bluuebunny/crossref_metadata_2025_split huggingface dataset:
Formulation and Evaluation of Topical Gel Loaded with Fluconazole Niosomes
Authors: Sravan Gajjala , Latha K. , Padmavathi R. , Fatima Maimuna , Sravani C. V. Sai , Saritha M. 
Published: April 2022

Aim: The study aims to formulate and evaluate topical gel-loaded fluconazole niosomes. Fluconazole is a macrolide antibacterial used against various susceptible bacteria. Niosomes have a substantial role in the delivery of drugs as they can reduce toxicity and modify pharmacokinetics and bioavailability. Niosomes which are applied topically improve the deposition of drugs within stratum corneum and epidermis at the same time reducing systemic availability.
Methodology: In current investigation, fluconazole was entrapped into niosomes by thin-film hydration technique with the optimization of various process parameters like entrapment efficiency, vesicle size, shape and in-vitro drug release studies.
Results: Optimized formulations FNS5 and FNT4 prepared with Span-60 and Tween-60 exhibited vesicle sizes of 845.6 nm and 164.2 nm, zeta potential -10.2 mV and -46.4 mV indicating the formulation has good stability. The optimized niosomes were integrated into carbopol 934 and guar gum gels and then extensively characterized for zeta potential and vesicle size.
Conclusion: The study demonstrated that entrapment of drugs into niosomes led to prolonged drug release time, enhanced permeation and drug retention.
Impact of low injected activity on data driven respiratory gating for PET/CT imaging with continuous bed motion
Authors: Meier Joseph G. , Diab Radwan H. , Connor Trevor M. , Mawlawi Osama R. 
Published: April 2022

AbstractData driven respiratory gating (DDG) in positron emission tomography (PET) imaging extracts respiratory waveforms from the acquired PET data obviating the need for dedicated external devices. DDG performance, however, degrades with decreasing detected number of coincidence counts. In this paper, we assess the clinical impact of reducing injected activity on a new DDG algorithm designed for PET data acquired with continuous bed motion (CBM_DDG) by evaluating CBM_DDG waveforms, tumor quantification, and physician's perception of motion blur in resultant images. Forty patients were imaged on a Siemens mCT scanner in CBM mode. Reduced injected activity was simulated by generating list mode datasets with 50% and 25% of the original data (100%). CBM_DDG waveforms were compared to that of the original data over the range between the aortic arch and the center of the right kidney using the Pearson correlation coefficient (PCC). Tumor quantification was assessed by comparing the maximum standardized uptake value (SUVmax) and peak SUV (SUVpeak) of reconstructed images from the various list mode datasets using elastic motion deblurring (EMDB) reconstruction. Perceived motion blur was assessed by three radiologists of one lesion per patient on a continuous scale from no motion blur (0) to significant motion blur (3). The mean PCC of the 50% and 25% dataset waveforms was 0.74 ± 0.18 and 0.59 ± 0.25, respectively. In comparison to the 100% datasets, the mean SUVmax increased by 2.25% (p = 0.11) for the 50% datasets and by 3.91% (p = 0.16) for the 25% datasets, while SUVpeak changes were within ±0.25%. Radiologist evaluations of motion blur showed negligible changes with average values of 0.21, 0.3, and 0.28 for the 100%, 50%, and 25% datasets. Decreased injected activities degrades the resultant CBM_DDG respiratory waveforms; however this decrease has minimal impact on quantification and perceived image motion blur.
Early‐onset leukoencephalomyelopathy due to a biallelic NDUFV1 variant in a mid‐forties patient
Authors: Gschwind Markus , Garcia Segarra Nuria , Schaller André , Bolognini Ramona , Nuoffer Jean‐Marc , Hourez Raphael , Deprez Manuel , Lhermitte Benoit , Maeder Philippe , Tran Christel , Kuntzer Thierry 
Published: April 2022

AbstractWe present a patient who developed, after an early‐onset, a stable course of spastic paraplegia and ataxia for 4 decades and eventually succumbed to two episodes of postinfectious lactic acidosis. Diagnostic workup including muscle biopsy and postmortem analysis, oxymetric analysis, spectrophotometric enzyme analysis, and MitoExome sequencing revealed a necrotizing leukoencephalomyelopathy due to the so far unreported biallelic variant of the NDUFV1 gene (p.(Pro122Leu)). This case extends our understanding of NDUFV1 variants with a 14‐fold longer lifetime than so far reported cases, and will foster sensitivity toward respiratory chain disease also in adult patients with sudden deteriorating neurological deficits.
Bacterial Toxin‐Triggered Release of Antibiotics from Capsosomes Protects a Fly Model from Lethal Methicillin‐Resistant Staphylococcus aureus (MRSA) Infection
Authors: Tonkin Renée L. , Klöckner Anna , Najer Adrian , Simoes da Silva Carolina J. , Echalier Cécile , Dionne Marc S. , Edwards Andrew M. , Stevens Molly M. 
Published: April 2022

AbstractAntibiotic resistance is a severe global health threat and hence demands rapid action to develop novel therapies, including microscale drug delivery systems. Herein, a hierarchical microparticle system is developed to achieve bacteria‐activated single‐ and dual‐antibiotic drug delivery for preventing methicillin‐resistant Staphylococcus aureus (MRSA) bacterial infections. The designed system is based on a capsosome structure, which consists of a mesoporous silica microparticle coated in alternating layers of oppositely charged polymers and antibiotic‐loaded liposomes. The capsosomes are engineered and shown to release their drug payloads in the presence of MRSA toxins controlled by the Agr quorum sensing system. MRSA‐activated single drug delivery of vancomycin and synergistic dual delivery of vancomycin together with an antibacterial peptide successfully kills MRSA in vitro. The capability of capsosomes to selectively deliver their cargo in the presence of bacteria, producing a bactericidal effect to protect the host organism, is confirmed in vivo using a Drosophila melanogaster MRSA infection model. Thus, the capsosomes serve as a versatile multidrug, subcompartmentalized microparticle system for preventing antibiotic‐resistant bacterial infections, with potential applications to protect wounds or medical device implants from infections.
Au@MnSe2 Core–Shell Nanoagent Enabling Immediate Generation of Hydroxyl Radicals and Simultaneous Glutathione Deletion Free of Pre‐Reaction for Chemodynamic‐Photothermo‐Photocatalytic Therapy with Significant Immune Response
Authors: Wang Yuanlin , Sun Xiang , Han Yaqian , Wang Kai , Cheng Lixin , Sun Ye , Besenbacher Flemming , Yu Miao 
Published: April 2022

AbstractAs a typical tumor microenvironment‐responsive therapy, chemodynamic therapy (CDT), producing hydroxyl radicals (•OH) to eliminate tumor cells, has demonstrated great promise. Nevertheless, there are still major challenges: •OH generated from endogenous H2O2 is usually insufficient; the CDT effect is strongly dependent on the pre‐reaction with glutathione. Addressing the challenges, Au@MnSe2 core–shell nanoagent for synergetic chemodynamic‐photothermo‐photocatalytic therapy combined with tetramodal imaging, including magnetic resonance imaging, computed tomography, photoacoustic, and infrared thermal imaging is reported. Distinct from the reported glutathione‐depleting agents, Mn2+ in MnSe2 allows immediate generation of •OH, independent of pre‐reaction. Meanwhile, Mn3+ consumes glutathione by its conversion to Mn2+. The Au‐MnSe2 combination promotes photothermal conversion and photocatalytic reaction, resulting in largely enhanced •OH generation from endogenous H2O2 and significant hyperthermia. Meanwhile, immune response is effectively activated: the intratumoral expression of programmed cell death‐1 and proinflammatory cytokines increase to 4–7 folds; the cytotoxic and helper T lymphocytes cells in the tumor area increase to more than 2.5‐folds; an evident, temporary systemic immunostimulatory effect is demonstrated. High tumor inhibition rate (≈97.3%) and greatly prolonged survival are obtained. This highly‐integrated design coordinating three different therapies with four different imaging modals provide new possibilities for high‐performance theranostic nanoagents.
Mobile Nanobots for Prevention of Root Canal Treatment Failure
Authors: Dasgupta Debayan , Peddi Shanmukh , Saini Deepak Kumar , Ghosh Ambarish 
Published: April 2022

AbstractMillions of root canal treatments fail worldwide due to remnant bacteria deep in the dentinal tubules located within the dentine tissue of human teeth. The complex and narrow geometry of the tubules renders current techniques relying on passive diffusion of antibacterial agents ineffective. Here, the potential of actively maneuvered nanobots is investigated to disinfect dentinal tubules, which can be incorporated during a standard root canal procedure. It is demonstrated that magnetically driven nanobots can reach the depths of the tubules not possible with current clinical practices. Subtle alterations of the magnetic drive allow both deep implantations of the nanobots isotopically distributed throughout the dentine and spatially controlled recovery from selected regions, further supported by numerical simulations. Finally, the integration of bactericidal therapeutic modality with the nanobots is demonstrated, thereby validating the tremendous potential of nanobots in dentistry and nanomedicine in general.
Surface Modification of Poly(ether ether ketone) by Simple Chemical Grafting of Strontium Chondroitin Sulfate to Improve its Anti‐Inflammation, Angiogenesis, Osteogenic Properties
Authors: Zheng Zhe , Hu Liqiu , Ge Yongmei , Qi Jianchao , Sun Qili , Li Zhenjian , Lin Lijun , Tang Bin 
Published: April 2022

AbstractBesides inducing osteogenic differentiation, the surface modification of poly(ether ether ketone) (PEEK) is highly expected to improve its angiogenic activity and reduce the inflammatory response in the surrounding tissue. Herein, strontium chondroitin sulfate is first attempted to be introduced into the surface of sulfonated PEEK (SPEEK‐CS@Sr) based on the Schiff base reaction between PEEK and ethylenediamine (EDA) and the amidation reaction between EDA and chondroitin sulfate (CS). The surface characteristics of SPEEK‐CS@Sr implant are systematically investigated, and its biological properties in vitro and in vivo are also evaluated. The results show that the surface of SPEEK‐CS@Sr implant exhibits a 3D microporous structure and good hydrophilicity, and can steadily release Sr ions. Importantly, the SPEEK‐CS@Sr not only displays excellent biocompatibility, but also can remarkably promote cell adhesion and spread, improve osteogenic activity and angiogenic activity, and reduce the inflammatory response compared to the original PEEK. Therefore, this study presents the surface modification of PEEK material by simple chemical grafting of strontium chondroitin sulfate to improve its angiogenesis, anti‐inflammation, and osteogenic properties, and the as‐fabricated SPEEK‐CS@Sr has the potential to serve as a promising orthopedic implant in bone tissue engineering.
iP & OEIP – Cytokinin Micro Application Modulates Root Development with High Spatial Resolution
Authors: Pařízková Barbora , Antoniadi Ioanna , Poxson David J. , Karady Michal , Simon Daniel T. , Zatloukal Marek , Strnad Miroslav , Doležal Karel , Novák Ondřej , Ljung Karin 
Published: April 2022

AbstractState‐of‐the‐art technology based on organic electronics can be used as a flow‐free delivery method for organic substances with high spatial resolution. Such highly targeted drug micro applications can be used in plant research for the regulation of physiological processes on tissue and cellular levels. Here, for the first time, an organic electronic ion pump (OEIP) is reported that can transport an isoprenoid‐type cytokinin, N6‐isopentenyladenine (iP), to intact plants. Cytokinins (CKs) are plant hormones involved in many essential physiological processes, including primary root (PR) and lateral root (LR) development. Using the Arabidopsis thaliana root as a model system, efficient iP delivery is demonstrated with a biological output – cytokinin‐related PR and LR growth inhibition. The spatial resolution of iP delivery, defined for the first time for an organic compound, is shown to be less than 1 mm, exclusively affecting the OEIP‐targeted LR. Results from the application of the high‐resolution OIEP treatment method confirm previously published findings showing that the influence of CKs may vary at different stages of LR development. Thus, OEIP‐based technologies offer a novel, electronically controlled method for phytohormone delivery that could contribute to unraveling cytokinin functions during different developmental processes with high specificity.
A Review on Printing of Responsive Smart and 4D Structures Using 2D Materials
Authors: Cataldi Pietro , Liu Mufeng , Bissett Mark , Kinloch Ian A. 
Published: April 2022

Abstract3D printing is revolutionizing the manufacturing sector due to the myriad of materials and techniques available. Furthermore, it allows decentralized production sites for both industry and the public. However, it is restricted to static structures that cannot react to external stimuli or adapt to the environment and are, therefore, not suitable for functional and motile parts. Recently, two approaches are proposed to give dynamism to 3D printed structures: the printing of “stimulus‐responsive” (a.k.a. smart) materials and “4D printing,” the first implying features change due to a stimulus while the second indicating the time evolution of properties after a stimulus activation. Nanomaterials, particularly 2D nanomaterials, exhibit a broad and distinctive combination of features. Thus, they are highly effective at enabling this dynamism due to their morphological, optoelectrical, and mechanical properties. This review summarizes recent advances in 3D/4D printing of smart deformable and stimuli‐responsive materials which utilize 2D nanomaterials. The benefits of 2D materials in this framework are summarized, and how to translate their potential into 3D/4D printing is also discussed. The most promising achievements to date are deformable piezoresistive materials for strain sensing, Joule heaters, and actuators. Future advancements and possible upcoming application areas are finally proposed.
Hybrid Chiral MoS2 Layers for Spin‐Polarized Charge Transport and Spin‐Dependent Electrocatalytic Applications
Authors: Bian Zhiyun , Kato Kenichi , Ogoshi Tomoki , Cui Zhou , Sa Baisheng , Tsutsui Yusuke , Seki Shu , Suda Masayuki 
Published: April 2022

AbstractThe chiral‐induced spin selectivity effect enables the application of chiral organic materials for spintronics and spin‐dependent electrochemical applications. It is demonstrated on various chiral monolayers, in which their conversion efficiency is limited. On the other hand, relatively high spin polarization (SP) is observed on bulk chiral materials; however, their poor electronic conductivities limit their application. Here, the design of chiral MoS2 with a high SP and high conductivity is reported. Chirality is introduced to the MoS2 layers through the intercalation of methylbenzylamine molecules. This design approach activates multiple tunneling channels in the chiral layers, which results in an SP as high as 75%. Furthermore, the spin selectivity suppresses the production of H2O2 by‐product and promotes the formation of ground state O2 molecules during the oxygen evolution reaction. These potentially improve the catalytic activity of chiral MoS2. The synergistic effect is demonstrated as an interplay of the high SP and the high catalytic activity of the MoS2 layer on the performance of the chiral MoS2 for spin‐dependent electrocatalysis. This novel approach employed here paves way for the development of other novel chiral systems for spintronics and spin‐dependent electrochemical applications.
Computational Identification and Experimental Demonstration of High‐Performance Methane Sorbents
Authors: Nath Karabi , Ahmed Alauddin , Siegel Donald J. , Matzger Adam J. 
Published: April 2022

AbstractRemarkable methane uptake is demonstrated experimentally in three metal‐organic frameworks (MOFs) identified by computational screening: UTSA‐76, UMCM‐152 and DUT‐23‐Cu. These MOFs outperform the benchmark sorbent, HKUST‐1, both volumetrically and gravimetrically, under a pressure swing of 80 to 5 bar at 298 K. Although high uptake at elevated pressure is critical for achieving this performance, a low density of high‐affinity sites (coordinatively unsaturated metal centers) also contributes to a more complete release of stored gas at low pressure. The identification of these MOFs facilitates the efficient storage of natural gas via adsorption and provides further evidence of the utility of computational screening in identifying overlooked sorbents.
Binaphthyl‐Bridged Pyrenophanes: Intense Circularly Polarized Luminescence Based on aD2Symmetry Strategy
Authors: Takaishi Kazuto , Murakami Sho , Yoshinami Fumiya , Ema Tadashi 
Published: April 2022

AbstractA series ofD2‐symmetric macrocycles composed of alternately linked pyrene and binaphthyl moieties (binaphthyl‐bridged pyrenophanes) have been synthesized. Among them, a pyrenophane possessing ether linkers at the 2,7‐positions of the pyrenes exhibited intense circularly polarized luminescence (CPL) with a |glum| value of 0.053. This value is by far the highest for excimers and was not sensitive to temperature, solvent, or concentration. The CPL originated from a twisting pyrene excimer, with the (R)‐binaphthyl moieties producing a left‐handed twist excimer, which exhibited (−)‐CPL. The electric and magnetic transition dipole moments are perfectly parallel, which is the best relationship for strong CPL.
Dynamic metal–ligand cross‐link promoted mechanically robust and pH responsive hydrogels for shape memory, programmable actuation and resistive sensing application
Authors: Ghosh Ashis , Panda Prachishree , Ganguly Debabrata , Chattopadhyay Santanu , Das Rajat K. 
Published: April 2022

AbstractEmploying Fe3+‐dicarboxylate dynamic metal–ligand cross‐links in combination with low density chemical cross‐links, herein we have developed a mechanically robust and stretchable poly(acrylamide‐co‐maleic acid) hydrogel. The mechanical properties of these hydrogels can be controlled by altering the concentrations of maleic acid and Fe3+ ions. The hydrogels showed high tensile strength (~1–2 MPa), toughness (~3.3 MJ m−3) and stretchability (up to ~5 times of their original length) along with high compressive strength (~13.5 MPa). Because of the dynamic nature of the metal–ligand cross‐links, the hydrogels exhibited good self‐recovery, anti‐fatigue properties and fast self‐healing capacity. Since the Fe3+‐dicarboxylate cross‐links can be dissociated at low pH, the mechanical properties could further be tuned in response to the pH of the medium. This property is exploited to demonstrate shape memory behavior of these hydrogel materials. A temperature responsive bilayer actuator is reported, with poly(N‐isopropylacrylamide) as the thermoresponsive layer and the Fe3+ cross‐linked poly(acrylamide‐co‐maleic acid) hydrogel as the memorizing layer, demonstrating programmable and reversible shape transition. The application of these ionically conducting hydrogels as highly sensitive and flexible resistive strain sensor is also demonstrated.
Quadruply Fused Aromatic Heterocycles toward 4 V‐Class Robust Organic Cathode‐Active Materials
Authors: Hatakeyama‐Sato Kan , Go Choitsu , Akahane Tomoki , Kaseyama Takahiro , Yoshimoto Takuji , Oyaizu Kenichi 
Published: April 2022

AbstractQuadruply fused aromatic heterocycles are examined as 4 V‐class organic cathode‐active materials. A newly synthesized dimethylfluoflavin‐substituted polymer displays reversible charge/discharge at high potentials of 3.5 and 4.1 V (vs. Li/Li+) as a cathode‐active material for organic secondary batteries. The robust redox‐active heterocycles enable the long cycle‐life (>1000) while maintaining the high potential over 4 V. The linear polymer backbone and radical spin configuration in the heterocycles are the keys to enhancing the voltages and the cycle life.
Coupling CRISPR interference with FACS enrichment: New approach in glycoengineering of CHO cell lines for therapeutic glycoprotein production
Authors: Glinšek Katja , Kramer Lovro , Krajnc Aleksander , Kranjc Eva , Pirher Nina , Marušič Jaka , Hellmann Leon , Podobnik Barbara , Štrukelj Borut , Ausländer David , Gaber Rok 
Published: April 2022

AbstractDifficulties in obtaining and maintaining the desired level of the critical quality attributes (CQAs) of therapeutic proteins as well as the pace of the development are major challenges of current biopharmaceutical development. Therapeutic proteins, both innovative and biosimilars, are mostly glycosylated. Glycans directly influence the stability, potency, plasma half‐life, immunogenicity, and effector functions of the therapeutic. Hence, glycosylation is widely recognized as a process‐dependent CQA of therapeutic glycoproteins. Due to the typically high heterogeneity of glycoforms attached to the proteins, control of glycosylation represents one of the most challenging aspects of biopharmaceutical development. Here, we explored a new glycoengineering approach in therapeutic glycoproteins development, which enabled us to achieve the targeted glycoprofile of the Fc‐fusion protein in a fast manner. Coupling CRISPRi technology with lectin‐FACS sorting enabled downregulation of the endogenous gene involved in fucosylation and further enrichment of CHO cells producing Fc‐fusion proteins with reduced fucosylation levels. Enrichment of cells with targeted glycoprofile can lead to time‐optimized clone screening and speed up cell line development. Moreover, the presented approach allows isolation of clones with varying levels of fucosylation, which makes it applicable to a broad range of glycoproteins differing in target fucosylation level.
Synthesis of 6,6‐ and 7,7‐Difluoro‐1‐acetamidopyrrolizidines and Their Oxidation Catalyzed by the Nonheme Fe Oxygenase LolO
Authors: Panth Nabin , Wenger Eliott S. , Krebs Carsten , Bollinger J. Martin , Grossman Robert B. 
Published: April 2022

AbstractLolO, a 2‐oxoglutarate‐dependent nonheme Fe oxygenase, catalyzes both the hydroxylation of 1‐exo‐acetamidopyrrolizidine (AcAP), a pathway intermediate in the biosynthesis of the loline alkaloids, and the cycloetherification of the resulting alcohol. We have prepared fluorinated AcAP analogues to aid in continued mechanistic investigation of the remarkable LolO‐catalyzed cycloetherification step. LolO was able to hydroxylate 6,6‐difluoro‐AcAP (prepared from N,O‐protected 4‐oxoproline) and then cycloetherify the resulting alcohol, forming a difluorinated analogue of N‐acetylnorloline and providing evidence for a cycloetherification mechanism involving a C(7) radical as opposed to a C(7) carbocation. By contrast, LolO was able to hydroxylate 7,7‐difluoro‐AcAP (prepared from 3‐oxoproline) but failed to cycloetherify it, forming (1R,2R,8S)‐7,7‐difluoro‐2‐hydroxy‐AcAP as the sole product. The divergent LolO‐catalyzed reactions of the difluorinated AcAP analogues provide insight into the LolO cycloetherification mechanism and indicate that the 7,7‐difluorinated compound, in particular, may be a useful tool to accumulate and characterize the iron intermediate that initiates the cycloetherification reaction.