bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nitrogen‐Radical‐Triggered Trifunctionalizing ipso‐Spirocyclization of Unactivated Alkenes with Vinyl Azides: A Modular Access to Spiroaminal Frameworks
Authors: Qi Zhongyu , Zhang Zhijie , Yang Li , Zhang Di , Lu Ji , Wei Jun , Wei Siping , Fu Qiang , Du Xi , Yi Dong 
Published: July 2021

AbstractWe report an example of non‐dearomative trifunctionalizing ipso‐spirocyclization of unactivated alkenes through photoredox‐catalyzed, nitrogen‐radical‐triggered cyclization‐trapping‐translocation‐cyclization cascade, providing a single‐step modular access to spiroaminal frameworks through the sequential formation of one C−C bond and two geminal C−N bonds. The developed protocol utilizes not only internal and terminal olefinic oxime esters, but also olefinic amides as nitrogen radical precursors, and features a broad substrate scope, wide functional group compatibility, easy scalability, and potential for product derivatization and late‐stage functionalization of bioactive estrone derivatives. Importantly, the mechanistic studies including DFT calculations indicate that the photocatalytic trifunctionalizing ipso‐spirocyclization undergoes a radical relay cascade of intramolecular 5‐exo‐trig cyclization, intermolecular radical trapping, 1,5‐hydrogen atom transfer, and sequential 5‐endo‐trig cyclization, which provides another reaction mode of alkenes.magnified image
Advanced Immunotherapy Approaches for Glioblastoma
Authors: Ma Yifan , Yang Zhaogang , Huntoon Kristin , Jiang Wen , Kim Betty Y. S. 
Published: July 2021

AbstractGlioblastoma multiforme (GBM) is the most aggressive primary central nervous system (CNS) tumor, and treatment for GBM is regarded as the most challenging task in clinical oncology. Although multiple treatments are available, including surgery, chemotherapy, and radiotherapy, these conventional therapies barely improve the functional prognosis and life quality of patients with glioblastoma. Immunotherapy, has become a promising approach for treating GBM because of the ability to overcome the blood–brain barrier (BBB) and complicated unique tumor immune microenvironment. Developing an efficient immunotherapy for GBM requires understanding the glioblastoma immune microenvironment; accordingly, this study begins by summarizing this and what it indicates for the development of immunological effects. Then current immunotherapy management for GBM and advanced studies including checkpoint inhibitors, cell vaccines, and extracellular vesicle‐based immunotherapy is reviewed. Because monotherapies are inadequate for treating GBM, combinational GBM immunotherapy with other classical cancer therapies, especially chemo‐immunotherapy, radiotherapy‐immunotherapy, and the combination of gene therapy and immunotherapy, is introduced and discussed. The recent progress introduced in this review suggests that cancer immunotherapy and its combinatory therapies are highly promising treatment modalities for glioblastoma patients. However, systematical and in‐depth investigations are required to improve the efficacy of GBM immunotherapy for future clinical translation.
Selective C–F Bond Allylation of Trifluoromethylalkenes
Authors: Zhu Chuan , Sun Meng‐Meng , Chen Kai , Liu Haidong , Feng Chao 
Published: July 2021

AbstractSelective C−F bond functionalization of CF3 group represents an appealing strategy for the incorporation of pharmaceutically privileged difluoromethylene moiety. Despite the recent significant advancement attained in the functionalization of Ar‐CF3 molecules, prescriptions amenable for alkenyl‐CF3 congeners remain sufficiently inadequate. Herein, we report a strategically novel protocol for the C−F bond elaboration of trifluoromethylalkene derivatives. By using readily available allyl metallics as nucleophilic coupling partner, the present reaction enables an expedient construction of structurally diversified CF2‐bridged 1,5‐dienes. Furthermore, the exquisite selectivity observed in this transformation is revealed to be based on the underlying mechanism that consists of a cascade of nucleophilic SN2′ defluorinative allylation and electronically promoted Cope rearrangement.
General α‐Amino 1,3,4‐Oxadiazole Synthesis via Late‐Stage Reductive Functionalization of Tertiary Amides and Lactams**
Authors: Matheau‐Raven Daniel , Dixon Darren J. 
Published: July 2021

AbstractAn iridium‐catalyzed reductive three‐component coupling reaction for the synthesis of medicinally relevant α‐amino 1,3,4‐oxadiazoles from abundant tertiary amides or lactams, carboxylic acids, and (N‐isocyanimino) triphenylphosphorane, is described. Proceeding under mild conditions using (<1 mol %) Vaska's complex (IrCl(CO)(PPh3)2) and tetramethyldisiloxane to access the key reactive iminium ion intermediates, a broad range of α‐amino 1,3,4‐oxadiazole architectures were accessed from carboxylic acid feedstock coupling partners. Extension to α‐amino heterodiazole synthesis was readily achieved by exchanging the carboxylic acid coupling partner for C‐, S‐, or N‐centered Brønsted acids, and provided rapid and modular access to these desirable, yet difficult‐to‐access, heterocycles. The high chemoselectivity of the catalytic reductive activation step allowed late‐stage functionalization of 10 drug molecules, including the synthesis of heterodiazole‐fused drug–drug conjugates.
Role of additives in fabrication of soy‐based rigid polyurethane foam for structural and thermal insulation applications
Authors: Bose Mousumi , Dhaliwal Gurjot , Chandrashekhara K. , Nam Paul 
Published: July 2021

AbstractEnvironmental concerns continue to pose the challenge to replace petroleum‐based products with renewable ones completely or at least partially while maintaining comparable properties. Herein, rigid polyurethane (PU) foams were prepared using soy‐based polyol for structural and thermal insulation applications. Cell size, density, thermal resistivity, and compression force deflection (CFD) values were evaluated and compared with that of petroleum‐based PU foam Baydur 683. The roles of different additives, that is, catalyst, blowing agent, surfactants, and different functionalities of polyol on the properties of fabricated foam were also investigated. For this study, dibutyltin dilaurate was employed as catalyst and water as environment friendly blowing agent. Their competitive effect on density and cell size of the PU foams were evaluated. Five different silicone‐based surfactants were employed to study the effect of surface tension on cell size of foam. It was also found that 5 g of surfactant per 100 g of polyol produced a foam with minimum surface tension and highest thermal resistivity (R value: 26.11 m2·K/W). However, CFD values were compromised for higher surfactant loading. Additionally, blending of 5 g of higher functionality soy‐based polyol improved the CFD values to 328.19 kPa, which was comparable to that of petroleum‐based foam Baydur 683.
Biopolymer‐based microparticles for encapsulation of all‐trans‐retinoic acid
Authors: A. Silva Letícia , Dambros Roberta , R. Leonardi Gislaine , Perrechil Fabiana 
Published: July 2021

AbstractThis work aims to investigate the potential of complex coacervation technique to encapsulate and protect all‐trans retinoic acid (RA). Gelatin and κ‐carrageenan were used as wall material and pequi oil was employed as a hydrophobic phase. Three formulations with different protein: polysaccharide ratio and pH were defined to produce the microparticles based on the zeta potential and turbidity analysis: (F1) ratio 3:1 and pH 3.5, (F2) ratio 8:1 and pH 3.5, and (F3) ratio 8:1 and pH 5.0. Microparticles were evaluated regarding their morphology, yield, encapsulation efficiency (EE), and stability. The properties of microparticles were mainly affected by the protein: polysaccharide ratio and the turbidity of the mixtures, which is directly related to the protein‐polysaccharide interaction. Formulation 1 showed the optimal values of yield (75.6%), EE (100.2%), and stability (85% of the encapsulated RA remained in the particle). The results demonstrated the high potential of this innovative technique to encapsulate RA for a future application in topical formulations.
Integrated Suzuki Cross‐Coupling/Reduction Cascade Reaction of meta‐/para‐Chloroacetophenones and Arylboronic Acids under Batch and Continuous Flow Conditions
Authors: Li Yilong , Wang Chengyi , Chen Qipeng , Li Hongyu , Su Yu , Cheng Tanyu , Liu Guohua , Tan Chunxia 
Published: July 2021

AbstractOvercoming the incompatibility of a pair of conflicting catalysts via a flow methodology has great significance in the practical applications for multistep organic transformations. In this study, a multiple continuous‐flow system is developed, which can boost the reactivity and selectivity in a sequential enantioselective cascade reaction. During this process, a periodic mesoporous organosilica‐supported Pd/carbene species as a Suzuki cross‐coupling catalyst is packed in the first column reactor, whereas another periodic mesoporous organosilica‐supported Ru/diamine species as an asymmetric transfer hydrogenation catalyst is packed in the second column reactor. As we envisioned, the initially Pd‐catalyzed cross‐coupling reaction of meta‐/para‐chloroacetophenones and aryl boronic acids followed by the subsequentially Ru‐catalyzed reduction provides chiral biarylols with enhanced yields and enantioselectivities. Furthermore, the advantages of the easy handling and the simple procedure make this system an attractive application in a scale‐up preparation of optically pure organic molecules under environmentally‐friendly conditions.
18O/16O‐Encoding Strategy for Microscale Stereochemical Determination of Peptidic Natural Products
Authors: Takeuchi Aoi , Itoh Hiroaki , Inoue Masayuki 
Published: July 2021

AbstractThe demand for more efficient methods of establishing the undetermined stereochemistries of peptidic natural products continues unabated. A new method for microscale stereochemical determination was devised by integrating solid‐phase synthesis, split‐and‐mix randomization, 18O/16O‐encoding of d/l‐configurations, tandem mass spectrometry, and biological evaluation. Here we applied gramicidin A as the molecule for a blind test. Gramicidin A and its 31 diastereomers were randomly prepared in microgram scale with 18O/16O‐stereochemical encoding and subjected to MS/MS‐structural determination and cytotoxicity assay. Only the parent gramicidin A was selected from among the 32 stereoisomers, validating the high reliability of the present strategy.
Design of Vacuum Post‐Drying Procedures for Electrodes of Lithium‐Ion Batteries
Authors: Huttner Fabienne , Marth Axel , Eser Jochen C. , Heckmann Thilo , Mohacsi Jonas , Mayer Julian K. , Scharfer Philip , Schabel Wilhelm , Kwade Arno 
Published: July 2021

AbstractIn order to reduce the residual moisture in lithium‐ion batteries, electrodes and separators need to be post‐dried prior to cell assembly. On an industrial scale, this is often conducted batch‐wise in vacuum ovens for larger electrode and separator coils. Especially for electrodes, the corresponding post‐drying parameters have to be carefully chosen to sufficiently reduce the moisture without damaging the sensitive microstructure. This requires a fundamental understanding of structural limitations as well as heat transfer and water mass transport in coils. The aim of this study is to establish a general understanding of the vacuum post‐drying process of coils. Moreover, the targeted design of efficient, well‐adjusted and application‐oriented vacuum post‐drying procedures for electrode coils on the basis of modelling is employed, while keeping the post‐drying intensity as low as possible, in order to maintain the sensitive microstructure and to save time and costs. In this way, a comparatively short and moderate 2‐phase vacuum post‐drying procedure is successfully designed and practically applied. The results show that the designed procedure is able to significantly reduce the residual moisture of anode and cathode coils, even with greater electrode lengths and coating widths, without deteriorating the sensitive microstructure of the electrodes.
Design for the environment: An ontology‐based knowledge management model for green product development
Authors: Benabdellah Abla Chaouni , Zekhnini Kamar , Cherrafi Anass , Garza‐Reyes Jose Arturo , Kumar Anil 
Published: July 2021

AbstractThrough appropriate operations and policies, such as green processes and product development process (PDP), companies can respond to environmental sustainability. To remain competitive, one such approach, Design for X (DFX), involves considering different environment and sustainable strategies through different factors Xs. With regard to the availability of different DFX techniques that consider environmental issues, the decision as to which approach needs to be adopted remains absent. This paper aims at presenting an overview from 1980 to 2020 of the developed research, applications, and DFX techniques for assessing green issues. Selected DFX techniques are linked with strategies used in organizations. Following a literature analysis, a collaborative knowledge‐based framework that addresses the design concepts needed to assess environmental, safety, and health concerns in the development of green products is proposed. Furthermore, as a pillar for considering the Semantic Web and an evolving approach linked with natural language processing (NLP) and artificial intelligence (AI), an ontology‐based knowledge management model for green assessment is developed for the representation, acquisition, organization, and capitalization of knowledge in a computer interpretable manner. The findings are useful for both managers and practitioners as they provide a coherent domain ontology that can help them manage knowledge, improve teamwork, and make decisions in a collaborative green PDP. Besides, an understanding of the essential design considerations that are required to implement environmental, safety, and health issues, as well as competencies used in the PDP is presented. Key barriers, managerial and strategic implications, and mitigation actions are also identified in this paper.
Moxibustion for treating cancer‐related fatigue: A multicenter, assessor‐blinded, randomized controlled clinical trial
Authors: Han Kyungsun , Kim Mikyung , Kim Eun‐Jung , Park Yeon‐Cheol , Kwon Ojin , Kim Ae‐Ran , Park Hyo‐Ju , Park Yang‐Chun , Cho Jung Hyo , Kim Joo‐Hee , Lee Jun‐Hwan 
Published: July 2021

AbstractCancer‐related fatigue (CRF) is one of the most common chronic symptoms experienced by cancer patients. As moxibustion is a popular traditional therapy for managing fatigue, it can be an alternative strategy to treat CRF as well. Therefore, we rigorously designed a full‐scale, multicenter, assessor‐blinded, randomized controlled trial to evaluate the efficacy and safety of moxibustion treatment for CRF. Ninety‐six subjects suffering from CRF were recruited and randomly assigned to moxibustion group, sham moxibustion group, or usual care group. Both the moxibustion group and the sham group received moxibustion treatment for 8 weeks and the usual care group did not. Brief fatigue inventory (BFI) score and Functional Assessment of Cancer Therapy‐Fatigue score were used to assess CRF at baseline and weeks 5, 9, and 13. Questionnaires for the assessment of cognitive impairment, quality of life, and Cold–Heat and Deficiency–Excess patterns were also evaluated. BFI scores significantly decreased in moxibustion group compared to the usual care group (mean difference of −1.92, p < 0.001 at week 9 and mean difference of −2.36, p < 0.001 at week 13). Although the sham group also showed significant improvement during the treatment period, only the moxibustion group showed improvement after 4 weeks of follow‐up period (mean difference of −1.06, p < 0.001). There were no serious adverse events. Our findings confirmed the efficacy and safety of moxibustion for CRF compared to usual care. We also found that moxibustion has a prolonged treatment effect during 4 weeks of follow‐up period.
The impact of socioeconomic status on survival in stage III colon cancer patients: A retrospective cohort study using the SEER census‐tract dataset
Authors: Dhahri Amina , Kaplan Jori , Naqvi Syeda M. H. , Brownstein Naomi C. , Ntiri Shana O. , Imanirad Iman , Felder Seth I. , Dineen Sean P. , Sanchez Julian , Dessureault Sophie , Carballido Estrella , Powers Benjamin D. 
Published: July 2021

AbstractBackgroundThe impact of socioeconomic status (SES) has been described for screening and accessing treatment for colon cancer. However, little is known about the “downstream” effect in patients who receive guideline‐concordant treatment. This study assessed the impact of SES on cancer‐specific survival (CSS) and overall survival (OS) for stage III colon cancer patients.MethodsThe SEER Census Tract‐Level SES Dataset from 2004 to 2015 was used to identify stage III colon adenocarcinoma patients who received curative‐intent surgery and adjuvant chemotherapy. The predictor variable was census tract SES. SES was analyzed as quintiles. The outcome variables were OR and CSS. Statistical analysis included chi square tests for association, Kaplan–Meier, Cox, Fine and Gray regression for survival analysis.ResultsIn total, 27,222 patients met inclusion criteria. Lower SES was associated with younger age, Black or Hispanic race/ethnicity, Medicaid/uninsured, higher T stage, and lower grade tumors. CSS at the 25th percentile was 54 months for the lowest SES quintile and 80 for the highest. Median OS was 113 months for the lowest SES quintile and not reached for highest. The 5‐year CSS rate was 72.4% for the lowest SES quintile compared to 78.9% in the highest (p < 0.001). The 5‐year OS rate was 66.5% for the lowest SES quintile and 74.6% in the highest (p < 0.001).ConclusionThis is the first study to evaluate CSS and OS in an incidence‐based cohort of stage III colon cancer patients using a granular, standardized measure of SES. Despite receipt of guideline‐based treatment, SES was associated with disparities in CSS and OS.
A prognostic nomogram based on competing endogenous RNA network for clear‐cell renal cell carcinoma
Authors: Peng Yun , Wu Shangrong , Xu Zihan , Hou Dingkun , Li Nan , Zhang Zheyu , Wang Lili , Wang Haitao 
Published: July 2021

AbstractBackgroundClear‐cell renal cell carcinoma (ccRCC) is stubborn to traditional chemotherapy and radiation treatment, which makes its clinical management a major challenge. Recently, we have made efforts in understanding the etiology of ccRCC. Increasing evidence revealed that the competing endogenous RNA (ceRNA) was involved in the development of varied tumors. However, a comprehensive analysis of the prognostic model based on lncRNA‐miRNA‐mRNA ceRNA regulatory network of ccRCC with large‐scale sample size and RNA‐sequencing expression data is still limited.MethodsRNA‐sequencing expression data were taken out from GTEx database and TCGA database, a total of 354 samples with ccRCC and 157 normal controlled samples were included in our study. The ccRCC‐specific genes were obtained by WGCNA and differential expression analysis. Following, the communication of mRNAs and lncRNAs with targeted miRNAs were predicted by MiRcode, starBase, miRTarBase, and TargetScan. A gene signature of eight genes was further constructed by univariate Cox regression, Lasso methods, and multivariate Cox regression analysis.ResultsA total of 2191 mRNAs and 1377 lncRNAs was identified, and a dysregulated ceRNA network for ccRCC was established using 7 mRNAs, 363 lncRNAs, and 3 miRNAs. Further, a gene signature including eight genes based on this ceRNA was determined followed by the development of a nomogram predicting 1‐, 3‐, and 5‐year survival probability for ccRCC.ConclusionIt could contribute to a better understanding of ccRCC tumorigenesis mechanism and guide clinicians to make a more accurate treatment decision.
The transcription factor TEAD4 enhances lung adenocarcinoma progression through enhancing PKM2 mediated glycolysis
Authors: Hu Yan , Mu Hanshuo , Deng Zhiping 
Published: July 2021

AbstractLung adenocarcinoma (LUAD) is a deadly disease with a hallmark of aberrant metabolism. TEA domain 4 (TEAD4) is involved in the progression of several forms of cancer including LUAD. However, the role of TEAD4 in LUAD glucose metabolism is rarely reported as well as its potential mechanisms. Pyruvate kinase isozymes M2 (PKM2), the key regulatory enzymes in glycolysis, was predicted to be a target for TEAD4 by bioinformatics analysis. Thus, we aimed to explore whether TEAD4/PKM2 axis was related to LUAD glucose metabolism and malignant phenotype. The expression level of TEAD4 and PKM2 was measured by quantitative real‐time PCR and Western blot. Luciferase reporter assay were employed to verify the effect of TEAD4 on PKM2 promoter as well as TEAD4/PKM2 axis on reporter activity of hypoxia inducible factor‐1α (HIF‐1α). Glycolysis was investigated according to glucose consumption, lactate production and the extracellular acidification rate. The present study indicated that TEAD4 and PKM2 were upregulated in LUAD and closely related to prognosis. Mechanistic investigations identified that TEAD4 played a key role as a transcription factor and promoted PKM2 transcription and expression, which further altered the reporter activity of HIF‐1α and upregulated HIF‐1α‐targeted glycolytic genes glucose transporter‐1 and hexokinase II. Functional assays revealed that TEAD4 and PKM2 affected glycolytic and 2‐DG blocked the positive function of TEAD4 and PKM2 on glycolytic. Besides, TEAD4/PKM2 axis affects LUAD cell viability, apoptosis, migration, and invasion. Together, these data provided evidence that both TEAD4 and PKM2 were poor prognosticator. Targeting TEAD4/PKM2 axis might be an effective therapeutic strategy for LUAD.
(NH4)2V7O16 Microbricks as a Novel Anode for Aqueous Lithium‐Ion Battery with Good Cyclability
Authors: Ma Yining , Wu Mingchen , Jin Xiaodong , Shu Rui , Hu Chenchen , Xu Tongxiang , Li Jing , Meng Xinyu , Cao Xun 
Published: July 2021

AbstractSearching for novel anode materials to address the issues of poor cycle stability in the aqueous lithium‐ion battery system is highly desirable. In this work, ammonium vanadium bronze (NH4)2V7O16 with brick‐like morphology has been investigated as an anode material for aqueous lithium‐ion batteries and Li+/Na+ hybrid ion batteries. The two novel full cell systems (NH4)2V7O16||Li2SO4||LiMn2O4 and (NH4)2V7O16||Na2SO4||LiMn2O4 both demonstrate good rate capability and excellent cycling performance. A capacity retention of 78.61 % after 500 cycles at 300 mA g−1 was demonstrated in the (NH4)2V7O16||Li2SO4||LiMn2O4 system, whereas no capacity attenuation is observed in the (NH4)2V7O16||Na2SO4||LiMn2O4 system. The reaction mechanisms of the (NH4)2V7O16 electrode and impedance variation of the two full cells were also researched. The excellent cycling stability suggests that layered (NH4)2V7O16 can be a promising anode material for aqueous rechargeable lithium‐ion batteries.