Search

The development of efficient synthetic strategies for the preparation of tetrasubstituted N−H pyrrole derivatives, especially in an environmentally benign fashion is important yet challenging. Herein, we report a copper(II)‐catalyzed tandem reaction involving 1,3‐dipolar cycloaddition of α,β‐ynones and glycine iminoesters, followed by copper(II)‐promoted oxidative (air) dehydrogenative aromatization, allowing de novo access to tetrasubstituted N−H pyrroles in up to 81 % yield under green reaction conditions. A possible reaction pathway is tentatively proposed. Finally, fully substituted pyrroles are available by N‐alkylation, and a preliminary phase‐transfer catalytic asymmetric N‐alkylation was also studied to give an axially chiral pyrrole. [ABSTRACT FROM AUTHOR]

Objective: We aim to determine the effect of region of residence (urban vs. rural) on the odds of receiving standard of care treatment for locally advanced BCa in Louisiana and its impact on survival outcomes. Methods: Using the Louisiana Tumor Registry, we identified American Joint Committee on Cancer (AJCC) stage II or III, BCa diagnoses in Louisiana residents between 2010 and 2020. Treatment received was classified as standard or non‐standard of care according to American Urological Association (AUA) guidelines and location of residence was determined using Rural Urban Commuting Area‐Tract‐level 2010 (RUCA). Multivariable logistic regression analyses and multivariate cox proportional hazard analyses were performed. Results: Of 983 eligible patients, 85.6% (841/983) lived in urban areas. Overall, only 37.5% received standard‐of‐care (SOC) for the definitive management of locally advanced bladder cancer. Individuals living in rural areas (OR 0.53, 95% CI: 0.31–0.91, p = 0.02) were less likely to receive standard of care treatment. Both rural residence and receipt of non‐standard of care therapy were associated with an increased risk of bladder cancer‐specific (adj HR 1.53, 95% CI: 1.09–2.14, p = 0.01 and adj HR: 1.85, 95% CI: 1.43–2.39, <0.0001) and overall mortality (adj HR: 1.28, 95% CI: 1.01–1.61, p = 0.04 and adj HR: 1.73 95% CI: 1.44–2.07, p < 0.0001). Conclusions: Most patients with locally advanced bladder cancer in Louisiana do not receive SOC therapy. Individuals living in rural locations are more likely to receive non‐standard of care therapy than individuals in urban areas. Nonstandard of care treatment and rural residence are both associated with worse survival outcomes for Louisiana residents with locally advanced bladder cancer. [ABSTRACT FROM AUTHOR]

Calcium‐ion batteries (CIBs) are considered as potential next‐generation energy storage systems due to their abundant reserves and relatively low cost. However, irreversible structural changes and weak conductivity still hinder in current CIBs cathode materials. Herein, an organic molecular intercalation strategy is proposed, in which V2O5 regulated with quinoline, pyridine, and water molecules are studied as cathode material to provide fast ion diffusion channels, large storage host, and high conductivity for Ca ions. Among them, V2O5‐quinoline (QVO) owns the largest interplanar spacing of 1.25 nm and the V‐O chains are connected with organic molecular by hydrogen bond, which stabilizes the crystal structure. As a result, QVO exhibits a specific capacity of 168 mAh g−1 at 1 A g−1 and capacity retention of 80% after 500 cycles at 5 A g−1 than the other materials. Furthermore, X‐Ray diffraction and X‐ray absorption spectroscopy results reveal a reversible order‐disorder transformation mechanism of Ca2+ for QVO, which can make full use of the abundant active sites for high capacity and simultaneously achieve fast reaction kinetics for excellent rate performance. These results demonstrate that QVO is a promising cathode material for CIBs, providing more choices for the development of high‐performance CIBs. [ABSTRACT FROM AUTHOR]

Vanadate materials are feasible cathodes for metal–ion batteries due to their stable layered structure, abundant valence states, and high capacity. However, much uncertainty still exists about precisely modulating intercalants to facilitate ion storage. Here, V2O5 pre‐intercalated with various transition metal ions M2+ (M═Ni, Co, Mn) are developed as model materials to analyze the coupling effect between guest ions and host material. Through density functional theory simulations, it is found that M2+ interacts with V–O chain via M 3d‐O 2p covalent bonds, and extended X‐ray absorption fine structure reveals the Ni─O interatomic distance at 1.56 Å shorter than Co─O (1.60 Å) and Mn─O (1.72 Å), suggesting the M–O band type with different covalency degree can optimize VOx polyhedron and local electronic structure. Furthermore, NiVO cathode materials with the smallest layer spacing shows higher redox voltage and better rate/cycling performance for Ca2+ storage than CoVO/MnVO, elucidating that Ni has stronger tendency to attract electrons and bonds with V–O layer tightly, thus supplying a reliable ion diffusion channel for Ca2+. Through ions pre‐intercalated techniques, this work highlights both layer spacing and physicochemical properties of intercalants affect electrochemical process, which is significant for developing high‐performance vanadate cathode materials. [ABSTRACT FROM AUTHOR]

The development of novel synthetic methodologies to incorporate fluorine/s or fluoroalkyl group/s into the frameworks of organic molecules has become a highly prioritized research area because such modifications can tune their physiochemical and biological properties. In recent years, nucleophilic phosphine catalysis has been extensively explored to achieve this goal, and significant progress has been made. This review summarizes the methodological advancements of cycloaddition, addition and coupling reactions employing fluorinated building blocks as electrophilic and/or nucleophilic reaction partners under phosphine catalysis to construct structurally and synthetically valuable organofluorine compounds, with special emphasis on the synthetic strategies, proposed reaction mechanisms and synthetic utilities. [ABSTRACT FROM AUTHOR]

Head and neck squamous cell carcinoma (HNSCC) is one of the most prevalent cancers worldwide. Heat shock factor 1 (HSF1) is a conserved transcriptional factor that plays a critical role in maintaining cellular proteostasis. However, the role of HSF1 in HNSCC development remains largely unclear. Here, we report that HSF1 promotes forkhead box protein O3a (FOXO3a)‐dependent transcription of ΔNp63α (p63 isoform in the p53 family; inhibits cell migration, invasion, and metastasis), which leads to upregulation of cyclin‐dependent kinase 4 expression and HNSCC tumour growth. Ablation of HSF1 or treatment with KRIBB11, a specific pharmacological inhibitor of HSF1, significantly suppresses ΔNp63α expression and HNSCC tumour growth. Clinically, the expression of HSF1 is positively correlated with the expression of ΔNp63α in HNSCC tumours. Together, this study demonstrates that the HSF1–ΔNp63α pathway is critically important for HNSCC tumour growth. [ABSTRACT FROM AUTHOR]

Background: Breast‐conserving surgery plus radiation (BCT) yields equivalent or better survival than mastectomy for early‐stage breast cancer (ESBC) women. However, nationwide mastectomy trends increased in recent decades, attracting studies on underlying causes. Prior research identified that long distance to the radiation treatment facility (RTF) was associated with mastectomy. Still, it is unclear whether such association applies to young and old ESBC women comparably. We sought to delineate such impacts by age. Methods: Women diagnosed with stages 0–II breast cancer in 2013–2017 receiving either BCT or mastectomy were identified from the Louisiana Tumor Registry. We assessed the association of surgery (mastectomy vs. BCT) with the distance to the nearest or nearest accessible RTFs using multivariable logistic regression adjusting the socio‐demographic and tumor characteristics. The nearest accessible RTF was determined based on patients' health insurance. For Medicaid, uninsured, and unknown insurance patients, the nearest accessible RTF is the nearest RTF owned by the government. The interaction effect of age and distance was evaluated as well. Results: Of 11,604 patients, 46.7% received mastectomy. Compared with distance ≤5 miles to the nearest RTF, those with distance ≥40 miles or 15–40 miles had higher odds of mastectomy (adjusted (adj) OR = 1.39, 95% CI = 1.07–1.82; adj OR = 1.17, 95% CI = 1.02–1.34). To the nearest accessible RTF, the adj ORs were 1.25 (95% CI = 1.03–1.51) and 1.19 (95% CI = 1.04–1.35), respectively. Age‐stratified analysis showed the significant association (p < 0.05) only presented among women aged ≥65, but not those aged <65 years. Conclusion: Distance to the nearest or nearest accessible RTF influences the surgery choice, especially among women in Louisiana ≥65 years with ESBC. Further understanding of factors leading to the decision for mastectomy in this age group is needed. [ABSTRACT FROM AUTHOR]

Polymer microspheres can be used as fuel containers for laser inertial confinement fusion (ICF) due to their low atomic number, low density, and high thermal stability. The thin‐walled polymer microspheres are prone to cracking due to an increase in the diameter to thickness ratio (diameter/wall thickness). The effect of polystyrene (PS) and Poly (α‐methyl styrene) (PAMS) materials commonly used in ICF experiments on the quality of thin‐walled microspheres is investigated. PS hollow microspheres show better sphericity, smoother surface, and lower cracking rate than PAMS microspheres. Moreover, the heat treatment of solidified PS microspheres can improve the strength so that the cracking rate of the microspheres decreases. The relative mechanism of how the molecular structure affect the quality is also discussed. This study provides some guidance for the preparation of thin‐walled polymer microspheres with high quality for ICF experiments. [ABSTRACT FROM AUTHOR]

BACKGROUND: Fermented capsicum (i.e. pickled pepper) is one of the most popular fermented vegetables. However, the effect of inoculated microbial fermentation on pickled pepper is not yet fully understood. RESULTS: Cyberlindnera rhodanensis J52 with a rich ester flavour and Pediococcus pentosaceus AL with a strong inhibitory effect on foodborne pathogenic bacteria were selected to prepare single- and double-strain fermented capsicum under low salt (< 10 g L-1 sodium chloride) conditions. The inhibition zone of P. pentosaceus AL against Escherichia coli was up to 44 mm in diameter. Biochemical indicator analyses found that co-fermentation of P. pentosaceus AL and C. rhodanensis J52 changed the contents of vitamin C and short-chain fatty acids. Analysis of microbial diversity and volatile metabolome showed that 125 microbial species and 72 volatile compounds were detected, and P. pentosaceus was the dominant bacterium that inhibited the growth of other bacteria, while C. rhodanensis was the fungus that contributed the most to flavour. Correlation analysis between microorganisms and flavour compounds showed 725 correlations, and 124 microbial species may have participated in the formation of 69 compounds. Furthermore, 10 and 29 correlations were detected between P. pentosaceus AL or C. rhodanensis J52 and flavour compounds, respectively. Among them, 3-methyl-1-butanol acetate is speculated to be the main substance affecting the flavour of fermented capsicum by inoculation with C. rhodanensis J52. CONCLUSION: The inoculation of P. pentosaceus and C. rhodanensis had a significant impact on the microbial community and volatile compounds of fermented capsicum and helped to improve its organoleptic qualities. [ABSTRACT FROM AUTHOR]

Aims: Etiology of the majority patients with idiopathic partial epilepsy (IPE) remains elusive. We thus screened the potential disease‐associated variants in the patients with IPE. Methods: Trios‐based whole exome sequencing was performed in a cohort of 320 patients with IPE. Frequency and molecular effects of variants were predicted. Results: Three novel BRWD3 variants were identified in five unrelated cases with IPE, which were four male cases and one female case. The variants included two recurrent missense variants (c.836C>T/p.Thr279Ile and c.4234A>C/p.Ile1412Leu) and one intronic variant close to splice site (c.2475 + 6A>G). The two missense variants were located in WD40 repeat domain and bromodomain, respectively. They were predicted to be damaging by silico tools and change hydrogen bonds with surrounding amino acids. The frequency of mutant alleles in this cohort was significantly higher than that in the controls of East Asian and all population of gnomAD. All these variants were inherited from the asymptomatic mothers. Four male cases presented frequent seizures at onset, while the female case only had two fever‐triggered seizures. They showed good responses to valproate and lamotrigine, then finally became seizure free. All the cases had no intellectual disability. Further analysis demonstrated that all previously reported destructive variants of BRWD3 caused intellectual disability, while missense variants located in WD40 repeat domains and bromodomains of BRWD3 were associated with epilepsy. Conclusion: BRWD3 gene is potentially associated with X‐linked partial epilepsy without intellectual disability. The genotypes and locations of BRWD3 variants may explain for their phenotypic variation. [ABSTRACT FROM AUTHOR]

Lewis base and Brønsted base controlled chemodivergent annulations of α‐methyl substituted allenyl imide and o‐aminotrifluoroacetophenones are realized to afford highly valuable furo[3,2‐b]indol‐2‐ones and dihydroquinolines bearing a CF3‐substituted quaternary stereogenic center. The possible reaction mechanisms are proposed through deuterium labelling experiments. This work demonstrates the unprecedented dual reactivities of α‐methyl substituted allenyl imide with electrophilic−nucleophilic compounds in annulation reactions, and features chemodivergence in transforming allenyl imide through β'‐C−H functionalization via phosphine catalysis and β/γ‐bisfunctionalization via Brønsted base catalysis. [ABSTRACT FROM AUTHOR]

Using star‐branched polyamide 6 (SPA6) with hexafunctional cyclotriphosphazene core as a matrix resin and glass fiber (GF) as a reinforcing material, star‐branched polyamide 6/glass fiber (SPA6/GF) composites with different GF content were prepared by melt‐compounding method. The star‐branched structure of SPA6 and GF content have great effects on the properties of SPA6/GF composites. Compared with linear polyamide 6 (LPA6), SPA6 with star‐branched structure has low viscosity, high melt flowability and good impregnation and adhesion to GF, which endow SPA6/GF composites outstanding processability, good surface qualities and excellent mechanical properties even when the content of GF reaches 60 wt%. The use of SPA6 resin with star‐branched structure fundamentally solves the industry problem of traditional LPA6 resin in high‐filled modification. Such high‐performance SPA6/GF composites will provide great promise for large‐scale applications. [ABSTRACT FROM AUTHOR]

Aims: To identify novel pathogenic gene of febrile seizures (FS)/epilepsy with antecedent FS (EFS+). Methods: The trio‐based whole‐exome sequencing was performed in a cohort of 462 cases with FS/EFS+. Silico programs, sequence alignment, and protein modeling were used to predict the damaging of variants. Statistical testing was performed to analyze gene‐based burden of variants. Results: Five heterozygous missense variants in CELSR3 were detected in five cases (families) with eight individuals (five females, three males) affected. Two variants were de novo, and three were identified in families with more than one individual affected. All the variants were predicted to be damaging in silico tools. Protein modeling showed that the variants resulted in disappearance of multiple hydrogen bonds and one disulfide bond, which potentially caused functional impairments of protein. The frequency of CELSR3 variants identified in this study was significantly higher than that in controls. All affected individuals were diagnosed with FS/EFS+, including six patients with FS and two patients with EFS+. All cases presented favorable outcomes without neurodevelopmental disorders. Conclusions: CELSR3 variants are potentially associated with FS/EFS+. [ABSTRACT FROM AUTHOR]

The fuel cell has attracted researchers' attention owing to its advantages of being adjustable and controllable, wide application, high efficiency, and low energy, etc. However, the main cost of fuel cells still comes from catalysts at present. Platinum‐based catalysts are still the most widely used catalysts in both cathodic ORR reactions and anodic EOR reactions. For the anodic EOR process, combined with in‐situ improved self‐gelling and Galvanic Replacement methods, a kind of Pt−Ni aerogel composite with a three‐dimensional porous network structure was prepared. The obtained Pt−Ni bimetallic aerogel materials were characterized by using scanning electron microscopy (SEM), X‐ray photoelectron spectroscopy (XPS) and X‐ray diffraction (XRD). Furthermore, the electrocatalytic activity of the synthesized Pt−Ni aerogels for the oxidation of EtOH in KOH was measured. The prepared Pt−Ni aerogel has the characteristics of high conductivity and catalytic activity of metal itself and high specific surface area and porosity of aerogels. The peak current density of Pt−Ni aerogel was about two times of the Ni aerogel prepared under the same situation, and the ECSA of Pt−Ni aerogel was about twice that of Ni aerogel, indicating that the addition of Pt could increase the active site of Pt−Ni aerogel, which made the Pt−Ni aerogel composite material have excellent catalytic activity. [ABSTRACT FROM AUTHOR]

1,3‐Dipolar cycloaddition of α‐fluoro‐α,β‐unsaturated arylketones and azomethine ylides has been experimentally and theoretically investigated. The reaction proceeded in a diastereodivergent fashion: in contrast to our previous results where exo‐adducts were obtained under Cu(II) catalysis, herein we have achieved the endo‐selective 1,3‐dipolar cycloaddition using Ag(I) catalyst. Theoretical DFT calculations have been performed to understand the origin of diastereoselectivity switch, possible mechanism, and geometrical features of organometallic intermediates of both catalytic processes. The free‐energy profiles suggested that the Michael addition step is the rate determining step, and the coordination between silver atom and carbonyl oxygen atom of enone is the driving force behind endo‐selectivity. [ABSTRACT FROM AUTHOR]

Aims: CHD4 gene, encoding chromodomain helicase DNA‐binding protein 4, is a vital gene for fetal development. In this study, we aimed to explore the association between CHD4 variants and idiopathic epilepsy. Methods: Trios‐based whole‐exome sequencing was performed in a cohort of 482 patients with childhood idiopathic epilepsy. The Clinical Validity Framework of ClinGen and an evaluating method from five clinical‐genetic aspects were used to determine the association between CHD4 variants and epilepsy. Results: Four novel heterozygous missense mutations in CHD4, including two de novo mutations (c.1597A>G/p.K533E and c.4936G>A/p.E1646K) and two inherited mutations with co‐segregation (c.856C>G/p.P286A and c.4977C>G/p.D1659E), were identified in four unrelated families with eight individuals affected. Seven affected individuals had sinus arrhythmia. From the molecular sub‐regional point of view, the missense mutations located in the central regions from SNF2‐like region to DUF1087 domain were associated with multisystem developmental disorders, while idiopathic epilepsy‐related mutations were outside this region. Strong evidence from ClinGen Clinical Validity Framework and evidences from four of the five clinical‐genetic aspects suggested an association between CHD4 variants and epilepsy. Conclusions: CHD4 was potentially a candidate pathogenic gene of childhood idiopathic epilepsy with arrhythmia. The molecular sub‐regional effect of CHD4 mutations helped explaining the mechanisms underlying phenotypic variations. [ABSTRACT FROM AUTHOR]

Background & Aims: Hepatocellular carcinoma (HCC) is a fatal disease characterized by vast molecular heterogeneity. Although major advances in tumour genetics has led to the identification of new biomarkers, the prognosis of patients with HCC remains dismal. Methods: Quantitative reverse‐transcription polymerase chain reaction (qRT‐PCR) and western blot (WB) were used to evaluate meiosis‐specific nuclear structural 1 (MNS1) expression in HCC cells. Immunohistochemistry staining was used to evaluate MNS1 expression in HCC tissues. Clinical significance of MNS1 was evaluated by Cox regression analysis. Transwell assays were conducted to assess cells migration ability. Cell counting kit‐8 and colony formation assays were performed to detect cells proliferation ability. NOD/SCID/γc(null) (NOG) mice model was adopted to investigate functions of MNS1 in vivo. Results: The expression of MNS1, which is elevated in most HCC tissues, correlated with poor survival in HCC patients. Functional experiments revealed the oncogenic role of MNS1, which promotes HCC growth and metastasis through AKT‐dependent modulation of β‐catenin. β‐Catenin expression was crucial for MNS1's oncogenic effects. MNS1 indirectly translocated β‐catenin from the cytoplasm to the nucleus via the MNS1‐GSK3β axis. Conclusions: MNS1 promotes HCC growth and metastasis via activating PI3K/AKT signalling and may serve as an important prognostic biomarker as well as potential novel therapeutic target for HCC. [ABSTRACT FROM AUTHOR]

Background: Louisiana is one of the few Southern states that enacted the Medicaid expansion of the Patient Protection and Affordable Care Act (ACA). To the authors' knowledge, the issue of how this has affected the breast cancer landscape in Louisiana is unknown. The authors have postulated that ACA expansion had a positive impact for Louisiana women diagnosed with breast cancer. Methods: Data from the Louisiana Tumor Registry regarding 14,640 women aged 20 to 64 years who resided in Louisiana and were diagnosed with American Joint Committee on Cancer stage 0 to stage IV breast cancer between 2012 and 2018 were analyzed. The study period was divided into 2 groups: 1) before ACA expansion (January 1, 2012–May 31, 2016); and 2) after ACA expansion (June 1, 2016–December 31, 2018). The chi‐square test and multivariable logistic regression models were used to assess the impact of ACA expansion. A P value <.05 was considered statistically significant. Results: After ACA expansion, the rate of uninsured patients decreased from 5.4% to 3.0% (P <.0001), and the rate of Medicaid recipients increased from 11.6% to 17.7% (P <.0001). The diagnosis of stage I breast cancer increased from 36.8% to 44.7% (P <.0001), whereas the diagnosis of stage III breast cancer decreased from 10.7% to 8.5% (P <.0001). The receipt of radiotherapy after breast‐conserving surgery increased from 81.2% to 84.0% (P =.0035), and the receipt of radiotherapy within 90 days increased from 57.2% to 61.7% (P =.0012). After adjustment for sociodemographic and clinical variables, the models demonstrated that ACA expansion decreased the uninsured rate by 48% (odds ratio [OR], 0.52; 95% CI, 0.43‐0.63), increased the diagnosis of early‐stage disease (stage0 to stage II) by 27% (OR, 1.27; 95% CI, 1.15‐1.41), increased receipt of radiotherapy after breast‐conserving surgery by 19% (OR, 1.19; 95% CI, 1.03‐1.37), and reduced the delay of receipt of radiotherapy by 16% (OR, 0.84; 95% CI, 0.74‐0.95). Conclusions: ACA expansion in Louisiana reduced the uninsured rate, increased the diagnosis of early‐stage disease, and increased access to treatment. Medicaid expansion under the Patient Protection and Affordable Care Act (ACA) in Louisiana was found to result in a decrease in the uninsured rate, an increase in the amount of early‐stage disease detected at diagnosis, and increasing access to treatment. These results provide guidance for other nonexpansion states as they deliberate the advantages and disadvantages of ACA expansion for their own state. [ABSTRACT FROM AUTHOR]

T‐cell exhaustion is one of the hallmarks in cancer, but the mechanisms underlying T‐cell dysregulation remains unclear. Here, we reported that down‐regulation of transcription factor EOMES contributed to increased levels of inhibitory receptors in T cell among the tumour tissues and resulted in the poor prognosis of hepatocellular carcinoma (HCC). By analysing the correlation between EOMES in tumour‐infiltrating T cells and the clinical features, we demonstrated that the EOMES was related to the advanced stage and poor prognosis of HCC. Further mechanistic studies revealed that the EOMES mainly expressed in the CD8+ T cells and were down‐regulated in tumour samples. Moreover, we demonstrated that the EOMES directly bound at the transcriptional regulatory regions of the key inhibitory factors including PD‐1, CTAL‐4 and CD39, and lower levels of EOMES contributed to overexpression of these factors in T cells. Together, our studies provide new insight into the transcriptional deregulation of the inhibitory receptors on T cells during the tumorigenesis. [ABSTRACT FROM AUTHOR]

Objective: Treatment of massive irreparable rotator cuff tears (RCT) has shown limited clinical success and a variety of subsequent complications. Superior capsule reconstruction (SCR) has been proved to reestablish superior stability but does not restore the dynamic force or shoulder kinematics. There are numerous reports of the short‐term failure of SCR grafts at the glenoid side, which relate to the non‐biological healing of grafts. To restore both dynamic and static stability and to provide biologic augmentation, an integrated procedure for massive irreparable RCT using an Achilles tendon–bone allograft (ATBA) was developed. Method: This was a retrospect study completed between October 2019 and April 2020. A 71‐year‐old woman with massive and irreparable rotator cuff tears was enrolled in our study. The ATBA was folded into a double‐layer structure. The superior layer (proximal portion) served as a bridge patch to dynamic the glenohumeral joint, while the inferior layer (distal portion) served as the superior capsule to restore static stability of glenohumeral joint. To enhance biologic healing on the glenoid side, we fixed the calcaneus of the graft on the superior–posterior side of the superior glenoid rim. The recovery of shoulder function (including strength, range of motion, acromiohumeral interval, and fatty infiltration) was assessed at 6 months postoperation. Result: At 6‐month follow‐up, the patient's strength had improved significantly (from abduction of grade 3 preoperatively to grade 4 at 6 months). Radiographic analysis showed an increase in the acromiohumeral interval from 3 to 7 mm. Magnetic resonance imaging revealed an intact graft, with the thickness of the ligament part maintained (at 6–7 mm). Most importantly, recovery of atrophy and fatty infiltration of the supraspinatus were observed. No graft tears were observed on the glenoid side. Conclusion: This technique could provide a preferable treatment option by restoring shoulder kinematics and augmentating biological healing for patients with massive irreparable RCT. [ABSTRACT FROM AUTHOR]

Brønsted acid‐catalyzed general Petasis allylation and isoprenylation of unactivated ketones were developed by using o‐hydroxyaniline and the corresponding pinacolyl boronic esters. This robust methodology provided access to a broad variety of quaternary homoallylic amines and dienyl amines in high yields, proved to be applicable to a gram‐scale synthesis, and allowed the synthesis of a potentially bioactive quaternary homoallylic aminodiol. [ABSTRACT FROM AUTHOR]

Carbon‐supported nano‐platinum catalyst is extensively used as electrocatalyst in proton exchange membrane fuel cells (PEMFCs) due to its high catalytic activity towards the oxygen reduction reaction (ORR). phloroglucinol‐resorcinol‐formaldehyde carbon aerogel (CPRF) microsphere with adjustable pore sizes can be prepared by adding template, PEG‐200, on the basis of inverse micro emulsion method. Without cumbersome solvent exchange and supercritical drying, CPRF microspheres with a unique 3D structure can be obtained, which has a suitable microporous structure (10‐35 nm) and applicable mesoporous size (∼20 nm). As the support of the platinum, the CPRF microspheres with high specific surface area (798.3 m2 g−1) show excellent catalytic activity for ORR in alkaline electrolytes. The initial electrochemical active surface area and mass activity of the prepared Pt/CPRF are 2.5 and 2.7 times higher than that of commercial Pt/C respectively. After the accelerated durability test (ADT), the Pt/CPRF still keeps a stable electrochemical active surface area and mass activity up to 56 m2 g−1 and 0.11 A mg−1, while the commercial Pt/C lost to 42.8 m2 g−1 and 0.02 A mg−1. The stability of the Pt/CPRF shows about 5.5 times enhancement for ORR compared to commercial Pt/C. [ABSTRACT FROM AUTHOR]

Boron‐reagents are very useful tools in synthetic organic chemistry and have been extensively explored in the asymmetric methodology development. The past decade has witnessed an upsurge of interest in exploring their application in the asymmetric total synthesis. Several synthetic strategies, such as the transmetalation strategy, the boronate ligand exchange strategy, the Lewis base and Brønsted acid activation strategies, and the lithiation‐borylation strategy, offered very powerful platforms for the development of innovative synthetic routes for asymmetric total synthesis. This review highlights the progress (2007–2019) of the application of these synthetic strategies in the asymmetric total synthesis of natural products, and of biologically and medicinally relevant molecules. [ABSTRACT FROM AUTHOR]

Unprecedented phosphine‐catalyzed [4+1] cycloadditions of allenyl imides have been discovered using various N‐based substrates including methyl ketimines, enamines, and a primary amine. These transformations provide a one‐pot access to cyclopentenoyl enamines and imines, or (chiral) γ‐lactams through two geminal C−C bond or two C−N bond formations, respectively. Several P‐based key intermediates including a 1,4‐(bis)electrophilic α,β‐unsaturated ketenyl phosphonium species have been detected by 31P NMR and HRMS analyses, which shed light on the postulated catalytic cycle. The synthetic utility of this new chemistry has been demonstrated through a gram‐scaling up of the catalytic reaction as well as regioselective hydrogenation and double condensation to form cyclopentanoyl enamines and fused pyrazole building blocks, respectively. [ABSTRACT FROM AUTHOR]

Carbon aerogel (CA) microspheres are modified CA materials that can be prepared by reverse microemulsion and ambient pressure drying and without solvent exchanged. However, mesopore size of traditional resorcinol‐formaldehyde (RF) carbon aerogel microsphere is too small (3‐5 nm) to support nano‐platinum catalyst. In this study, we utilize reverse microemulsion polymerization and ambient pressure drying to develop a series of phloroglucinol‐resorcinol‐formaldehyde (PRF) carbon aerogel microspheres. These carbon aerogel microspheres possess large mesopore size (10–30 nm) and high specific surface area (1300–2000 m2 g−1). Compared with commercial Pt/C, the PRF carbon aerogel as nano‐platinum catalyst support shows the better and durable catalytic activity. The initial mass and electrochemical active surface area of the best performance of Pt/CA are 2.9 and 2.8 times higher than that of commercial Pt/C respectively. After the accelerated stability test (ADT), Pt/CA still keeps a mass and electrochemical active surface area up to 0.15 A mg−1 and 86.4 m2 g−1, while the commercial Pt/C lost to 0.02 A mg−1 and 42.8 m2 g−1. The stability of Pt/CA shows about 7.5 times enhancements compared to commercial Pt/C. [ABSTRACT FROM AUTHOR]

The 1,3‐dipolar cycloadditions of β‐fluoroalkyl vinylsulfones and nitrile oxides to deliver 5‐fluoroalkyl‐3‐substituted 2‐isoxazolines has been established under mild conditions in up to 85% yield with excellent regio‐ and diastereoselectivities (all d.r. >99 : 1), and thus facilitated rapid access to 5‐fluoroalkyl‐3‐Ph‐2‐isoxazoles by DBU‐mediated elimination of the pyridyl sulfone group. [ABSTRACT FROM AUTHOR]

A CuII‐catalyzed asymmetric 1,3‐dipolar cycloaddition using β‐fluoroalkyl alkenyl arylsulfones as dipolarophiles and glycine/alanine iminoesters as azomethine ylide precursors has been developed. Remarkably, a catalyst loading as low as 0.5 mol % is highly efficient. Accordingly, a wide range of enantioenriched 3‐fluoroalkyl pyrrolidines, as well as Δ2‐pyrroline and pyrrole derivatives, are generated in good to excellent yields with high asymmetric induction. This synthetic approach is diastereodivergent in that exo‐adducts could be converted into the corresponding exo′‐adducts by 1,8‐diazabicyclo[5.4.0]undec‐7‐ene mediated epimerization at C2 of the pyrrolidine core. The free‐energy profiles from DFT calculations suggest the Michael addition of the 1,3‐dipole to be the rate‐ and enantiodetermining step, and the origin of stereoselectivity is studied by means of the noncovalent interaction (NCI) analysis. [ABSTRACT FROM AUTHOR]

The BINOL‐derived chiral phosphoric acid (R)‐TRIP is utilized as an organocatalyst in the asymmetric isoprenylboration reaction of aldehydes, wherein hydrogen‐bond interactions play a key role in the control of enantioselectivity. A wide arrays of enantioenriched dienyl homoallyl alcohols, including two natural products (−)‐Ipsdienol and (−)‐Ipsenol, have been successfully constituted. The synthetic application to chiral isoprenylated isobenzofuranone, vinyloxirane and cyclohexene derivatives has also been disclosed. [ABSTRACT FROM AUTHOR]

This experiment focuses on specific user factors and hardware factors that affect to presence and motion sickness in virtual reality. The experimental results show that Motion Sickness Susceptibility, ocular refraction disorder and motor nerve have an influence on presence and motion sickness along with display resolution. [ABSTRACT FROM AUTHOR]

The present study aims to investigate the effects of smartphone use by college students on their perceived academic performance. Using five hypotheses derived from the literature related to smartphone use, the initial model was set up for path analysis to reveal the relationships among variables regarding college students' smartphone use in the academic setting. Moreover, multiple group analyses were additionally conducted to verify whether students exhibited different relationships in the hypothesized model depending on their majors. The results from path analyses showed that all path coefficients were positive and statistically significant, which indicated that all five hypothesized paths were supported. Above all, the results from multiple group analysis showed that one path (from Behavioural Intention to Use Smartphone to Academic Performance) differed significantly across groups. The findings from the current study provide educational policymakers and educators with information on how smartphone utilization in learning activities influences students' academic performance. Lay Description: What is already known about this topic: Smartphones foster interaction with people and multitasking.College students use smartphones as learning aids in e‐learning and web‐based learning.College students have high smartphone self‐efficacy.Smartphones have both positive and negative effects on academic performance.What this paper adds: College students' interaction competency influences behavioural intention for using smartphones for academic activities.College students' smartphone self‐efficacy has positive impacts on their behavioural intention for using smartphones for academic purposes.College students' behavioural intention to use smartphones positively influences perceived academic performances.Students' behavioural intention to use smartphones presents distinct impacts on academic performances depending on their major fields: natural science and humanities.Implications for practice and/or policy: Educational policymakers and educators may benefit information on how smartphone utilization in learning activities influences students' academic performances.The instrument developed in the present study could be used for future studies on smartphone use and students' psychological factors such as self‐efficacy and behavioural intention to use smartphones. [ABSTRACT FROM AUTHOR]

The Geum River has been faced with extreme environmental change due to the construction of three dams in midstream since 2012 (Four Major River Restoration Project). We hypothesized that suspended solids (SS) and total particulate phosphorus (TPP) decreased after the dam construction. To test our hypothesis, we investigated the influence of the dam construction on water quality by measuring possible impacts of decreasing SS, total phosphorus (TP), and TPP on the ecosystem in the lower Geum River and the Geum River estuary. For this study, we chose one site to compare the monthly water quality data pre‐construction (2008) and post‐construction (2015). Dissolved oxygen and pH were not significantly different between pre‐ and post‐construction, while electric conductivity (EC) increased. The increase in the EC may be related to a decrease in river discharge (RD) after the dam construction. As we expected, TP and TPP decreased post‐construction, but SS did not show significant differences between pre‐ and post‐construction. This suggests that the decline of TPP concentrations post‐construction were not related to SS levels. The explosive algal bloom and sedimentation of the algae may be an important factor in explaining the decrease in TP and TPP. The decline of SS, TP, and TPP flux to the lower Geum River was observed. This could be a potential reason for the erosion of the mud flat of the Geum River estuary in the future. Therefore, to determine the long‐term effects of the SS and the phosphorus fluxes to the lower Geum River, these factors should be monitored periodically over longer periods of time than this study. [ABSTRACT FROM AUTHOR]

The predictive calculation and wind effect on the ion flow environment of dc transmission line are evaluated by embedded short‐term wind speed based ionised flow model. The wind has a major impact on the electric field and ion current density profiles. In the ionised flow model of embedded short‐term wind speed, the short‐term wind speed is calculated by using time series model and Kalman filter algorithm. The ionised field considering short‐term wind speed is solved by finite‐element method with acceleration technique and time‐domain finite volume method. The algorithm is validated by the coaxial cylinder electrode configuration and practical bipolar dc transmission configuration. Computational results are made to provide a physical understanding of wind effect on the corona formation process. In the timescale of long‐term prediction, the time evolution behaviour of ground‐level ion current density and electric field with time‐varying wind speed is estimated. [ABSTRACT FROM AUTHOR]

Abstract: A highly atom‐economic, regio‐ and stereospecific synthesis of fluorinated pyrazolidinones and isoxazolidines is disclosed under catalyst‐ and additive‐free mild conditions. The diastereoselectivity with different type of 1,3‐dipoles is elucidated by using DFT calculations in CH3CN. Furthermore, a reaction using a chiral azomethine imine, a gram‐scale synthesis, and a reductive desulfonylation are also presented. [ABSTRACT FROM AUTHOR]

A time‐domain virtual electromagnetic interference (EMI) receiver model algorithm for corona‐originated EMI of dc transmission line is proposed. The presented model is based on short‐time fast Fourier transform (FFT) and digital quasi‐peak, peak and average detector algorithms together with the measured corona current. The virtual EMI receiver model algorithm is verified by comparing with measurement results of conducted interference of the three regular waveforms. The influences of computational accuracy on the conducted interference are discussed. Through utilising the laboratory‐scale corona cage to generate corona current, the 0.5 MHz excitation current is calculated by using short‐time FFT and excitation function theory. The measured and computational average value, root mean square value, quasi‐peak value and peak value of EMI receiver response to corona current sequence are obtained. It is found that computations of radio interference have a good agreement with the measured results. [ABSTRACT FROM AUTHOR]

Summary: As suspensions critically affect the ride and handling performance of vehicles, considerable efforts have been made to improve their design by an optimization method. In this paper, we propose a topology optimization–based method for suspension synthesis by using a 3‐dimensional model constructed with nonlinear bars and zero‐length springs that discretize the 3‐dimensional space between the chassis frame and a vehicle wheel. For optimization, bar cross‐sections and spring stiffness values are used as design variables alongside the nodal positions of bar elements as shape optimization variables to simultaneously optimize the topology and shape. To verify the proposed approach, 2 types of design problems were solved: recovering known suspension mechanisms for a given set of wheel trajectories and synthesizing unknown suspension mechanisms that satisfy several design constraints typically used in the automobile industry. Through these examples, possibilities to design new and advanced suspensions by the proposed optimization method are clearly demonstrated. [ABSTRACT FROM AUTHOR]

Bombyx mori, an insect with significant economic importance in China contains a large amount of lipids among different developmental stages, especially the pupal stage. Silkworms are fed with a base diet and fish oil supplemented diet, and the fatty acid (FA) compositions of different strains, life stages, and sexes are determined by GC‐MS. No C20 or C22 polyunsaturated fatty acids (PUFAs) are detected in silkworms fed with the base diet. Females accumulates more unsaturated fatty acids (USFAs) than males in the pupal stage, and the relative amount of USFAs decreases from the wandering stage to the moth stage, especially in females, suggesting that silkworms prefer the utilization of USFAs. In addition, when silkworms are fed with a diet supplemented with fish oil, which contained C20 and C22 PUFAs, they accumulates C20 and C22 PUFAs in proportion to the concentration of fish oil added to the diet. Practical Applications: Currently, the main dietary source of C20 and C22 PUFAs is marine fish, however, of which the stocks are declining because of environmental pollution and overfishing. Because of its excellent capability to accumulate C20 and C22 PUFAs, silkworm could be developed as a potential new source of these long‐chain FAs by transferring ?5 and ?6 desaturases to silkworm or its primary food, mulberry. The silkworm (Bombyx mori) can accumulate C20 and C22 polyunsaturated fatty acids (PUFAs) from diet supplemented with these PUFAs (B). The accumulation efficiency of eicosapentaenoic acid (EPA) in silkworm is particularly outstanding. This capacity may make silkworm a potential new source of C20 and C22 PUFAs. [ABSTRACT FROM AUTHOR]

A new type of single-ion conducting polymer electrolyte for lithium-ion batteries, poly(hexafluorobutyl methacrylate- co-lithium allyl sulfonate) (P (HFMA- co-ASLi)), was firstly prepared by copolymerizing hexafluorobutyl methacrylate (HFMA) and sodium allyl sulfonate (SAS) with a subsequent lithiation process. The prepared polymer electrolyte exhibits high lithium ionic conductivity (10−4 S cm−1 at 80 °C) and excellent cycle performance at high temperature, which could be attributed to the good thermal stability (remains stable up to 300 °C), mechanical properties (7.1 MPa for breaking strength) and high lithium-ion transference number (0.92). The electrolyte also displays good electrochemical stability (4.6 V). Our obtained results prove that the polymer P (HFMA- co-ASLi) is a promising candidate electrolyte for lithium-ion batteries. [ABSTRACT FROM AUTHOR]

Vulvovaginal candidiasis/candidosis is a common fungal infection afflicting approximately 75% of women globally caused primarily by the yeast Candida albicans. Fluconazole is widely regarded as the antifungal drug of choice since its introduction in 1990 due to its high oral bioavailability, convenient dosing regimen and favourable safety profile. However, its widespread use has led to the emergence of fluconazole-resistant C. albicans, posing a universal clinical concern. Coupled to the dearth of new antifungal drugs entering the market, it is imperative to introduce new drug classes to counter this threat. Antimicrobial peptides (AMPs) are potential candidates due to their membrane-disrupting mechanism of action. By specifically targeting fungal membranes and being rapidly fungicidal, they can reduce the chances of resistance development and treatment duration. Towards this goal, we conducted a head-to-head comparison of 61 short linear AMPs from the literature to identify the peptide with the most potent activity against fluconazole-resistant C. albicans. The 11-residue peptide, P11-6, was identified and assayed against a panel of clinical C. albicans isolates followed by fungicidal/static determination and a time-kill assay to gauge its potential for further drug development. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

2-Pyridylsulfone- and fluoroalkylated group-activated olefins underwent highly efficient diastereo- and enantioselective 1,3-dipolar cycloadditions across various aromatic and aliphatic nitrones in the presence of a chiral NiII/bis(oxazoline) catalyst. The process was tuned by 4 Å molecular sieves, chiral bis(oxazoline) ligands, reaction solvents, and temperature. A wide array of optically pure fluoroalkylated isoxazolidines were obtained, thus facilitating the asymmetric synthesis of an enantioenriched α-trifluoromethylated γ-amino alcohol in gram-scale and a trifluoromethylated derivative of 1,3-oxazinan-2-one with potential pharmaceutical interest. A stereochemical model, based on the absolute configuration of one adduct and some control experiments, was postulated to account for the observed endo- and enantioselectivity. [ABSTRACT FROM AUTHOR]

In this study, the positive inception voltage of bare and dielectric‐coated stranded conductors has been researched by numerical calculations and corona cage experiments. The charge simulation method is used to calculate the potential gradient distribution of the coated stranded conductors. Then, based on the positive inception criterion, the photoionisation inception model considering the effective radiation wavelength is proposed and employed to evaluate the inception voltage of the coated stranded conductors. In addition, in the laboratory, the inception voltage test platform is build up to measure the inception voltage. The results reveal that with the increase of the coating layer thickness, the inception voltage increases. For the same thickness, the inception voltage reduces slightly with the increase of relative permittivity. The calculated values are in good agreement with experimental results of the laboratory corona cage. The conclusion lays a foundation for studying the effect of the coating layer on the corona performance. [ABSTRACT FROM AUTHOR]

In this study, the influence of aerosols on the ion‐flow field has been researched by numerical calculations and experiments. The steady‐state model of ion‐flow field, considering the aerosols, is developed and solved by finite‐element finite‐difference method. The transport model of the particles is introduced by the Lagrangian method and the motion equations are solved by the fourth‐order Runge–Kutta method. In the laboratory, a reduced‐scale line platform is build up to test the influence of the aerosols and used to verify the calculations. From the results of measurements and calculations, it is observed that the calculated results are in good agreement with experimental results. [ABSTRACT FROM AUTHOR]

Given the important agricultural and medicinal application of optically pure heterocycles bearing a trifluoromethyl group at the stereogenic carbon center in the heterocyclic framework, the exploration of efficient and practical synthetic strategies to such types of molecules remains highly desirable. Catalytic enantioselective synthesis has one clear advantage that it is more cost-effective than other synthetic methods, but remains limited by challenges in achieving excellent yield and stereoselectivities with a low catalyst loading. Thus far, numerous models of organo- and organometal-catalyzed asymmetric reactions have been exploited to achieve this elusive goal over the past decade. This review article describes recent progress on this research topic, and focuses on an understanding of the catalytic asymmetric protocols exemplified in the catalytic enantioselective synthesis of a wide range of complex enantioenriched trifluoromethylated heterocycles. [ABSTRACT FROM AUTHOR]

Checkpoint kinase 2 ( CHK2) plays pivotal function as an effector of cell cycle checkpoint arrest following DNA damage. Recently, we found that co-treatment of NSC109555 (a potent and selective CHK2 inhibitor) potentiated the cytotoxic effect of gemcitabine ( GEM) in pancreatic cancer MIA PaCa-2 cells. Here, we further examined whether NSC109555 could enhance the antitumour effect of GEM in pancreatic adenocarcinoma cell lines. In this study, the combination treatment of NSC109555 plus GEM demonstrated strong synergistic antitumour effect in four pancreatic cancer cells ( MIA PaCa-2, CFPAC-1, Panc-1 and Bx PC-3). In addition, the GEM/NSC109555 combination significantly increased the level of intracellular reactive oxygen species ( ROS), accompanied by induction of apoptotic cell death. Inhibition of ROS generation by N-acetyl cysteine ( NAC) significantly reversed the effect of GEM/NSC109555 in apoptosis and cytotoxicity. Furthermore, genetic knockdown of CHK2 by si RNA enhanced GEM-induced apoptotic cell death. These findings suggest that inhibition of CHK2 would be a beneficial therapeutic approach for pancreatic cancer therapy in clinical treatment. [ABSTRACT FROM AUTHOR]

Background and Aim Regulatory T cells ( Treg) play a vital role in immunosuppressive crosstalk; however, Tregs from different locations lead to different clinical outcomes. Our aim was, therefore, to compare the prevalences and suppressive phenotypes of Tregs in the peripheral blood, peritumor, and intratumor of patients with hepatocellular carcinoma ( HCC). Methods The frequencies and phenotypes of CD4+ CD25+ CD127low/− CD49d− Tregs in the periphery, peritumor, and intratumor of 78 HCC patients and 12 healthy controls were evaluated by flow cytometry. Treg-cell suppressive activity was determined using an in vitro CD154 expression assay. Tregs from tumor and paired peritumor were then hybridized using an Agilent whole genome oligo microarray, and selected genes were validated by real-time polymerase chain reaction. Functional analysis of the microarray data was performed using Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses. Results Intratumoral Tregs exhibited higher frequencies and more suppressive phenotypic functions than those in peritumor and periphery, whereas there was no difference between the latter two. Functional analysis showed that complement cascades, p53, and glycosylphosphatidylinositol-anchor biosynthesis pathways were significantly upregulated in intratumoral Tregs; the salivary secretion pathway was significantly downregulated in intratumoral Tregs, and immune cells and tumor-immuno-related Gene Ontology terms were significantly affected. Conclusions Tregs in different locations exhibited different functional statuses. A higher prevalence and more suppressive phenotype suggested a critical role for intratumoral Tregs in the formation of multicellular immunosuppressive networks. HCC immunotherapy may be improved, therefore, by specific locational Tregs elimination or suppression. [ABSTRACT FROM AUTHOR]