bluuebunny/crossref_metadata_2025_split huggingface dataset:
Facile Synthesis of a Fluorinated‐Squaramide Covalent Organic Framework for the Highly Efficient and Broad‐Spectrum Removal of Per‐ and Polyfluoroalkyl Pollutants
Authors: Huang Junlong , Shi Yueru , Huang Guo‐zhang , Huang Shuyao , Zheng Juan , Xu Jianqiao , Zhu Fang , Ouyang Gangfeng 
Published: May 2022

AbstractThe escalating contamination by per‐ and polyfluoroalkyl substances (PFAS) has become an urgent issue in recent years, and the structural diversity of PFAS is the major challenge for effective pollution control. Herein, we take the intrinsic advantages of squaramide and prepare a new two‐dimensional covalent organic framework (FSQ‐1) that exhibits broad‐spectrum PFAS affinity. The tailor‐made linker forges hydrogen‐bond donors, hydrogen‐bond acceptors, and fluorophilic segments into one framework. The obtained material exhibits multipoint and multitype affinity to PFAS with different structures, by which high‐efficient and broad‐spectrum removal of various PFAS can be simultaneously achieved. Notably, the thermodynamic profiles provided by isothermal titration calorimetry (ITC) experiments further illustrate the underlying mechanism of the broad‐spectrum affinity. FSQ‐1 can also be applied for efficient PFAS extraction in trace‐level PFAS analysis.
Jojoba seed powder as eco‐friendly antioxidant for rubber products
Authors: Kandil Heba , Nashar Doaa E. El. , Ward Azza A. , Khalaf Aman I. 
Published: May 2022

AbstractIn search of a new class of antioxidants for rubber products, plant based antioxidants have emerged as a suitable alternative to traditional antioxidants. Therefore, this study aimed to explore the efficiency of jojoba seed meal (JSM) as a natural antioxidant in rubber compounds. Hence, JSM was ground and sieved into a very fine powder (JSMP) where it was applied here in silica‐filled acrylonitrile butadiene rubber (NBR) composite at different loadings. Its effect on the curing, swelling, physico‐mechanical, aging and dielectric properties of the resulting composites was investigated. It was found that the incorporation of JSMP into silica‐NBR composites enhanced the curing, mechanical, and swelling properties compared to those of the composite prepared with the commercial antioxidant 2,2,4‐trimethyl‐1,2‐dihydroquinoline (TMQ) and the optimum concentration of JSMP was 4 phr. This result was proved by SEM which showed that using up to 4 phr of JSMP enhanced the dispersion of silica within the NBR matrix. Aging process results showed that the composites with JSMP exhibited a high resistance to the aging process compared to that with TMQ. Furthermore, the dielectric results revealed that the presence of JSMP caused an increase in the permittivity, dielectric loss, and conductivity of the resulting composites. The conductivity value reached to 8 × 10−7 S/cm which recommends the use of such composites for electrostatic dissipation applications.
The effect of curricular reform on gross anatomy laboratory examination performance: An institutional analysis
Authors: Taylor Melissa A. , Loder Danielle M. , Herr Michael J. , Nichols Richard A. 
Published: May 2022

AbstractMany medical schools have undergone curricular reform recently. With these reforms, time spent teaching anatomy has been reduced, and there has been a general shift to a pass/fail grading system. At Indiana University School of Medicine (IUSM), a new curriculum was implemented in fall 2016. The year‐long human gross anatomy course taught in 2015 was condensed into an integrated, semester‐long course starting in 2016. Additionally, the grading scale shifted to pass/fail. This study examined first‐year medical student performance on anatomy practical laboratory examinations—specifically, among lower‐order (pure identification) questions and higher‐order (function, innervation) questions. Participants included medical students from a pre‐curricular reform cohort (year 2015, 34 students) and two post‐curricular reform cohorts (years 2016, 30 students and 2017, 33 students). A Kruskal–Wallis ANOVA test was used to determine differences of these questions among the three cohorts. Additionally, 40 of the same lower‐order questions that were asked on gross anatomy laboratory examinations from medical student cohort year 2015 and year 2016 were further analyzed using an independent samples t‐test. Results demonstrated that the pre‐curricular reform cohort scored significantly higher on both lower‐order (median = 81, p < 0.001) and higher‐order questions (median = 82.5, p < 0.05) than both post‐curricular reform cohorts. Additionally, when reviewing the selected 40 similar questions, it was found that the pre‐curricular reform cohort averaged significantly higher (82.1 ± 16.1) than the post‐curricular reform cohort from 2016 (69.3 ± 21.8, p = 0.004). This study provides evidence about the impact of curricular reform on medical student anatomical knowledge.
Recent Advances of Chemosensors for Nerve Agents
Authors: Wang Xiao , Wang Xuechuan , Feng Rong , Fu Tao , Jiang Ying , Zhang Jie , Sun Xiaolong 
Published: May 2022

AbstractNerve agents are a branch of organophosphorus (OP) compounds that chemically cause irreversible inhibition of acetylcholinesterase, thereby failing the hydrolysis of acetylcholine, resulting in severe neurological disease and death in organisms. Thus, the unreasonable use of such compounds threatens public and national security, so it is a high demand to establish portable, low‐cost, sensitive, and highly selective methods for their precise detection. In this review, we introduced the recent development of spectroscopy‐based optical chemosensors that aimed for the detection of nerve agents, focusing on the progress made in the molecular design, sensing principle and applications. We conclude this Review by highlighting the current challenges associated with the future development and outlook.
Quadruple Functionalized Pyrazole Pharmacophores by One‐pot Regioselective [3+2] Cycloaddition of Fluorinated Nitrile Imines and Dicyanoalkenes
Authors: Zhou Yin , Gao Cheng‐Feng , Ma Hai , Nie Jing , Ma Jun‐An , Zhang Fa‐Guang 
Published: May 2022

AbstractHere we present a quadruple functionalization approach for the modular construction of fully substituted N1‐aryl 3‐di/trifluoro‐methyl‐4/5‐cyanopyrazole pharmacophores from readily available hydrazonyl chlorides and dicyanoalkenes. The realization of this [3+2] cycloaddition reaction hinges upon the employment of N‐aryl di/trifluoromethyl nitrile imines as the 1,3‐dipoles to bypass external synthetic steps and dicyanoalkenes as the dipolarophiles to tune the regioselectivity. This one‐pot strategy offers access to a divergent library of cyano analogues of prevalent 3‐di/trifluoromethyl pyrazole pharmacophores, among which several compounds have shown potent inhibitory activity towards cyclooxygenase 2 (COX‐2) compared with marketed drug Celecoxib.
The medial prefrontal cortex to the medial amygdala connections may affect the anxiety level in aged rats
Authors: Sotoudeh Narges , Namavar Mohammad Reza , Bagheri Farshid , Zarifkar Asadollah 
Published: May 2022

AbstractBackgroundAging changes brain function and behavior differently in male and female individuals. Changes in the medial prefrontal cortex (mPFC)–medial amygdala (MeA) connectivity affect anxiety‐like behavior.ObjectivesTherefore, this study aimed to investigate the effect of aging and sex on the mPFC–MeA connection and its association with the level of anxiety‐like behavior.MethodsWe divided the Wistar rats into the male and female young rats (2‐3‐month‐old) and male and female old rats (18–20 months old). First, the open field test (OFT) was performed, and then 80 nl of Fluoro‐Gold (FG) was injected by stereotaxic surgery in the right or left MeA. After 10 days, the animals were perfused, their brain removed, coronal sections cut, and the number of FG‐labeled cells in the right and left mPFC of each sample was estimated.ResultsBased on our results, old animals revealed less anxiety‐like behavior than young ones, and young females were less anxious than young males, too. Interestingly, MeA of old male rats received more fibers from the bilateral mPFC than young ones. Also, this connection was stronger in the young females than young males. Altogether, the present study indicated that old individuals had less anxiety‐like behavior and stronger mPFC–MeA connection, and young female rats were less anxious and had a stronger connection of mPFC–amygdala than males of the same age.ConclusionThus, it seems that there is a negative relationship between anxiety levels based on the rat's performance in the OFT apparatus and the mPFC–MeA connection.
Examining organic acid production potential and growth‐coupled strategies in Issatchenkia orientalis using constraint‐based modeling
Authors: Suthers Patrick F. , Maranas Costas D. 
Published: May 2022

AbstractGrowth‐coupling product formation can facilitate strain stability by aligning industrial objectives with biological fitness. Organic acids make up many building block chemicals that can be produced from sugars obtainable from renewable biomass. Issatchenkia orientalis is a yeast strain tolerant to acidic conditions and is thus a promising host for industrial production of organic acids. Here, we use constraint‐based methods to assess the potential of computationally designing growth‐coupled production strains for I. orientalis that produce 22 different organic acids under aerobic or microaerobic conditions. We explore native and engineered pathways using glucose or xylose as the carbon substrates as proxy constituents of hydrolyzed biomass. We identified growth‐coupled production strategies for 37 of the substrate‐product pairs, with 15 pairs achieving production for any growth rate. We systematically assess the strain design solutions and categorize the underlying principles involved.
Anti‐Aging Potential of a Rosa centifolia Stem Extract with Focus on Phytochemical Composition by Bioguided Fractionation
Authors: Dubois Camille , Plainfossé Hortense , Delcroix Maïlys , Trinel Manon , Verger‐Dubois Grégory , Azoulay Stéphane , Burger Pauline , Fernandez Xavier 
Published: May 2022

AbstractAgricultural practices generate huge amounts of by‐products, often simply discarded as waste that must be processed at some cost. The natural by‐products revalorisation as raw material to produce high‐added value ingredients for various industrial sectors may pave the way towards more sustainable industrial practices, via an optimised utilisation of natural resources. Integrating the circular economy precepts to production systems is considered to be a more and more promising management solution to significantly reduce the environmental impact of economic activities. This article discusses the valorisation of Rosa centifolia stem to produce a natural extract with cosmetic anti‐aging potential. To do so, the cosmetic potential of 30 extracts obtained by maceration of agricultural by‐products in a hydroalcoholic solvent was evaluated: their activities, as well as their inhibitory activities of specific enzymes were assessed in vitro to identify those that could be used effectively as anti‐ageing actives while meeting the consumer's expectations in terms of sustainability, naturality, transparency and traceability.[1] A hydroalcoholic extract of R. centifolia stem revealed itself particularly promising due to its valuable anti‐hyaluronidase and antioxidant activities, and its interesting anti‐elastase and anti‐inflammatory potential. The bio‐guided fractionation of this extract allows the characterisation of three major compounds, e. g., isoquercitrin, quercitrin and euscaphic acid, never identified in R. centifolia previously.
Hupertimines A–E, Fawcettimine‐Type Lycopodium Alkaloids from Huperzia serrata
Authors: Deng Zhen‐Tao , Liu Yu‐Chen , Zhu Qin‐Feng , Jiang Shuai , Wu Xing‐De , Zhao Qin‐Shi 
Published: May 2022

AbstractFive new fawcettimine‐type Lycopodium alkaloids, hupertimines A–E (1–5), were discovered from the whole plant of Huperzia serrata, along with two known alkaloids, 8α‐hydroxyphlegmariurine B (6) and 8β‐hydroxyphlegmariurine B (7). The structures of 1–7 were identified through HR‐MS, IR, 1H, 13C, and 2D NMR, and single‐crystal X‐ray diffraction analysis. Structurally, compound 1 was the fourth example of Lycopodium alkaloid with an ether linkage between C‐5 and C‐13 and 2 was the third example of Lycopodium alkaloid with a 5/5/5/5/6 pentacyclic ring system and featuring a 1‐aza‐7‐oxabicyclo[2.2.1]heptane unit. Compounds 1–7 were tested for their BACE1 inhibitory activity. In addition, the correct 1H‐ and 13C‐NMR data for 7 were reported in current study.
Computational targeting of allosteric site of MEK1 by quinoline‐based molecules
Authors: Singh Rahul , Bhardwaj Vijay K. , Purohit Rituraj 
Published: May 2022

AbstractMEK1 is an attractive target due to its role in selective extracellular‐signal‐regulated kinase phosphorylation, which plays a pivotal role in regulating cell proliferation. Another benefit of targeting the MEK protein is its unique hydrophobic pocket that can accommodate highly selective allosteric inhibitors. To date, various MEK1 inhibitors have reached clinical trials against several cancers, but they were discarded due to their severe toxicity and low efficacy. Thus, the development of allosteric inhibitors for MEK1 is the demand of the hour. In this in‐silico study, molecular docking, long‐term molecular dynamics (5 µs), and molecular mechanics Poisson–Boltzmann surface area analysis were undertaken to address the potential of quinolines as allosteric inhibitors. We selected four reference MEK1 inhibitors for the comparative analysis. The drug‐likeness and toxicity of these molecules were also examined based on their ADMET and Toxicity Prediction by Komputer Assisted Technology profiles. The outcome of the analysis revealed that the quinolines (4m, 4o, 4s, and 4n) exhibited better stability and binding affinity while being nontoxic compared to reference inhibitors. We have reached the conclusion that these quinoline molecules could be checked by experimental studies to validate their use as allosteric inhibitors against MEK1.
One‐step purification and regulation of fructose 1,6‐bisphosphatase from the liver of the freeze‐tolerant wood frog, Rana sylvatica
Authors: Varma Anchal , Storey Kenneth B. 
Published: May 2022

AbstractThe wood frog (Rana sylvatica) undergoes numerous changes to its physiology and metabolic processes to survive the winter months, including adaptations that let them endure whole‐body freezing. The regulation of key enzymes of central carbohydrate metabolism in the liver plays a crucial role in mediating the synthesis and maintenance of high concentrations of glucose as a cryoprotectant during freezing as well as glucose reconversion to glycogen after thawing. The present study characterized the regulation of fructose‐1,6‐bisphosphatase (FBPase; EC 3.1.3.11) from wood frog liver during freezing, FBPase being a crucial enzyme regulating gluconeogenesis. Liver FBPase was purified to homogeneity from control and frozen wood frogs by a one‐step chromatographic process. Kinetic and regulatory parameters of the enzyme were investigated and demonstrated a significant decrease in sensitivity to its substrate fructose‐1,6‐bisphosphate in the liver of frozen frogs, as compared with controls. Immunoblotting also revealed freeze‐responsive changes in posttranslational modifications with a significant decrease in serine phosphorylation (by 53%) for FBPase from frozen frogs. Taken together, these results suggest that FBPase is suppressed, and gluconeogenesis is inhibited during freezing. This response acts as an important component of the metabolic survival strategy of the wood frog.
A General Strategy for the Design and Evaluation of Heterobifunctional Tools: Applications to Protein Localization and Phase Separation
Authors: Lackner Rachel M. , O'Connell Will , Zhang Huaiying , Chenoweth David M. 
Published: May 2022

AbstractTo mimic the levels of spatiotemporal control that exist in nature, tools for chemically induced dimerization (CID) are employed to manipulate protein‐protein interactions. Although linker composition is known to influence speed and efficiency of heterobifunctional compounds, modeling or in vitro experiments are often insufficient to predict optimal linker structure. This can be attributed to the complexity of ternary complex formation and the overlapping factors that impact the effective concentration of probe within the cell, such as efflux and passive permeability. Herein, we synthesize a library of modular chemical tools with varying linker structures and perform quantitative microscopy in live cells to visualize dimerization in real‐time. We use our optimized probe to demonstrate our ability to recruit a protein of interest (POI) to the mitochondria, cell membrane, and nucleus. Finally, we induce and monitor local and global phase separation. We highlight the importance of quantitative approaches to linker optimization for dynamic systems and introduce new, synthetically accessible tools for the rapid control of protein localization.
Development of metastatic Merkel cell carcinoma following the excision of same‐sided recurrent auricular melanoma
Authors: Cartwright Jake K. , Snyder Daniel H. , Moreno Francisco G. 
Published: May 2022

AbstractMerkel cell carcinoma (MCC) is a rare neuroendocrine malignancy of the skin that is highly aggressive and often metastasizes early. MCC is diagnosed based on histopathological findings and is most commonly treated with surgical resection, which may be accompanied by chemotherapy and/or radiation. This report describes a 55‐year‐old male patient with the history of recurrent malignant melanoma of the right pinna and subsequent excision. Three years following the excision of melanoma, he presented with a lesion to the right forehead as well as a right‐sided neck mass that were found to be metastatic Merkel cell carcinoma.
Advances towards Cell‐Specific Gene Transfection: A Small‐Molecule Approach Allows Order‐of‐Magnitude Selectivity
Authors: Dirksmeyer Thies , Stahl Paul , Vallet Cecilia , Knauer Shirley , Giese Michael , Schmuck Carsten , Hirschhäuser Christoph 
Published: May 2022

AbstractA transfection vector that can home in on tumors is reported. Whereas previous vectors that allow moderately cell selective gene transfection used larger systems, this small‐molecule approach paved the way for precise structure‐activity relationship optimization. For this, biotin, which mediates cell selectivity, was combined with the potent DNA‐binding motif tetralysine‐guanidinocarbonypyrrol via a hydrophilic linker, thus enabling SAR‐based optimization. The new vector mediated biotin receptor (BR)‐selective transfection of cell lines with different BR expression levels. Computer‐based analyses of microscopy images revealed a preference of one order of magnitude for the BR‐positive cell lines over the BR‐negative controls.
Carboxylate Catalyzed Isomerization of β,γ‐Unsaturated N‐Acetylcysteamine Thioesters**
Authors: Riuttamäki Saara , Laczkó Gergely , Madarász Ádám , Földes Tamás , Pápai Imre , Bannykh Anton , Pihko Petri M. 
Published: May 2022

AbstractWe demonstrate herein the capacity of simple carboxylate salts – tetrametylammonium and tetramethylguanidinium pivalate – to act as catalysts in the isomerization of β,γ‐unsaturated thioesters to α,β‐unsaturated thioesters. The carboxylate catalysts gave reaction rates comparable to those obtained with DBU, but with fewer side reactions. The reaction exhibits a normal secondary kinetic isotope effect (k1H/k1D=1.065±0.026) with a β,γ‐deuterated substrate. Computational analysis of the mechanism provides a similar value (k1H/k1D=1.05) with a mechanism where γ‐reprotonation of the enolate intermediate is rate determining.
Design and Synthesis of Glycosylated Cholera Toxin B Subunit as a Tracer of Glycoprotein Trafficking in Organelles of Living Cells
Authors: Maki Yuta , Kawata Kazuki , Liu Yanbo , Goo Kang‐Ying , Okamoto Ryo , Kajihara Yasuhiro , Satoh Ayano 
Published: May 2022

AbstractGlycosylation of proteins is known to be essential for changing biological activity and stability of glycoproteins on the cell surfaces and in body fluids. Delivering of homogeneous glycoproteins into the endoplasmic reticulum (ER) and the Golgi apparatus would enable us to investigate the function of asparagine‐linked (N‐) glycans in the organelles. In this work, we designed and synthesized an intentionally glycosylated cholera toxin B‐subunit (CTB) to be transported to the organelles of mammalian cells. The heptasaccharide, the intermediate structure of various complex‐type N‐glycans, was introduced to the CTB. The synthesized monomeric glycosyl‐CTB successfully entered mammalian cells and was transported to the Golgi and the ER, suggesting the potential use of synthetic CTB to deliver and investigate the functions of homogeneous N‐glycans in specific organelles of living cells.
Isosteroidal Alkaloids from Fritillaria verticillata Willd. and Their NMR Spectroscopic Characteristics
Authors: Ma Nan , Wang Ya‐Jing , Chen Gang , Meng Chu‐Ren , Guo Chun‐Lin , Lu Yong‐Fu , Dai Si‐Yang , Liu Si‐Xuan , Li Yong‐Fu , Li Chang , Pei Yue‐Hu 
Published: May 2022

Comprehensive SummaryChemical investigation of Fritillaria verticillata Willd. led to the isolation of eight novel isosteroidal alkaloids (1—4, 6, 9—11) and four known alkaloids (5, 7—8, 12), including three unprecedented cis‐fused D/E (13α, 17α) cevanine alkaloids (1—3), one rarely cis‐fused E/F (22α) cevanine alkaloid (6), and one uncommon 5β‐jervine‐type isosteroidal alkaloid featuring a cis‐fused A/B ring moiety (11). In order to establish the structures of 1, the calculated NMR with DP4+ evaluation was applied from the plausible structure candidates. The characteristic proton signals for distinguishing D/E conjunction of cevanine alkaloids were summarized. In addition, some proton and carbon signals α to nitrogen in 6 and 7 are unobservable due to the 14N nuclear quadrupolar relaxation, based on the NMR experiments in different solvents, calculated NMR method and X‐ray technology, their structures were determined. The NMR characteristics of cevanine alkaloids to distinguish orientation of long‐pair on nitrogen atom with β‐hydroxyl at C‐20 were also concluded. The anti‐inflammatory effects of compounds 1 and 4 were evaluated in LPS‐activated RAW 264.7 macrophages. Compound 4 decreased LPS‐induced releases of IL‐1β and IL‐17α in RAW264.7 cells in a dose‐dependent manner. Further mechanistic study revealed that 4 suppressed the phosphorylation of IκBα and p65 subunit to regulate the NF‐κB signaling pathway.