bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiple diverse ligands binding at a single protein site: A matter of pre‐existing populations
Authors: Ma Buyong , Shatsky Maxim , Wolfson Haim J. , Nussinov Ruth 
Published: July 2002

AbstractHere, we comment on the steadily increasing body of data showing that proteins with specificity actually bind ligands of diverse shapes, sizes, and composition. Such a phenomenon is not surprising when one considers that binding is a dynamic process with populations in equilibrium and that the shape of the binding site is strongly influenced by the molecular partner. It derives implicitly from the concept of populations. All proteins, specific and nonspecific, exist in ensembles of substates. If the library of ligands in solution is large enough, favorably matching ligands with altered shapes and sizes can be expected to bind, with a redistribution of the protein populations. Point mutations at spatially distant sites may exert large conformational rearrangements and hinge effects, consistent with mutations away from the binding site leading to population shifts and (cross‐)drug resistance. A similar effect is observed in protein superfamilies, in which different sequences with similar topologies display similar large‐scale dynamic motions. The hinges are frequently at analogous sites, yet with different substrate specificity. Similar topologies yield similar conformational isomers, although with different distributions of population times, owing to the change in the conditions, that is, the change in the sequences. In turn, different distributions relate to binding of different sizes and shapes. Hence, the binding site shape and size are defined by the ligand. They are not independent entities of fixed proportions and cannot be analyzed independently of the binding partner. Such a proposition derives from viewing proteins as dynamic distributions, presenting to the incoming ligands a range of binding site shapes. It illustrates how presumably specific binding molecules can bind multiple ligands. In terms of drug design, the ability of a single receptor to recognize many dissimilar ligands shows the need to consider more diverse molecules. It provides a rationale for higher affinity inhibitors that are not derived from substrates at their transition states and indicates flexible docking schemes.
Checkpoint Nano‐PROTACs for Activatable Cancer Photo‐Immunotherapy
Authors: Zhang Chi , Xu Mengke , He Shasha , Huang Jingsheng , Xu Cheng , Pu Kanyi 
Published: November 2022

AbstractCheckpoint immunotherapy holds great potential to treat malignancies via blocking the immunosuppressive signaling pathways, which however suffers from inefficiency and off‐target adverse effects. Herein, checkpoint nano‐proteolysis targeting chimeras (nano‐PROTACs) in combination with photodynamic tumor regression and immunosuppressive protein degradation to block checkpoint signaling pathways for activatable cancer photo‐immunotherapy are reported. These nano‐PROTACs are composed of a photosensitizer (protoporphyrin IX, PpIX) and an Src homology 2 domain‐containing phosphatase 2 (SHP2)‐targeting PROTAC peptide (aPRO) via a caspase 3‐cleavable segment. aPRO is activated by the increased expression of caspase 3 in tumor cells after phototherapeutic treatment and induces targeted degradation of SHP2 via the ubiquitin‐proteasome system. The persistent depletion of SHP2 blocks the immunosuppressive checkpoint signaling pathways (CD47/SIRPα and PD‐1/PD‐L1), thus reinvigorating antitumor macrophages and T cells. Such a checkpoint PROTAC strategy synergizes immunogenic phototherapy to boost antitumor immune response. Thus, this study represents a generalized PROTAC platform to modulate immune‐related signaling pathways for improved anticancer therapy.
Microenvironment‐Based Diabetic Foot Ulcer Nanomedicine
Authors: Huang Fang , Lu Xiangyu , Yang Yan , Yang Yushan , Li Yongyong , Kuai Le , Li Bin , Dong Haiqing , Shi Jianlin 
Published: November 2022

AbstractDiabetic foot ulcers (DFU), one of the most serious complications of diabetes, are essentially chronic, nonhealing wounds caused by diabetic neuropathy, vascular disease, and bacterial infection. Given its pathogenesis, the DFU microenvironment is rather complicated and characterized by hyperglycemia, ischemia, hypoxia, hyperinflammation, and persistent infection. However, the current clinical therapies for DFU are dissatisfactory, which drives researchers to turn attention to advanced nanotechnology to address DFU therapeutic bottlenecks. In the last decade, a large number of multifunctional nanosystems based on the microenvironment of DFU have been developed with positive effects in DFU therapy, forming a novel concept of “DFU nanomedicine”. However, a systematic overview of DFU nanomedicine is still unavailable in the literature. This review summarizes the microenvironmental characteristics of DFU, presents the main progress of wound healing, and summaries the state‐of‐the‐art therapeutic strategies for DFU. Furthermore, the main challenges and future perspectives in this field are discussed and prospected, aiming to fuel and foster the development of DFU nanomedicines successfully.
Substituent‐controlled aggregate luminescence: Computational unraveling of S1/S0 surface crossing
Authors: Yin Ping‐An , Ou Qi , Peng Qian , Shuai Zhigang 
Published: November 2022

AbstractWe computationally investigated the molecular aggregation effects on the excited state deactivation processes by considering both the direct vibrational relaxation and the S0/S1 surface crossing, that is, the minimum energy conical intersection (MECI). Taking classical AIEgens bis(piperidyl)anthracenes (BPAs) isomers and the substituted silole derivatives as examples, we show that the deformation of MECI always occurs at the atom with greater hole/electron overlap. Besides, the energetic and structural changes of MECI caused by substituent has been investigated. We find that effective substituent such as the addition of the electron‐donating groups, which can polarize the distribution of hole/electron density of molecules, will lead to the pyramidalization deformation of MECI occurring at the substituent position and simultaneously reduce the required energy to reach MECI. And MECI is sterically restricted by the surrounding molecules in solid phase, which remarkably hinders the non‐radiative decay through surface crossing. Through quantitative computational assessments of the fluorescence quantum efficiency for both solution and solid phases, we elucidate the role of MECI and its dependence on the substitutions through pyramidalization deformation, which give rise to the aggregation‐induced emission (AIE) phenomenon for 9,10‐BPA, to aggregation‐enhance emission (AEE) behavior for 1,4‐BPA, and to conventional aggregation‐caused quenching (ACQ) for 1,5‐BPA. We further verify such mechanism for siloles, for which we found that the substitutions do not change the AIE behavior. Our findings render a general molecular design approach to manipulating the aggregation effect for optical emission.
Alkaline‐Earth Metal Mediated Benzene‐to‐Biphenyl Coupling
Authors: Mai Jonathan , Morasch Michael , Jędrzkiewicz Dawid , Langer Jens , Rösch Bastian , Harder Sjoerd 
Published: November 2022

AbstractComplex [(DIPePBDI)Ca]2(C6H6), with a C6H62−dianion bridging two Ca2+ions, reacts with benzene to yield [(DIPePBDI)Ca]2(biphenyl) with a bridging biphenyl2−dianion (DIPePBDI=HC[C(Me)N‐DIPeP]2; DIPeP=2,6‐CH(Et)2‐phenyl). The biphenyl complex was also prepared by reacting [(DIPePBDI)Ca]2(C6H6) with biphenyl or by reduction of [(DIPePBDI)CaI]2with KC8in presence of biphenyl. Benzene‐benzene coupling was also observed when the deep purple product of ball‐milling [(DIPPBDI)CaI(THF)]2with K/KI was extracted with benzene (DIPP=2,6‐CH(Me)2‐phenyl) giving crystalline [(DIPPBDI)Ca(THF)]2(biphenyl) (52 % yield). Reduction of [(DIPePBDI)SrI]2with KC8gave highly labile [(DIPePBDI)Sr]2(C6H6) as a black powder (61 % yield) which reacts rapidly and selectively with benzene to [(DIPePBDI)Sr]2(biphenyl). DFT calculations show that the most likely route for biphenyl formation is a pathway in which the C6H62−dianion attacks neutral benzene. This is facilitated by metal‐benzene coordination.
Strong Coupling of Chiral Frenkel Exciton for Intense, Bisignate Circularly Polarized Luminescence
Authors: Li Minghao , Nizar Shahana , Saha Sudipta , Thomas Anoop , Azzini Stefano , Ebbesen Thomas W. , Genet Cyriaque 
Published: November 2022

AbstractWe show that chiral Frenkel excitons yield intense circularly polarized luminescence with an intrinsic dissymmetry factor in emission glum as high as 0.08. This outstanding value is measured through thin films of cyanine J‐aggregates that form twisted bundles. Our measurements, obtained by a Mueller polarization analysis, are artifact‐free and reveal a quasi‐perfect correlation between the dissymmetry factors in absorption, gabs, and in emission glum. We interpret the bisignate dissymmetry factors as the signature of a strong coupling between chiral Frenkel excitons longitudinally excited along the bundles. We further resolve by polarimetry analysis the split in energy between the excited states with a Davydov splitting as small as 28 meV. We finally show the anti‐Kasha nature of the chiral emission bands with opposite optical chirality. These mirror‐imaged emissive chiroptical features emerge from the structural rigidity of the bundles that preserves the ground‐ and excited‐state chirality.
Biosynthesis of Hybrid Neutral Lipids with Archaeal and Eukaryotic Characteristics in Engineered Saccharomyces cerevisiae
Authors: Zhang Jianzhi , Li Tuo , Hong Zhilai , Ma Chenfei , Fang Xiaoting , Zheng Fengfeng , Teng Wenkai , Zhang Chuanlun , Si Tong 
Published: November 2022

AbstractDiscovery of the Asgard superphylum of archaea provides new evidence supporting the two‐domain model of life: eukaryotes originated from an Asgard‐related archaeon that engulfed a bacterial endosymbiont. However, how eukaryotes acquired bacterial‐like membrane lipids with a sn‐glycerol‐3‐phosphate (G3P) backbone instead of the archaeal‐like sn‐glycerol‐1‐phosphate (G1P) backbone remains unknown. In this study, we reconstituted archaeal lipid production in Saccharomyces cerevisiae by expressing unsaturated archaeol‐synthesizing enzymes. Using Golden Gate cloning for pathway assembly, modular gene replacement was performed, revealing the potential biosynthesis of both G1P‐ and G3P‐based unsaturated archaeol by uncultured Asgard archaea. Unexpectedly, hybrid neutral lipids containing both archaeal isoprenoids and eukaryotic fatty acids were observed in recombinant S. cerevisiae. The ability of yeast and archaeal diacylglycerol acyltransferases to synthesize such hybrid lipids was demonstrated.
Cycling a Tether into Multiple Rings: Pt‐Bridged Macrocycles for Differentiated Guest Recognition, Pseudorotaxane Transformations, and Guest Capture and Release
Authors: Soto Miguel A. , Carta Veronica , Suzana Ingrid , Patrick Brian O. , Lelj Francesco , MacLachlan Mark J. 
Published: November 2022

AbstractMacrocycle engineering is a key topic in supramolecular chemistry. When synthesizing a ring, one can obtain either complex mixtures of macrocycles of different sizes or a single ring if a template is utilized. Here, we unite these approaches along with post‐synthetic modifications to transform a single tether into multiple rings—up to five per tether. The macrocycles contain two bridged phenylpyridine ligands that are connected through a Pt atom, which defines the rings’ shape, size, and host activity. All rings undergo redox reactions (between PtII and PtIV) that allow for large conformational changes. Their reactivity, together with their host performance, is a convenient way to control the capture and release of guests, to mediate ring transformations, and to control pseudorotaxane‐to‐pseudorotaxane conversions. This novel approach could serve to assemble other libraries of small ring molecules, create cyclic polymers bridged by responsive‐at‐metal nodes, and produce processable mechanically interlocked molecules.
Enhanced ethanol pervaporative selectivity of polydimethylsiloxane membranes by incorporating with graphene oxide@silica core‐shell structure
Authors: Peng Ping , Lan Yongqiang , Xu Amei , Liu Mengyao 
Published: November 2022

AbstractA graphene oxide@silica core‐shell structure (GO@silica) was prepared and embedded into the polydimethylsiloxane (PDMS) to fabricate mixed matrix membranes (MMMs). Meanwhile, (3,3,3‐trifluoropropyl)triethoxysilane (TFTS) was employed to improve the compatibility between PDMS and GO@silica and create a hydrophobic membrane surface for improving the ethanol pervaporative performance. The scanning electron microscope (SEM) result showed that the resultant PDMS/GO@silica MMMs were smooth and defect‐free. Meanwhile, the increase in hydrophobicity, swelling degree, and PV performance was achieved because of the incorporation of the modified GO@silica. The maximal separation factor of 11.43 coupled with a high permeation flux of 223 g·m−2·h−1was observed when separating a 10 wt. % ethanol/water mixture at 30°C. Moreover, the MMMs displayed a stable PV performance during a 168‐h continuous operation.
Joint Studies of Spin Frustration Induced by Doping Small ZnSe Nanoparticles with Fe Atoms
Authors: Gutsev Lavrenty G. , Bindra Jasleen K. , Strouse Geoffrey F. , Aldoshin Sergey M. , Gutsev Gennady L. 
Published: November 2022

AbstractAs a 1.8 nm ZnSe nanocrystal is progressively doped with 1%, 5%, and 10% Fe, it shows a progressive change in its magnetic properties from a superparamagnetic FM‐dominated exchange type to an onset of AFM exchange with evidence of spin frustration. Magnetization measurements allow to obtain exchange coupling constants that are compared to the results of a Broken‐Symmetry Density Functional Theory (BS‐DFT) model of a doped (ZnSe)34 cluster. DFT shows a capability to reproduce the experimental pattern of the increasing influence of AFM exchange as doping concentration increases. The material phase segregates at the edges where strained rhombic surface sites are the preferred doping sites of iron. Large concentrations of iron leads to the formation of Fe clusters and complex exchange patterns that result in spin frustration in some iron trimers but none in the others. The spin frustration of these complex systems by assuming mirror symmetry of the sites when fitting by using BS‐DFT formalism is classified and analyzed. While some individual J constants obtained have significant errors, the averaged exchange constants are generally in good agreement with our experimental data.
How Porosity Affects the Performance of Piezoelectric Energy Harvesters and Sensors
Authors: Hassanpour Amiri Morteza , Asadi Kamal 
Published: November 2022

AbstractPorosity has been experimentally employed to enhance the power output of piezoelectric energy harvesters. However, porosity lowers the breakdown voltage of the piezoelectric layer and hampers the pre‐poling of the piezoelectric, which is needed to achieve enhanced performance. Furthermore, the effect of fractional porosity and pore size on the poling conditions and the enhanced power output of the comprising piezoelectric harvesters is not yet known. Here, through finite‐element method simulations, it is shown that the enhanced performance of the porous piezoelectric harvesters is independent of the size and distribution of the pores and only depends on the fractional porosity. Moreover, it is shown that the presence of pores yields the emergence of local stress hot spots that are mainly responsible for improved performance. Moreover, it is suggested that the breakdown issue of the porous piezoelectric layers can be mitigated by poling the structures in a vacuum using electric fields below the threshold field for electron field emission from the piezoelectric layer.
Optimal tracking performance of communication‐constrained systems under energy constraints
Authors: Zhang Yuyao , Zhan Xisheng , Wu Jie , Yan Huaicheng 
Published: November 2022

AbstractThis paper investigates the optimal tracking performance of systems by considering packet dropouts, additive white Gaussian noise(AWGN), and coding under energy constraints. The optimal tracking performance of communication‐constrained systems is obtained by spectral decomposition and partial factorization. The results show that the optimal tracking performance of the system is related to intrinsic properties such as non‐minimum phase zeros and unstable poles. What's more, encoding, data loss rate, and AWGN are also able to affect the performance of the system. Finally, the correctness of the results is verified by specific examples.
Audiovisual temporal binding window narrows with age in autistic individuals
Authors: Ainsworth Kirsty , Bertone Armando 
Published: November 2022

AbstractAtypical sensory perception has been recognized in autistic individuals since its earliest descriptions and is now considered a key characteristic of autism. Although the integration of sensory information (multisensory integration; MSI) has been demonstrated to be altered in autism, less is known about how this perceptual process differs with age. This study aimed to assess the integration of audiovisual information across autistic children and adolescents. MSI was measured using a non‐social, simultaneity judgment task. Variation in temporal sensitivity was evaluated via Gaussian curve fitting procedures, allowing us to compare the width of temporal binding windows (TBWs), where wider TBWs indicate less sensitivity to temporal alignment. We compared TBWs in age and IQ matched groups of autistic (n = 32) and neurotypical (NT; n = 73) children and adolescents. The sensory profile of all participants was also measured. Across all ages assessed (i.e., 6 through 18 years), TBWs were negatively correlated with age in the autistic group. A significant correlation was not found in the NT group. When compared as a function of child (6–12 years) and adolescent (13–18 years) age groups, a significant interaction of group (autism vs NT) by age group was found, whereby TBWs became narrower with age in the autistic, but not neurotypical group. We also found a significant main effect of age and no significant main effect of group. Results suggest that TBW differences between autistic and neurotypical groups diminishes with increasing age, indicating an atypical developmental profile of MSI in autism which ameliorates across development.
Cancer‐testis gene STK31 is regulated by methylation and promotes the development of pancreatic cancer
Authors: Gao Hao , Cai Baobao , Lu Zipeng , Wang Guangfu , Gao Yong , Miao Yi , Jiang Kuirong , Zhang Kai 
Published: November 2022

AbstractBackgroudPancreatic cancer (PC) is a highly invasive malignancy with extremely poor prognosis. STK31 has been identified as a cancer‐testis (CT) gene, but its function in PC has not been elucidated well.MethodsThe effect of STK31 on cell proliferation, migration and invasion was investigated by in vitro and in vivo experiments and total RNA sequencing and targeted bisulfite sequencing was applied to explore the potential regulatory mechanisms of STK31 in PC.ResultsBy analysis of tissue samples and the clinicopathologic features, we found that STK31 was reactivated in PC and associated with poor prognosis. In addition, the vitro and vivo studies indicated that STK31 could promote PC progression by facilitating cell proliferation, migration and invasion, and the indication. Targeted Bisulfite Sequencing showed that STK31 was regulated by methylation. Furthermore, the results of total RNA sequencing suggested that STK31 was closely related to signal transduction, metabolism, and the immune system.ConclusionsThis study demonstrates that STK31, as a CT gene, can promote the development of PC and is regulated by methylation. STK31 could be considered as a potential therapeutic target for PC.
When quantity takes on a quality of its own: A retrospective exploration of the lived experience of cumulative harm
Authors: Bryce India , Beccaria Gavin , McIlveen Peter , Du Preez Jan 
Published: November 2022

AbstractCumulative harm refers to the effects of an accumulation of adverse experiences in a child's life. An understanding of cumulative harm and its integration into practice frameworks, legislation, policy and service delivery is hailed as an imperative of critical social concern and has been demanded by researchers, practitioners, commissioners and coroners. However, there is minimal research exploring the nature and defining qualities of cumulative harm and the implications for individuals in adulthood. The present study uses interpretive phenomenological analysis to explore the lived experiences of cumulative harm in a sample of helping professionals. The findings of this study contribute knowledge to the definitions and typologies of child abuse, neglect and adversity, and draw on empirical evidence to broaden the scope of what constitutes childhood maltreatment. Further, the findings catalyse a paradigm shift that positions accumulation as a distinct harm type and clarifies the qualities which embody cumulative harm: persistent dysfunction, dysregulation, disadvantage and disconnection.
Anticancer Effect of Chlorambucil Enhanced by Chiral Phthalidyl Promoiety
Authors: Zhang Long , Cheng Yisa , Liu Ying‐Guo , Chen Xingkuan , Liu Hongmei 
Published: November 2022

AbstractPhthalidyl promoiety has been used in several drugs, but they were all marketed in racemic form. The pharmaceutical effects of each enantiomer have not been clearly demonstrated. In this project, an anticancer chemotherapy drug, chlorambucil, was modified as enantiopure phthalidyl prodrugs. The enantiomers, together with phthalidyl unit and their racemic mixture, were then subject to the in vivo bioactivity tests against B16F10 melanoma cells. It was found that proper chirality within the promoiety had noticeably better in vivo pharmacological effects than the parent drug, the enantiomer and racemic mixture. This merit perhaps could be extended from the phthalidyl prodrugs to other chirality containing prodrugs.
PROTOCOL: The effectiveness of psychosocial interventions for reducing problematic substance use, improving mental health, and improving housing stability for adults experiencing homelessness: A systematic review and meta‐analysis
Authors: O'Leary Chris , Teixeira Ligia , Coren Esther , Kiss Zsolt , Roberts Anton , Amitage Harry 
Published: November 2022

AbstractThis systematic review is part of a broader evidence synthesis which aims to produce two systematic reviews to address a significant gap in the evidence base identified by Luchenski et al. (2018) and by (White, 2018). The first review (which is the subject of this protocol) will use meta‐analysis to examine the effectiveness of different psychosocial interventions in (1) reducing problematic substance use; (2) improving mental health; and (3) improving housing stability for adults experiencing homelessness. The second review (which is covered by a separate title registration and protocol) will be of the experiences of adults experiencing homelessness when accessing or using psychosocial interventions, and will be a qualitative evidence synthesis using thematic synthesis (Thomas & Harden, 2008).