bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modeling the Enzyme Specificity by Molecular Cages through Regulating Reactive Oxygen Species Evolution
Authors: Yuan Jiang‐Pei , Guan Zong‐Jie , Lin Heng‐Yu , Yan Bing , Liu Kang‐Kai , Zhou Hong‐Cai , Fang Yu 
Published: May 2023

AbstractMimicking the active site and the substrate binding cavity of the enzyme to achieve specificity in catalytic reactions is an essential challenge. Herein, porous coordination cages (PCCs) with intrinsic cavities and tunable metal centers have proved the regulation of reactive oxygen species (ROS) generating pathways as evidenced by multiple photo‐induced oxidations. Remarkably, in the presence of the Zn4‐μ4‐O center, PCC converted dioxygen molecules from triplet to singlet excitons, whereas the Ni4‐μ4‐O center promoted the efficient dissociation of electrons and holes to conduct electron transfer towards substrates. Accordingly, the distinct ROS generation behavior of PCC‐6‐Zn and PCC‐6‐Ni enables the conversion of O2 to 1O2 and O2⋅−, respectively. In contrast, the Co4‐μ4‐O center combined the 1O2 and O2⋅− together to generate carbonyl radicals, which in turn reacted with the oxygen molecules. Harnessing the three oxygen activation pathways, PCC‐6‐M (M=Zn/Ni/Co) display specific catalytic activities in thioanisole oxidation (PCC‐6‐Zn), benzylamine coupling (PCC‐6‐Ni), and aldehyde autoxidation (PCC‐6‐Co). This work not only provides fundamental insights into the regulation of ROS generation by a supramolecular catalyst but also demonstrates a rare example of achieving reaction specificity through mimicking natural enzymes by PCCs.
An Enzyme‐Loaded Metal–Organic Framework‐Assisted Microfluidic Platform Enables Single‐Cell Metabolite Analysis
Authors: Gao Yanfeng , Wang Yanping , He Bangshun , Pan Yongchun , Zhou Dongtao , Xiong Mengqiu , Song Yujun 
Published: May 2023

AbstractColonization of cancer cells at secondary sites, a decisive step in tumor metastasis, is strongly dependent on the formation of metastatic microenvironments regulated by intrinsic single‐cell metabolism traits. Herein, we report a single‐cell microfluidic platform for high‐throughput dynamic monitoring of tumor cell metabolites to evaluate tumor malignancy. This microfluidic device empowers efficient isolation of single cells (>99 %) in a squashed state similar to tumor extravasation, and employs enzyme‐packaged metal–organic frameworks to catalyze tumor cell metabolites for visualization. The microfluidic evaluation was confirmed by in vivo assays, suggesting that the platform allowed predicting the tumorigenicity of captured tumor cells and screening metabolic inhibitors as anti‐metastatic drugs. Furthermore, the platform efficiently detected various aggressive cancer cells in unprocessed whole blood samples with high sensitivity, showing potential for clinical application.
A Chemoenzymatic Approach To Produce a Cyclic Analogue of the Analgesic Drug MVIIA (Ziconotide)
Authors: Zhou Yan , Harvey Peta J. , Koehbach Johannes , Chan Lai Yue , Jones Alun , Andersson Åsa , Vetter Irina , Durek Thomas , Craik David J. 
Published: May 2023

AbstractZiconotide (ω‐conotoxin MVIIA) is an approved analgesic for the treatment of chronic pain. However, the need for intrathecal administration and adverse effects have limited its widespread application. Backbone cyclization is one way to improve the pharmaceutical properties of conopeptides, but so far chemical synthesis alone has been unable to produce correctly folded and backbone cyclic analogues of MVIIA. In this study, an asparaginyl endopeptidase (AEP)‐mediated cyclization was used to generate backbone cyclic analogues of MVIIA for the first time. Cyclization using six‐ to nine‐residue linkers did not perturb the overall structure of MVIIA, and the cyclic analogues of MVIIA showed inhibition of voltage‐gated calcium channels (CaV2.2) and substantially improved stability in human serum and stimulated intestinal fluid. Our study reveals that AEP transpeptidases are capable of cyclizing structurally complex peptides that chemical synthesis cannot achieve and paves the way for further improving the therapeutic value of conotoxins.
Functionalization of Olefinic C−H Bonds by an Aryl‐to‐Vinyl 1,4‐Nickel Migration/Reductive Coupling Sequence
Authors: Yang Jingjie , Gui Zhuofan , He Yuli , Zhu Shaolin 
Published: May 2023

AbstractAn attractive approach to selective functionalization of remote C−H bonds is a metal/hydride shift/cross‐coupling reaction sequence. Complimentary to the heavily exploited 1,2‐nickel/hydride shift along an sp3 chain, a chain‐walking process, the 1,4‐nickel/hydride shift along an sp2 chain is more complex. Here we report an unprecedented aryl‐to‐vinyl 1,4‐nickel/hydride shift reaction, in which the migratory alkenylnickel species generated in situ is selectively trapped by one of various coupling partners, such as isocyanates, alkyl bromides, aryl chlorides or alkynyl bromides, allowing regio‐ and stereoselective access to trisubstituted alkenes. In contrast to the well‐reported ipso‐aryl coupling reactions, this strategy provides remote alkenyl C−H functionalized products with good yield and with excellent chemo‐, regio‐ and E/Z‐selectivity.
Fabrication of poly(lactic acid), poly(butylene succinate), and poly(hydroxybutyrate) bio‐based and biodegradable blends for application in fused filament fabrication‐based 3D printing
Authors: Sabalina Alisa , Gaidukovs Sergejs , Jurinovs Maksims , Grase Liga , Platnieks Oskars 
Published: May 2023

AbstractThe present study highlights biodegradable and bio‐based polymer blends from poly(lactic acid), poly(butylene succinate) (PBS), and poly(hydroxybutyrate) (PHB) as potential filaments for additive manufacturing. Dog‐bone‐shaped parts were prepared using the fused filament fabrication (FFF) technique. To assess polymer compatibility, interface, and printing performance, vertical and horizontal models were prepared and compared. The ratios of PBS/PLA and PBS/PHB were fixed at 5:5 and 7:3 for this research, respectively. The design concept is based on combining high elastic modulus glassy polymers (PLA and PHB) with soft, ductile PBS. The addition of PBS enhanced thermal processing and rheological properties. Scanning electron microscopy images revealed that the blends produced high‐quality prints while maintaining the original resolution and input parameters. Tensile tests revealed that PBS/PLA blends had significantly higher performance properties than PBS/PHB blends. Vertical prints that coincided with strain direction produced significant plastic deformation in PBS/PLA blends, achieving uniform elongation values of up to 10.4% and elongation at break values exceeding 150%. PBS/PHB blends showed lower compatibility for FFF compared with PBS/PLA blends. Produced bio‐based prints showed an increase in elastic modulus and tensile properties distinct from pure‐polymers; thus, blends have excellent potential for tuning the mechanical properties of the final product.
Chitosan interpenetrating polymer network hydrogels for oil–water and emulsion separation
Authors: Wu Jiangqin , Lv Zaosheng , Lei Yang , Huang Yanfen , Liu Xuegang 
Published: May 2023

AbstractHydrogels have obtained extensive attention in oil–water separation due to their high hydrophilicity and weak viscosity. However, most hydrogels have limited applications due to their subpar mechanical qualities. The interpenetrating network gives the hydrogel material high mechanical properties due to the presence of physical and chemical crosslinking. Hence, polyvinyl alcohol/chitosan/polyacrylamide interpenetrating polymer network hydrogel (HAPC‐Gel) was created in this study. HAPC‐Gel coating filter cloth showed underwater super‐oleophobic (the oil contact angles about 159°) and could stably separate oil–water mixtures in different oil phases and complex environments (acids, bases, salts), and the removal rate is still above 99% after 20 cycles of separation. Furthermore, the water could be divided from the oil‐in‐water emulsion. These results indicate that HAPC‐Gel composites have promising applications in oil–water separation.
Preparation and mechanical properties of natural rubber composites reinforced by modified molybdenum disulfide
Authors: Haq Zaheer Ul , Zia‐ul‐Haq Muhammad , Jiang Yang , Wang Jinyuan , Zhang Yong 
Published: May 2023

AbstractThe filler‐rubber interaction and filler dispersion in natural rubber (NR) composites are important factors in determining mechanical properties. Herein, Molybdenum disulfide (MoS2) and Al2O3‐coated MoS2 nanospheres are incorporated in NR/carbon black composites. The effects of MoS2 and Al2O3‐coated MoS2 on the morphology, thermal and mechanical properties of the NR composites are investigated. The morphology analysis indicates that Al2O3‐coated MoS2 could greatly improve the dispersion of carbon black in NR composites. MoS2 filler and carbon black show a synergetic effect on improving the properties of NR composites, leading to high abrasion resistance, tensile strength, elongation at break and expected dynamic mechanical properties. The thermal conductivity of NR composites increases with increasing the content of MoS2 and Al2O3‐coated MoS2. The thermal stability of the NR composites is also effectively improved by filling MoS2 and Al2O3‐coated MoS2. Furthermore, a small amount of Al2O3‐coated MoS2 significantly improves the abrasion resistance, wet grip and decreases rolling resistance of the composites. Al2O3‐coated MoS2 exhibits its potential application in green tires with good performance.
Preparation and performance study of modified soybean oil polyurethane foam used for soccer equipment
Authors: Zhang Jincheng , Hao Ruoyu , Tian Xiaoke , Hao Tonghui 
Published: May 2023

AbstractSoccer is known as the world's largest sport and has a wide range of players. Most of the materials used in existing football equipment are polyurethane extracted from petrochemical resources, which are gradually reduced and non‐renewable. Finding an alternative new material is an inevitable trend. Soybean oil (SO) was quantitatively transformed into polyols to afford industrially important high resilience flexible polyurethane foam(HR‐PUF). Photoinduced thiol‐ene click chemistry was investigated for the efficient preparation of modified soybean oil polyols (MESO) with primary hydroxyl groups. In order to improve the reaction efficiency and the degree of carbon–carbon double bonds functionalization, reduce reaction time, we have chosen a step‐by‐step method of adding. The effects of different reaction times and [thiol]/[ene] ratios on conversion and degree of functionalization were discussed. It is realized that under room temperature conditions, after 12 h of reaction, the carbon–carbon double bond of SO is almost completely converted and quantitatively converted into a hydroxyl group to a degree of 89%. The corresponding HR‐PUFs were prepared by mixing MESO with L2000 (Polyether Polyol). The effect of the difference in the amount of MESO added to the foam properties was investigated. Through the apparent density and a scanning electron microscope (SEM), it can be concluded that with the amount of MESO added increases, the cell size, opening ratio and the number of cells of HR‐PUF are decreased, the density is increased. Through thermogravimetric analysis (TGA) and dynamic thermomechanical analysis (DMA), it was proved that the thermal stability of the foam increased with the addition of MESO. Through 40% compression strength (CLD40%), ball rebound experiments, and static compression experiment. It is proved that the increase of the addition of MESO, the rebound resilience of HR‐PUF can be improved.
Oxiforms: Unique cysteine residue‐ and chemotype‐specified chemical combinations can produce functionally‐distinct proteoforms
Authors: Cobley James N. 
Published: May 2023

AbstractA single protein molecule with one or more cysteine residues can occupy a plurality of unique residue and oxidation‐chemotype specified proteoforms that I term oxiforms. In binary reduced or oxidised terms, one molecule with three cysteines will adopt one of eight unique oxiforms. Residue‐defined sulfur chemistry endows specific oxiforms with distinct functionally‐relevant biophysical properties (e.g., steric effects). Their emergent complexity means a functionally‐relevant effect may only manifest when multiple cysteines are oxidised. Like how mixing colours makes new shades, combining discrete redox chemistries—colours—can create a kaleidoscope of oxiform hues. The sheer diversity of oxiforms co‐existing within the human body provides a biological basis for redox heterogeneity. Of evolutionary significance, oxiforms may enable individual cells to mount a broad spectrum of responses to the same stimulus. Their biological significance, however plausible, is speculative because protein‐specific oxiforms remain essentially unexplored. Excitingly, pioneering new techniques can push the field into uncharted territory by quantifying oxiforms. The oxiform concept can advance our understanding of redox‐regulation in health and disease.
Smoothed quantile regression for partially functional linear models in high dimensions
Authors: Wang Zhihao , Bai Yongxin , Härdle Wolfgang K. , Tian Maozai 
Published: May 2023

AbstractPractitioners of current data analysis are regularly confronted with the situation where the heavy‐tailed skewed response is related to both multiple functional predictors and high‐dimensional scalar covariates. We propose a new class of partially functional penalized convolution‐type smoothed quantile regression to characterize the conditional quantile level between a scalar response and predictors of both functional and scalar types. The new approach overcomes the lack of smoothness and severe convexity of the standard quantile empirical loss, considerably improving the computing efficiency of partially functional quantile regression. We investigate a folded concave penalized estimator for simultaneous variable selection and estimation by the modified local adaptive majorize‐minimization (LAMM) algorithm. The functional predictors can be dense or sparse and are approximated by the principal component basis. Under mild conditions, the consistency and oracle properties of the resulting estimators are established. Simulation studies demonstrate a competitive performance against the partially functional standard penalized quantile regression. A real application using Alzheimer's Disease Neuroimaging Initiative data is utilized to illustrate the practicality of the proposed model.
A platform for comparing subgroup identification methodologies
Authors: Ruberg Stephen , Zhang Ying , Showalter Hollins , Shen Lei 
Published: May 2023

AbstractSince the advent of the phrase “subgroup identification,” there has been an explosion of methodologies that seek to identify meaningful subgroups of patients with exceptional response in order to further the realization of personalized medicine. However, to perform fair comparison and understand what methods work best under different clinical trials situations, a common platform is needed for comparative effectiveness of these various approaches. In this paper, we describe a comprehensive project that created an extensive platform for evaluating subgroup identification methods as well as a publicly posted challenge that was used to elicit new approaches. We proposed a common data‐generating model for creating virtual clinical trial datasets that contain subgroups of exceptional responders encompassing the many dimensions of the problem or null scenarios in which there are no such subgroups. Furthermore, we created a common scoring system for evaluating performance of purported methods for identifying subgroups. This makes it possible to benchmark methodologies in order to understand what methods work best under different clinical trial situations. The findings from this project produced considerable insights and allow us to make recommendations for how the statistical community can better compare and contrast old and new subgroup identification methodologies.
The effects of length and sequence of gRNA on Cas13b and Cas13d activity in vitro and in vivo
Authors: Liu Yuhui , Jing Ping , Zhou Yi , Zhang Jingyu , Shi Jiahao , Zhang Mengjie , Yang Hua , Fei Jian 
Published: May 2023

AbstractCas13 are the only CRISPR/Cas systems found so far, which target RNA strand while preserving chromosomal integrity. Cas13b or Cas13d cleaves RNA by the crRNA guidance. However, the effect of the characteristics of the spacer sequences, such as the length and sequence preference, on the activity of Cas13b and Cas13d remains unclear. Our study shows that neither Cas13b nor Cas13d has a particular preference for the sequence composition of gRNA, including the sequence of crRNA and its flanking sites on target RNA. However, the crRNA, complementary to the middle part of the target RNA, seems to show higher cleavage efficiency for both Cas13b and Cas13d. As for the length of crRNAs, the most appropriate crRNA length for Cas13b is 22–25 nt and crRNA as short as 15 nt is still functional. Whereas, Cas13d requires longer crRNA, and 22–30 nt crRNA can achieve good effect. Both Cas13b and Cas13d show the ability to process precursor crRNAs. Our study suggests that Cas13b may have a stronger precursor processing ability than Cas13d.There are few in vivo studies on the application of Cas13b or Cas13d in mammals. With the methods of transgenic mice and hydrodynamic injection via tail vein, our study showed that both of them had high knock‐down efficiency against target RNA in vivo. These results indicate that Cas13b and Cas13d have great potential for in vivo RNA operation and disease treatment without damaging genomic DNA.
Microbiological hydrogen (H2) thresholds in anaerobic continuous‐flow systems: Effects of system characteristics
Authors: Karadagli Fatih , Marcus Andrew , Rittmann Bruce E. 
Published: May 2023

AbstractHydrogen (H2) concentrations that were associated with microbiological respiratory processes (RPs) such as sulfate reduction and methanogenesis were quantified in continuous‐flow systems (CFSs) (e.g., bioreactors, sediments). Gibbs free energy yield (ΔǴ ~ 0) of the relevant RP has been proposed to control the observed H2 concentrations, but most of the reported values do not align with the proposed energetic trends. Alternatively, we postulate that system characteristics of each experimental design influence all system components including H2 concentrations. To analyze this proposal, a Monod‐based mathematical model was developed and used to design a gas–liquid bioreactor for hydrogenotrophic methanogenesis with Methanobacterium bryantii M.o.H. Gas‐to‐liquid H2 mass transfer, microbiological H2 consumption, biomass growth, methane formation, and Gibbs free energy yields were evaluated systematically. Combining model predictions and experimental results revealed that an initially large biomass concentration created transients during which biomass consumed [H2]L rapidly to the thermodynamic H2‐threshold (≤1 nM) that triggerred the microorganisms to stop H2 oxidation. With no H2 oxidation, continuous gas‐to‐liquid H2 transfer increased [H2]L to a level that signaled the methanogens to resume H2 oxidation. Thus, an oscillatory H2‐concentration profile developed between the thermodynamic H2‐threshold (≤1 nM) and a low [H2]L (~10 nM) that relied on the rate of gas‐to‐liquid H2‐transfer. The transient [H2]L values were too low to support biomass synthesis that could balance biomass losses through endogenous oxidation and advection; thus, biomass declined continuously and disappeared. A stable [H2]L (1807 nM) emerged as a result of abiotic H2‐balance between gas‐to‐liquid H2 transfer and H2 removal via advection of liquid‐phase.
A field guide for implementing a flipped classroom
Authors: Poulain Pierre , Bertrand Mickael , Dufour Héloise , Taly Antoine 
Published: May 2023

AbstractThe way flipped classrooms are perceived and even practiced by teachers is sometimes approximate. For instance, while the Covid‐19 pandemic has pushed many universities to adopt distance learning, flipped classrooms have often been mentioned as a solution in that context. This inducement maintains a confusion between flipped classrooms and distance learning that might be detrimental for students and teachers. Moreover, embarking on a new pedagogical practice such as flipped classroom could be intimidating and time‐consuming for the newcomer teacher. For these reasons, this article aims to share some tips for implementing a flipped classroom, with examples from biology and biochemistry. Based on our experiences but also on the current scientific literature, we structured these advise around three phases: preparation, implementation, and follow‐up. In the preparation phase, we advise planning early to invert time in class and outside the classroom, but also to say it explicitly, as well as to identify (or optionally create) resources for students to learn in autonomy. In the implementation phase, we suggest to (i) be explicit in the acquisition of knowledge and foster students' autonomy; (ii) explore active learning in class; (iii) develop cooperation and sharing skills; and (iv) differentiate teaching practices to adapt to student needs. Lastly, in the follow‐up phase, we propose to (i) evaluate both student learning and the pedagogical setting; (ii) take care of the logistics and the teacher's posture; (iii) document the flipped classroom, and (iv) share the teaching experience.
Adjuvant chemotherapy non‐adherence, patient‐centered communication, and patient‐level factors in elderly breast and colon cancer patients
Authors: Mitchell Kerri‐Anne R. , Boyle Joseph R. , Juricekova Lenka , Brown Richard F. 
Published: May 2023

AbstractBackgroundWe examined patient‐level factors (patient characteristics, disease and treatment factors, and patient experience), patient‐centered communication (PCCM), and non‐adherence to adjuvant chemotherapy (AC) guidelines among breast and colon cancer patients to inform AC adherence promotion and improve clinical outcomes.MethodsDescriptive statistics for patient‐level factors, PCCM, and AC non‐adherence (primary non‐adherence, non‐persistence at 3 and 6 months) were obtained. Multiple logistic regression models were used to estimate AC non‐adherence after accounting for the identified patient‐level factors.ResultsThe majority of the sample (n = 577) were White (87%), breast cancer patients (87%), and reported PCCM (provider communication score ≥ 90%, 73%, provider communication score = 100%, 58%). All three levels of AC nonadherence were significantly higher in breast cancer patients (69%, 81%, and 89% for primary non‐adherence, and non‐persistence at 3 and 6 months, respectively) than colon cancer patients (43%, 46%, and 62%, respectively). Male sex, survey assistance, and low/average ratings of a personal doctor, specialist, and healthcare were associated with lower PCCM. Older age, breast cancer diagnosis, and diagnosis group following 2007–2009 increased the likelihood of all three levels of AC non‐adherence. Comorbidities and PCCM‐90 were exclusively associated with non‐persistence at 3 months.ConclusionsAdjuvant chemotherapy non‐adherence varied by cancer diagnosis and treatment factors. The relationship between PCCM and AC non‐adherence differed by level of PCCM, time period, and the presence of comorbidities. AC guideline adherence, communication, and value‐concordant treatment should be assessed and compared simultaneously to improve our understanding of their interrelationships.