bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stereocomplementary Synthesis of a Key Intermediate for Tofacitinib via Enzymatic Dynamic Kinetic Resolution‐Reductive Amination
Authors: Zhan Zhuangzhuang , Xu Zefei , Yu Shanshan , Feng Jinhui , Liu Fufeng , Yao Peiyuan , Wu Qiaqing , Zhu Dunming 
Published: June 2022

AbstractTofacitinib is an oral protein tyrosine kinase inhibitor approved for the treatment of rheumatoid arthritis, active psoriatic arthritis and ulcerative colitis. Its efficient production remains a challenge due to the two consecutive stereogenic centers associated to the piperidine ring. In this study, an enzymatic dynamic kinetic resolution‐asymmetric reductive amination was developed to prepare enantiomerically complementary cis‐1‐benzyl‐N,4‐ dimethylpiperidin‐3‐amine and its analogues. Two enantiocomplementary imine reductases (IREDs) were identified for the synthesis of (3R,4R)‐ and (3S,4S)‐1‐benzyl‐N,4‐dimethylpiperidin‐3‐amine in high isolated yields (83% and 91%) with excellent stereoselectivity (97% and >99% ee values) and diastereoselectivity (>99:1 dr), providing a green methodology for the production of the key intermediate of tofacitinib.magnified image
Copper‐Catalysed Synthesis of Propargyl Alcohol and Derivatives from Acetylene and other Terminal Alkynes
Authors: Sitte Nikolai A. , Ghiringhelli Francesca , Shevchenko Grigory A. , Rominger Frank , Hashmi A. Stephen K. , Schaub Thomas 
Published: June 2022

AbstractA copper(I)/phosphine system that homogeneously catalyses the alkynylation of formaldehyde with acetylene or terminal alkynes is reported. Using acetylene at atmospheric pressure, the catalyst consisting of <1 mol% copper(I) phenylacetylide and a trialkyl bisphosphine ligand shows a high selectivity towards the formation of propargyl alcohol rather than 1,4‐butynediol, which is not reported for common heterogeneous copper acetylide catalysts. The biphasic water/toluene reaction mixture allows the separation of targeted products with the aqueous layer and catalyst recycling via the organic layer.magnified image
Green Synthesis of Dimethyl Carbonate from CO2 and Methanol: New Strategies and Industrial Perspective
Authors: Raza Ali , Ikram Muhammad , Guo Song , Baiker Alfons , Li Gao 
Published: June 2022

AbstractDimethyl carbonate (DMC) is a commonly used and environmentally sustainable chemical compound and intermediate in a variety of industrial applications. To date, several large‐scale industrial DMC synthesis routes have been developed, including methanol phosgenation, transesterification, and oxidative carbonylation of methanol. However, these manufacturing routes have several disadvantages, such as the use of hypertoxic phosgene as raw material, costly processing, and explosion risks. The most encouraging and ecofriendly path is the green production of DMC from CO2 and methanol. Various catalytic materials have been examined concerning their suitability for DMC synthesis. The issues of low yield and difficulty in tests have not been resolved fundamentally, which is caused by the inherent problems of the synthetic pathway and limitations imposed by thermodynamics. The search for more efficient production routes has driven the activation of CO2 via electro‐assisted synthesis as well as membrane reactors, which can isolate products in real‐time to maximize DMC yield. The green synthesis of dimethyl carbonate catalyzed by different catalysts including Zr/Ce/Cu‐based nanocomposites, organometallic compounds, heteropoly acid, ionic liquid, metal‐organic frameworks, etc, is discussed in detail. Further, the structure–activity relationships and insights into molecular activation and catalytic mechanisms, as well as the identification of active sites on catalysts are addressed.
Stiffening Matrix Induces Age‐Mediated Microvascular Phenotype Through Increased Cell Contractility and Destabilization of Adherens Junctions
Authors: Schnellmann Rahel , Ntekoumes Dimitris , Choudhury Mohammad Ikbal , Sun Sean , Wei Zhao , Gerecht Sharon 
Published: June 2022

AbstractAging is a major risk factor in microvascular dysfunction and disease development, but the underlying mechanism remains largely unknown. As a result, age‐mediated changes in the mechanical properties of tissue collagen have gained interest as drivers of endothelial cell (EC) dysfunction. 3D culture models that mimic age‐mediated changes in the microvasculature can facilitate mechanistic understanding. A fibrillar hydrogel capable of changing its stiffness after forming microvascular networks is established. This hydrogel model is used to form vascular networks from induced pluripotent stem cells under soft conditions that mimic young tissue mechanics. Then matrix stiffness is gradually increased, thus exposing the vascular networks to the aging‐mimicry process in vitro. It is found that upon dynamic matrix stiffening, EC contractility is increased, resulting in the activation of focal adhesion kinase and subsequent dissociation of β‐catenin from VE‐Cadherin mediated adherens junctions, leading to the abruption of the vascular networks. Inhibiting cell contractility impedes the dissociation of β‐catenin, thereby preventing the deconstruction of adherens junctions, thus partially rescuing the age‐mediated vascular phenotype. The findings provide the first direct evidence of matrix's dynamic mechano‐changes in compromising microvasculature with aging and highlight the importance of hydrogel systems to study tissue‐level changes with aging in basic and translational studies.
Recapitulated Crosstalk between Cerebral Metastatic Lung Cancer Cells and Brain Perivascular Tumor Microenvironment in a Microfluidic Co‐Culture Chip
Authors: Kim Hyunho , Sa Jason K. , Kim Jaehoon , Cho Hee Jin , Oh Hyun Jeong , Choi Dong‐Hee , Kang Seok‐Hyeon , Jeong Da Eun , Nam Do‐Hyun , Lee Hakho , Lee Hye Won , Chung Seok 
Published: June 2022

AbstractNon‐small cell lung carcinoma (NSCLC), which affects the brain, is fatal and resistant to anti‐cancer therapies. Despite innate, distinct characteristics of the brain from other organs, the underlying delicate crosstalk between brain metastatic NSCLC (BM‐NSCLC) cells and brain tumor microenvironment (bTME) associated with tumor evolution remains elusive. Here, a novel 3D microfluidic tri‐culture platform is proposed for recapitulating positive feedback from BM‐NSCLC and astrocytes and brain‐specific endothelial cells, two major players in bTME. Advanced imaging and quantitative functional assessment of the 3D tri‐culture model enable real‐time live imaging of cell viability and separate analyses of genomic/molecular/secretome from each subset. Susceptibility of multiple patient‐derived BM‐NSCLCs to representative targeted agents is altered and secretion of serpin E1, interleukin‐8, and secreted phosphoprotein 1, which are associated with tumor aggressiveness and poor clinical outcome, is increased in tri‐culture. Notably, multiple signaling pathways involved in inflammatory responses, nuclear factor kappa‐light‐chain‐enhancer of activated B cells, and cancer metastasis are activated in BM‐NSCLC through interaction with two bTME cell types. This novel platform offers a tool to elucidate potential molecular targets and for effective anti‐cancer therapy targeting the crosstalk between metastatic cancer cells and adjacent components of bTME.
Superaerophobic Polyethyleneimine Hydrogels for Improving Electrochemical Hydrogen Production by Promoting Bubble Detachment
Authors: Bae Misol , Kang Yunseok , Lee Dong Woog , Jeon Dasom , Ryu Jungki 
Published: June 2022

AbstractRemoval of gas bubbles from the electrode surface is practically important to maintain the activity of electrochemical gas evolution reactions. Conventionally, most studies have focused on the development of electrocatalysts and paid less attention to the bubble removal issues. Recently, it has been reported that attached gas bubbles can be readily eliminated by imparting extremely gas‐repellent properties (so‐called superaerophobicity) to electrodes via controlling their nano/microstructure. However, this approach is material‐specific and requires harsh and expensive synthetic conditions, causing difficulties in scaling up to large‐area electrodes for commercialization. To address these issues, a universal method to impart superaerophobicity to various electrodes through simple coating with porous polymeric hydrogels without affecting the underlying target substrates is reported. The modification of electrodes with superaerophobic polymeric hydrogel substantially enhances the efficiency of the hydrogen evolution reaction because the hydrogel can facilitate the removal of as‐generated gas bubbles and thereby minimize ohmic and concentration overpotentials. Particularly, electrodes modified with the superaerophobic hydrogel outperform those modified with electrocatalysts at high current densities where more gas bubbles are generated and adhered to. The results provide insights into the design of various electrochemical devices that are based on gas‐involving reactions.
Application of an equation‐oriented framework to formulate and estimate parameters of chemical looping reaction models
Authors: Okoli Chinedu O. , Parker Robert , Chen Yu‐Yen , Ostace Anca , Lee Andrew , Bhattacharyya Debangsu , Tong Andrew , Biegler Lorenz T. , Burgard Anthony P. , Miller David C. 
Published: June 2022

AbstractAccurate, predictive reaction models are critical for the design and optimization of chemical looping combustion (CLC) reactors. The formulation and estimation of kinetic parameters for these reaction models using a first‐principles equation‐oriented (EO) approach is particularly beneficial as large amounts of experimental data spanning process‐relevant conditions can be used to estimate parameters in a computationally tractable way. This work demonstrates the application of a novel EO framework to develop reduction reaction kinetic models of an iron‐based CLC oxygen carrier (OC). An optimization problem is formulated to estimate kinetic parameters that provide the best fit to the experimental data. The model predicts the state of the OC with mean square error values of 2.5%–4.4% across the full range of validation data, including multiple reduction cycles.
Recent Advances in Cobalt‐catalyzed Functionalization of Unactivated Olefins
Authors: Patel Monak , Ajay Uppuluru , Padala Kishor , Naveen Togati 
Published: June 2022

AbstractOlefins are low‐cost starting materials that may be obtained in bulk quantities from petrochemical feedstocks and renewable resources. The transition metal‐catalyzed unactivated olefin functionalization is well explored and received an extensive interest from synthetic chemists. In recent times, chemists have successfully employed different transition metals for the functionalization of unactivated olefins. Among the different transition metals that have been used, cobalt catalysts have received great attention from synthetic chemists for C−H functionalization reactions, owing to their ready availability and high reactivity. Herein, we discuss the most recent reports in the field of cobalt‐catalyzed functionalization of unactivated olefins that enable C−C, C−X and C−hetero bond formation and covers the literature from 2016 to 2021.
Lipids, Apolipoproteins, Statins, and Intracerebral Hemorrhage: A Mendelian Randomization Study
Authors: Yu Zhou , Zhang Linjing , Zhang Gan , Xia Kailin , Yang Qiong , Huang Tao , Fan Dongsheng 
Published: June 2022

ObjectiveTo investigate the causal role of lipid or apolipoprotein traits in intracerebral hemorrhage (ICH) and determine the effect of lipid‐lowering interventions on the disease.MethodsTwo‐sample Mendelian randomization (MR) analyses were conducted to evaluate the associations of high‐density lipoprotein cholesterol, low‐density lipoprotein cholesterol (LDL‐C), triglycerides (TG), apolipoprotein (Apo)B and ApoA1 levels with risks for ICH, and those of LDL‐C‐ (HMGCR, PCSK9, and NPC1L1) and TG‐lowering targets (LPL and APOC3) with ICH.ResultsIncreased levels of ApoB was associated with a decreased risk of overall ICH (OR 0.623, 95% CI 0.413–0.940; p = 0.024) and lobar ICH (OR 0.579, 95% CI 0.342–0.979; p = 0.042). The inverse relationship remained stable in multivariable MR. In addition, elevated TGs showed a causal effect on lobar ICH in multivariable MR (OR 1.600, 95% CI 1.009–2.537; p = 0.046). The LDL‐C‐reducing genetic variation alleles at or near the HMGCR gene (mimicking the effect of statins) were predicted to increase the overall and deep ICH risk. Additionally, genetic variation at or near the APOC3 gene suggested that genetically reducing the activity of APOC3 (mimicking antisense anti‐apoC3 agents) was predicted to decrease lobar ICH.InterpretationGenetically predicted elevated ApoB may have a protective effect on overall ICH and lobar ICH, whereas elevated TG was associated with a higher risk of lobar ICH conditional on LDL‐C and ApoB. MR analysis supports the conclusion that statins may increase the risk of overall and deep ICH independent of their lipid‐lowering effect. More specific lipid‐lowering targets may end up being the future. ANN NEUROL 2022;92:390–399
Recent advances on food‐based applications of monoglyceride oleogels
Authors: Palla Camila A. , Dominguez Martina , Carrín María Elena 
Published: June 2022

AbstractMonoglyceride (MG) oleogels are soft matter structures designed to mimic the functionality of fats while maintaining a lipid profile comparable to that of edible oils. These novel fat materials have been mainly investigated as ingredients to reduce saturated fats and eliminate trans fats in the production of several foods, such as spreadables, bakeries, confectioneries, and meat products among others. Due to the versatility that oleogels offer, other relevant technological functionalities as well as the development of health‐promoting systems have been the subject of extensive research. MG oleogels have been explored as oil migration inhibitors, emulsion stabilizers, lipid oxidation stability enhancers, and even as 3D printing materials. Among the most recent applications are the use of MG oleogels as carriers of bioactive compounds as well as the development of systems able to modulate lipid digestion. This review exclusively focuses on the advances over the last decade in technological and nutritional applications of MG oleogels and MG oleogel‐based systems, outlining the most significant findings and conclusions from the literature, as well as challenges and trends for future studies.
Reutilization of crystalline waste plastics for modified asphalt using twin‐screw extrusion: Polyethylene and polypropylene as typical subjects
Authors: Li Junwei , Jia Shoubo , Yang Dan , Li Xin , Li Dongdong , Ye Xia , Guan Pengbing , Zhao Yongke 
Published: June 2022

AbstractThe key technologies for waste plastic modified asphalt were storage stability and low temperature performance. In order to reutilize waste plastics for modified asphalt, a simple strategy, which based on recrystallization of the waste plastics, was proposed in this article. It was found that the pretreated waste plastics had higher crystallinity and smaller crystal size. Moreover, the deformation resistance and stability of the modified asphalt were improved. In addition, a rational mechanism called “polymer crystals confinement effect” was proposed to reveal the intrinsic correlation between the properties of crystalline waste plastics and modified asphalt.
In vitro‐studies of adenosine‐ β‐cyclodextrin inclusion complexes loaded into chitosan, sodium alginate and bentonite‐based nanocomposite optimized by RSM as a sustained release system
Authors: Khushbu  , Jindal Rajeev 
Published: June 2022

AbstractDrugs with less aqueous solubility and permeability acquire significant hurdles in designing safe and effective formulations. The purpose of this study was to prepare an adenosine (ADS): β‐cyclodextrin (β‐CD) inclusion complex that could be consistently incorporated into a nanocomposite system for topical administration. Several procedures, including kneading, microwave irradiation, and co‐precipitation, were used to develop an adenosine: β‐CD inclusion complex. ROESY, DSC, XRD, and 1H NMR spectroscopy were used to analyze the adenosine‐β‐CD inclusion complex. Then bentonite (BN) incorporated chitosan (CH) and sodium alginate (ALG) nanocomposite were synthesized by microwave irradiation method. Response Surface Methodology (RSM) design was executed to optimize the reaction parameters. The Minimum Resolution V design was implemented to find significant variables to get maximum percentage swelling. The inclusion complexes of ADS: β‐CD were directly loaded into the CH/ALG/BN nanocomposite and the adenosine release was analyzed in simulated intestinal fluids (SIF) and simulated gastric fluids (SGF). Five kinetic models were investigated to know about the drug release mechanism. After a 24‐h interval, the ADS final release was 86 ppm at pH 2, 96 ppm at pH 7, and 85 ppm at pH 7.4. Bentonite has a layered structure that allows it to introduce the drug molecule into its cavity, resulting in sustainable adenosine release. The exploratory kinetic analysis demonstrated that β‐CD influences polymer relaxation, resulting in slow release.
A new pan‐kinosternid, Leiochelys tokaryki, gen. et sp. nov., from the late Maastrichtian Frenchman formation, Saskatchewan Canada
Authors: Brinkman Donald B. , Libke Caelan , McKellar Ryan C. , Gasilov Sergei , Somers Christopher M. 
Published: June 2022

AbstractPreviously, only a single member of Pan‐Kinosternidae (Yelmochelys rosarioae) had been documented from the Late Cretaceous epoch. In this report we describe a new pan‐kinosternid genus and species, herein named Leiochelys tokaryki, based on a nearly complete, articulated skeleton from the Late Cretaceous (Maastrichtian) Frenchman Formation of Saskatchewan, Canada. L. tokaryki differs most notably from the previously described Y. rosarioae in having triangular plastral lobes, and in that the suture between the hyo‐ and hypoplastron is in line with the suture between the fifth and sixth peripherals. A maximum parsimony analysis suggests that L. tokaryki is intermediate between Y. rosarioae and crown‐group kinosternids. Kinosternid features present in L. tokaryki include the presence of a reduced plastral bridge that extends from the posterior tip of peripheral 4 to the anterior tip of peripheral 7, two inframarginals that contact one another, a smooth triturating surface, and participation of the palatine in the triturating surface. An unexpected feature of the skull is the presence of a large stapedial canal, suggesting that the decrease in size of the stapedial canal and increase in the canalis caroticus cerebralis occurred independently in Dermatemydidae and Kinosternidae. The character‐states of the skull and skeleton of L. tokaryki indicate that morphological changes occurring during the diversification of Kinosternoidea were more complex than expected based on data from derived members of the group.
Morphologies in‐between: The impact of the first steps on the human talus
Authors: Figus Carla , Stephens Nicholas B. , Sorrentino Rita , Bortolini Eugenio , Arrighi Simona , Higgins Owen A. , Lugli Federico , Marciani Giulia , Oxilia Gregorio , Romandini Matteo , Silvestrini Sara , Baruffaldi Fabio , Belcastro Maria Giovanna , Bernardini Federico , Festa Anna , Hajdu Tamás , Mateovics‐László Orsolya , Pap Ildiko , Szeniczey Tamás , Tuniz Claudio , Ryan Timothy M. , Benazzi Stefano 
Published: June 2022

AbstractObjectiveThe development of bipedalism is a very complex activity that contributes to shaping the anatomy of the foot. The talus, which starts ossifying in utero, may account for the developing stages from the late gestational phase onwards. Here, we explore the early development of the talus in both its internal and external morphology to broaden the knowledge of the anatomical changes that occur during early development.Materials and MethodsThe sample consists of high‐resolution microCT scans of 28 modern juvenile tali (from 36 prenatal weeks to 2 years), from a broad chronological range from the Late Roman period to the 20th century. We applied geometric morphometric and whole‐bone trabecular analysis to investigate the early talar morphological changes.ResultsIn the youngest group (<6 postnatal months), the immature external shell is accompanied by an isotropic internal structure, with thin and densely packed trabeculae. After the initial attempts of locomotion, bone volume fraction decreases, while anisotropy and trabecular thickness increase. These internal changes correspond to the maturation of the external shell, which is now more defined and shows the development of the articular surfaces.DiscussionThe internal and external morphology of the human talus reflects the diverse load on the foot during the initial phases of the bipedal locomotion, with the youngest group potentially reflecting the lack of readiness of the human talus to bear forces and perform bipedal walking. These results highlight the link between mechanical loading and bone development in the human talus during the acquisition of bipedalism, providing new insight into the early phases of talar development.
Design, synthesis, biological evaluation, and in silico studies of 2‐aminobenzothiazole derivatives as potent PI3Kα inhibitors
Authors: Haider Kashif , Ahmad Kamal , Najmi Abul Kalam , Das Subham , Joseph Alex , Shahar Yar M. 
Published: June 2022

AbstractA new series of 2‐aminobenzothiazole derivatives was designed, synthesized and evaluated for their anticancer activity against the MCF7, MDAMB‐231, and HepG2 cancer cell lines. All synthesized derivatives (8a–8n) demonstrated moderate to high anticancer activity against the tested cell lines. As the most potent compound in the series, compound 8i displayed excellent inhibitory potency with an IC50 value of 6.34 μM and compound 8m displayed an IC50 value of 8.30 µM against the MCF7 cell line compared to the standard drug HS‐173 (IC50 = 10.25 μM). PI3K enzyme activity assays demonstrated that compound 8i is highly selective against PI3Kα, with an IC50 value of 1.03 nM. Wound healing assays and cell cycle analysis of compounds 8i and 8m revealed that both compounds suppressed the migration of MCF7 cells and induce cell cycle arrest in the S phase. In the cell death assay, compound 8i was revealed to induce apoptosis in a dose‐dependent pattern; further Western blot assays revealed that compound 8i obviously decreases the levels of the antiapoptotic proteins Bcl‐xL and Mcl‐1. Downregulation of the expression of p‐Akt confirmed the PI3K inhibitory activity of compound 8i. The molecular docking and molecular dynamics simulation studies performed were found in agreement with the PI3Kα inhibitory activity assessments performed experimentally.