bluuebunny/crossref_metadata_2025_split huggingface dataset:
An Enabling Peptide Ligation Induced by Thiol‐Salicylaldehyde Ester for Chemical Protein Synthesis
Authors: Li Cuicui , Ma Wenge , Jin Kang 
Published: October 2024

AbstractChemical protein synthesis by amide‐forming ligation of two unprotected peptide segments offers an effective strategy for the preparation of protein derivatives that are not accessible through bioengineering approaches. Herein, an unprecedented chemical ligation between peptides with C‐terminal 2‐mercaptobenzaldehyde (thiol‐salicylaldehyde, TSAL) esters and peptides bearing N‐terminal cysteine/penicillamine is reported. Reactive peptide TSAL esters can be obtained from peptide hydrazides in an operationally simple and highly effective manner. This chemoselective peptide ligation enables the rapid production of N,S‐benzylidene acetal intermediates, which can readily be converted into native amide bonds even at sterically hindered junctions. In addition, the current method can be applied compatibly in concert with other types of ligations and subsequent desulfurization chemistry, thereby facilitating convergent protein synthesis. The effectiveness of this new method is also showcased by the total synthesis of proteins ubiquitin and hyalomin‐3 (Hyal‐3), the efficient synthesis of protein ubiquitin‐fold modifier 1 (UFM1) via a C‐to‐N sequential TSAL ester‐induced ligation strategy, and the chemical synthesis of protein Mtb CM through a combined strategy of Ser/Thr ligation and TSAL ester‐induced ligations.
Micro‐Scale Ice Shoveling Effect Induced by Magnetic‐Responsive Microfins
Authors: Chen Yiyi , Liu Ming , Zhou Lijing , Deng Jian , Hou Xianghui , Mao Xuerui 
Published: October 2024

AbstractIcing is ubiquitous in nature and engineering applications, and imposes threats to road and air transportations, wind energy infrastructures, etc. However, current active de‐icing solutions, especially the most popular one, i.e., heating, suffer from high energy consumption whilst passive methods are often ineffective at high‐speed, long‐term, or large‐particle conditions. Herein, a promising strategy adopting magnetic‐responsive microfins (MRS) featuring reversible deformations is developed for de‐icing. A novel micro‐scale ice shoveling effect induced by the localized destruction of the ice adhesion interface owing to the inhomogeneous deformation is demonstrated, and its dependence on the ice particle size and temperature is investigated. An analytical model is proposed to describe the mechanism of this effect, showing a linear relation between the position of the magnet and the induced force agreeing well with experiments, leading to a system straightforward to predict and control. Specifically, the de‐icing capacity of the surface becomes prominent when small‐scale ice particles merge to large ones, providing a promising solution for applications on aircraft, wind turbines, etc., as the first of its kind to remove large particles under high‐speed conditions effectively.
Reconstructing Molecular Networks by Causal Diffusion Do‐Calculus Analysis with Deep Learning
Authors: Wang Jiachen , Zhang Yuelei , Chen Luonan , Liu Xiaoping 
Published: October 2024

AbstractQuantifying molecular regulations between genes/molecules causally from observed data is crucial for elucidating the molecular mechanisms underlying biological processes at the network level. Presently, most methods for inferring gene regulatory and biological networks rely on association studies or observational causal‐analysis approaches. This study introduces a novel approach that combines intervention operations and diffusion models within a do‐calculus framework by deep learning, i.e., Causal Diffusion Do‐calculus (CDD) analysis, to infer causal networks between molecules. CDD can extract causal relations from observed data owing to its intervention operations, thereby significantly enhancing the accuracy and generalizability of causal network inference. Computationally, CDD has been applied to both simulated data and real omics data, which demonstrates that CDD outperforms existing methods in accurately inferring gene regulatory networks and identifying causal links from genes to disease phenotypes. Especially, compared with the Mendelian randomization algorithm and other existing methods, the CDD can reliably identify the disease genes or molecules for complex diseases with better performances. In addition, the causal analysis between various diseases and the potential factors in different populations from the UK Biobank database is also conducted, which further validated the effectiveness of CDD.
Tailored Polymer Hole‐Transporting Materials with Multisite Passivation Functions for Effective Buried‐Interface Engineering of Inverted Quasi‐2D Perovskite Solar Cells
Authors: Zhao Xiujie , Bao Yinyu , Pan Zhengwu , Su Qianyu , Peng Darui , Gao Deqing , Yin Chengrong , Wang Jianpu , Huang Wei 
Published: October 2024

AbstractAlthough quasi‐2D Ruddlesden‒Popper (RP) perovskite exhibits advantages in stability, their photovoltaic performance are still inferior to 3D counterparts. Optimizing the buried interface of RP perovskite and suppress energetic losses can be a promising approach for enhancing efficiency and stability of inverted quasi‐2D RP perovskite solar cells (PSCs). Among which, constructing polymer hole‐transporting materials (HTMs) with defect passivation functions is of great significance for buried‐interface engineering of inverted quasi‐2D RP PSCs. Herein, by employing side‐chain tailoring strategy to extend the π‐conjugation and regulate functionality of side‐chain groups, target polymer HTMs (PVCz‐ThSMeTPA and PVCz‐ThOMeTPA) with high mobility and multisite passivation functions are achieved. The presence of more sulfur atom‐containing groups in side‐chain endows PVCz‐ThSMeTPA with increased intra/intermolecular interaction, appropriate energy level, and enhanced buried interfacial interactions with quasi‐2D RP perovskite. The hole mobility of PVCz‐ThSMeTPA is up to 9.20 × 10−4 cm2 V−1 S−1. Furthermore, PVCz‐ThSMeTPA as multifunctional polymer HTM with multiple chemical anchor sites for buried‐interface engineering of quasi‐2D PSCs can enable effective charge extraction, defects passivation, and perovskite crystallization modulation. Eventually, the PVCz‐ThSMeTPA‐based inverted quasi‐2D PSC achieves a champion power conversion efficiency of 22.37%, which represents one of the highest power conversion efficiencies reported to date for quasi‐2D RP PSCs.
Comparative brain metabolomics reveals shared and distinct metabolic alterations in Alzheimer's disease and progressive supranuclear palsy
Authors: Batra Richa , Krumsiek Jan , Wang Xue , Allen Mariet , Blach Colette , Kastenmüller Gabi , Arnold Matthias , Ertekin‐Taner Nilüfer , Kaddurah‐Daouk Rima ,   for the Alzheimer's Disease Metabolomics Consortium (ADMC)
Published: October 2024

AbstractBACKGROUNDMetabolic dysregulation is a hallmark of neurodegenerative diseases, including Alzheimer's disease (AD) and progressive supranuclear palsy (PSP). Although metabolic dysregulation is a common link between these two tauopathies, a comprehensive brain metabolic comparison of the diseases has not yet been performed.METHODSWe analyzed 342 postmortem brain samples from the Mayo Clinic Brain Bank and examined 658 metabolites in the cerebellar cortex and the temporal cortex between the two tauopathies.RESULTSOur findings indicate that both diseases display oxidative stress associated with lipid metabolism, mitochondrial dysfunction linked to lysine metabolism, and an indication of tau‐induced polyamine stress response. However, specific to AD, we detected glutathione‐related neuroinflammation, deregulations of enzymes tied to purines, and cognitive deficits associated with vitamin B.DISCUSSIONOur findings underscore vast alterations in the brain's metabolome, illuminating shared neurodegenerative pathways and disease‐specific traits in AD and PSP.Highlights
First high‐throughput metabolic comparison of Alzheimer's diesease (AD) versus progressive supranuclear palsy (PSP) in brain tissue.
Cerebellar cortex (CER) shows substantial AD‐related metabolic changes, despite limited proteinopathy.
AD impacts both CER and temporal cortex (TCX); PSP's changes are primarily in CER.
AD and PSP share metabolic alterations despite major pathological differences.
Inhibiting mtDNA transcript translation alters Alzheimer's disease‐associated biology
Authors: Gabrielli Alexander P. , Novikova Lesya , Ranjan Amol , Wang Xiaowan , Ernst Nicholas J. , Abeykoon Dhanushki , Roberts Anysja , Kopp Annie , Mansel Clayton , Qiao Linlan , Lysaker Colton R. , Wiedling Ian W. , Wilkins Heather M. , Swerdlow Russell H. 
Published: October 2024

AbstractINTRODUCTIONAlzheimer's disease (AD) features changes in mitochondrial structure and function. Investigators debate where to position mitochondrial pathology within the chronology and context of other AD features.METHODSTo address whether mitochondrial dysfunction alters AD‐implicated genes and proteins, we treated SH‐SY5Y cells and induced pluripotent stem cell (iPSC)‐derived neurons with chloramphenicol, an antibiotic that inhibits mtDNA‐generated transcript translation. We characterized adaptive, AD‐associated gene, and AD‐associated protein responses.RESULTSSH‐SY5Y cells and iPSC neurons responded to mtDNA transcript translation inhibition by increasing mtDNA copy number and transcription. Nuclear‐expressed respiratory chain mRNA and protein levels also changed. There were AD‐consistent concordant and model‐specific changes in amyloid precursor protein, beta amyloid, apolipoprotein E, tau, and α‐synuclein biology.DISCUSSIONPrimary mitochondrial dysfunction induces compensatory organelle responses, changes nuclear gene expression, and alters the biology of AD‐associated genes and proteins in ways that may recapitulate brain aging and AD molecular phenomena.Highlights
In AD, mitochondrial dysfunction could represent a disease cause or consequence.
We inhibited mitochondrial translation in human neuronal cells and neurons.
Mitochondrial and nuclear gene expression shifted in adaptive‐consistent patterns.
APP, Aβ, APOE, tau, and α‐synuclein biology changed in AD‐consistent patterns.
Mitochondrial stress creates an environment that promotes AD pathology.
Pathway enrichment in genome‐wide analysis of longitudinal Alzheimer's disease biomarker endophenotypes
Authors: Rosewood Thea J. , Nho Kwangsik , Risacher Shannon L. , Liu Shiwei , Gao Sujuan , Shen Li , Foroud Tatiana , Saykin Andrew J. ,   for the Alzheimer's Disease Neuroimaging Initiative
Published: October 2024

AbstractINTRODUCTIONThe genetic pathways that influence longitudinal heterogeneous changes in Alzheimer's disease (AD) may provide insight into disease mechanisms and potential therapeutic targets.METHODSLongitudinal endophenotypes from the Alzheimer's Disease Neuroimaging Initiative (ADNI) representing amyloid, tau, neurodegeneration (A/T/N), and cognition were selected. Genome‐wide association analysis was performed using a linear mixed model (LMM) approach, followed by gene and pathway enrichment with significant and functionally relevant SNPs.RESULTSA total of 33 and 19 statistically significant pathways were identified associating with the intercept and longitudinal trajectory, respectively. The longitudinal intercept pathways represent eight groups: immune, metabolic, cell growth and survival, DNA maintenance, neuronal signaling, RAS/MAPK/ERK signaling pathways, vesicle and lysosomal transport, and transcription modification. Longitudinal trajectory pathways represented six groups: Immune, metabolic, cell signaling, cytoskeleton, and glycosylation.DISCUSSIONLongitudinal enrichment identified pathways that uniquely associate with trajectories of key AD biomarkers and cognition, providing new insight into AD course‐related mechanisms and potential new therapeutic targets.Highlights
A systematic genome‐wide analysis with longitudinal AD biomarker endophenotypes was performed.
Enriched pathways were identified with functionally derived SNP to gene analysis.
Fifty‐two pathways were associated with longitudinal trajectory and intercept.
Many of the identified pathways are specific steps in larger pathways implicated in AD.
The identified pathways may provide therapeutic targets and areas for further study.
Microscopy assessment of a fluorescence [18F] flortaucipir analog (T726) shows neuropathological overlap with 3R and 4R tau lesions
Authors: Gatto Rodolfo G. , Hossam Youssef , Reichard R. Ross , Lowe Val J. , Whitwell Jennifer L. , Josephs Keith A. 
Published: October 2024

AbstractBACKGROUND[18F] flortaucipir (FTP) binding to paired helical filament (PHF) tau in Alzheimer's disease (AD) is well accepted. Binding to 3R and 4R tau in frontotemporal lobar degeneration (FTLD) is controversial. We aimed to investigate whether an FTP fluorescent analog (T726) can help shed light on this controversy.METHODWe assessed T726 binding to amyloid beta (Aβ) and different tau isoforms in nine subjects (one control, three with Alzheimer's disease [AD], and five with FTLD) with different 3R and 4R tauopathies using fluorescence confocal microscopy.RESULTST726 did not colocalize with Aβ but showed significant co‐localization with PHF tau in AD. We also observed some, albeit limited, co‐localization of T726 with 3R and 4R tau lesions in FTLD.DISCUSSIONThis study's findings support FTP binding to some 3R and 4R tau lesions in FTLD. Further studies are needed to understand the biology of why FTP binds some but not all FTLD tau lesions.Highlights
Flortaucipir analog (T726) showed significant co‐localization with paired helical filament (PHF) tau in Alzheimer's disease (AD).
Colocalization between T726 with 3R and 4R tau lesions was observed in frontotemporal lobar degeneration (FTLD).
Not all 4R tau lesions bind to T726 across different FTLD brain regions.
A Double‐walled Noncovalent Carbon Nanotube by Columnar Packing of Nanotube Fragments
Authors: Imoto Daiki , Shudo Hiroki , Yagi Akiko , Itami Kenichiro 
Published: October 2024

AbstractHerein, we report the synthesis of double‐walled noncovalent carbon nanotubes (CNTs) through host–guest complexation of nanotube fragments and tube‐forming crystal engineering. As the smallest fragment of double‐walled CNTs, a host–guest complex of perfluorocycloparaphenylene (PFCPP) and carbon nanobelt (CNB) was synthesized by mixing them in solvents. The immediate complexation of the PF[12]CPP⸧(6,6)CNB complex with a remarkably high association constant (Ka) of 2×105 L/mol was observed. Time‐dependent 1H NMR and thermogravimetry measurements revealed that the stability of (6,6)CNB was significantly improved by encapsulation. X‐ray crystallography confirmed the robust belt‐in‐ring structure of this complex. As indicated by the short distance between PF[12]CPP and (6,6)CNB (2.8 Å), intermolecular orbital interactions exist between the belt and the ring, which were further supported by theoretical calculation and phosphorescence quenching experiments. While the PF[12]CPP⸧(6,6)CNB complex adopts various crystal packing structures, chloroform was discovered to be a magic “glue” solvent inducing one‐dimensional alignment of the PF[12]CPP⸧(6,6)CNB complex to build an unprecedented double‐walled noncovalent CNT structure.
The Paradoxical Influence of Hydrothermally Treated Zeolites on the Hydrocarbon Pool Mechanism
Authors: Gong Xuan , Jiang Shican , Dikhtiarenko Alla , Nastase Stefan Adrian F. , Abou‐Hamad Edy , Ye Yiru , Zhou Hexun , You Xinyu , Khairova Rushana , Patarroyo Javier , Cavallo Luigi , Gascon Jorge , Chowdhury Abhishek Dutta 
Published: October 2024

AbstractUnderstanding the mechanistic intricacies of hydrothermally treated zeolite is crucial for valorizing any oxygen‐containing renewable feedstocks (e. g., methanol, carbon dioxide, biomass). Additionally, the regeneration of deactivated zeolite catalysts under oxidative conditions, akin to hydrothermal treatment, is essential in industrial processes. While research in this area has predominantly focused on characterizing steaming‐induced physicochemical changes in zeolite, their ultimate impact on the organic reaction mechanism governed by the hydrocarbon pool dual‐cycle mechanism remains unclear. To bridge this knowledge gap, this study investigates the effect of steamed zeolite on the organic reaction mechanism during the industrially significant methanol‐to‐hydrocarbons process. We achieved this objective by strategically integrating catalytic and control experiments over the pristine and steamed zeolites and their advanced characterization, including under operando conditions, XRD structural refinement, and using “mobility‐dependent” solid‐state NMR spectroscopy. This multimodal characterization approach was instrumental in elucidating elusive mechanistic information in the dual‐cycle mechanism, shedding light on phenomena such as the unchanged ethylene selectivity despite decreasing aromatics selectivity, while ethylene could solely be derived from arene‐based reaction intermediates. This study could improve the process efficiency in zeolite catalysis by connecting steaming‐induced changes in the organic reaction mechanisms with inorganic material aspects.
Regulating the Spin‐State of Cobalt in Three‐Dimensional Covalent Organic Frameworks for High‐Performance Sodium‐Iodine Rechargeable Batteries
Authors: Guo Chaofei , Liu Tiancun , Wang Zhenzhen , Wang Yu‐Xuan , Steven Mfitumucunguzi , Luo Yuhan , Luo Xiping , Wang Yong 
Published: October 2024

AbstractAlthough the catalytic activity is heavily reliant on the electronic structure of the catalyst, understanding the impact of electron spin regulation on electrocatalytic performance is still rarely investigated. This work presents a novel approach involving the single‐atom coordination of cobalt (Co) within metalloporphyrin‐based three‐dimensional covalent organic frameworks (3D‐COFs) to facilitate the catalytic conversion for sodium‐iodine batteries. The spin state of Co is modulated by altering the oxidation state of the porphyrin‐centered Co, achieving optimal catalysis for iodine reduction. Experimental results demonstrate that CoII and CoIII are incorporated into the 3D‐COFs, exhibiting spin ground states of S=1/2 and S=0, respectively. The low spin state of CoIII is favorable to hybridize with the sp 3d orbitals of I3−, thus facilitating the conversion of I3− to I−. Density‐functional theory (DFT) calculations further reveal that the presence of CoIII enhances iodide adsorption and accelerates the formation of NaI in 3D‐COFs‐CoIII, thereby promoting its rapid kinetic behaviors. Notably, the I2@3D‐COFs‐CoIII cathode achieves a high reversible capacity of 227.7 mAh g−1 after 200 cycles at 0.5 C and demonstrates exceptional cyclic stability, exceeding 2000 cycles at 10 C with a minor capacity fading rate of less than one 0.01 % per cycle.
A Discrete Four‐Stranded β‐Sheet through Catenation of M2L2 Metal–Peptide Rings
Authors: Tsunekawa Eisuke , Fujita Makoto , Sawada Tomohisa 
Published: October 2024

AbstractMethods for precisely constructing a β‐sheet assembly with number‐defined strands in solution remains quite limited due to its intense aggregation property. Here, we report the precise construction of a four‐stranded anti‐parallel β‐sheet by utilizing a non‐covalent approach. This was achieved by folding and assembly of Ag+ and a pentapeptide (1) with the Ala‐D3pa‐Gly‐3pa‐Val (3pa: β‐(3‐pyridyl)‐alanine) sequence, which was designed to form an interlocking Ag2(1)2 ring through metal cross‐linking of the side chains. NMR analyses and X‐ray crystallographic studies characterized the structure of the discrete β‐sheet assembly as well as the remarkable structural selectivity in terms of strands’ number, orientation and the sheet type.
Asymmetrische Synthese von β‐Ketoamiden durch eine Sulfoniumumlagerung
Authors: Porte Vincent , Nascimento Vinicius R. , Sirvent Ana , Tiefenbrunner Irmgard , Feng Minghao , Kaiser Daniel , Maulide Nuno 
Published: October 2024

AbstractDie Synthese von enantiomerenangereicherten α‐substituierten 1,3‐Dicarbonylen stellt, aufgrund deren Tendenz über Keto‐Enol‐Tautomerie zu racemisieren, nach wie vor eine Herausforderung dar. Hier beschreiben wir eine Methode zur Herstellung von enantiomerenangereicherten β‐Ketoamiden durch eine [3,3]‐sigmatrope Sulfoniumumlagerung, die durch ein chirales Sulfinimin ermöglicht wird. Dabei wird ein guter Chiralitätstransfer, sowie eine exzellente Chemoselektivität und Toleranz verschiedener funktionellen Gruppen erzielt. Darüber hinaus können enantiomerenangereicherte β‐Hydroxyamide durch eine diastereoselektive Reduktion der Keto‐Gruppe synthetisiert werden. Dies ist sowohl in einem Zwei‐ als auch in einem Ein‐Topf‐Verfahren möglich.
A Fentanyl Hapten‐Displaying Lipid Nanoparticle Vaccine that Non‐Covalently Encapsulates a TLR7/8 Agonist and T‐Helper Epitope Induces Protective Anti‐Fentanyl Immunity
Authors: Zhong Zifu , Deventer Marie H. , Chen Yong , Vanhee Stijn , Lammens Inés , Deswarte Kim , Huang Yi , Ye Tingting , Wang Haixiu , Nuhn Lutz , Vandeputte Marthe M. , Gontsarik Mark , Cui Xiaole , Sanders Niek N. , Lienenklaus Stefan , N. Lambrecht Bart , Baptista Antonio P. , Stove Christophe P. , G. De Geest Bruno 
Published: October 2024

AbstractOpioid use disorder ‐ particularly involving fentanyl ‐ has precipitated a public health crisis characterized by a significant increase in addiction and overdose‐related deaths. Fentanyl‐specific immunotherapy, which aims at inducing fentanyl‐specific antibodies capable of binding fentanyl molecules in the bloodstream, preventing their entry in the central nervous system, is therefore gaining momentum. Conventional opioid designs rely on the covalent conjugation of fentanyl analogues to immunogenic carrier proteins that hold the inherent capacity of mounting immunodominant responses. Here, we present an alternative fentanyl vaccine design that utilizes a non‐covalent assembly of lipid nanoparticles (LNPs) to deliver fentanyl haptens in conjunction with a CD4+ T‐helper peptide epitope and an imidazoquinoline TLR7/8 agonist. Our results demonstrate that a single intramuscular administration of the LNP‐based nanovaccine elicits fentanyl‐specific antibodies, significantly mitigating the effects of opioid overdose in preclinical mouse models. Furthermore, we analyzed the immunobiological behavior of the vaccine in vivo in mouse models, providing evidence that covalent attachment of a fentanyl hapten to a carrier proteins or peptide epitope is not necessary for inducing an effective immune response. However, co‐delivery ‐ specifically, the physical assembly of all immune cues into an LNP ‐ remains essential for inducing hapten‐specific immunity.