bluuebunny/crossref_metadata_2025_split huggingface dataset:
A patient with compound heterozygosity of SMPD4: Another example of utility of exome‐based copy number analysis in autosomal recessive disorders
Authors: Yamada Mamiko , Suzuki Hisato , Shima Taiki , Uehara Tomoko , Kosaki Kenjiro 
Published: October 2021

AbstractFor the efficient diagnosis of rare and undiagnosed diseases, the parallel detection of copy number variants (CNVs) and single nucleotide variants using exome analysis is required. Recently, our group reported the usefulness of a program called EXCAVATOR2, which screens for CNVs from aligned exome data in bam format. This method is expected to contribute to the identification of structural variants and to improve the diagnosis rate, especially for the diagnosis of autosomal recessive disease, when a conventional exome analysis identifies a pathogenic variant in one allele but not the other. Here we report a 2‐year‐old Japanese boy with an undiagnosed disease. He had severe neonatal asphyxia, severe intellectual disability, intractable seizures, cerebellar and brainstem hypoplasia and dysmorphic features including a prominent supraorbital ridge, thin upper lip, and prominent antihelix. An exome analysis reinforced with a copy number analysis using the EXCAVATOR2 method revealed that the patient had a hemizygous variant in chr2(GRCh37):g.130925108G>A, NM_017951.4 c.832C>T, p.(Arg278*) in SMPD4 that was derived from his father and a deletion of SMPD4 derived from his mother. The presence of the deletion spanning SMPD4 was confirmed by short‐read and long‐read whole‐genome sequencing. The successful diagnosis of this reported patient demonstrates the diagnostic utility of EXCAVATOR2 and overcomes the weakness of exome analysis for the detection of autosomal recessive diseases in nonconsanguineous families, significantly impacting genetic counseling for family planning.
Tau‐Atrophy Variability Reveals Phenotypic Heterogeneity in Alzheimer's Disease
Authors: Das Sandhitsu R. , Lyu Xueying , Duong Michael Tran , Xie Long , McCollum Lauren , de Flores Robin , DiCalogero Michael , Irwin David J. , Dickerson Bradford C. , Nasrallah Ilya M. , Yushkevich Paul A. , Wolk David A. ,   Alzheimer's Disease Neuroimaging Initiative
Published: October 2021

ObjectiveTau neurofibrillary tangles (T) are the primary driver of downstream neurodegeneration (N) and subsequent cognitive impairment in Alzheimer's disease (AD). However, there is substantial variability in the T‐N relationship – manifested in higher or lower atrophy than expected for level of tau in a given brain region. The goal of this study was to determine if region‐based quantitation of this variability allows for identification of underlying modulatory factors, including polypathology.MethodsCortical thickness (N) and 18F‐Flortaucipir SUVR (T) were computed in 104 gray matter regions from a cohort of cognitively‐impaired, amyloid‐positive (A+) individuals. Region‐specific residuals from a robust linear fit between SUVR and cortical thickness were computed as a surrogate for T‐N mismatch. A summary T‐N mismatch metric defined using residuals were correlated with demographic and imaging‐based modulatory factors, and to partition the cohort into data‐driven subgroups.ResultsThe summary T‐N mismatch metric correlated with underlying factors such as age and burden of white matter hyperintensity lesions. Data‐driven subgroups based on clustering of residuals appear to represent different biologically relevant phenotypes, with groups showing distinct spatial patterns of higher or lower atrophy than expected.InterpretationThese data support the notion that a measure of deviation from a normative relationship between tau burden and neurodegeneration across brain regions in individuals on the AD continuum captures variability due to multiple underlying factors, and can reveal phenotypes, which if validated, may help identify possible contributors to neurodegeneration in addition to tau, which may ultimately be useful for cohort selection in clinical trials. ANN NEUROL 2021;90:751–762
Structure–Reactivity Relationship for Nano‐Catalysts in the Hydrogenation/Dehydrogenation Controlled Reaction Systems
Authors: Shen Tonghao , Yang Yuqi , Xu Xin 
Published: October 2021

AbstractFor the activity of a nano‐catalyst, a general and quantitative solution to building direct structure–reactivity relationship has not yet been established. On top of the first‐principle‐based kinetic Monte Carlo (KMC) simulations, we developed a model to build the adsorption site dependence of the activity. We applied this model to study the nano effects of Cu catalysts in the water‐gas shift reaction. By accumulating the activities of different adsorption sites, our model satisfactorily reproduced the experimental apparent activation energies for catalysts with sizes over hundreds of nanometers, which were out of reach for conventional KMC simulations. Our results disclose that, even for a cubic catalyst with size of 877 nm, its activity can still be closely related to the activity of edge sites, instead of only the exposed Cu(100) facets as might be expected. The present model is expected to be useful for systems that are controlled by the hydrogenation/dehydrogenation processes.
Non‐uniform Photoinduced Unfolding of Supramolecular Polymers Leading to Topological Block Nanofibers
Authors: Tashiro Keigo , Katayama Kosuke , Tamaki Kenta , Pesce Luca , Shimizu Nobutaka , Takagi Hideaki , Haruki Rie , Hollamby Martin J. , Pavan Giovanni M. , Yagai Shiki 
Published: October 2021

AbstractSynthesis of one‐dimensional nanofibers with distinct topological (higher‐order structural) domains in the same main chain is one of the challenging topics in modern supramolecular polymer chemistry. Non‐uniform structural transformation of supramolecular polymer chains by external stimuli may enable preparation of such nanofibers. To demonstrate feasibility of this post‐polymerization strategy, we prepared a photoresponsive helically folded supramolecular polymers from a barbiturate monomer containing an azobenzene‐embedded rigid π‐conjugated scaffold. In contrast to previous helically folded supramolecular polymers composed of a more flexible azobenzene monomer, UV‐light induced unfolding of the newly prepared helically folded supramolecular polymers occurred nonuniformly, affording topological block copolymers consisting of folded and unfolded domains. The formation of such blocky copolymers indicates that the photoinduced unfolding of the helically folded structures initiates from relatively flexible parts such as termini or defects. Spontaneous refolding of the unfolded domains was observed after visible‐light irradiation followed by aging to restore fully folded structures.
One‐Pot Green Process to Synthesize MXene with Controllable Surface Terminations using Molten Salts
Authors: Shen Miao , Jiang Weiyan , Liang Kun , Zhao Sufang , Tang Rui , Zhang Linjuan , Wang Jian‐Qiang 
Published: October 2021

AbstractSurface terminations of two‐dimensional MXene (Ti3C2Tx) considerably impact its physicochemical properties. Commonly used etching methods usually introduce ‐F surface terminations or metallic impurities in MXene. We present a new molten‐salt‐assisted electrochemical etching method to synthesize fluorine‐free Ti3C2Cl2. Using electrons as reaction agents, cathode reduction and anode etching can be spatially isolated; thus, no metallics are present in the Ti3C2Cl2 product. The surface terminations can be in situ modified from −Cl to −O and/or −S, which considerably shortens the modification steps and enriches the variety of surface terminations. The obtained −O‐terminated Ti3C2Tx are excellent electrode materials for supercapacitors, exhibiting capacitances of 225 F g−1 at 1.0 Ag−1, good rate performance (91.1 % at 10 Ag−1), and excellent capacitance retention (100 % after 10000 charge/discharge cycles at 10 Ag−1), which is superior to multi‐layered Ti3C2Tx prepared by other etching methods.
Luminescence Ratiometric Nanothermometry Regulated by Tailoring Annihilators of Triplet–Triplet Annihilation Upconversion Nanomicelles
Authors: Li Lin , Zhang Chun , Xu Lei , Ye Changqing , Chen Shuoran , Wang Xiaomei , Song Yanlin 
Published: October 2021

AbstractTriplet–triplet annihilation (TTA) upconversion is a special non‐linear photophysical process that converts low‐energy photons into high‐energy photons based on sensitizer/annihilator pairs. Here, we constructed a novel luminescence ratiometric nanothermometer based on TTA upconversion nanomicelles by encapsulating sensitizer/annihilator molecules into a temperature‐sensitive amphiphilic triblock polymer and obtained good linear relationships between the luminescence ratio (integrated intensity ratio of upconverted luminescence peak to the downshifted phosphorescence peak) and the temperature. We also found chemical modification of annihilators would rule out the interference of the polymer concentration and stereochemical engineering of annihilators would readily regulate the thermal sensitivity.
Tetraphenylethylene‐Featured Fluorescent Supramolecular Nanoparticles for Intracellular Trafficking of Protein Delivery and Neuroprotection
Authors: Liu Ji , Sheng Jinhan , Shao Leihou , Zheng Qizhen , Li Wenting , Chen Xianghan , Mao Lanqun , Wang Ming 
Published: October 2021

AbstractThe delivery of protein into mammalian cells enables the dissection and manipulation of biological processes; however, this potency is challenged by the lack of an efficient protein delivery tool and a means to monitor its intracellular trafficking. Herein, we report that the hierarchical self‐assembly of tetraphenylethylene (TPE)‐featured metal–organic cages (MOCs) and β‐cyclodextrin‐conjugated polyethylenimine can generate fluorescent supramolecular nanoparticles (FSNPs) to deliver protein into neural cells, a cell line that is hard to transfect using conventional strategy. Further, the aggregation‐induced emission (AIE) of TPE enabled the fluorescent monitoring of cytosolic protein release. It is found that FSNPs can deliver and release protein into cytosol for subcellular targeting as fast as 18 h post‐delivery. Moreover, the delivery of molecular chaperone DJ‐1 using FSNPs activates MAPK/ERK signaling of neural cells to protect cells from oxidative stress.
Structural and Molecular Basis of the Catalytic Mechanism of Geranyl Pyrophosphate C6‐Methyltransferase: Creation of an Unprecedented Farnesyl Pyrophosphate C6‐Methyltransferase
Authors: Tsutsumi Hayama , Moriwaki Yoshitaka , Terada Tohru , Shimizu Kentaro , Shin‐ya Kazuo , Katsuyama Yohei , Ohnishi Yasuo 
Published: October 2021

AbstractPrenyl pyrophosphate methyltransferases enhance the structural diversity of terpenoids. However, the molecular basis of their catalytic mechanisms is poorly understood. In this study, using multiple strategies, we characterized a geranyl pyrophosphate (GPP) C6‐methyltransferase, BezA. Biochemical analysis revealed that BezA requires Mg2+ and solely methylates GPP. The crystal structures of BezA and its complex with S‐adenosyl homocysteine were solved at 2.10 and 2.56 Å, respectively. Further analyses using site‐directed mutagenesis, molecular docking, molecular dynamics simulations, and quantum mechanics/molecular mechanics calculations revealed the molecular basis of the methylation reaction. Importantly, the function of E170 as a catalytic base to complete the methylation reaction was established. We also succeeded in switching the substrate specificity by introducing a W210A substitution, resulting in an unprecedented farnesyl pyrophosphate C6‐methyltransferase.
Identification of Inhibitors of Cholesterol Transport Proteins Through the Synthesis of a Diverse, Sterol‐Inspired Compound Collection
Authors: Whitmarsh‐Everiss Thomas , Olsen Asger Hegelund , Laraia Luca 
Published: October 2021

AbstractCholesterol transport proteins regulate a vast array of cellular processes including lipid metabolism, vesicular and non‐vesicular trafficking, organelle contact sites, and autophagy. Despite their undoubted importance, the identification of selective modulators of this class of proteins has been challenging due to the structural similarities in the cholesterol‐binding site. Herein we report a general strategy for the identification of selective inhibitors of cholesterol transport proteins via the synthesis of a diverse sterol‐inspired compound collection. Fusion of a primary sterol fragment to an array of secondary privileged scaffolds led to the identification of potent and selective inhibitors of the cholesterol transport protein Aster‐C, which displayed a surprising preference for the unnatural‐sterol AB‐ring stereochemistry and new inhibitors of Aster‐A. We propose that this strategy can and should be applied to any therapeutically relevant sterol‐binding protein.
Oil–Water–Oil Triphase Synthesis of Ionic Covalent Organic Framework Nanosheets
Authors: Guo Zheyuan , Jiang Haifei , Wu Hong , Zhang Leilang , Song Shuqing , Chen Yu , Zheng Chenyang , Ren Yanxiong , Zhao Rui , Li Yonghong , Yin Yan , Guiver Michael D. , Jiang Zhongyi 
Published: October 2021

AbstractIonic covalent organic framework nanosheets (iCOFNs) with long‐range ordered and mono‐dispersed ionic groups hold great potential in many advanced applications. Considering the inherent drawbacks of oil–water biphase method, herein, we explore an oil–water–oil triphase method based on phase engineering strategy for the bottom‐up synthesis of iCOFNs. The middle water phase serves as a confined reaction region, and the two oil phases are reservoirs for storing and supplying monomers to the water phase. A large aqueous space and low monomer concentration lead to the anisotropic gradual growth of iCOFNs into few‐layer thickness, large lateral size, and high crystallinity. Notably, the resulting three cationic and anionic iCOFNs exhibit ultra‐high aspect ratios of up to 20,000. We further demonstrate their application potential by processing into ultrathin defect‐free COF membranes for efficient biogas separation. Our triphase method may offer an alternative platform technology for the synthesis and innovative applications of iCOFNs.
Achieving Short‐Wavelength Phase‐Matching Second Harmonic Generation in Boron‐Rich Borosulfate with Planar [BO3] Units
Authors: Li Zijian , Jin Wenqi , Zhang Fangfang , Chen Zilong , Yang Zhihua , Pan Shilie 
Published: October 2021

AbstractUltraviolet (UV) nonlinear optical (NLO) crystals which can produce short‐wavelength lasers via a direct second harmonic generation (SHG) process are of great importance in modern laser technology. Currently, the exploration of UV NLO crystals in borosulfates is nearly stagnant since the non‐phase matching (PM) property lies on the small birefringence induced by the intrinsically small optical anisotropy of the tetrahedral groups. Herein, for the first time, the planar [BO3] units were introduced into borosulfates leading to a boron‐rich borosulfate (NH4)2B4SO10 with unprecedented [B4SO10]∞ layers and evidently enhanced birefringence. To the best of our knowledge, it achieves the shortest SHG PM wavelength of 252 nm in all reported borosulfates with deep UV cutoff edge (184 nm), large SHG response (1.1×KDP at 1064 nm and 0.15×β‐BBO at 532 nm) and large birefringence (0.053 at 1064 nm) and is easy to grow single crystals via simple chemical vapor deposition method. These results confirm the feasibility of utilizing planar [BO3] units to optimize birefringence of borosulfates, and also open up broad prospects for UV NLO crystals in boron‐rich borosulfates.
Engineering Lattice Oxygen Activation of Iridium Clusters Stabilized on Amorphous Bimetal Borides Array for Oxygen Evolution Reaction
Authors: Wang Chen , Zhai Panlong , Xia Mingyue , Wu Yunzhen , Zhang Bo , Li Zhuwei , Ran Lei , Gao Junfeng , Zhang Xiaomeng , Fan Zhaozhong , Sun Licheng , Hou Jungang 
Published: October 2021

AbstractDeveloping robust oxygen evolution reaction (OER) catalysts requires significant advances in material design and in‐depth understanding for water electrolysis. Herein, we report iridium clusters stabilized surface reconstructed oxyhydroxides on amorphous metal borides array, achieving an ultralow overpotential of 178 mV at 10 mA cm−2 for OER in alkaline medium. The coupling of iridium clusters induced the formation of high valence cobalt species and Ir–O–Co bridge between iridium and oxyhydroxides at the atomic scale, engineering lattice oxygen activation and non‐concerted proton‐electron transfer to trigger multiple active sites for intrinsic pH‐dependent OER activity. The lattice oxygen oxidation mechanism (LOM) was confirmed by in situ 18O isotope labeling mass spectrometry and chemical recognition of negative peroxo‐like species. Theoretical simulations reveal that the OER performance on this catalyst is intrinsically dominated by LOM pathway, facilitating the reaction kinetics. This work not only paves an avenue for the rational design of electrocatalysts, but also serves the fundamental insights into the lattice oxygen participation for promising OER application.
Simultaneous Kinetic Resolution and Asymmetric Induction within a Borrowing Hydrogen Cascade Mediated by a Single Catalyst
Authors: Jin Ming Yu , Zhou Yali , Xiao Dengmengfei , You Yipeng , Zhen Qianqian , Tao Guanyu , Yu Peiyuan , Xing Xiangyou 
Published: October 2021

AbstractThe mechanistic uniqueness and versatility of borrowing hydrogen catalysis provides an opportunity to investigate the controllability of a cascade reaction, and more importantly, to realize either one or both of chiral recognition and chiral induction simultaneously. Here we report that, in a borrowing hydrogen cascade starting from racemic allylic alcohols, one of the enantiomers could be kinetically resolved, while the other enantiomer could be purposely converted to various targeted products, including α,β‐unsaturated ketones, β‐functionalized ketones and γ‐functionalized alcohols. By employing a robust Ru‐catalyst, both kinetic resolution and asymmetric induction were achieved with remarkable levels of efficiency and enantioselectivity. Density functional theory (DFT) calculations suggest that corresponding catalyst–substrate π–π interactions are pivotal to realize the observed stereochemical diversity.
Real‐Time Simultaneous Imaging of Acidification and Proteolysis in Single Phagosomes Using Bifunctional Janus‐Particle Probes
Authors: Lee Seonik , Zhang Zihan , Yu Yan 
Published: October 2021

AbstractThe digestion of pathogens inside phagosomes by immune cells occurs through a sequence of reactions including acidification and proteolysis, but how the reactions are orchestrated in the right order is unclear due to a lack of methods to simultaneously measure more than one reaction in phagosomes. Here we report a bifunctional Janus‐particle probe to simultaneously monitor acidification and proteolysis in single phagosomes in live cells. Each probe consists of a pH reporter and a proteolysis reporter that are spatially separated but function concurrently. Using the Janus probes, we found the acidic pH needed to initiate and maintain proteolysis, revealing the mechanism for the sequential occurrence of both reactions during pathogen digestion. We showed how bacterium‐derived lipopolysaccharides alter the acidification and proteolysis in phagosomes. This study showcases Janus‐particle probes as a generally applicable tool for monitoring multiple reactions in intracellular vesicles.
Sequential Selective C−H and C(sp3)−+P Bond Functionalizations: An Entry to Bioactive Arylated Scaffolds
Authors: Babu K. Naresh , Massarwe Fedaa , Shioukhi Israa , Masarwa Ahmad 
Published: October 2021

AbstractOrganophosphonium salts containing C(sp3)−+P bonds are among the most utilized reagents in organic synthesis for constructing C−C double bonds. However, their use as C‐selective electrophilic groups is rare. Here, we explore an efficient and general transition‐metal‐free method for sequential chemo‐ and regioselective C−H and C(sp3)−+P bond functionalizations. In the present study, C−H alkylation resulting in the synthesis of benzhydryl triarylphosphonium salts was achieved by one‐pot, four‐component cross‐coupling reactions of simple and commercially available starting materials. The utility of the resulting phosphonium salt building blocks was demonstrated by the chemoselective post‐functionalization of benzylic C(sp3)−+PPh3 groups to achieve aminations, thiolations, and arylations. In this way, benzhydrylamines, benzhydrylthioethers, and triarylmethanes, structural motifs that are present in many pharmaceuticals and agrochemicals, are readily accessed. These include the synthesis of two anticancer agents from simple materials in only two to three steps. Additionally, a protocol for late‐stage functionalization of bioactive drugs has been developed using benzhydrylphosphonium salts. This new approach should provide novel transformations for application in both academic and pharmaceutical research.
Donor/π‐Bridge Manipulation for Constructing a Stable NIR‐II Aggregation‐Induced Emission Luminogen with Balanced Phototheranostic Performance**
Authors: Yan Dingyuan , Xie Wei , Zhang Jianyu , Wang Lei , Wang Dong , Tang Ben Zhong 
Published: October 2021

AbstractOwing to their versatile functionality and tunable energy dissipation, aggregation‐induced emission luminogens (AIEgens) have emerged as a potential platform for multimodal theranostics. Nevertheless, the construction of AIE‐active phototheranostic agents in the second near‐infrared window (NIR‐II, 1000–1700 nm), which allows superior resolution and minimized photodamage, is still a formidable challenge. Herein, benzo[c]thiophene serves as an electron‐rich and bulky donor (D)/π‐bridge, which can enlarge the conjugation length and distort the backbone of an AIEgen. By precise D/π‐bridge engineering, highly stable NIR‐II AIEgen DPBTA‐DPTQ nanoparticles are obtained with acceptable NIR‐II fluorescence quantum yield and excellent photothermal conversion efficiency. In addition, the spatial conformation of DPBTA‐DPTQ is determined for the first time by X‐ray single crystal diffraction and theoretical simulations. DPBTA‐DPTQ NPs have good biocompatibility and show efficient photothermal therapeutic effects in in vitro tests. Furthermore, DPBTA‐DPTQ NPs were used in fluorescence‐photoacoustic‐photothermal trimodal imaging‐guided photothermal eradication of tumors in HepG2 and B16‐F10 tumor‐xenografted mice.
DNA Tiling Enables Precise Acylation‐Based Labeling and Control of mRNA
Authors: Xiao Lu , Jun Yong Woong , Kool Eric T. 
Published: October 2021

AbstractMethods for the site‐selective labeling of long, native RNAs are needed for studying mRNA biology and future therapies. Current approaches involve engineering RNA sequences, which may alter folding, or are limited to specific sequences or bases. Here, we describe a versatile strategy for mRNA conjugation via a novel DNA‐tiling approach. The method, TRAIL, exploits a pool of “protector” oligodeoxynucleotides to hybridize and block the mRNA, combined with an “inducer” DNA that extrudes a reactive RNA loop for acylation at a predetermined site. Using TRAIL, an azido‐acylimidazole reagent was employed for labeling and controlling RNA for multiple applications in vitro and in cells, including analysis of RNA‐binding proteins, imaging mRNA in cells, and analysis and control of translation. The TRAIL approach offers an efficient and accessible way to label and manipulate RNAs of virtually any length or origin without altering native sequence.