bluuebunny/crossref_metadata_2025_split huggingface dataset:
Random, de novo, and conserved proteins: How structure and disorder predictors perform differently
Authors: Middendorf Lasse , Eicholt Lars A. 
Published: January 2024

AbstractUnderstanding the emergence and structural characteristics of de novo and random proteins is crucial for unraveling protein evolution and designing novel enzymes. However, experimental determination of their structures remains challenging. Recent advancements in protein structure prediction, particularly with AlphaFold2 (AF2), have expanded our knowledge of protein structures, but their applicability to de novo and random proteins is unclear. In this study, we investigate the structural predictions and confidence scores of AF2 and protein language model‐based predictor ESMFold for de novo and conserved proteins from Drosophila and a dataset of comparable random proteins. We find that the structural predictions for de novo and random proteins differ significantly from conserved proteins. Interestingly, a positive correlation between disorder and confidence scores (pLDDT) is observed for de novo and random proteins, in contrast to the negative correlation observed for conserved proteins. Furthermore, the performance of structure predictors for de novo and random proteins is hampered by the lack of sequence identity. We also observe fluctuating median predicted disorder among different sequence length quartiles for random proteins, suggesting an influence of sequence length on disorder predictions. In conclusion, while structure predictors provide initial insights into the structural composition of de novo and random proteins, their accuracy and applicability to such proteins remain limited. Experimental determination of their structures is necessary for a comprehensive understanding. The positive correlation between disorder and pLDDT could imply a potential for conditional folding and transient binding interactions of de novo and random proteins.
Cover Image
Authors: Su Zhikang , Chen Ding , Huang Jiangyon , Liang Zitian , Ren Wen , Zhang Zeyu , Jiang Qianzhou , Luo Tao , Guo Lvhua 
Published: January 2024

The cover image is based on the Research Article Isoliquiritin treatment of osteoporosis by promoting osteogenic differentiation and autophagy of bone marrow mesenchymal stem cells by Zhikang Su et al., https://doi.org/10.1002/ptr.8032image
Inclusion of deuterated glycopeptides provides increased sequence coverage in hydrogen/deuterium exchange mass spectrometry analysis of SARS‐CoV‐2 spike glycoprotein
Authors: Haynes Christopher A. , Keppel Theodore R. , Mekonnen Betlehem , Osman Sarah H. , Zhou Yu , Woolfitt Adrian R. , Baudys Jakub , Barr John R. , Wang Dongxia 
Published: January 2024

RationaleHydrogen/deuterium exchange mass spectrometry (HDX‐MS) can provide precise analysis of a protein's conformational dynamics across varied states, such as heat‐denatured versus native protein structures, localizing regions that are specifically affected by such conditional changes. Maximizing protein sequence coverage provides high confidence that regions of interest were located by HDX‐MS, but one challenge for complete sequence coverage is N‐glycosylation sites. The deuteration of peptides post‐translationally modified by asparagine‐bound glycans (glycopeptides) has not always been identified in previous reports of HDX‐MS analyses, causing significant sequence coverage gaps in heavily glycosylated proteins and uncertainty in structural dynamics in many regions throughout a glycoprotein.MethodsWe detected deuterated glycopeptides with a Tribrid Orbitrap Eclipse mass spectrometer performing data‐dependent acquisition. An MS scan was used to identify precursor ions; if high‐energy collision‐induced dissociation MS/MS of the precursor indicated oxonium ions diagnostic for complex glycans, then electron transfer low‐energy collision‐induced dissociation MS/MS scans of the precursor identified the modified asparagine residue and the glycan's mass. As in traditional HDX‐MS, the identified glycopeptides were then analyzed at the MS level in samples labeled with D2O.ResultsWe report HDX‐MS analysis of the SARS‐CoV‐2 spike protein ectodomain in its trimeric prefusion form, which has 22 predicted N‐glycosylation sites per monomer, with and without heat treatment. We identified glycopeptides and calculated their average isotopic mass shifts from deuteration. Inclusion of the deuterated glycopeptides increased sequence coverage of spike ectodomain from 76% to 84%, demonstrated that glycopeptides had been deuterated, and improved confidence in results localizing structural rearrangements.ConclusionInclusion of deuterated glycopeptides improves the analysis of the conformational dynamics of glycoproteins such as viral surface antigens and cellular receptors.
SAR Guided Synthesis of Potent, Selective and Artemisinin Synergistic New Imidazole Derivatives with Promising In Vitro Antiplasmodial and In Vivo Antimalarial Activities
Authors: Ratanlal Malavath , Mohankrishnan Dinesh , Jayaram Vankudoth , Sahal Dinkar , Sharma Gangavaram V. M. 
Published: January 2024

AbstractGuided by Structural Activity Relationship (SAR), a series of synthetic tri‐ and tetra‐substituted imidazoles were studied for in vitro antiplasmodial activities against erythrocytic stages of chloroquine sensitive and resistant strains of Plasmodium falciparum using SYBR green I assay. This led to the identification of three potent (IC50 μM) derivatives : Im2 (0.75), Im5 (0.75) and Im22 (0.5). These three lead molecules present unique structural features with a common molecular architecture. Thus, Im2 and Im22 have phenyl rings at positions 4 and 5 of imidazole ring along with n‐hexyl at N3 position, and differ in the C2 substituent (3‐cyclopentyloxy‐4‐methoxy phenyl for Im2) versus naphthyl for Im22. In contrast, positions 4 and 5 in Im5 have pyridyl rings, with unsubstituted N3. Further, curative antimalarial studies with Im2 and Im5 in a Plasmodium berghei (ANKA) infected mouse model of malaria, revealed an increase in average survival time to 28.6±4.2 and 27.4±4 days respectively, as compared to 20.2±2.3 days for untreated control mice. Results of in vitro combination (Im22+Artemisinin) with ΣFIC50: 0.34–0.79, indicated promising synergy and prospects for the use of Im22 as a new constituent in Artemisinin combination therapy (ACT).
Hypochlorous Acid Scavenger Activity of Heteroaryl‐Nitrones. A Combined Experimental and Theoretical Study
Authors: Dimarco Palencia Frida C. D. , Diaz Mario G. , Vega‐Hissi Esteban G. , Gomez Mejiba Sandra E. , Ramirez Dario C. , Garro Martinez Juan C. 
Published: January 2024

AbstractThe HClO scavenging capacity of a group of heteroaryl‐nitrones (HA−N) that contain a substituted five‐membered ring (furan or thiophene) in their structure was studied using experimental and quantum computational methods. Experimentally, it was found that four HA−N showed scavenging activity with IC50 values ranging from 26.15 to 61.20 nM, while two HA−N were found to be inactive. To explain the HClO activity of the analyzed HA−N, we proposed and investigated a reaction mechanism based on a nucleophilic attack by the hypochlorous anion (pKa=7.46) on α‐carbon of each HA−N, taking into account the results obtained by calculating the electrostatic potential. For this purpose, we used the B3LYP functional of the density functional theory (DFT) and the basis set 6‐311+G(d,p) included in the Gaussian 09 program. We calculated the rate constants (k), the HOMO and LUMO energies, and several reactivity indices such as the electronic chemical potential (μ), chemical hardness (η), and global electrophilicity (ω) to establish a quantified relationship with the observed activities. The SAR analysis and the correlation between the rate constants and the global electrophilicity with the HClO scavenging activity allow us to explain the experimental activity presented by the six HA−N analyzed here.
Continuous Flow Synthesis of 4‐methyl‐3‐oxo‐n‐phenyl‐pentanamide
Authors: He Yiguo , Li Mengxiang , Peng Liming , Yang Tong , Zhang Dong , Zhang Yadong 
Published: January 2024

Abstract4‐methyl‐3‐oxo‐n‐phenyl‐pentanamide, as a crucial component of atorvastatin calcium, often generates a large amount of by‐products in conventional synthesis. Here, we first developed a continuous microflow system for the continuous flow synthesis of 4‐methyl‐3‐oxo‐n‐phenyl‐pentanamide. Compared to traditional batch reactors, the reaction time was reduced by 1/12 in the microreactor. Using this device, the kinetic parameters of the reaction were determined, and a reaction kinetics model was established to investigate the effects of channel geometry and material inlet velocity on the entire reaction system. Furthermore, we studied the subsequent reactions and successfully established a fully continuous synthesis device, where the two‐step continuous flow chemical reactions were achieved at 40 minutes and a total yield of 32 %.
Buoyancy‐Driven Micro/‐Nanomotors: From Fundamentals to Applications
Authors: Shukla Ashish Kumar , Bhandari Satyapriya , Mitra Shirsendu , Kim Byungki , Dey Krishna Kanti 
Published: January 2024

AbstractThe progression of self‐powered micro/‐nanomotors (MNMs) has rapidly evolved over the past few decades, showing applications in various fields such as nanotechnology, biomedical engineering, microfluidics, environmental science, and energy harvesting. Miniaturized MNMs transduce chemical/biochemical energies into mechanical motion for navigating through complex fluidic environments with directional control via external forces fields such as magnetic, photonic, and electric stimuli. Among various propulsion mechanisms, buoyancy‐driven MNMs have received noteworthy recognition due to their simplicity, efficiency, and versatility. Buoyancy force‐driven motors harness the principles of density variation‐mediated force to overcome fluidic resistance to navigate through complex environments. Restricting the propulsion in one direction helps to control directional movement, making it more efficient in isotropic solutions. The changes in pH, ionic strength, chemical concentration, solute gradients, or the presence of specific molecules can influence the motion of buoyancy‐driven MNMs as evidenced by earlier reports. This review aims to provide a fundamental and detailed analysis of the current state‐of‐the‐art in buoyancy‐driven MNMs, aiming to inspire further research and innovation in this promising field.
An Ultrasound‐Triggered STING Pathway Nanoagonist for Enhanced Chemotherapy‐Induced Immunogenic Cell Death
Authors: Tian Ye , Tian Hao , Li Bei , Feng Chuanliang , Dai Yunlu 
Published: January 2024

AbstractAlthough chemotherapy has the potential to induce tumor immunotherapy via immunogenic cell death (ICD) effects, how to control the intensity of the immune responses still deserves further exploration. Herein, a controllable ultrasound (US)‐triggered chemo‐immunotherapy nanoagonist is successfully synthesized by utilizing the pH and reactive oxygen species (ROS) dual‐responsive PEG‐polyphenol to assemble sonosensitizer zinc oxide (ZnO) and doxorubicin (DOX). The PZnO@DOX nanoparticles have an intelligent disassembly to release DOX and zinc ions in acidic pH conditions. Notably, US irradiation generates ROS by sonodynamic therapy and accelerates the drug release process. Interestingly, after the PZnO@DOX+US treatment, the injured cells release double‐stranded DNA (dsDNA) from the nucleus and mitochondria into the cytosol. Subsequently, both the dsDNA and zinc ions bind with cyclic GMP‐AMP synthase and activate the stimulator of interferon genes (STING) pathway, resulting in the dendritic cell maturation, ultimately promoting DOX‐induced ICD effects and antigen‐specific T cell immunity. Therefore, chemotherapy‐induced immune responses can be modulated by non‐invasive control of US.
Designing Tough Hydrogel Shells for Glucose Sensing
Authors: Ko Yeounju , Oh Yoonjin , Park Chan Ho , Kim Shin‐Hyun 
Published: January 2024

AbstractConventional hydrogel microcapsules often suffer from inadequate mechanical stability, hindering their use. Here, water‐cored double‐network (DN) hydrogel shells are designed, formed by polyacrylamide and calcium alginate networks using triple‐emulsion templates. These DN hydrogel shells offer robust mechanical stability, optical transparency, and a precisely‐defined cut‐off threshold. The feasibility of this platform is demonstrated through the development of a fluorometric glucose sensor. Glucose oxidase is enclosed within the water core, while a pH‐responsive fluorescent dye is incorporated into the DN shells. Glucose diffuses into the core through the DN shells, where the glucose oxidase converts glucose into gluconic acid, leading to pH reduction and a subsequent decrease in fluorescence intensity of DN shells. Additionally, the pH‐sensitive colorant dissolved in the medium enables visual pH assessment. Thus, glucose levels can be determined using both fluorometric and colorimetric methods. Notably, the DN shells exhibit exceptional stability, enduring intense mechanical stress and cycles of drying and rehydration without leakage. Moreover, the DN shells act as effective barriers, safeguarding glucose oxidase against proteolysis by large disruptive proteins, like pancreatin. This versatile DN shell platform extends beyond glucose oxidase encapsulation, serving as a foundation for various capsule sensors utilizing enzymes and heterogeneous catalysts.
Multi‐dimensional micro/nanorobots with collective behaviors
Authors: Wang Bin , Lu Yuan 
Published: January 2024

AbstractRecently, the collective behavior of micro/nanorobots has shown unprecedented potential in biomedicine and environmental remediation. Collective behavior can work more efficiently, adaptively, and robustly than individual micro/nanorobots. The paradigm of collective behavior needs to be understood in different dimensions, including from individual to cluster, from planar to spatial, and from mono‐functional to multifunctional. In this review, the focus will be on summarizing the achievements of collective control of micro/nanorobot swarms in recent years from different dimensions, in an attempt to better understand how the structure and materials of individuals should be designed, how collective behavior should be implemented, and how robots are functionalized to cope with practical applications under the introduction of collective control. The opportunities and challenges that collective control faces at this stage are illustrated to provide perspectives for its future development.
Effects of flow rate and wastewater concentration on the transformation of nitrogen in sediment–water system of sewage pipelines
Authors: Xie Yuling , Liu Cuiyun , Zhou Changfeng , Wei Haodong , Tao Yang , Zhou Jie 
Published: January 2024

AbstractIn this work, the transformation law of nitrogen in sediment–water system under different flow rates and wastewater concentrations were investigated in a simulated sewage pipeline system. Results showed that the different flow rates and wastewater concentrations in the pipeline caused differences in microbial community in sediments and nitrogen transformation. When the flow rate increased from 0.05 to 0.2 m/s, the scouring effect was enhanced, resulting in higher concentrations of NH4+–N and NO3−–N in the overlying water. At 0.2 m/s, the relative abundance of Clostridium_sensu_stricto_1 in sediments was higher, resulting in a greater conversion of amino acid nitrogen (AAN) to NH4+–N. Meanwhile, many denitrifying bacteria (Trichococcus, Dechloromonas, norank_f__norank_o__Gaiellales, Thiobacillus) had high relative abundance in the sediments, and the denitrification process was common. When the wastewater concentration was high, the nitrification reaction was great in overlying and interstitial water. Moreover, the ammoniation process was great in the sediments, and the variation flux of AAN was large (remarkably reduced).Practitioner Points
AAN transformed to NH4+–N in sediment under different flow rate and concentration.
Scouring was enhanced at 0.2 m/s, increasing nitrogen contents in overlying water.
Difference in microbial community led to more AAN conversion to NH4+–N at 0.2 m/s.
The ammoniation process was greater in sediment at a high concentration of sewage.
NH4+–N migrated from overlying water to sediment at a high concentration of sewage.
Assessing groundwater quality, health risks, and policy implications: A case study of West Medinipur District, West Bengal, India
Authors: Alam Md Anjar , Mailapalli Damodhara Rao , Maheshwari Basant 
Published: January 2024

AbstractGroundwater is a vital freshwater resource for various uses, including drinking, irrigation, and industry needs. The increasing dependence of India on groundwater due to dwindling surface water sources and climate extremes has led to concerns about its availability and quality. This study focuses on the groundwater quality and associated human health risks in the West Medinipur district of West Bengal, India. The region, situated between the Kangsabati and Subarnarekha rivers, faces challenges from anthropogenic activities such as agricultural practices and industrial pollution. A comprehensive analysis of physicochemical parameters was conducted on well water samples collected during the monsoon and post‐monsoon periods. The study examined the suitability of groundwater for drinking and irrigation purposes. Water quality indices were calculated to assess its fitness for human consumption. Despite several parameters meeting the water quality standards, elevated iron (Fe) and ammonia (NH4+) levels were observed, potentially impacting groundwater use for drinking. Similarly, groundwater's suitability for irrigation was evaluated based on parameters like sodium adsorption ratio (SAR) and sodium percentage (Na%). The groundwater types dominated by magnesium bicarbonate and the quality could affect soil structure and crop productivity in certain areas. The elevated levels of Fe and NH4+ showed potential human health risks, indicating the need to mitigate adverse effects on human well‐being through appropriate policy and other interventions. The study highlights the complexity of groundwater quality in the study area. It underscores the necessity for comprehensive water policy and management strategies to safeguard water resources and human health in rural India. The findings emphasize the importance of ongoing monitoring and intervention measures to ensure the sustainability and safety of groundwater for present and future generations.
Accidentally light scalars from large representations
Authors: Brümmer F. , Ferrante G. , Frigerio M. , Hambye T. 
Published: January 2024

Abstract
In models with spontaneous symmetry breaking by scalar fields in large group representations, we observe that some of the scalar masses can be loop-suppressed with respect to the naive expectation from symmetry selection rules. We present minimal models — the SU(2) five-plet and SU(3) ten-plet — with such accidentally light scalars, featuring compact tree-level flat directions lifted by radiative corrections. We sketch some potential applications, from stable relics and slow roll in cosmology, to hierarchy and fine-tuning problems in particle physics.
Fast-Track-Endoprothetik
Authors: Greimel Felix , Schiegl Julia , Meyer Matthias , Grifka Joachim , Maderbacher Günther 
Published: January 2024

Zusammenfassung
Einführung
Wesentliche Bestandteile von Fast-Track- oder Enhanced-Recovery-Programmen in der Endoprothetik sind die Optimierung der interdisziplinär-organisatorischen Abläufe sowie der prä-, intra- und postoperativen Vorgehensweisen im klinischen Alltag. Die frühpostoperative Mobilisation der Patienten ist nach Gelenkersatzoperation von zentraler Bedeutung, mit dem Ziel, Schmerzen und Komplikationen nachweislich zu vermeiden. Dieser Beitrag gibt einen detaillierten Überblick hinsichtlich der zwischenzeitlich zunehmend verbreiteten Fast-Track-Vorgehensweisen. Zudem zeigt er die klinischen Vorteile von Fast-Track für die Hüftendoprothetik im Rahmen eines randomisierten Studiendesigns evidenzbasiert auf.

Material und Methoden
Es wurden 194 Patienten mit primärer HTEP nach einfach verblindeter Randomisierung in zwei Gruppen untersucht: Fast-Track (n = 98) oder konventioneller Behandlungspfad (n = 96). Als primärer Outcomeparameter war die Mobilisierung definiert, gemessen mit dem Timed-Up-and-Go-Test (TUG) in Sekunden. Sekundäre Parameter waren erreichbare Gehstrecke in Metern sowie Schmerzen auf der Numerische Rating-Skala (NRS). Alle Parameter wurden präoperativ und täglich bis zum 6. postoperativen Tag erfasst.

Ergebnisse
Innerhalb der ersten postoperativen Woche wurden keine Komplikationen oder Revisionen verzeichnet. Die Fast-Track-Gruppe zeigte im Vergleich zur konventionellen Gruppe bis zum 6. postoperativen Tag signifikant bessere TUG-Werte sowie Gehstreckenergebnisse (jeweils p < 0,05). Bezüglich der Bewertung von Schmerzen (NRS) zeigte sich kein signifikanter Unterschied (p > 0,05).

Fazit
Die Anwendung von Fast-Track-Konzepten in der Hüftendoprothetik kann evidenzbasiert die klinischen Ergebnisse verbessern. Diese prospektive, einfach verblindete randomisierte kontrollierte Studie konnte ein sehr gutes kurzfristiges Ergebnis mit vergleichbaren Schmerzen nach Fast-Track-HTEP im Vergleich zu einem konventionellen Behandlungspfad aufzeigen. Fast-Track-Konzepte sind hochwirksam in Bezug auf Frühmobilisierung und klinisches Ergebnis – ohne in der Frühphase ein höheres Komplikationsrisiko einzugehen.

Graphic abstract
Die eigene professionelle Altersversorgung sichern – der Rettungsdienst als mobiler Sozial- und Gesundheitsdienstleister
Authors: Redelsteiner Christoph 
Published: January 2024

ZusammenfassungDer Rettungsdienst hat sich auf operativer Ebene im Einsatzgeschehen u. a. durch den demografischen Wandel und Leistungsreduktionen im Sozial- und Gesundheitswesen von einer Notfallversorgungseinrichtung zu einem rund um die Uhr erreichbarem sozialmedizinischen Dienstleister verändert. Die Mehrzahl der Fälle stellen Menschen mit chronischen, subakuten Erkrankungen und psychosozialen Herausforderungen dar. Eine Verweisung auf pflegerische, hausärztliche oder soziale Dienste wird nur dann erfolgreich sein, wenn diese auch verlässlich durch die Leitstellen disponierbar sind und keine Fallabweisung und somit Rückdelegation an die Leitstelle durchführen können.Der Leitstelle kommt somit eine fachliche Beratungs-, Lenkungs- und Maklerfunktion zu, die idealerweise auch auf Ressourcen wie Acute Community Nurses, Gemeinde-Notfallsanitäter und Akutsozialarbeiter zurückgreifen kann. Damit können für einen Teil der Anliegen passender und zielgerichtetere Strategien angewandt werden und der Rettungsdienst entlastet werden. Auf planerischer und strategischer Ebene muss dieser Paradigmenwechsel in Bereichen wie Ausbildungsschwerpunkte, Leitstellenberatung, Einsatztaktik, eingesetzte Berufsgruppen noch mit vollzogen werden.Diese Änderungen gilt es als Chance zu einer fairen und gleichmässigen sozialen, medizinischen und pflegerischen Versorgung seitens der Führungskräfte, Mitarbeiter und Kostenträger des Rettungswesen aktiv mitzugestalten.
Optimization methods and algorithms
Authors: Biró Péter , Bozóki Sándor , Király Tamás , Kristály Alexandru 
Published: January 2024

AbstractRecent results of three areas, pickup and delivery, optimal mass transportation, matching under preferences are highlighted. The topics themselves have been selected from the active research fields of Hungarian Operations Research. We also provide a short summary of selected research results from the 34th Hungarian Operations Research Conference, held in Cegléd, Hungary, August 31–September 2, 2021.