bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transformable Neuropeptide Prodrug with Tumor Microenvironment Responsiveness for Tumor Growth and Metastasis Inhibition of Triple‐Negative Breast Cancer
Authors: Cao Yi , Ge Xiaojiao , Zhu Xueli , Han Yingying , Wang Pin , Akakuru Ozioma Udochukwu , Wu Aiguo , Li Juan 
Published: May 2023

AbstractTriple‐negative breast cancer (TNBC) has the worst prognosis among all breast cancer subtypes due to lack of specific target sites and effective treatments. Herein, a transformable prodrug (DOX‐P18) based on neuropeptide Y analogue with tumor microenvironment responsiveness is developed for TNBC treatment. The prodrug DOX‐P18 can achieve reversible morphological transformation between monomers and nanoparticles through the manipulation of protonation degree in different environments. It can self‐assemble into nanoparticles to enhance the circulation stability and drug delivery efficiency in the physiological environment while transforming from nanoparticles to monomers and being endocytosed into the breast cancer cells in the acidic tumor microenvironment. Further, the DOX‐P18 can precisely be enriched in the mitochondria, and efficiently activated by matrix metalloproteinases. Then, the cytotoxic fragment (DOX‐P3) can subsequently be diffused into the nucleus, generating a sustained cell toxicity effect. In the meanwhile, the hydrolysate residue P15 can assemble into nanofibers to construct nest‐like barriers for the metastasis inhibition of cancer cells. After intravenous injection, the transformable prodrug DOX‐P18 demonstrated superior tumor growth and metastasis suppression with much better biocompatibility and improved biodistribution compared to free DOX. As a novel tumor microenvironment‐responsive transformable prodrug with diversified biological functions, DOX‐P18 shows great potential in smart chemotherapeutics discovery for TBNC.
Enhancing the Performance of Fa‐Based Printable Mesoscopic Perovskite Solar Cells via the Polymer Additive
Authors: Zheng Ziwei , Xia Minghao , Chen Xiayan , Xiao Xuan , Gong Jinwei , Liu Jiale , Du Jiankang , Tao Yiran , Hu Yue , Mei Anyi , Lu Xinhui , Han Hongwei 
Published: May 2023

AbstractThe low cost and scalability advantages of printable mesoscopic perovskite solar cells (p‐MPSCs) are impaired by the issue of limited power conversion efficiency (PCE). Herein, the PCE of p‐MPSCs is improved by introducing the polymer additive polyacrylonitrile (PAN) into the formamidinium (FA)‐based perovskite for crystallization and defect modulation. PAN forms hydrogen bond and coordination bond with halide perovskite through its C≡N group. Such interactions improve the crystallization and filling of FA‐based perovskite in the mesoscopic scaffold and bring a long carrier lifetime by passivating defects. The synergy improves the PCE of p‐MPSCs from 16.80% to 18.33%. Meanwhile, the hydrophobic nature of PAN enhances the device's resistance against moisture. This work demonstrates that the polymer additive is a promising choice for breaking the PCE limit of p‐MPSCs.
Effects of electronic markets on prices, spikes in prices, and price dispersion: A case study of the tea market in India
Authors: Rajkhowa Pallavi , Kornher Lukas 
Published: May 2023

AbstractBuyers and sellers in developing countries are often restricted from accessing distant markets by asymmetric price information and costly searches. Electronic marketplaces can reduce transaction costs and improve market performance. This study uses monthly panel data from 2000 to 2017 and applies a fixed effects approach using Driscoll and Kraay standard errors to address spatial and temporal correlations to provide empirical evidence on the effects of electronic markets on prices, spikes in prices, and price dispersion of an agro‐based commodity in India. The findings indicate that, between 2000 and 2017, the introduction of electronic markets reduced prices and short‐term variability in tea prices by nearly 2%. Moreover, electronic markets initially increased price dispersion between markets by 11%–14%; however, with further reduction in market friction over time, price dispersion reduced by 16%. [EconLit Citations: Q11, Q13].
Copper‐Catalyzed Enantioconvergent Radical C(sp3)−N Cross‐Coupling: Access to α,α‐Disubstituted Amino Acids
Authors: Zhang Yu‐Feng , Wang Jia‐Huan , Yang Ning‐Yuan , Chen Zheng , Wang Li‐Lei , Gu Qiang‐Shuai , Li Zhong‐Liang , Liu Xin‐Yuan 
Published: May 2023

AbstractTransition‐metal catalyzed enantioconvergent cross‐coupling of tertiary alkyl halides with ammonia offers a rapid avenue to chiral unnatural α,α‐disubstituted amino acids. However, the construction of chiral C−N bonds between tertiary‐carbon electrophiles and nitrogen nucleophiles presented a great challenge owing to steric congestion. We report a copper‐catalyzed enantioconvergent radical C−N cross‐coupling of alkyl halides with sulfoximines (as ammonia surrogates) under mild conditions by employing a chiral anionic N,N,N‐ligand with a long spreading side arm. An array of α,α‐disubstituted amino acid derivatives were obtained with good efficiency and enantioselectivity. The synthetic utility of the strategy has been showcased by the elaboration of the coupling products into different chiral α‐fully substituted amine building blocks.
Solar Light Driven H2O2 Production and Selective Oxidations Using a Covalent Organic Framework Photocatalyst Prepared by a Multicomponent Reaction
Authors: Das Prasenjit , Roeser Jérôme , Thomas Arne 
Published: May 2023

AbstractA chemically stable 2D microporous COF (PMCR‐1) was synthesized via the multicomponent Povarov reaction. PMCR‐1 exhibits a remarkable and long‐term stable photocatalytic H2O2 production rate (60 h) from pure and sea water under visible light. The H2O2 production is markedly enhanced when benzyl alcohol (BA) is added as reductant, which is also due to a strong π–π interaction of BA with dangling phenyl moieties in the COF pores introduced by the multicomponent Povarov reaction. Motivated by the concomitant BA oxidation to benzaldehyde during H2O2 formation, the photocatalytic oxidation of various organic substrates such as benzyl amine and methyl sulfide derivatives was investigated. It is shown that the well‐defined micropores of PMCR‐1 enable size‐selective photocatalytic oxidation.
Discovery of the Azaserine Biosynthetic Pathway Uncovers a Biological Route for α‐Diazoester Production
Authors: Van Cura Devon , Ng Tai L. , Huang Jing , Hager Harry , Hartwig John F. , Keasling Jay D. , Balskus Emily P. 
Published: May 2023

AbstractAzaserine is a bacterial metabolite containing a biologically unusual and synthetically enabling α‐diazoester functional group. Herein, we report the discovery of the azaserine (aza) biosynthetic gene cluster from Glycomyces harbinensis. Discovery of related gene clusters reveals previously unappreciated azaserine producers, and heterologous expression of the aza gene cluster confirms its role in azaserine assembly. Notably, this gene cluster encodes homologues of hydrazonoacetic acid (HYAA)‐producing enzymes, implicating HYAA in α‐diazoester biosynthesis. Isotope feeding and biochemical experiments support this hypothesis. These discoveries indicate that a 2‐electron oxidation of a hydrazonoacetyl intermediate is required for α‐diazoester formation, constituting a distinct logic for diazo biosynthesis. Uncovering this biological route for α‐diazoester synthesis now enables the production of a highly versatile carbene precursor in cells, facilitating approaches for engineering complete carbene‐mediated biosynthetic transformations in vivo.
Pnictogen Interactions with Nitrogen Acceptors
Authors: Lin Binzhou , Liu Hao , Karki Ishwor , Vik Erik C. , Smith Mark D. , Pellechia Perry J. , Shimizu Ken D. 
Published: May 2023

AbstractStabilizing nitrogen pnictogen bond interactions were measured using molecular rotors. Intramolecular C=O⋅⋅⋅N interactions were formed in the bond rotation transition states which lowered the rotational barriers and increased the rates of rotation, as measured by EXSY NMR. The pnictogen interaction energies show a very strong correlation with the positive electrostatic potential on nitrogen, which was consistent with a strong electrostatic component. In contrast, the NBO perturbation and pyramidalization analyses show no correlation, suggesting that the orbital‐orbital component is minor. The strongest C=O⋅⋅⋅N pnictogen interactions were comparable to C=O⋅⋅⋅C=O interactions and were stronger than C=O⋅⋅⋅Ph interactions, when measured using the same N‐phenylimide rotor system. The ability of the nitrogen pnictogen interactions to stabilize transition states and enhance kinetic processes demonstrates their potential in catalysis and reaction design.
Multi‐stage Transformations of a Cluster‐Based Metal‐Organic Framework: Perturbing Crystals to Glass‐Forming Liquids that Re‐Crystallize at High Temperature
Authors: Chen Ming‐Zhu , Li Jian , Liao Sheng , Guo Yi‐Hang , Liu Tao , Ma Rui‐Fang , Xie Tian‐Yi , Liu Wei‐Dong , Peng Si‐Xu , Kuang Xiaojun , Yin Zheng , Zhao Yingbo , Zeng Ming‐Hua 
Published: May 2023

AbstractGlassy and liquid state metal–organic frameworks (MOFs) are emerging type of materials subjected to intense research for their rich physical and chemical properties. In this report, we obtained the first glassy MOF that involves metal‐carboxylate cluster building units via multi‐stage structural transformations. This MOF is composed of linear [Mn3(COO)6] node and flexible pyridyl‐ethenylbenzoic linker. The crystalline MOF was first perturbed by vapor hydration and thermal dehydration to give an amorphous state, which can go through a glass transition at 505 K into a super‐cooled liquid. The super‐cooled liquid state is stable through a wide temperature range of 40 K and has the largest fragility index of 105, giving a broad processing window. Remarkably, the super‐cooled liquid can not only be quenched into glass, but also recrystallize into the initial MOF when heated to a higher temperature above 558 K. The mechanism of the multi‐stage structural transformations was studied by systematic characterizations of in situ X‐ray diffraction, calorimetry, rheological, spectroscopic and pair‐distribution function analysis. These multi‐stage transformations not only represent a rare example of high temperature coordinative recognition and self‐assembly, but also provide new MOF processing strategy through crystal‐amorphous‐liquid‐crystal transformations.
Macroscopic and mesoscopic simulation of polystyrene melt in the filling process of injection molding
Authors: Liu Qingsheng , Liu Youqiong , Jiang Chuntao 
Published: May 2023

AbstractIn this article, a fluid flow and heat transfer model which consist of the mass, momentum, and energy conservation equations together with the level set equation and Rolie‐Poly constitution equation is proposed and applied to simulate the rheological behaviors of viscoelastic polystyrene melt in the filling process of injection molding. The macroscopic velocity, pressure, temperature, stress, and mesoscopic molecular conformation of polystyrene melt are shown and analyzed detailedly during the mold filling process. The single‐mode Rolie‐Poly model is employed to describe the stress–strain relationship of polystyrene melt, and the level set method is used to capture the evolution of melt front interface. The governing equations for polymer melt are discretized by the finite volume method on collocated mesh, and solved by the SIMPLE algorithm. Numerical simulations have been implemented based on rectangular cavities with different gate locations, and rectangular and circular inserts. Numerical results indicate that the gate locations, gate numbers, insert size and shape are major factors that affect the rheological behaviors of polystyrene melt in the filling stage of injection molding, and polymer chains experienced higher shear and extension effects in the regions near to mold walls and obstacle. In addition, the length and position of weld lines are discussed in the current study.
Effect of printing parameters on tensile, thermal and structural properties of 3D‐printed poly (ether ketone ketone) PEKK material using fused deposition modeling
Authors: El Magri Anouar , Vaudreuil Sébastien , Ben Ayad Anass , El Hakimi Abdelhadi , El Otmani Rabie , Amegouz Driss 
Published: May 2023

AbstractPoly(ether ketone ketone) (PEKK) is a thermoplastic of the poly(aryl ether ketone) (PAEK) family, with excellent mechanical and thermal performances and high chemical resistance properties. This makes it an appealing material in high‐performance applications as a replacement for poly (ether ether ketone) (PEEK). PEKK was thus selected in this study as a base material for application in 3D printing. The effects of nozzle temperature, layer orientation and layer thickness on the final properties of 3D‐printed PEKK parts were investigated. Furthermore, we assessed the mechanical and morphological features of printed samples through tensile tests and scanning electron microscope, respectively. Thermal properties of samples were also evaluated through DSC and DMA analysis. Optimum printing parameters were found at 0.15 mm layer thickness, 380°C nozzle temperature, and [45/−45°] layer orientation. The printed PEKK samples were annealed at various temperatures to allow the relaxation of residual stress and enhance the degree of crystallinity. Samples annealed for 1 h at 240°C have shown an improved elastic modulus by ~14%, tensile strength by 17%, and glass transition temperature by 17.2°C from the increased by 24% degree of crystallinity.
Synthesis, Anti‐adipogenic, and Insulin‐sensitizing Potential of Benzosuberene‐alkyl Sulfone (BSAS) Analogues
Authors: Goel Abhishek , Yamini  , Gusain Chitralekha , Sharma Bhanu , Purohit Rituraj , Das Pralay , Padwad Yogendra 
Published: May 2023

AbstractObesity and diabetes are the leading cause of mortality worldwide. Promising modulators exhibiting insulin sensitivity and anti‐adipogenic actions are highly desirable. Organic sulfone analogues are prominent structural units present in diverse bioactive molecules. However, sulfones‐derived anti‐adipogenic agents are currently unavailable. Therefore, different benzosuberene‐alkyl sulfone (BSAS) analogues were synthesized inspired by the molecular diversity of the essential oil of Cedrus deodara. Among the series, five BSAS analogues were assessed in‐silico for their binding towards native Peroxisome Proliferator‐Activated Receptor Gamma (PPARγ) and further validated in‐vitro for their anti‐adipogenic potential in differentiated 3T3‐L1 pre‐adipocytes. Their ability to improve insulin sensitivity was also examined in L6 myotubes to ascertain their role in insulin resistance. Our results demonstrated that BSAS‐1 was the partial PPARγ agonist. It has reduced adipogenesis efficiently by downregulating adipogenic genes, resulting in lower triglyceride levels. BSAS‐1 lowered oxidative stress, protected myotubes from insulin resistance, and improved glucose uptake by promoting GLUT4 translocation. Overall, BSAS‐1 has the potential to treat obesity and obesity‐induced insulin resistance.
Harnessing the cooperation between DNA‐PK and cGAS in cancer therapies
Authors: Taffoni Clara , Schüssler Moritz , Vila Isabelle K. , Laguette Nadine 
Published: May 2023

AbstractThe cyclic GMP‐AMP synthase–stimulator of interferon genes (cGAS‐STING) pathway is central for the initiation of anti‐tumoural immune responses. Enormous effort has been made to optimise the design and administration of STING agonists to stimulate tumour immunogenicity. However, in certain contexts the cGAS‐STING axis fuels tumourigenesis. Here, we review recent findings on the regulation of cGAS expression and activity. We particularly focus our attention on the DNA‐dependent protein kinase (DNA‐PK) complex, that recently emerged as an activator of inflammatory responses in tumour cells. We propose that stratification analyses on cGAS and DNA‐PK expression/activation status should be carried out to predict treatment efficacy. We herein also provide insights into non‐canonical functions borne by cGAS and cGAMP, highlighting how they may influence tumourigenesis. All these parameters should be taken into consideration concertedly to choose strategies aiming to effectively boost tumour immunogenicity.
Improvement of enzymatic saccharification by simultaneous pulping of sugarcane bagasse and washing of its cellulose fibers in a batch reactor
Authors: Nogueira Bruno L. , Secchi Argimiro R. , Machado Fabricio , Rodrigues Carime V. S. , Gambetta Rossano , Rodrigues Dasciana S. 
Published: May 2023

AbstractA modification of the conventional batch organosolv process is proposed in a way where the solid biomass remains inside a basket, physically separated from the liquid phase, with the vapor promoting the fractionation of the biomass and the extracted compounds and fragments being washed down to the liquid phase. The modified organosolv process applied to sugarcane bagasse (SB‐M) delivers a rich cellulosic solid phase that after enzymatic hydrolysis leads to a hydrolyzed with approximately 100 g L−1 of glucose. At the same enzymatic hydrolysis conditions, the conventional organosolv process (SB‐C) delivers a hydrolyzed with 80 g L−1 of glucose, while the autohydrolysis process (SB‐A) leads to 55 g L−1 of glucose. These different results are related to the cellulose content: SB‐M (70%), SB‐C (57%), e SB‐A (44%), as well the reduced lignin content in the SB‐M. The novelty of this study is the confirmation that it is possible to degrade lignin from sugarcane bagasse and simultaneously remove its fragments from the cellulose fibers in a batch reactor containing an internal basket. This study describes a simple and rapid protocol for the isolation of the main components of lignocellulosic biomass (cellulose, hemicellulose, and lignin), which may lead to the study of new catalysts for the chemical transformation of these components separately or simultaneously to the step of pretreatment.
Chemical inhibitors of hexokinase‐2 enzyme reduce lactate accumulation, alter glycosylation processing, and produce altered glycoforms in CHO cell cultures
Authors: Naik Harnish Mukesh , Kumar Swetha , Reddy Jayanth Venkatarama , Gonzalez Jacqueline E. , McConnell Brian O. , Dhara Venkata Gayatri , Wang Tiexin , Yu Marcella , Antoniewicz Maciek R. , Betenbaugh Michael J. 
Published: May 2023

AbstractChinese hamster ovary (CHO) cells, predominant hosts for recombinant biotherapeutics production, generate lactate as a major glycolysis by‐product. High lactate levels adversely impact cell growth and productivity. The goal of this study was to reduce lactate in CHO cell cultures by adding chemical inhibitors to hexokinase‐2 (HK2), the enzyme catalyzing the conversion of glucose to glucose 6‐phosphate, and examine their impact on lactate accumulation, cell growth, protein titers, and N‐glycosylation. Five inhibitors of HK2 enzyme at different concentrations were evaluated, of which 2‐deoxy‐
d‐glucose (2DG) and 5‐thio‐
d‐glucose (5TG) successfully reduced lactate accumulation with only limited impacts on CHO cell growth. Individual 2DG and 5TG supplementation led to a 35%–45% decrease in peak lactate, while their combined supplementation resulted in a 60% decrease in peak lactate. Inhibitor supplementation led to at least 50% decrease in moles of lactate produced per mol of glucose consumed. Recombinant EPO‐Fc titers peaked earlier relative to the end of culture duration in supplemented cultures leading to at least 11% and as high as 32% increase in final EPO‐Fc titers. Asparagine, pyruvate, and serine consumption rates also increased in the exponential growth phase in 2DG and 5TG treated cultures, thus, rewiring central carbon metabolism due to low glycolytic fluxes. N‐glycan analysis of EPO‐Fc revealed an increase in high mannose glycans from 5% in control cultures to 25% and 37% in 2DG and 5TG‐supplemented cultures, respectively. Inhibitor supplementation also led to a decrease in bi‐, tri‐, and tetra‐antennary structures and up to 50% lower EPO‐Fc sialylation. Interestingly, addition of 2DG led to the incorporation of 2‐deoxy‐hexose (2DH) on EPO‐Fc N‐glycans and addition of 5TG resulted in the first‐ever observed N‐glycan incorporation of 5‐thio‐hexose (5TH). Six percent to 23% of N‐glycans included 5TH moieties, most likely 5‐thio‐mannose and/or 5‐thio‐galactose and/or possibly 5‐thio‐N‐acetylglucosamine, and 14%–33% of N‐glycans included 2DH moieties, most likely 2‐deoxy‐mannose and/or 2‐deoxy‐galactose, for cultures treated with different concentrations of 5TG and 2DG, respectively. Our study is the first to evaluate the impact of these glucose analogs on CHO cell growth, protein production, cell metabolism, N‐glycosylation processing, and formation of alternative glycoforms.
Downstream process design for Gag HIV‐1 based virus‐like particles
Authors: Lorenzo Elianet , Miranda Laia , Gòdia Francesc , Cervera Laura 
Published: May 2023

AbstractVirus‐like particles‐based vaccines have been gaining interest in recent years. The manufacturing of these particles includes their production by cell culture followed by their purification to meet the requirements of its final use. The presence of host cell extracellular vesicles represents a challenge for better virus‐like particles purification, because both share similar characteristics which hinders their separation. The present study aims to compare some of the most used downstream processing technologies for capture and purification of virus‐like particles. Four steps of the purification process were studied, including a clarification step by depth filtration and filtration, an intermediate step by tangential flow filtration or multimodal chromatography, a capture step by ion exchange, heparin affinity and hydrophobic interaction chromatography and finally, a polishing step by size exclusion chromatography. In each step, the yields were evaluated by percentage of recovery of the particles of interest, purity, and elimination of main contaminants. Finally, a complete purification train was implemented using the best results obtained in each step. A final concentration of 1.40 × 1010 virus‐like particles (VLPs)/mL with a purity of 64% after the polishing step was achieved, with host cell DNA and protein levels complaining with regulatory standards, and an overall recovery of 38%. This work has resulted in the development of a purification process for HIV‐1 Gag‐eGFP virus‐like particles suitable for scale‐up.