bluuebunny/crossref_metadata_2025 huggingface dataset:
Electrospun Stacked Dual‐Channel Transistors with High Electron Mobility Using a Planar Heterojunction Architecture
Authors: He Bo , He Gang , Jiang Shanshan , Liu Jiangwei , Fortunato Elvira , Martins Rodrigo
Published: December 2022

Thin‐film transistors based on metal oxide semiconductors have become a mainstream technology for application in driving low‐cost backplanes of active matrix liquid crystal displays. Although significant progress has been made in traditional marketable devices based on physical vapor deposition derived metal oxides, it has still been hindered by low yield and poor compatibility. Fortunately, developing solution‐based 1D nanofiber networks to act as the fundamental building blocks for transistor has proven to be a simpler, higher‐throughput approach. However, oxide transistors based on such princesses suffer from degraded carrier mobility and operational instability, preventing the ability of such devices from replacing present polycrystalline Si technologies. Herein, it is shown that double channel heterojunction transistors with high electron mobility (>40 cm2 V−1 s−1) and operational stability can be achieved from electrospun double channels composed of In2O3 and ZnO layers. Adjusting the stacking order and the stacking density of In2O3 and ZnO layers can effectively optimize the interface electron trap, leading to the formation of 2D electron gas and the reduction of stress‐induced instability. These findings further elucidate the significant advance of electrospinning‐derived double channel heterojunction transistors toward practical applications for future low‐cost and high‐performance electronics.
Emerging Antibodies in Cancer Therapy
Authors: Sun Yaping , Xu Jian
Published: December 2022

Since the first monoclonal antibody, Orthoclone OKT3, was approved in 1986 for the treatment of acute allograft rejection in renal transplant recipients, the number of antibody‐based therapies has increased remarkably, with more than 130 monoclonal antibodies being currently available. In particular, due to their robust binding affinity and high specificity, various monoclonal antibodies have achieved success as complementary antitumor drugs. Moreover, therapeutic potency can be improved by engineering Y‐shaped binding sites of the antibodies to simultaneously recognize two distinct antigens; such molecules are called bispecific antibodies and function as a bridge, with one site binding to a tumor‐specific antigen and the other to immune cells to activate host immune responses. In addition, the development of trispecific antibodies has led to further enhancement of therapeutic specificity and effects. Indeed, a variety of structurally engineered antibodies have proven effective in tumor therapy. This article provides insights into the clinical translation of emerging antibody constructs, firstly describing conventional T cell‐redirecting bispecific antibodies and subsequently discussing the application of bispecific and trispecific antibody constructs based on innate immune cell recruitment. Finally, bispecific antibodies against mutant p53 and KRAS that have been actively studied in cancer treatment are introduced.
A series of nanosized Cu(II) complexes based on sulfonamide azo dye ligands: An insight into complexes molecular structures, antimicrobial, antitumor and catalytic performance for oxidative dimerization of 2‐aminophenol
Authors: El‐Ghamry Hoda A. , Alharbi Bushra K. , Takroni Khadiga M. , Khedr Abdalla M.
Published: December 2022

The two azo dye ligands named 4‐(2,4‐dihydroxy‐5‐formylphen‐1‐ylazo)‐N‐thiazol‐2‐yl‐benzenesulfon amide (H3TPBS) and 4‐(2,4‐dihydroxy‐phenylazo)‐N‐(3,4‐dimethyl‐1,2‐oxazol‐5 yl)benzenesulfonamide (H3IPBS) were employed for the synthesis of a series of Cu(II) chelates through the reaction of the ligands with Cu(II) salts of different anions. Full structure affirmation of all complexes has been done. Analytical results confirmed the formation of the metal chelates in the molar ratio 2:1 (M:L). Ultraviolet–visible spectra and magnetic moment proved the formation of complexes in square planar and square pyramidal geometries. Antimicrobic activity of the synthesized complexes has been assigned and compared with their parent ligands and also compared with standard antibiotic drugs showing enhanced activity over both the ligands and the standard drugs. The antitumor efficacy of the complexes has been also evaluated contra the two cell lines A‐549 cells (human Lung cancer cell line) and Panc‐1 (Pancreatic carcinoma) and compared with the standard drug Vinblastine. Additionally, The Cu(II) chelates were examined for their activity in oxidation coupling of o‐aminophenol (OAP) to 2‐aminophenoxazine‐3‐one (APX) in DMF solvent in open air atmosphere. The examined complexes afforded low to relatively high efficiency with TOF number from 0.27–78.12 h−1 with increased activity for complexes 1, 3, 5 and 7 incorporating Cl− or NO3− anions in their first coordination sphere.
Dicyanoimidazole resin with bisphenol A moiety: Synthesis, processing, properties, and composites
Authors: Zhu Zhengzhu , He Xian , Lv Jiangbo , Xiao Hang , Pu Yu , Hong Jinlang , Zeng Ke , Hu Jianghuai , Yang Gang
Published: December 2022

Developing high‐performance polymer (HPP) with improved properties by green processing method is one of the core parts of HPP research. In this paper, a new monomer (4,4′‐((propane‐2,2‐diylbis(4,1‐phenylene))bis(oxy))dibenzaldehyde (PBhDCI)) of high‐performance aromatic nitrile‐based (AN) resins with good solubility in ethanol was designed. The rheological analysis showed that PBhDCI is suitable for the processing by laminating process. The cured resins and the corresponding carbon fiber reinforced plastics (CFRP) showed outstanding thermal and mechanical properties. The thermal decomposition temperature (T5%) of the cured PBhDCI under nitrogen up to 510°C, the glass transition temperature (Tg) of both resin matrix and CFRP exceeds 500°C, and the flexural strength and modulus of CFRP were 507 ± 5 MPa and 59 ± 2 GPa. This work will offer some guidance for the preparation of high‐performance resins and corresponding CFRP with a green processing and high thermal and mechanical properties.
Robust fabrication of poly(lactic acid) membrane with good hemocompatibility over heparin‐mimetic graphene‐based nanosheets
Authors: Huang Lilan , Ma Lankun , Chen Haimei , Qiao Lei , Zhang Leitao , Pan Jian , Li Jinwei , Zhang Yuzhong
Published: December 2022

Developing dislysis membranes with outstanding hemocompatibility is the key of hemodialysis used for curing the kidney malfunction. Herein, polylactic acid (PLA) membrane with high water flux (640.2 L m−2 h−1) and bovine serum albumin (BSA) rejection (>97%) is prepared and subsequently modified by heparin‐mimetic sulfonated graphene oxide (SGO) via modified mussel‐inspired method. The (NH4)2Fe(SO4)2 serves as Fenton catalyst significantly accelerates the oxidized polymerization of dopamine (DA) in DA‐g‐SGO to form polydopamine‐g‐SGO (PDA‐g‐SGO). The uniform immobilization of SGO significantly improves the hydrophilicity and electronegativity of the PLA membranes, inhibiting platelets adhesion. Moreover, the sulfonic group of SGO plays the role of anticoagulant as heparin. The obtained PLA/PDA‐g‐SGO membrane exhibits excellent hemocompatibility with longer recalcification time (230 s) and lower hemolysis ratio (1.6%) than those of original PLA membrane (120 s, 10.7%). This study demonstrates a potential way to improve the hemocompatibility of polymeric membranes.
Solvent‐free synthesis of phosphate‐containing imidazole fluid for flame retardant one‐component epoxy resin with long pot life, low curing temperature and fast curing rate
Authors: Wang Wei , Chen Gang , Wu Shulong , Liu Yuan , Wang Qi
Published: December 2022

The design of flame retardant one‐component epoxy resin (EP) with long pot life, low curing temperature and fast curing rate has been challenging in the industry. Herein, we synthesized a phosphate‐containing imidazole fluid (TA) as the thermal latent curing agent of EP. Based on simple structural design, TA endows EP with excellent curing properties, storage properties, and flame retardant properties. According to DSC results, EP/TA systems exhibit low curing temperature and fast curing rate during operation. The rotary rheometer test confirms that the viscosity curve of EP/TA system maintains long‐term stability at 40°C. The X‐ray photoelectron spectroscopy (XPS) data reveals that TA releases imidazole intermediates and phosphorous compounds during curing. The former provides conditions for fast curing of EP, while the latter gives EP intrinsic flame retardant properties. With the addition of 20 wt.% TA, EP/TA‐4 achieves UL‐94 V‐0 rating and 28.5% of LOI value. The study of flame retardant mechanism shows that the flame retardancy of TA mainly comes from the protective effect of phosphorus‐rich char layer, the dilution effect of non‐combustible gas and quenching effect of phosphorous compound. Besides, due to no solvent involved, the synthesis strategy of TA is environmentally friendly, showing a great potential of industrial application.
Picolinamide Ligands: Nickel‐Catalyzed Reductive Cross‐Coupling of Aryl Bromides with Bromocyclopropane and Beyond
Authors: Han Dongyang , Sun Jie , Jin Jian
Published: December 2022

The arylcyclopropane motif as the combination of aryl and cyclopropyl ring systems can be found in an increasing amount of approved and investigational drugs. Herein, we have developed a mild, efficient nickel‐catalyzed reductive cross‐coupling protocol, featuring a simple Ni(II) precatalyst and a novel picolinamide NN2 pincer ligand. A variety of (hetero)aryl bromides could successfully couple with cyclopropyl bromide to furnish the valued arylcyclopropanes in good to excellent yields. This method is applicable to other alkyl bromides as well. Notably, the reaction is tolerant of a broad range of functionalities including free amines. Furthermore, the synthesis of several significant intermediates of bioactive molecules was achieved in grams, proving the practicability of this method.
Estimation of First Order Plus Dead Time and Second Order Plus Dead Time models from noisy step response data
Authors: Maxim Anca , De Keyser Robin
Published: December 2022

This paper proposes the estimation of first‐order‐plus‐dead‐time (FOPDT) and second‐order‐plus‐dead‐time (SOPDT) models from noisy step response data. The model parameters are estimated by computation of areas, which makes it robust in the presence of stochastic disturbances in the step response data. The efficiency of the methodology is extensively tested in various numerical examples as well as in real‐life experimental tests. The results—comparing our proposed estimation method with some other methods—suggest that the novel algorithm can be used with noisy step response data and adequately approximates high‐order systems. Moreover, it does not require any system identification expertise, making it readily accessible for the nonexperienced user in industrial practice. The method is successfully validated for overdamped, reasonably underdamped, as well as highly oscillatory processes, hence offering a comprehensive estimation method.
Increasing production of spinosad inSaccharopolyspora spinosaby metabolic engineering
Authors: Bridget Adzemye Fovennso , Nguyen Chung Thanh , Magar Rubin Thapa , Sohng Jae Kyung
Published: December 2022

Spinosad, a combination of spinosyn A and D produced bySaccharopolyspora spinosa, is a highly efficient pesticide. There has been a considerable interest in the improvement of spinosad production because of a low yield achieved by wild‐typeS. spinosa. In this study, we designed and constructed a pIBR‐SPN vector. pIBR‐SPN is an integrative vector that can be used to introduce foreign genes into the chromosome ofS. spinosa. Different combinations of genes encoding forasamine and rhamnose were synthesized and used for the construction of different recombinant plasmids. The following recombinant strains were developed:S. spinosapIBR‐SPN (only the vector),S. spinosapIBR‐SPN F (forosamine genes),S. spinosapIBR‐SPN R (rhamnose genes),S. spinosapIBR‐SPN FR (forosamine and rhamnose genes),S. spinosapIBR‐SPN FRS (forosamine, rhamnose, and SAM [S‐adenosyl‐L‐methionine synthetase] genes), andS. spinosaMUV pIBR‐SPN FR. Among these recombinant strains,S. spinosapIBR‐SPN FR produced 1394 ± 163 mg/L spinosad, which was 13‐fold higher than the wild‐type.S. spinosaMUV pIBR‐SPN FR produced 1897 (±129) mg/L spinosad, which was seven‐fold higher thanS. spinosaMUV and 17‐fold higher than the wild‐type strain.
Systematic review of reported association studies of monogenic genes and bladder cancer risk and confirmation analysis in a large population cohort
Authors: Mian Abrar , Wei Jun , Shi Zhuqing , Rifkin Andrew S. , Zheng S. Lilly , Glaser Alexander P. , Kearns James T. , Helfand Brian T. , Xu Jianfeng
Published: December 2022

Objectives

To evaluate which of previously reported monogenic genes are associated with increased bladder cancer risk, we reviewed published papers on associations of genes and bladder cancer risk and performed a confirmation study of these genes in a large population‐based cohort.

Subjects and methods

A systematic review of published papers prior to June 2022 was performed first to identify all genes where germline mutations were associated with bladder cancer risk. The associations of these candidate genes with bladder cancer risk were then tested among 1695 bladder cancer cases and 186 271 controls in the UK Biobank (UKB). The robust SKAT‐O, a gene‐based analysis that properly controls for type I error rates due to unbalanced case–control ratio, was used for association tests adjusting for age at recruitment, gender, smoking status, and genetic background.

Results

The systematic review identified nine genes that were significantly associated with bladder cancer risk in at least one study (p < 0.05), including MUTYH, MSH2, MSH6, MLH1, ATM, BRCA2, ERCC5, TGFB1 and CHEK2. When pathogenic/likely pathogenic mutations were aggregated within each gene, the association was confirmed for three genes in the UKB at p < 0.0056 (Bonferroni correction for nine tests), including CHEK2, ATM and BRCA2, all also known to be associated with hereditary breast cancer. Suggestive evidence of association was found for two other genes, including MLH1 (p = 0.006) and MSH2 (p = 0.007), both known to be associated with Lynch syndrome. Among these five genes, the bladder cancer risks range from 1.60 (ATM) to 4.88 (MLH1), and mutation carrier rates in cases range from 0.06% (MSH2) to 2.01% (CHEK2).

Conclusion

This study provides statistical evidence for association of previously reported genes and bladder cancer risk and has clinical utility for risk assessment and genetic counselling.
Looking up or down on the social ladder: How socioeconomic comparisons shape judgments about monetary and time donations
Authors: Demczuk Rafael , Mantovani Danielle , Fernandes Daniel
Published: December 2022

The increasing inequality rate within countries worldwide makes social comparisons more evident. In seven experiments, we demonstrate that people comparing themselves to others in a superior socioeconomic position (upward comparison) judge that wealthier others should donate more time and money to charity. However, social comparison to others in an inferior position (downward comparison) does not always increase monetary donations. This discrepancy in prescriptions for monetary donations between those who make upward and downward social comparisons is driven by judgments about relative spare money; while people making upward comparisons believe that others have more spare money, people making downward comparisons only think they have more spare money, and should donate more, when reminded of their hierarchical position at the time of judgment. Low meritocracy beliefs exacerbate the difference between the prescriptions of how much oneself and others should donate given their socioeconomic position. This differential pattern among individuals making upward and downward social comparisons helps to propagate economic inequality. People making upward comparisons prescribe to wealthier others the responsibility to donate to charity, who in turn may not think they should donate more money. These findings have implications for charitable and non‐profit organizations and contribute to research on social comparison, inequality, and judgments about monetary and time donations.
“K‐synthesis”: Recent advancements in natural product synthesis enabled by unique methods and strategies development in Korea
Authors: Han Sunkyu
Published: December 2022

Natural product synthesis has lain at the heart of organic chemistry. Complex structures of natural products have inspired chemists to develop new methods and strategies. The utility and robustness of newly developed methodologies have been tested by their application into total synthesis. With the necessity to establish a solid health‐related and biomedical Korean industrial ecosystem, a historically belittled sector when compared to well‐invested manufacturing and electronics industries in Korea, there has been enormous recent progress in the Korean organic chemical research. Accordingly, impressive syntheses of complex secondary metabolites that feature unique tactics and ingenious strategies have been reported by synthetic organic chemists in Korea. Herein, recent advancements (mostly after 2010) in natural product synthesis from Korea are depicted. Representative accomplishments from researchers in Korea are presented with an emphasis on unique methods and strategies that are utilized into their synthetic approaches.
Using memes to promote student engagement and classroom community during remote learning
Authors: Tu Kevin , Sun Angela , Levin Daniel M.
Published: December 2022

As colleges moved to online teaching during the COVID‐19 pandemic, many instructors found it difficult to maintain student engagement and classroom community in the virtual environment. We developed a semester‐long activity for a molecular biology research methodology course where students created, and shared original memes related to course content with peers through group chat. Surveys and semi‐structured interviews revealed that the exercise was effective in promoting student engagement, a sense of community, and relieving stress.
Characterization of CPH:SA microparticle‐based delivery of interleukin‐1 alpha for cancer immunotherapy
Authors: Hasibuzzaman M. M. , He Rui , Khan Ishrat Nourin , Sabharwal Rasna , Salem Aliasger K. , Simons‐Burnett Andrean Llewela
Published: December 2022

Background

Interleukin‐1 alpha (IL‐1α) is a pro‐inflammatory cytokine that can activate immune effector cells and trigger anti‐tumor immune responses. However, dose‐limiting toxicities including cytokine storm and hypotension has limited its use in the clinic as a cancer therapy. We propose that polymeric microparticle (MP)‐based delivery of IL‐1α will suppress the acute pro‐inflammatory side effects by allowing for slow and controlled release of IL‐1α systemically, while simultaneously triggering an anti‐tumor immune response.

Methods

Polyanhydride copolymers composed of 1,6‐bis‐(p‐carboxyphenoxy)‐hexane:sebacic 20:80 (CPH:SA 20:80) was utilized to fabricate MPs. Recombinant IL‐1α (rIL‐1α) was encapsulated into CPH:SA 20:80 MPs (IL‐1α‐MPs) and the MPs were characterized by size, charge, loading efficiency, and in‐vitro release and activity of IL‐1α. IL‐1α‐MPs were injected intraperitonially into head and neck squamous cell carcinoma (HNSCC)‐bearing C57Bl/6 mice and monitored for changes in weight, tumor growth, circulating cytokines/chemokines, hepatic and kidney enzymes, blood pressure, heart rate, and tumor‐infiltrating immune cells.

Results

CPH:SA IL‐1α‐MPs demonstrated sustained release kinetics of IL‐1α (100% protein released over 8–10 days) accompanied by minimal weight loss and systemic inflammation compared to rIL‐1α‐treated mice. Blood pressure measured by radiotelemetry in conscious mice demonstrates that rIL‐1α‐induced hypotension was prevented in IL‐1α‐MP‐treated mice. Liver and kidney enzymes were within normal range for all control and cytokine‐treated mice. Both rIL‐1α and IL‐1α‐MP‐treated mice showed similar delays in tumor growth and similar increases in tumor‐infiltrating CD3+ T cells, macrophages, and dendritic cells.

Conclusions

CPH:SA‐based IL‐1α‐MPs generated a slow and sustained systemic release of IL‐1α resulting in reduced weight loss, systemic inflammation, and hypotension accompanied by an adequate anti‐tumor immune response in HNSCC‐tumor bearing mice. Therefore, MPs based on CPH:SA formulations may be promising as delivery vehicles for IL‐1α to achieve safe, effective, and durable antitumor responses for HNSCC patients.
Prognostic nomogram based on the lymph node metastasis indicators for patients with bladder cancer: A SEER population‐based study and external validation
Authors: Li Shuai , Wang Yicun , Hu Xiaopeng
Published: December 2022

Purpose

This study aimed to compare the prognostic value of multiple lymph node metastasis (LNM) indicators and to develop optimal prognostic nomograms for bladder cancer (BC) patients.

Methods

BC patients were obtained from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015, and randomly partitioned into training and internal validation cohorts. Genomic and clinical data were collected from The Cancer Genome Atlas (TCGA) as external validation cohort. The predictive efficiency of LNM indicators was compared by constructing multivariate Cox regression models. We constructed nomograms on basis of the optimal models selected for overall survival (OS) and cause‐specific survival (CSS). The performance of nomograms was evaluated with calibration plot, time‐dependent area under the curve (AUC) and decision curve analysis (DCA) in three cohorts. We subsequently estimated the difference of biological function and tumor immunity between two risk groups stratified by nomograms in TCGA cohort.

Results

Totally, 10,093 and 107 BC patients were screened from the SEER and TCGA databases. N classification, positive lymph nodes (PLNs), lymph node ratio (LNR) and log odds of positive lymph nodes (LODDS) were all independent predictors for OS and CSS. The filtered models containing LODDS had minimal Akaike Information Criterion, maximal concordance indexes and AUCs. Age, LODDS, T and M classification were integrated into nomogram for OS, while nomogram for CSS included gender, tumor grade, LODDS, T and M classification. The nomograms were successfully validated in predictive accuracy and clinical utility in three cohorts. Additionally, the tumor microenvironment was different between two risk groups.

Conclusions

LODDS demonstrated superior prognostic performance over N classification, PLN and LNR for OS and CSS of BC patients. The nomograms incorporating LODDS provided appropriate prediction of BC, which could contribute to the tumor assessment and clinical decision‐making.
Preoperative systemic immune‐inflammation index as a significant prognostic factor after TURBT in patients with non‐muscle‐invasive bladder cancer: A retrospective study based on propensity score matching analysis
Authors: Ding Li , Wang Xiangbu , Deng Xiaobin , Xia Wentao , Wang Kun , Yu Xianlin , Huang Yaotian , Wang Junqi
Published: December 2022

Objective

To investigate the association of the preoperative systemic immune‐inflammation index (SII) with recurrence‐free survival (RFS) after transurethral resection of the bladder tumor (TURBT) of non‐muscle‐invasive bladder cancer (NMIBC) using propensity score matching (PSM) analysis.

Methods

The clinicopathological characteristics and follow‐up data of NMIBC patients were collected retrospectively from two tertiary medical centers. A 1:1 PSM analysis was carried out using the nearest‐neighbor method (caliper size: 0.02). Cox regression analysis was used to identify the risk factors associated with RFS.

Results

A total of 416 NMIBC patients were included in this study. Before and after matching, patients with increased SII had worse RFS (p < 0.0001 and p = 0.027, respectively). Multivariate Cox analysis identified SII as an independent predictor of RFS before (HR [95% CI]: 1.789 [1.232, 2.599], p = 0.002) and after matching (HR [95% CI]: 1.646 [1.077, 2.515], p = 0.021). In the matched subgroup analysis, an elevated SII had a significant association with postoperative worse RFS in the T1 stage (p = 0.025), primary status (p = 0.049), high‐grade (p = 0.0015), and multiple lesions (p = 0.043) subgroups.

Conclusion

SII could accurately stratify the prognosis of NMIBC patients before and after PSM analysis. An elevated SII was significantly associated with worse RFS in NMIBC patients.
Isolation and Chemical Characterization of Antifungal, Antioxidant, and Anti‐Inflammatory Compounds from Centrosema coriaceum using GC/MS, UFLC‐QTOF‐MS, and FACE
Authors: Lemos Ari S. O. , Campos Lara M. , Souza Thalita F. , Paula Priscila L. , Da Silva João Victor G. , Coimbra Elaine S. , Hottz Eugenio D. , Dib Paula R. B. , Aguiar Jair A. K. , Grazul Richard M. , Chedier Luciana M. , Fabri Rodrigo L.
Published: December 2022

In recent years, natural products with biological activities have been increasingly researched. The elucidation of phytoconstituents is necessary for the development of drugs as a natural alternative for the treatment of various diseases. The work aimed to evaluate in vitro and in silico bioactivities of hexane (CCHE) and methanol (CCME) fractions of ethanolic extract from Centrosema coriaceum Benth (Fabaceae) leaves and elucidate their phytoconstituents. CCHE and CCME showed antifungal activity for Candida glabrata (MIC of 1000 μg/mL) with fungistatic effect and action in cell envelope by sorbitol and ergosterol assays. CCHE and CCME presented promising antioxidant activity against the DPPH radical with IC50 of 13.61±0.50 and 6.31±0.40 μg/mL, respectively, and relative antioxidant activity (RAA%) of 45.77±3.61/ 28.53±2.25 % for CCHE and 82.18±2.25/51.99±3.23 % for CCME when compared to rutin and quercetin, respectively. Moreover, these fractions demonstrated promising results for the inhibition of lipid peroxidation by β‐carotene/linoleic acid assay. For anti‐inflammatory and cytotoxicity activities, CCHE and CCME significantly inhibited the production of nitric oxide and TNF‐α, without toxicity on murine intraperitoneal macrophages, respectively. Esters, alkanes, steroids, tocopherols, and terpenes were identified in CCHE by GC/MS. Flavonoids, phenolic acids, and disaccharides were detected in CCME by UFLC‐QTOF‐MS and FACE. Furthermore, rutin was purified from CCME. In silico predictions evidenced that compounds present in both fractions have high affinity to the fungal membrane besides antioxidant and anti‐inflammatory activities. Based on these observations, CCHE and CCME have a noteworthy potential for the design of novel antifungal and anti‐inflammatory agents that should be explored in future studies.
Antioxidant, Cytotoxicity, Apoptotic Properties of Extracts ofAndricus sternlichtigalls and Their Phenolic Characterisation by HPLC
Authors: Kılınçarslan Aksoy Özge , Seçme Mücahit , Mammadov Ramazan
Published: December 2022

QuercusL. galls have been used in Western and Eastern cultures for various diseases in traditional medicine. Galls are also used in the East for many purposes, including consumption as food, commercial inks, leather tanning. In the current study,Andricus sternlichtiBellido, Pujade‐Villar & Melika, 2003 galls were extracted in different solvents. The possible antioxidant effects of gall extracts were determined using 7 different methods (β‐carotene‐linoleic acid assay, Phosphomolybdenum assay, DPPH and ABTS radical scavenging activity, CUPRAC and FRAP assay, Metal Chelating activity) to support each other. Total phenolic, flavonoid and tannin amounts of extracts are calculated by using standard curves. In addition, HPLC method used to characterize the phenolic component with 15 different standards. The MIA PaCa‐2 cell lines was preferred to identify possible cytotoxic activities of galls. Expression of some genes (Bax,Bcl‐2,FAS,BID,caspase‐3,caspase‐8,caspase‐9,caspase‐10,FADD,TRADD) role in the apoptosis was determined to investigate apoptotic effects of extracts. According the results, the gall extracts ofA. sternlichtimay be considered as a potential source of biological agents for their antioxidant capacity and rich bioactive compounds. The gall extracts exhibit antiproliferative activity via regulating expressions of apoptotic genes.
TBADT‐Mediated C‐C Bond Formation Exploiting Aryl Aldehydes in a Photochemical Flow Reactor
Authors: Cruise Adam , Baumann Marcus
Published: December 2022

A robust and general photochemical process is reported converting various aryl aldehydes into β‐ketonitriles and related species. Tetrabutylammonium decatungstate (TBADT) is used as photocatalyst in combination with a high‐power LED emitting at 365 nm. Standardization and scalability are enabled by using a flow reactor platform integrating the LED light source placed within an encased reactor coil. Under optimized conditions a variety of aromatic and heteroaromatic aldehydes is reacted with acrylonitrile, methyl methacrylate and phenyl vinyl sulfone to give the desired products in high yields, short residence times of 5–30 minutes and a throughput of up to 41 mmol/h. This continuous process overcomes limitations previously encountered for aromatic substrates and represents an effective means to generate a variety of difunctionalized building blocks for further elaborations with an ideal atom economy.
Fast quantification of diclofenac sodium content in commercially available tablets by transmission Raman spectroscopy with PLS
Authors: Zhao Xuejia , Wang Ning , Liu Yitong , Jiang Yifei , Sun Shengnan , Wang Xiaohui , Yao Jing , Shan Guangzhi
Published: December 2022

A new technology based on transmission Raman spectroscopy was developed for the determination of diclofenac sodium (DS) in commercially available tablets using chemometric tools such as partial least squares (PLS). Based on multifactor orthogonal design of experiment (DOE), we established an initial model consisting of 150 handmade tablets. By adding only two commercially available tablets spectra to the initial model, it was successfully applied to the determination of the active pharmaceutical ingredient (API) of three commercially available diclofenac sodium tablets. The results showed that the relative error of content measured by TRS for three brands of tablets was less than 4% and the RSD of 20 commercially available tablets under brand of Ouyi was 0.49%. The method can ensure high accuracy and good repeatability in rapid nondestructive quantitative analysis and can be used as a new technology for quality control on production lines to monitor drugs in real time.
Layered‐residual herbicide programs for waterhemp control in glufosinate‐resistant soybean
Authors: Arneson Nicholas J. , Smith Daniel H. , DeWerff Ryan P. , Oliveira Maxwel C. , Werle Rodrigo
Published: December 2022

Core Ideas

Glufosinate is an important POST herbicide for waterhemp control in glufosinate‐resistant soybean.

The layered‐residual herbicide approach improved season‐long waterhemp control.

Glufosinate POST combined with layered soil residual herbicides improved season‐long waterhemp control.

Glufosinate is an important POST herbicide for waterhemp control in glufosinate‐resistant soybean.

The layered‐residual herbicide approach improved season‐long waterhemp control.

Glufosinate POST combined with layered soil residual herbicides improved season‐long waterhemp control.
Three‐ and Five‐Membered Anionic Chains of Pnictogenylboranes
Authors: Moussa Mehdi Elsayed , Kahoun Tobias , Marquardt Christian , Ackermann Matthias T. , Hegen Oliver , Seidl Michael , Timoshkin Alexey Y. , Virovets Alexander V. , Bodensteiner Michael , Scheer Manfred
Published: December 2022

An unprecedented family of three‐ and five‐membered substituted anionic derivatives of parent pnictogenylboranes is herein reported. Reacting various combinations of the pnictogenylboranes H2E′−BH2−NMe3 (E′=P, As) with pnictogen‐based nucleophiles MER1R2 (E=P, As; R1=H, R2=tBu; R1=R2=Ph; M=Na, K) allows for the isolation of the unsymmetrical products [Na(18‐crown‐6)][H2E′−BH2−EHtBu] (3: E=E′=P; 4: E=E′=As; 5: E=As, E′=P) and [M(C)][H2E′−BH2−EPh2] (7: E=E′=P, M=Na, C=18‐crown‐6; 8: E=E′=As; M=K, C=[2.2.2]cryptand; 9: E=P, E′=As, M=Na, C=[2.2.2]cryptand; 10: E=As, E′=P, M=K, C=[2.2.2]cryptand). [Na(18‐crown‐6)][H2As−BH2‐tBuPH−BH3] (6) is only accessible by a different pathway, using tBuPH2, BH3 ⋅ SMe2 and NaNH2 as starting materials. Additionally, the synthesis of symmetrical diphenyl‐substituted compounds [M(18‐crown‐6)][Ph2E−BH2−EPh2] (11: E=P, M=Na; 12: E=As, M=K) is reported which can be regarded as isostructural inorganic, negatively charged analogs of dppm (1,1‐bis(diphenylphosphino)methane) and dpam (1,1‐bis(diphenylarsino)methane). Furthermore, an elongation of the pnictogen boron backbone in compounds 3, 7 and 9′ (similar compound to 9, stabilized however by 18‐crown‐6), is attainable by reacting them with the pnictogenylboranes H2E′−BH2−NMe3 leading to corresponding five‐membered chain‐like compounds [Na(18‐crown‐6)][H2E−BH2−R1R2P−BH2−E′H2] (E=E′=P, R1=H, R2=tBu (13); E=E′=P, R1=R2=Ph (14); E=E′=As, R1=R2=Ph (15); E=P, E′=As, R1=R2=Ph (16)). Finally, the thermodynamics of the reaction pathways were evaluated by quantum chemical computations.
LiHMDS‐Mediated Deprotonative Coupling of Toluenes with Ketones
Authors: Shigeno Masanori , Kajima Akihisa , Toyama Eito , Korenaga Toshinobu , Yamakoshi Hiroyuki , Nozawa‐Kumada Kanako , Kondo Yoshinori
Published: December 2022

We demonstrate that lithium hexamethyldisilazide (LiHMDS) acts as an effective base for deprotonative coupling reactions of toluenes with ketones to afford stilbenes. Various functionalities (halogen, OCF3, amide, Me, aryl, alkenyl, alkynyl, SMe, and SPh) are allowed on the toluenes. Notably, this system proved successful with low‐reactive toluenes bearing a large pKa value compared to that of the conjugate acid of LiHMDS (hexamethyldisilazane, 25.8, THF), as demonstrated by 4‐phenyltoluene (38.57, THF) and toluene itself (∼43, DMSO).
Preparation and Functionalization of Mono‐ and Polyfluoroepoxides via Fluoroalkylation of Carbonyl Electrophiles
Authors: Guo Shuo , Sun Wei , Tucker Joseph W. , Hesp Kevin D. , Szymczak Nathaniel K.
Published: December 2022

We outline a new synthetic method to prepare mono‐ and polyfluoroepoxides from a diverse pool of electrophiles (ketones, acyl chlorides, esters) and fluoroalkyl anion equivalents. The initially formed α‐fluoro alkoxides undergo subsequent intramolecular ring closure when heated. We demonstrated the versatility of the method through the isolation of 16 mono‐ and polyfluoroepoxide products. These compounds provide unique entry points for further diversification via either fluoride migration coupled with ring opening, or defluorinative functionalization reactions, the latter of which can be used as a late‐stage method to install select bioactive moieties. The reaction sequences described herein provide a pathway to functionalize the commonly observed products formed from 1,2‐addition into carbonyl electrophiles
Circularly polarized luminescence in molecular recognition systems: Recent achievements
Authors: Takaishi Kazuto , Maeda Chihiro , Ema Tadashi
Published: December 2022

Circularly polarized luminescence (CPL) dyes are recognized to be new generation materials and have been actively developed. Molecular recognition systems provide nice approaches to novel CPL materials, such as stimuli‐responsive switches and chemical sensing materials. CPL may be induced simply by mixing chiral or achiral, luminescent or nonluminescent host and guest; there are several combinations. Molecular recognition can potentially save time and effort to construct well‐ordered chiral structures with noncovalent attractive interactions as compared with the multi‐step synthesis of covalently bonded dyes. It is a challenging subject to engage molecular recognition events with CPL, and it is important and interesting to see how it is achieved. In fact, simple molecular recognition systems can even enable the fine adjustment of CPL performance and detailed conformational/configurational analysis of the excited state. Here we overview the recent achievements of simple host–guest complexes capable of exhibiting CPL, summarizing concisely the host/guest structures, CPL intensities, and characteristics.
Use of machine learning models to predict in‐hospital mortality in patients with acute coronary syndrome
Authors: Li Rong , Shen Lan , Ma Wenyan , Yan Bo , Chen Wenchang , Zhu Jie , Li Linfeng , Yuan Junyi , Pan Changqing
Published: December 2022

Background

Cardiovascular diseases are a significant health burden with the prevalence increasing worldwide. Thus, a highly accurate assessment and prediction of death risk are crucial to meet the clinical demand. This study sought to develop and validate a model to predict in‐hospital mortality among patients with the acute coronary syndrome (ACS) using nonlinear algorithms.

Methods

A total of 2414 ACS patients were enrolled in this study. All samples were divided into five groups for cross‐validation. The logistic regression (LR) model and XGboost model were applied to predict in‐hospital mortality. The results of two models were compared between the variable set by the global registry of acute coronary events (GRACE) score and the selected variable set.

Results

The in‐hospital mortality rate was 3.5% in the dataset. Model performance on the selected variable set was better than that on GRACE variables: a 3% increase in area under the receiver operating characteristic (ROC) curve (AUC) for LR and 1.3% for XGBoost. The AUC of XGBoost is 0.913 (95% confidence interval [CI]: 0.910–0.916), demonstrating a better discrimination ability than LR (AUC = 0.904, 95% CI: 0.902–0.905) on the selected variable set. Almost perfect calibration was found in XGBoost (slope of predicted to observed events, 1.08; intercept, −0.103; p < .001).

Conclusions

XGboost modeling, an advanced machine learning algorithm, identifies new variables and provides high accuracy for the prediction of in‐hospital mortality in ACS patients.
Novel cryotherapy in non–muscle‐invasive bladder cancer
Authors: Ho Matthew D. , Modi Parth K.
Published: December 2022

In this editorial, the recently published trial examining endoscopic balloon cryoablation after resection of non–muscle‐invasive bladder cancers is discussed. Several issues with the control group, design, and inclusion criteria that limit the application of these data to current urologic practice are identified.
Triple combination targeting methyltransferase, BCL‐2, and PD‐1 facilitates antileukemia responses in acute myeloid leukemia
Authors: Zeng Zhihong , Maiti Abhishek , Herbrich Shelley , Cai Tianyu , Cavazos Antonio , Manzella Taylor , Ma Helen , Hayes Kala , Matthews Jairo , DiNardo Courtney D. , Daver Naval G. , Konopleva Marina Y.
Published: December 2022

Background

A recent breakthrough therapy combining the BCL‐2 inhibitor venetoclax with hypomethylating agents (HMAs) targeting DNA methyltransferase has improved outcomes for patients with acute myeloid leukemia (AML), but the responses and long‐term survival in older/unfit patients and in patients with relapsed/refractory AML remain suboptimal. Recent studies showed that inhibition of BCL‐2 or DNA methyltransferase modulates AML T‐cell immunity.

Methods

By using flow cytometry and time‐of‐flight mass cytometry, the authors examined the effects of the HMA decitabine combined with the BCL‐2 inhibitor venetoclax (DAC/VEN therapy) on leukemia cells and T cells in patients with AML who received DAC/VEN therapy in a clinical trial. The authors investigated the response of programmed cell death protein 1 (PD‐1) inhibition in the DAC/VEN–treated samples in vitro and investigated the triple combination of PD‐1 inhibition with HMA/venetoclax in the trial patients who had AML.

Results

DAC/VEN therapy effectively targeted leukemia cells and upregulated the expression of the immune checkpoint‐inhibitory receptor PD‐1 in T cells while preserving CD4‐positive and CD8‐positive memory T cells in a subset of patients with AML who were tested. In vitro PD‐1 inhibition potentiated the antileukemia response in DAC/VEN–treated AML samples. The combined use of azacitidine, venetoclax, and nivolumab eliminated circulating blasts and leukemia stem cells/progenitor cells and expanded the percentage of CD8‐positive memory T cells in an illustrative patient with relapsed AML who responded to the regimen in an ongoing clinical trial.

Conclusions

Immunomodulation by targeting PD‐1 enhances the therapeutic effect of combining an HMA and venetoclax in patients with AML.
Chain Walking in the AlCl3 Catalyzed Cationic Polymerization of α‐Olefins
Authors: Rahbar Amene , Falcone Bruno , Pareras Gerard , Nekoomanesh‐Haghighi Mehdi , Bahri‐Laleh Naeimeh , Poater Albert
Published: December 2022

Continuing efforts aimed at performing the 1‐decene polymerization to low viscosity polyalphaolefins (PAO)s using a less hazardous AlCl3 catalyst than boron‐based analogs, the basic mechanisms of this system were revealed in this research. In this aspect, neat AlCl3 and AlCl3/toluene were carried out to perform 1‐decene polymerizations. Microstructure analyses of the as‐synthesized oils revealed low molecular weight (708 vs. 1529 g/mol), kinematic viscosity (KV100=6.4 vs. 22.2 cSt), and long chain branching (82.1 vs. 84.7) of PAO from the system containing toluene solvent. Furthermore, NMR analysis confirmed various types of short chain branch (SCB) with the inclusion of toluene ring in the structure of final PAO chains. Then, to shed light on the basic mechanisms of cationic polymerization of 1‐decene including: i) chain initiation, ii) chain transfer to the monomer, iii) isomerization of the carbocation via a chain walking mechanism (causes different SCB length), and iv) binding of toluene ring to the propagating PAO chain (to yield aromatic containing oligomers), molecular modeling at the DFT level was employed. The energies obtained confirmed the ease of carbocation isomerization and chain transfer mechanisms in toluene medium, which well confirms the highly branched structure experimentally obtained for related PAO.
How long does a single oral dose of cannabidiol persist in plasma? Findings from three clinical trials
Authors: McCartney Danielle , Kevin Richard C. , Suraev Anastasia S. , Sahinovic Ayshe , Doohan Peter T. , Bedoya‐Pérez Miguel A. , Grunstein Ronald R. , Hoyos Camilla M. , McGregor Iain S.
Published: December 2022

A growing number of clinical trials (CTs) are investigating the therapeutic potential of cannabidiol (CBD), a non‐intoxicating phytocannabinoid found in Cannabis sativa. These CTs often use crossover experimental designs requiring ‘washout’ (clearance) periods. However, the length of time CBD persists in plasma (its ‘window of detection’) is unclear and could be significant. Indeed, the structurally related phytocannabinoid, Δ9‐tetrahydrocannabinol (THC), has a long window of detection in plasma. We investigated the extent to which CBD and its major metabolites persist in plasma. Data from three CTs that measured plasma cannabinoid concentrations ≥7 days after administering a single oral dose of CBD were pooled. The CBD doses were as follows: CT #1: 300 mg; CT #2: 200 mg (and 10 mg THC); and CT #3: 15, 300 and 1500 mg (one per treatment session). Thirty‐two participants were included in the analysis, 17 of whom (from CT #3) provided repeated measures. Overall, 0% (15 mg), 60% (200 mg), 28% (300 mg) and 100% (1500 mg) of participants had detectable concentrations (i.e., >0.25 ng·ml−1) of CBD in plasma ≥7 days post‐treatment (some, several weeks post‐treatment). A zero‐inflated negative binomial mixed‐effects regression analysis (R2m = 0.44; R2c = 0.73) predicted that, on average, a 13 day washout period would reduce plasma CBD concentrations to ‘zero’ (i.e., <0.25 ng·ml−1) if a single oral dose of 300 mg was consumed. Higher doses require longer washout periods; concomitant medications may also affect clearance. In conclusion, CBD has a long window of detection in plasma. Crossover studies involving CBD should, therefore, be conducted with caution, particularly when higher doses and/or chronic dosing regimens are used.
Model selection in occupancy models: Inference versus prediction
Authors: Stewart Peter S. , Stephens Philip A. , Hill Russell A. , Whittingham Mark J. , Dawson Wayne
Published: December 2022

Occupancy models are a vital tool for ecologists studying the patterns and drivers of species occurrence, but their use often involves selecting among models with different sets of occupancy and detection covariates. The information‐theoretic approach, which employs information criteria such as Akaike's information criterion (AIC) is arguably the most popular approach for model selection in ecology and is often used for selecting occupancy models. However, the information‐theoretic approach risks selecting models that produce inaccurate parameter estimates due to a phenomenon called collider bias, a type of confounding that can arise when adding explanatory variables to a model. Using simulations, we investigated the consequences of collider bias (using an illustrative example called M‐bias) in the occupancy and detection processes of an occupancy model, and explored the implications for model selection using AIC and a common alternative, the Schwarz criterion (or Bayesian information criterion, BIC). We found that when M‐bias was present in the occupancy process, AIC and BIC selected models that inaccurately estimated the effect of the focal occupancy covariate, while simultaneously producing more accurate predictions of the site‐level occupancy probability than other models in the candidate set. In contrast, M‐bias in the detection process did not impact the focal estimate; all models made accurate inferences, while the site‐level predictions of the AIC/BIC‐best model were slightly more accurate. Our results show that information criteria can be used to select occupancy covariates if the sole purpose of the model is prediction, but must be treated with more caution if the purpose is to understand how environmental variables affect occupancy. By contrast, detection covariates can usually be selected using information criteria regardless of the model's purpose. These findings illustrate the importance of distinguishing between the tasks of parameter inference and prediction in ecological modeling. Furthermore, our results underline concerns about the use of information criteria to compare different biological hypotheses in observational studies.