , Abdul Sater Houssein , Zhu Kenneth Y. , Liu Naili , Ma Yinyan , Gavrilova Oksana , Cypess Aaron M. 
Published: November 2021

AbstractObjectivesBeta‐3 adrenergic receptors (β3‐AR) stimulate lipolysis and thermogenesis in white and brown adipose tissue (WAT and BAT). Obesity increases oxidative stress and inflammation that attenuate AT β3‐AR signaling. The objective of this study was to test the hypothesis that the combination of the β3‐AR agonist CL‐316,243 (CL) and the antioxidant alpha‐lipoic acid (ALA) would lower inflammation in diet‐induced obesity (DIO) and improve β3‐AR function.MethodsA total of 40 DIO mice were separated into four groups: Control (per os and intraperitoneal [IP] vehicle); CL alone (0.01 mg/kg IP daily); ALA alone (250 mg/kg in drinking water); or ALA+CL combination, all for 5 weeks.ResultsFood intake was similar in all groups; however, mice receiving ALA+CL showed improved body composition and inflammation as well as lower body weight (+1.7 g Control vs. −2.5 g ALA+CL [−7%]; p < 0.01) and percentage of body fat (−9%, p < 0.001). Systemic and epididymal WAT inflammation was lower with ALA+CL than all other groups, with enhanced recruitment of epididymal WAT anti‐inflammatory CD206+ M2 macrophages. β3‐AR signaling in WAT was enhanced in the combination‐treatment group, with higher mRNA and protein levels of thermogenic uncoupling protein 1 and AT lipases.ConclusionsChronic treatment with ALA and a β3‐AR agonist reduces DIO‐induced inflammation. AT immune modulation could be a therapeutic target in patients with obesity.image
Computational Study of Mechanism and Enantioselectivity of Imine Reductase from Amycolatopsis orientalis
Authors: Prejanò Mario , Sheng Xiang , Himo Fahmi 
Published: November 2021

AbstractImine reductases (IREDs) are NADPH‐dependent enzymes (NADPH=nicotinamide adenine dinucleotide phosphate) that catalyze the reduction of imines to amines. They exhibit high enantioselectivity for a broad range of substrates, making them of interest for biocatalytic applications. In this work, we have employed density functional theory (DFT) calculations to elucidate the reaction mechanism and the origins of enantioselectivity of IRED from Amycolatopsis orientalis. Two substrates are considered, namely 1‐methyl‐3,4‐dihydroisoquinoline and 2‐propyl‐piperideine. A model of the active site is built on the basis of the available crystal structure. For both substrates, different binding modes are first evaluated, followed by calculation of the hydride transfer transition states from each complex. We have also investigated the effect of mutations of certain important active site residues (Tyr179Ala and Asn241Ala) on the enantioselectivity. The calculated energies are consistent with the experimental observations and the analysis of transition states geometries provides insights into the origins of enantioselectivity of this enzyme.
Exfoliation of hexagonal boron nitride assisted with hierarchical ionic fragments by ball‐milling for achieving high thermally conductive polymer nanocomposite
Authors: Nie Xiangdao , Sang Xinxin , Fu Yongsheng , Shi Xianbin , Zheng Kun , Ma Yongmei 
Published: November 2021

AbstractHexagonal boron nitride nanosheets (BNNSs) are considered as ideal candidates for preparing thermally and insulating composite because of its excellent thermal and electrical properties. Herein, we propose a facile and efficient ball‐milling way to exfoliate hexagonal boron nitride (h‐BN) with the assistance of coordination polymers (CPs). During the exfoliation process, the CPs occurs crystal to liquid/glass transition, forming diverse molecular fragments. The hierarchical ionic fragments can interact with and intercalate into the layered h‐BN, leading to a high efficiency in exfoliation and good dispersion. The exfoliated BNNSs reach a yield of up to 34% approximately. Furthermore, the BNNSs were incorporated to poly(vinyl alcohol) to prepare composite with thermal conductivity reaching up to 11.5 W m−1 K−1 at 30 wt% of BNNSs loading. The composite exhibits good performance on LED thermal management. This work demonstrates an efficient way to exfoliate BN, which can shed some light on other two dimensional materials exfoliation and application.
Assessment of students with autism spectrum disorder for emergency response planning
Authors: Kwolek Heather A. , Bray Adeline , Bunyea Alyssa M. , DeMaio Erin , Bray Melissa , Ottone‐Cross Karen 
Published: November 2021

AbstractStudents with autism have varied support needs, which may impact their safety in an emergency. Schools may want to create individualized emergency support plans for their students with autism, especially given that schools that receive public funding are required to ensure that all people, including those with disabilities, receive the benefit of emergency response planning. This article reviews the difficulties students with autism may face in an emergency and provides guidelines for assessing the support needs of students with autism that may impact them in an emergency. Specifically, it reviews assessment practices for communication, adaptive skills, sensory needs, and medical concerns as well as how needs in those areas may impact the student in an emergency. Finally, it concludes by briefly discussing how to create an individualized emergency response plan for a student based on the assessment results.
One‐pot, one‐step, and selective terpolymerization of ethylene oxide, propylene oxide, and COS to copoly(thioether)s with tunable thermal properties
Authors: Kiriratnikom Jiraya , Zhang Xun , Cao Xiaohan , Chu Bo , Zhang Chengjian , Zhang Xinghong 
Published: November 2021

AbstractFacile construction of sulfur‐rich polymers using readily available raw chemicals is an area aggressively pursued but challenging. Herein we use common feedstocks of ethylene oxide (EO), propylene oxide (PO), and carbonyl sulfide (COS) to synthesize copoly(thioether)s which are traditionally produced from unpleasant and difficult to store episulfides. In this protocol, the EO/COS coupling selectively generates a pure poly(ethylene sulfide) (PES) with melting temperature (Tm) values up to 172°C and high yields up to 98%. The EO/PO/COS terpolymerization leads to the incorporation of soft poly(propylene sulfide) (PPS) and hard PES segments together, affording a random PES‐co‐PPS copoly(thioether) with the complete consumption of EO and PO. Additionally, by simply varying the EO/PO feeding ratio, the obtained copoly(thioether)s possess tunable thermal properties, Tm values in the range of 76–144°C, and excellent solubility. These copolymerizations are conducted in one‐pot/one‐step at industrially favored reaction temperatures of 100–120°C using catalysts of common organic bases, suggesting a facile and practical manner. Especially, the copoly(thioether) exhibits high refractive indices up to 1.68 owing to its high sulfur content, suggesting a broad application prospect in optical materials.
The abrupt pathological deterioration of cisplatin‐induced acute kidney injury: Emerging of a critical time point
Authors: Gong Qin , Wang Mulan , Jiang Ya , Zha Chengliang , Yu Dong , Lei Fan , Luo Yingying , Feng Yulin , Yang Shilin , Li Jun , Du Lijun 
Published: November 2021

AbstractCisplatin (CP), an anticancer drug, often causes kidney damage. However, the mechanism of CP‐induced acute kidney injury (AKI) is not completely understood. AKI was induced by intravenous injection (i.v.) of cisplatin at doses of 5, 8, and 10 mg/kg. Anemoside B4 (B4) (20 mg/kg, i.m.) and dexamethasone (DXM) (0.5 mg/kg, i.v.) were used for AKI treatment. Biochemical indicators were assessed using an automatic biochemical analyzer, protein expression was analyzed by western blotting, and morphological changes in the kidney were examined by PAS staining. The serum creatinine (Cre) and blood urea nitrogen (BUN) levels did not change significantly in the first 2 days but abruptly increased on the third day after CP injection. The serum albumin (ALB) and total protein (TP) levels decreased in both a time‐ and dose‐dependent manner. The urine protein level increased, the clearing rate of Cre decreased distinctly, and morphologic changes appeared in a dose‐dependent manner. The protein expression of p53/caspase‐3, NLRP3, IL‐6, and TNF‐α was obviously upregulated on day 3; concurrently, nephrin and podocin were downregulated. The expression of LC3II and p62 was upregulated significantly as the CP dose increased. B4 and DXM obviously decreased the BUN and Cre levels after 3 or 5 days of treatment. AKI appeared distinctly in a time‐dependent manner at 2 to 5 days after the administration of 5 mg/kg CP and in a dose‐dependent manner upon the administration of 5, 8, and 10 mg/kg CP. The third day was a significant time point for renal deterioration, and treatment with B4 and DXM within the first 3 days provided significant protection against AKI.
Influence of seasonal migration on the development of the insecticide resistance of oriental armyworm (Mythimna separata) to λ‐cyhalothrin
Authors: Yang Xueqing , Li Xinru , Cang Xinzhu , Guo Jianglong , Shen Xiujing , Wu Kongming 
Published: November 2021

AbstractBACKGROUNDThe seasonal long‐distance migration of pests amongst different seasonal habitats may encounter different degrees of insecticide selection pressure, but knowledge of the evolution of resistance and the underlying mechanisms remains sparse. Here, we show that the development of resistance of the oriental armyworm Mythimna separata (Walker), a notorious agricultural pest that migrates between northern and northeast China seasonally across the Bohai Gulf, is influenced by seasonal migration.RESULTSThere are two conspicuous migrations of M. separata, the northeastwards population in the second half of May and the returning population in the second half of August, between northern and northeast China per year, and the abundance values of migrants from April to October are significantly different. The resistance levels of seasonal migratory populations to λ‐cyhalothrin vary in different months, and the resistance levels and estimated frequency of the resistance allele of the first northeastward population (second half of May, May.‐2) in spring are significantly higher than those of the returning populations in autumn. Moreover, resistance decline was observed in migrating population Jul.‐2, with the resistance levels in the F1 progeny higher than those in their F2 progeny. Synergism tests indicate that cytochrome P450 monooxygenases (P450s) play a major role in resistance. Enzymatic assays show that P450 activity is significantly correlated with resistance levels in migratory populations, indicating that increased P450 activity is the main mechanism of resistance. The expression levels and correlation analysis of the relative expression of P450s with resistance levels show that three (CYP9A144, CYP9G40, and CYP6B79) out of 23 genes from CYP6 and CYP9 subfamilies are potentially involved in resistance to λ‐cyhalothrin.CONCLUSIONOur results show that the resistance of M. separata to λ‐cyhalothrin is unstable and likely to be metabolically driven by enhanced P450 activity mediated by the overexpression of multiple P450 genes. Notably, the development of resistance is probably affected by seasonal migration.
Oesophageal intramural pseudodiverticulosis presenting as non‐resolving pneumonia: A sinister cause diagnosed by EUS‐B‐FNA
Authors: Joshi Sharad , Majumdar Subhasish , Bhatia Ankit , Tayal Nitesh 
Published: November 2021

AbstractWe report a case of an oesophageal intramural pseudodiverticulosis leading to a mediastinal collection caused by Candida glabrata presenting as a non‐resolving pneumonia and mimicking an oesophageal mass. The patient was a 60‐year‐old diabetic male who was referred from another hospital and presented with a history of low‐grade fever and breathlessness. His computed tomography (CT) of the chest disclosed a mediastinal mass alongside the oesophagus with pleural collection. Endobronchial ultrasound scope was inserted through the oesophagus (EUS‐B) and fine‐needle aspirate was taken from the mass. The cultures of specimen from the mediastinum grew drug‐resistant C. glabrata. The patient was managed with oral voriconazole along with oesophageal stenting after which he showed remarkable recovery. Repeat CT revealed a near‐complete reduction of the mediastinal infection. The case highlights the need of a high degree of suspicion, right approach to diagnostic work‐up and appropriate histopathological and microbiological examination of clinical specimens.
Rylene‐Fullerene Hybrid an Emerging Electron Acceptor for High‐Performing and Photothermal‐Stable Ternary Solar Cells
Authors: Wei Yi , Liang Ningning , Jiang Wei , Zhai Tianrui , Wang Zhaohui 
Published: November 2021

AbstractMolecular carbon imides, especially extended perylene diimides (PDIs) have been the best wide‐band‐gap nonfullerene acceptors. Despite their excellent photothermal/chemical stability, flexible reaction sites, and unique photoelectronic properties, there is still a lack of fundamental understanding of their molecular characteristics as a third component. Here, generations of PDIs with distinctive molecular architecture, are deliberately screened out as the third component to PM6:Y6. Only a rylene‐fullerene hybrid, S‐Fuller‐PMI, surprisingly boosts the fill factor (FF) of ternary organic solar cells (OSCs) to 0.77 from 0.72 for PM6:Y6 binary ones, and therefore the power conversion efficiency (PCE) of ternary cells is enhanced from 15.3% to 16.2%. Compared with highly‐flexible rylene dimer and rigid multimer, S‐Fuller‐PMI exhibits higher electron mobility, favorable surface tension, and, therefore tailored compatibility with Y6. These formed Y6:S‐Fuller‐PMI alloys play as a morphological controller to improve charge separation and transport process. Simultaneously, the suppressed photothermal‐induced traps, along with inherent enlarged entropy effect, endow the ternary OSCs still with ≈70% of initial PCE even after 500 h continuous illumination, whereas only 53% is left in their binary counterparts. These results provide new insight into the molecular design principle for distinctive molecular carbon imides as the third component for efficient and durable PM6:Y6‐based OSCs.
Programmable Knot Microfibers from Piezoelectric Microfluidics
Authors: Yang Chaoyu , Yu Yunru , Wang Xiaocheng , Shang Luoran , Zhao Yuanjin 
Published: November 2021

AbstractMicrofibers have demonstrated significant application values in a large number of areas. Current efforts focus on developing new technologies to prepare microfibers with controllable morphological and structural features to enhance their functions. Here, a piezoelectric microfluidic platform is presented for consecutive spinning of functional microfibers with programmable spindle‐knots. In this platform, a jet of a pregel‐solution flowing in the channel can be subjected to a programmable piezoelectric signal and vibrates synchronously. Following a rapid polymerization of the wavy jet, microfibers with corresponding morphologies can be generated, including uniform, gradient, and symmetrical knots. Such a unique knot structure contributes to a water‐collection mechanism. Thus, it has been observed that microfibers with programmed knots enable even more flexible droplet handling and active water transport. In addition, by constructing higher‐order knot fiber networks, practical applications including spray reaction, lab‐on‐a‐chip vapor detection, etc., can also be demonstrated. it is believed that this platform opens a new avenue for fiber spinning, and the programmable microfibers would be highly applicable in chemical, biomedical, and environmental areas.
Rational Design of Tungsten Selenide @ N‐Doped Carbon Nanotube for High‐Stable Potassium‐Ion Batteries
Authors: Chen Xiaoxia , Muheiyati Haliya , Sun Xiuping , Zhou Pan , Wang Peican , Ding Xuyang , Qian Yitai , Xu Liqiang 
Published: November 2021

AbstractPotassium‐ion batteries (PIBs) are deemed as one of the most promising energy storage systems due to their high energy density and low cost. However, their commercial application is far away from satisfactory because of limited suitable electrode materials. Herein, core‐shell structured WSe2@N‐doped C nanotubes are rationally designed and synthesized via selenizing WO3@ polypyrrole for the first time. The large interlayer spacing of WSe2 can facilitate the intercalation/deintercalation of K+. Meanwhile, the core‐shell structured nanotube provides favorable interior void space to accommodate the volume expansion of WSe2 during cycling. Thus, the obtained electrode exhibits superb electrochemical performance with a high capacity of 301.7 mAh g−1 at 100 mA g−1 over 120 cycles, and 122.1 mAh g−1 can remain at 500 mA g−1 even after 1300 cycles. Ex‐situ X‐ray diffraction analysis reveals the K‐ion storage mechanism of WSe2@N‐doped C includes intercalation and conversion reaction. Density function theory (DFT) calculation demonstrates the reasonable diffusion pathway of K+. In addition, the obtained WSe2@N‐doped C nanotubes have been used as anode material for lithium‐ion batteries, which also show good rate performance and high cycle stability. Therefore, this work offers a new methodology for the ration design of new structure electrode materials with long cycle stability.