bluuebunny/crossref_metadata_2025 huggingface dataset:
An Impedance Study of the Density of States Distribution in Blends of PM6:Y6 in Relation to Barrierless Dissociation of CT States
Authors: Kroh Daniel , Athanasopoulos Stavros , Nádaždy Vojtech , Kahle Frank‐Julian , Bässler Heinz , Köhler Anna
Published: June 2023

In an endeavor to understand why the dissociation of charge‐transfer (CT) states in a PM6:Y6 solar‐cell is not a thermally activated process, measurements of energy‐resolved impedance as well as of intrinsic photoconduction are employed. This study determines the density of states distributions of the pertinent HOMO and LUMO states and obtains a Coulomb binding energy (Eb,CT) of ≈150 meV. This is 250 meV lower than the value expected for a pair of localized charges with 1 nm separation. The reason is that the hole is delocalized in the polymer and the electron is shared among Y6 molecules forming a J‐like aggregate. There are two key reasons why this binding energy of the CT state is not reflected in the temperature dependence of the photocurrent of PM6:Y6‐diode: i) The e–h dissociation in a disordered system is a multi‐step process whose activation energy is principally different from the binding energy of the CT state and can be substantially less than Eb,CT, and ii) since dissociation of the CT state competes with its intrinsic decay, the dissociation yield saturates once the rate of dissociation grossly exceeds the rate of intrinsic decay. This study argues that these conditions are met in a PM6:Y6‐solar cell.
Broad and Durable Humoral Responses Following Single Hydrogel Immunization of SARS‐CoV‐2 Subunit Vaccine
Authors: Ou Ben S. , Saouaf Olivia M. , Yan Jerry , Bruun Theodora U. J. , Baillet Julie , Zhou Xueting , King Neil P. , Appel Eric A.
Published: June 2023

Most vaccines require several immunizations to induce robust immunity, and indeed, most SARS‐CoV‐2 vaccines require an initial two‐shot regimen followed by several boosters to maintain efficacy. Such a complex series of immunizations unfortunately increases the cost and complexity of populations‐scale vaccination and reduces overall compliance and vaccination rate. In a rapidly evolving pandemic affected by the spread of immune‐escaping variants, there is an urgent need to develop vaccines capable of providing robust and durable immunity. In this work, a single immunization SARS‐CoV‐2 subunit vaccine is developed that can rapidly generate potent, broad, and durable humoral immunity. Injectable polymer–nanoparticle (PNP) hydrogels are leveraged as a depot technology for the sustained delivery of a nanoparticle antigen (RND‐NP) displaying multiple copies of the SARS‐CoV‐2 receptor‐binding domain (RBD) and potent adjuvants including CpG and 3M‐052. Compared to a clinically relevant prime‐boost regimen with soluble vaccines formulated with CpG/alum or 3M‐052/alum adjuvants, PNP hydrogel vaccines more rapidly generated higher, broader, and more durable antibody responses. Additionally, these single‐immunization hydrogel‐based vaccines elicit potent and consistent neutralizing responses. Overall, it is shown that PNP hydrogels elicit improved anti‐COVID immune responses with only a single administration, demonstrating their potential as critical technologies to enhance overall pandemic readiness.
Diatomite‐Templated Synthesis of Single‐Atom Cobalt‐Doped MoS2/Carbon Composites to Boost Sodium Storage
Authors: Wen Xia , Feng Wang , Li Xiaohui , Yang Junbo , Du Ruofan , Wang Peng , Li Hui , Song Luying , Wang Yuzu , Cheng Mo , He Jun , Shi Jianping
Published: June 2023

2D transition metal dichalcogenides (TMDCs) and single‐atom catalysts (SACs) are promising electrodes for energy conversion/storage because of the layered structure and maximum atom utilization efficiency. However, the integration of such two type materials and the relevant sodium storage applications remain daunting challenges. Here, an ingenious diatomite‐templated synthetic strategy is designed to fabricate single‐atom cobalt‐doped MoS2/carbon (SA Co‐MoS2/C) composites toward the high‐performance sodium storage. Benefiting from the unique hierarchical structure, high electron/sodium‐ion conductivity, and abundant active sites, the obtained SA Co‐MoS2/C reveals remarkable specific capacity (≈604.0 mAh g−1 at 0.1 A g−1), high rate performance, and outstanding long cyclic stability. Particularly, the sodium‐ion full cell composed of SA Co‐MoS2/C anode and Na3V2(PO4)3 cathode demonstrates unexpected stability with the cycle number exceeded 1200. The internal sodium storage mechanism is clarified with the aid of density functional theory calculations and in situ experimental characterizations. This work not only represents a substantial leap in terms of synthesizing SACs on 2D TMDCs but also provides a crucial step toward the practical sodium‐ion battery applications.
Renally Clearable Ultraminiature Chain‐Like Gold Nanoparticle Clusters for Multimodal Molecular Imaging of Choroidal Neovascularization
Authors: Nguyen Van Phuc , Qian Wei , Zhe Josh , Henry Jessica , Wang Mingyang , Liu Bing , Zhang Wei , Wang Xueding , Paulus Yannis M.
Published: June 2023

Currently, available gold nanoparticles (GNPs) typically accumulate in the liver and spleen, leading to concerns for their long‐term biosafety. To address this long‐standing problem, ultraminiature chain‐like gold nanoparticle clusters (GNCs) are developed. Via self‐assembly of 7–8 nm GNP monomers, GNCs provide redshifted optical absorption and scattering contrast in the near‐infrared window. After disassembly, GNCs turn back to GNPs with a size smaller than the renal glomerular filtration size cutoff, allowing their excretion via urine. A one‐month longitudinal study in a rabbit eye model demonstrates that GNCs facilitate multimodal molecular imaging of choroidal neovascularization (CNV) in vivo, non‐invasively, with excellent sensitivity and spatial resolution. GNCs targeting αvβ3 integrins enhance photoacoustic and optical coherence tomography (OCT) signals from CNV by 25.3‐fold and 150%, respectively. With excellent biosafety and biocompatibility demonstrated, GNCs render a first‐of‐its‐kind nanoplatform for biomedical imaging.
Fe‐Intercalation Dominated Ferromagnetism of van der Waals Fe3GeTe2
Authors: Wu Yueshen , Hu Yuxiong , Wang Cong , Zhou Xiang , Hou Xiaofei , Xia Wei , Zhang Yiwen , Wang Jinghui , Ding Yifan , He Jiadian , Dong Peng , Bao Song , Wen Jinsheng , Guo Yanfeng , Watanabe Kenji , Taniguchi Takashi , Ji Wei , Wang Zhu‐Jun , Li Jun
Published: June 2023

Fe3GeTe2 have proven to be of greatly intrigue. However, the underlying mechanism behind the varying Curie temperature (Tc) values remains a puzzle. This study explores the atomic structure of Fe3GeTe2 crystals exhibiting Tc values of 160, 210, and 230 K. The elemental mapping reveals a Fe‐intercalation on the interstitial sites within the van der Waals gap of the high‐Tc (210 and 230 K) samples, which are observed to have an exchange bias effect by electrical transport measurements, while Fe intercalation or the bias effect is absent in the low‐Tc (160 K) samples. First‐principles calculations further suggest that the Fe‐intercalation layer may be responsible for the local antiferromagnetic coupling that gives rise to the exchange bias effect, and that the interlayer exchange paths greatly contribute to the enhancement of Tc. This discovery of the Fe‐intercalation layer elucidates the mechanism behind the hidden antiferromagnetic ordering that underlies the enhancement of Tc in Fe3GeTe2.
Controllable Synthesis of 2H‐1T′ MoxRe(1‐x)S2 Lateral Heterostructures and Their Tunable Optoelectronic Properties
Authors: Sun Xiaona , Liu Yang , Shi Jianwei , Si Chen , Du Jiantao , Liu Xinfeng , Jiang Chengbao , Yang Shengxue
Published: June 2023

Constructing heterostructures and doping are valid ways to improve the optoelectronic properties of transition metal dichalcogenides (TMDs) and optimize the performance of TMDs‐based photodetectors. Compared with transfer techniques, chemical vapor deposition (CVD) has higher efficiency in preparing heterostructures. As for the one‐step CVD growth of heterostructures, cross‐contamination between the two materials may occur during the growth process, which may provide the possibility of one‐step simultaneous realization of controllable doping and formation of alloy‐based heterostructures by finely tuning the growth dynamics. Here, 2H‐1T′ MoxRe(1‐x)S2 alloy‐to‐alloy lateral heterostructures are synthesized through this one‐step CVD growth method, utilizing the cross‐contamination and different growth temperatures of the two alloys. Due to the doping of a small amount of Re atoms in 2H MoS2, 2H MoxRe(1‐x)S2 has a high response rejection ratio in the solar‐blind ultraviolet (SBUV) region and exhibits a positive photoconductive (PPC) effect. While the 1T′ MoxRe(1‐x)S2 formed by heavily doping Mo atoms into 1T' ReS2 will produce a negative photoconductivity (NPC) effect under UV laser irradiation. The optoelectronic property of 2H‐1T′ MoxRe(1‐x)S2‐based heterostructures can be modulated by gate voltage. These findings are expected to expand the functionality of traditional optoelectronic devices and have potential applications in optoelectronic logic devices.
Recent Progress on Plasmonic and Dielectric Chiral Metasurfaces: Fundamentals, Design Strategies, and Implementation
Authors: Khaliq Hafiz Saad , Nauman Asad , Lee Jae‐Won , Kim Hak‐Rin
Published: June 2023

Over the years, researchers have been exploring ways to artificially design chiral structures and materials, namely metamaterials and metasurfaces. They exhibit unique optical properties that can be used for various applications. However, metasurfaces comprise symmetry‐breaking structures that provide a more convenient solution for planar chiral optics regardless of whether they are plasmonic or dielectric. In general, plasmonic chiral metasurfaces are more suitable for applications requiring a high confinement level and substantial optical near‐field enhancement. In contrast, dielectric chiral metasurfaces are ideal for wide operating wavelength ranges and low losses. This review summarizes the recent progress on plasmonic and dielectric chiral metasurfaces. It includes the fundamental concepts, design strategies, and their implementation for applications in holographic displays, imaging and sensing, and detection. Moreover, an overview of chiral metasurfaces to generate the nonlinear effects, hosting bound states in the continuum, and the significant role of machine‐learning‐based design approaches are also discussed. Finally, some future developments are highlighted where chiral metasurfaces are expected to play a vital role.
Palladium‐Catalyzed Ring‐Opening Diarylation of Cyclobutanols for the Synthesis of Acylindanes
Authors: Yan Wen‐Jing , Tu Hai‐Yong , Liao Zhiyong , Shen Xiao‐Qin , Zhang Xing‐Guo
Published: June 2023

A method for the construction of the indane skeleton through palladium‐catalyzed ring‐opening diarylation of Cyclobutanols with aryl 1,2‐dihalides has been described. The ring‐expansion reaction involves β‐carbon elimination of Cyclobutanols and subsequent α‐carbon arylation of ketone to give 2‐acylindanes in 42–93% yields.
Developing Hypoimmunogenic Human iPSC‐Derived Oligodendrocyte Progenitor Cells as an Off‐The‐Shelf Cell Therapy for Myelin Disorders
Authors: Feng Lizhao , Chao Jianfei , Ye Peng , Luong Qui , Sun Guoqiang , Liu Wei , Cui Qi , Flores Sergio , Jackson Natasha , Shayento Afm Nazmul Hoque , Sun Guihua , Liu Zhenqing , Hu Weidong , Shi Yanhong
Published: June 2023

Demyelinating disorders are among the most common and debilitating diseases in neurology. Canavan disease (CD) is a lethal demyelinating disease caused by mutation of the aspartoacylase (ASPA) gene, which leads to the accumulation of its substrate N‐acetyl‐l‐aspartate (NAA), and consequently demyelination and vacuolation in the brain. In this study, hypoimmunogenic human induced pluripotent stem cell (iPSC)‐derived oligodendrocyte progenitor cells (OPC) are developed from a healthy donor as an “off‐the‐shelf” cell therapy. Hypoimmunogenic iPSCs are generated through CRISPR/Cas9 editing of the human leukocyte antigen (HLA) molecules in healthy donor‐derived iPSCs and differentiated into OPCs. The OPCs are engrafted into the brains of CD (nur7) mice and exhibit widespread distribution in the brain. The engrafted OPCs mature into oligodendrocytes that express the endogenous wildtype ASPA gene. Consequently, the transplanted mice exhibit elevated human ASPA expression and enzymatic activity and reduced NAA level in the brain. The transplanted OPCs are able to rescue major pathological features of CD, including defective myelination, extensive vacuolation, and motor function deficits. Moreover, the hypoimmunogenic OPCs exhibit low immunogenicity both in vitro and in vivo. The hypoimmunogenic OPCs can be used as “off‐the‐shelf” universal donor cells to treat various CD patients and many other demyelinating disorders, especially autoimmune demyelinating diseases, such as multiple sclerosis.
Biomimetic and NOS‐Responsive Nanomotor Deeply Delivery a Combination of MSC‐EV and Mitochondrial ROS Scavenger and Promote Heart Repair and Regeneration
Authors: Zhang Ning , Fan Mengkang , Zhao Yongchao , Hu Xiaolong , Zhu Qiongjun , Jiao Xiaolu , Lv Qingbo , Li Duanbin , Huang Zheyong , Fu Guosheng , Ge Junbo , Li Hongjun , Zhang Wenbin
Published: June 2023

Mesenchymal stem cell‐derived extracellular vesicle (MSC‐EV) is shown to promote cardiac repair, however, it still falls short in initiating myocardia proliferation restart. In this regard, ROS‐induced DNA damage and responses are the culprit of cellcycle arrest. Here, this work constructs a hybrid cell‐derived extracellular vesicle that is composed of MSC and macrophage membranes and encompasses MitoN, a ROS scavenger, to boost the healing of the heart. The MitoN, a NAD(P)H mimic, could target the mitochondrial to eliminate the ROS resuming the arrested cell cycle. The hybrid extracellular vesicle (N@MEV) could respond to the inflammatory signals generated during myocardial injury and thus enable superior targeting and enrichment to the location of the damage. L‐arginine, which could be catalyzed by NOS and ROS into NO and SO provide a driving force, is immobilized within the vesicle (NA@MEV) to further enhance the N@MEV's potential to penetrate the cardiac stroma. In combination with multiple mechanisms, NA@MEV increased heart function 1.3‐fold EF% versus MSC‐EV in mouse myocardial injury model. A more in‐depth mechanistic study found that the NA@MEV could modulate M2 macrophage; promote angiogenesis; reduce DNA damage and response, and thereby restart cardiomyocyte proliferation. Thus, this combined therapy shows synthetic effects in heart repair and regeneration.
Engineering Cooperative Catalysis in Li–S Batteries
Authors: Qin Jinlei , Wang Rui , Xiao Pei , Wang Deli
Published: June 2023

Lithium–sulfur (Li–S) batteries are regarded to be one of the most promising next‐generation batteries owing to the merits of high theoretical capacity and low cost. However, the aprotic S electrochemistry is hampered by the shuttling effect and sluggish conversion of soluble lithium polysulfides (LiPSs). Various electrocatalysts have been designed to optimize the conversion kinetics of the LiPSs. Heteroatom doping or polar catalyst incorporation plays an important role to remedy these shortcomings. Here, the cooperative catalytic effects engendered by heteroatom codoping engineering, catalyst/heteroatom doping composite strategy, and integrating polar‐metal‐based material design are summarized. First, the design principles of the cooperative catalytic effect on the conductive interface are described in detail. Moreover, a systematic investigation of electrocatalytic kinetics characterization techniques that establish a bridge between the cooperative solid–liquid interface and the macroscopic electrochemical performance is highlighted, providing more scientific guidance for the catalyst design. In conclusion, stemming from the current achievements, future directions targeting the high‐energy‐density Li–S batteries for commercialization are proposed.
Waterlogging tolerance of winter crops: Root mass density and canopy dynamics
Authors: Ploschuk Rocio Antonella , Miralles Daniel Julio , Striker Gustavo Gabriel
Published: June 2023

Waterlogging has become an increasingly important abiotic stress. To develop strategies for mitigating its effects, it is crucial to identify traits that confer tolerance. Root mass density (RMD) is a pivotal trait for waterlogging tolerance; however, the behavior of this trait during waterlogging is not well understood. Therefore, two experimental years were conducted to study the effects of early‐ and late‐waterlogging at the canopy level on wheat (Triticum aestivum L., barley (Hordeum vulgare L.), oilseed rape (Brassica napus L.), and pea (Pisum sativum L.) crops in 1 m3 containers. The results showed that early‐waterlogging reduced RMD, green leaf, and stem dry weights (DWs) in wheat and barley. Nevertheless, they were able to recover without yield penalties. Late‐waterlogging had little impact on RMD in wheat and barley; however, it lowered the tiller number and caused accelerated leaf senescence, resulting in a 65% yield reduction in barley. Early‐waterlogged oilseed rape and pea also exhibited reduced RMD, with oilseed rape recovering with a 17% yield reduction, whereas pea was the most sensitive crop, showing no recovery and a 90% yield reduction. Overall, early‐ waterlogging generally reduces RMD, particularly in the shallow soil layer, but with recovery potential. In contrast, late‐ waterlogging affects yield by reducing tillers/branches and accelerating senescence, with little impact on RMD. Identifying these traits and their responses to waterlogging stress can aid in the development of strategies to mitigate the negative impacts of waterlogging on crops.
Using geometric morphometrics to determine the “fittest” floral shape: A case study in large‐flowered, buzz‐pollinated Meriania hernandoi
Authors: Dellinger Agnes S. , Hanusch Daniela , Oswald Mario , Fernández‐Fernández Diana , Schönenberger Jürg
Published: June 2023

Premise

Floral shape (relative arrangement and position of floral organs) is critical in mediating fit with pollinators and maximizing conspecific pollen transfer particularly in functionally specialized systems. To date, however, few studies have attempted to quantify flowers as the inherently three‐dimensional (3D) structures they are and determine the effect of intraspecific shape variation on pollen transfer. We here addressed this research gap using a functionally specialized system, buzz pollination, in which bees extract pollen through vibrations, as a model. Our study species, Meriania hernandoi (Melastomataceae), undergoes a floral shape change from pseudocampanulate corollas with more actinomorphically arranged stamens (first day) to open corollas with a more zygomorphic androecium (second day) over anthesis, providing a natural experiment to test how variation in floral shape affects pollination performance.

Methods

In one population of M. hernandoi, we bagged 51 pre‐anthetic flowers and exposed half of them to bee pollinators when they were in either stage of their shape transition. We then collected flowers, obtained 3D flower models through x‐ray computed tomography for 3D geometric morphometric analyses, and counted the pollen grains remaining per stamen (male pollination performance) and stigmatic pollen loads (female pollination performance).

Results

Male pollination performance was significantly higher in open flowers with zygomorphic androecia than in pseudo‐campanulate flowers. Female pollination performance did not differ among floral shapes.

Conclusions

These results suggest that there is an “optimal” shape for male pollination performance, while the movement of bees around the flower when buzzing the spread‐out stamens results in sufficient pollen deposition regardless of floral shape.
Synthesis of 2,3‐Disubstituted Indoles by Nickel(0)‐Catalyzed Migratory Cycloisomerization of o‐Alkynylanilides
Authors: Koshiba Mikiko , Furuki Yuto , Morisaki Kazuhiro , Doi Ryohei , Sato Yoshihiro
Published: June 2023

We herein report a nickel‐catalyzed migratory cycloisomerization of o‐alkynylanilides, giving 2,3‐disubstituted indoles in good yields. The cyclization proceeded via acyl transfer on the nitrogen atom of the substrate to C3‐position in the product, and an N‐heterocyclic carbene (NHC) ligand such as ICy or SICy was found to be suitable in this reaction. It was thought that the reaction proceeds via an aza‐nickelcyclepentene intermediate formed from alkyne and the C=O bond of the amide moiety in o‐alkynylanilides.
Anti‐apoptotic protein BCL‐XL as a therapeutic vulnerability in gastric cancer
Authors: Wei Yumin , Zhang Liping , Wang Chao , Li Zefeng , Luo Mingjie , Xie Guomin , Yang Xingjiu , Li Mengyuan , Ren Shuyue , Zhao Dongbing , Gao Ran , Gong Jia‐Nan
Published: June 2023

Background

New therapeutic targets are needed to improve the outcomes for gastric cancer (GC) patients with advanced disease. Evasion of programmed cell death (apoptosis) is a hallmark of cancer cells and direct induction of apoptosis by targeting the pro‐survival BCL2 family proteins represents a promising therapeutic strategy for cancer treatment. Therefore, understanding the molecular mechanisms underpinning cancer cell survival could provide a molecular basis for potential therapeutic interventions.

Method

Here we explored the role of BCL2L1 and the encoded anti‐apoptotic BCL‐XL in GC. Using Droplet Digital PCR (ddPCR) technology to investigate the DNA amplification of BCL2L1 in GC samples and GC cell lines, the sensitivity of GC cell lines to selective BCL‐XL inhibitors A1155463 and A1331852, pan‐inhibitor ABT‐263, and VHL‐based PROTAC‐BCL‐XL was analyzed using (CellTiter‐Glo) CTG assay in vitro. Western Blot (WB) was used to detect the protein expression of BCL2 family members in GC cell lines and the manner in which PROTAC‐BCL‐XL kills GC cells. Co‐immunoprecipitation (Co‐IP) was used to investigate the mechanism of A1331852 and ABT‐263 kills GC cell lines. DDPCR, WB, and real‐time PCR (RTPCR) were used to investigate the correlation between DNA, RNA, protein levels, and drug activity.

Results

The functional assay showed that a subset of GC cell lines relies on BCL‐XL for survival. In gastric cancer cell lines, BCL‐XL inhibitors A1155463 and A1331852 are more sensitive than the pan BCL2 family inhibitor ABT‐263, indicating that ABT‐263 is not an optimal inhibitor of BCL‐XL. VHL‐based PROTAC‐BCL‐XL DT2216 appears to be active in GC cells. DT2216 induces apoptosis of gastric cancer cells in a time‐ and dose‐dependent manner through the proteasome pathway. Statistical analysis showed that the BCL‐XL protein level predicts the response of GC cells to BCL‐XL targeting therapy and BCL2L1 gene CNVs do not reliably predict BCL‐XL expression.

Conclusion

We identified BCL‐XL as a promising therapeutic target in a subset of GC cases with high levels of BCL‐XL protein expression. Functionally, we demonstrated that both selective BCL‐XL inhibitors and VHL‐based PROTAC BCL‐XL can potently kill GC cells that are reliant on BCL‐XL for survival. However, we found that BCL2L1 copy number variations (CNVs) cannot reliably predict BCL‐XL expression, but the BCL‐XL protein level serves as a useful biomarker for predicting the sensitivity of GC cells to BCL‐XL‐targeting compounds. Taken together, our study pinpointed BCL‐XL as potential druggable target for specific subsets of GC.
Visualizing the Fractional Orbital Angular Momentum
Authors: Zhang Yong , Tu Jialong , Liu Zihan , He Shangling , Chen Hechong , Yang Xiangbo , Wang Guanghui , Deng Dongmei
Published: June 2023

This paper proposes a novel approach to visualize the fractional orbital angular amentum (OAM) flow of light fields at the example of the Lommel tornado wave (LoTW) along the propagation direction in free space. The novel approach that is based on the transverse intensity distributions of the LoTWs can be used to identify and quantify the fractional OAM. The energy that is continuously distributed flexibly is controlled via the asymmetry factor and topological charge. Furthermore, the OAM density on concentric rings and chiral paths is employed to demonstrate convincingly as a manifestation of the energy flow. Such beams are anticipated to find potential applications in optical communication and optical micromanipulation.
Hydrocarbon Oxidation by a Porphyrin‐π‐Cation Radical Complex
Authors: Lovisari Marta , Reid Kelly Oscar , McDonald Aidan R.
Published: June 2023

Heme and chlorin π‐cation radical oxidants are widely implicated in biological and synthetic oxidation catalysis. Little insight into the role of π‐cation radicals in proton coupled electron transfer (PCET) oxidation is available. We prepared a NiII‐porphyrin‐π‐cation complex ([NiII(P⋅+)]) and found it to be capable of the oxidation of a variety of simple hydrocarbon substrates. Interestingly, some of the products were hydroxylated, with ([NiII(P⋅+)]) working in concert with atmospheric O2 to yield hydroxylated hydrocarbons. Kinetic data suggested that the porphyrin‐π‐cation radical species oxidised substrates through a concerted PCET mechanism, where the porphyrin‐π‐cation radical accepted the electron, and the proton was transferred to a free anion. Our findings highlight the potential role of π‐cation radicals as hydrocarbon activators, demonstrating that porphyrin ligand non‐innocence could be a readily manipulated resource for oxidation catalyst development.
Electrode/Electrolyte Synergy for Concerted Promotion of Electron and Proton Transfers toward Efficient Neutral Water Oxidation
Authors: Hao Yaming , Kang Yikun , Wang Shaoyan , Chen Zhe , Lei Can , Cao Xueting , Chen Lin , Li Yefei , Liu Zhipan , Gong Ming
Published: June 2023

Neutral water oxidation is a crucial half‐reaction for various electrochemical applications requiring pH‐benign conditions. However, its sluggish kinetics with limited proton and electron transfer rates greatly impacts the overall energy efficiency. In this work, we created an electrode/electrolyte synergy strategy for simultaneously enhancing the proton and electron transfers at the interface toward highly efficient neutral water oxidation. The charge transfer was accelerated between the iridium oxide and in situ formed nickel oxyhydroxide on the electrode end. The proton transfer was expedited by the compact borate environment that originated from hierarchical fluoride/borate anions on the electrolyte end. These concerted promotions facilitated the proton‐coupled electron transfer (PCET) events. Due to the electrode/electrolyte synergy, Ir−O and Ir−OO− intermediates could be directly detected by in situ Raman spectroscopy, and the rate‐limiting step of Ir−O oxidation was determined. This synergy strategy can extend the scope of optimizing electrocatalytic activities toward more electrode/electrolyte combinations.
Combining Solid‐State NMR with Structural and Biophysical Techniques to Design Challenging Protein‐Drug Conjugates
Authors: Cerofolini Linda , Vasa Kristian , Bianconi Elisa , Salobehaj Maria , Cappelli Giulia , Bonciani Alice , Licciardi Giulia , Pérez‐Ràfols Anna , Padilla‐Cortés Luis , Antonacci Sabrina , Rizzo Domenico , Ravera Enrico , Viglianisi Caterina , Calderone Vito , Parigi Giacomo , Luchinat Claudio , Macchiarulo Antonio , Menichetti Stefano , Fragai Marco
Published: June 2023

Several protein‐drug conjugates are currently being used in cancer therapy. These conjugates rely on cytotoxic organic compounds that are covalently attached to the carrier proteins or that interact with them via non‐covalent interactions. Human transthyretin (TTR), a physiological protein, has already been identified as a possible carrier protein for the delivery of cytotoxic drugs. Here we show the structure‐guided development of a new stable cytotoxic molecule based on a known strong binder of TTR and a well‐established anticancer drug. This example is used to demonstrate the importance of the integration of multiple biophysical and structural techniques, encompassing microscale thermophoresis, X‐ray crystallography and NMR. In particular, we show that solid‐state NMR has the ability to reveal effects caused by ligand binding which are more easily relatable to structural and dynamical alterations that impact the stability of macromolecular complexes.
Direct Comparison of Lysine versus Site‐Specific Protein Surface Immobilization in Single‐Molecule Mechanical Assays**
Authors: Liu Haipei , Liu Zhaowei , Sá Santos Mariana , Nash Michael A.
Published: June 2023

Single‐molecule force spectroscopy (SMFS) is powerful for studying folding states and mechanical properties of proteins, however, it requires protein immobilization onto force‐transducing probes such as cantilevers or microbeads. A common immobilization method relies on coupling lysine residues to carboxylated surfaces using 1‐ethyl‐3‐(3‐dimethyl‐aminopropyl) carbodiimide and N‐hydroxysuccinimide (EDC/NHS). Because proteins typically contain many lysine groups, this strategy results in a heterogeneous distribution of tether positions. Genetically encoded peptide tags (e.g., ybbR) provide alternative chemistries for achieving site‐specific immobilization, but thus far a direct comparison of site‐specific vs. lysine‐based immobilization strategies to assess effects on the observed mechanical properties was lacking. Here, we compared lysine‐ vs. ybbR‐based protein immobilization in SMFS assays using several model polyprotein systems. Our results show that lysine‐based immobilization results in significant signal deterioration for monomeric streptavidin‐biotin interactions, and loss of the ability to correctly classify unfolding pathways in a multipathway Cohesin‐Dockerin system. We developed a mixed immobilization approach where a site‐specifically tethered ligand was used to probe surface‐bound proteins immobilized through lysine groups, and found partial recovery of specific signals. The mixed immobilization approach represents a viable alternative for mechanical assays on in vivo‐derived samples or other proteins of interest where genetically encoded tags are not feasible.
Pd‐Enriched‐Core/Pt‐Enriched‐Shell High‐Entropy Alloy with Face‐Centred Cubic Structure for C1 and C2 Alcohol Oxidation
Authors: Lao Xianzhuo , Liao Xuejiang , Chen Chen , Wang Jiasheng , Yang Likang , Li Ze , Ma Jun‐Wei , Fu Aiping , Gao Hongtao , Guo Peizhi
Published: June 2023

High‐entropy alloy nanoparticles (HEA NPs) have aroused great interest globally with their unique electrochemical, catalytic, and mechanical properties, as well as diverse activity and multielement tunability for multi‐step reactions. Herein, a facile low‐temperature synthesis method at atmospheric pressure is employed to synthesize Pd‐enriched‐HEA‐core and Pt‐enriched‐HEA‐shell NPs with a single phase of face‐centred cubic structure. Interestingly, the lattice of both Pd‐enriched‐HEA‐core and Pt‐enriched‐HEA‐shell enlarge during the formation process of HEA, with tensile strains included in the core and shell of HEA. The as‐obtained PdAgSn/PtBi HEA NPs show excellent electrocatalytic activity and durability for methanol oxidation reaction (MOR) and ethanol oxidation reaction (EOR). The specific (mass) activity of PdAgSn/PtBi HEA NPs for MOR is 4.7 mA cm−2 (2874 mA mg(Pd+Pt)−1), about 1.7 (5.9) and 1.5 (4.8) times higher than that of commercial Pd/C and Pt/C catalysts, respectively. Additional to high‐entropy effect, Pt sites and Pd sites on the interface of the HEA act synergistically to facilitate the multi‐step process towards EOR. This study offers a promising way to find a feasible route for scalable HEA manufacturing with promising applications.
Stepwise O2‐Induced Rearrangement and Disassembly of the [NiFe4(OH)(μ3‐S)4] Active Site Cluster of CO Dehydrogenase
Authors: Basak Yudhajeet , Jeoung Jae‐Hun , Domnik Lilith , Dobbek Holger
Published: June 2023

Ni,Fe‐containing carbon monoxide dehydrogenases (CODHs) catalyze the reversible reduction of carbon dioxide to carbon monoxide. CODHs are found in anaerobic microorganisms and can rapidly lose their activity when exposed to air. What causes the loss of activity is unclear. In this study, we analyzed the time‐dependent structural changes induced by the presence of air on the metal centers of CODH‐II. We show that inactivation is a multistep process. In a reversible step, the open coordination site on the Ni ion is blocked by a Ni,Fe‐bridging μ‐sulfido or chlorido ligand. Blocking this open coordination site with a cyanide ligand stabilizes the cluster against O2‐induced decomposition, indicating that O2 attacks at the Ni ion. In the subsequent irreversible phase, nickel is lost, the Fe ions rearrange and the sulfido ligands disappear. Our data are consistent with a reversible reductive reactivation mechanism to protect CODHs from transient over‐oxidation.
Platinum/Copper Dual‐Catalyzed Asymmetric Vinylogous Addition Reactions for the Synthesis of Functionalized Indoles
Authors: Hu Qingdong , Guo Chang
Published: June 2023

The development of multicomponent ligands to improve catalytic reactivity and selectivity remains a significant challenge for the synthesis of chiral building blocks. Here, a modular synthesis of structurally diverse multiligated platinum complexes, characterized by X‐ray crystallography, was revealed to open up a previously inaccessible reaction space. A library of more than 16 binary component‐ligated platinum complexes was identified as a practical toolkit to enable faster screening. The isolated bench‐stable PtII(oxazoline)(phosphine) complex paired with a chiral copper complex exhibits fundamentally new cooperative reactivity. The newly designed Pt/Cu dual catalytic system contributed to the development of highly enantioselective vinylogous addition reactions between a Pt‐activated electrophilic α,β‐unsaturated carbene and a Cu‐activated nucleophile, resulting in a reliable process for the asymmetric synthesis of valuable functionalized indoles in good yields and excellent enantioselectivities.
Platinum Metallacycle‐Based Molecular Recognition: Establishment and Application in Spontaneous Formation of a [2]Rotaxane with Light‐Harvesting Property
Authors: Shi Bingbing , Li Xupeng , Chai Yongping , Qin Peng , Zhou Yi , Qu Wen‐Juan , Lin Qi , Wei Tai‐Bao , Sun Yan , Stang Peter J.
Published: June 2023

Macrocyclic molecule‐based host–guest systems, which provide contributions for the design and construction of functional supramolecular structures, have gained increasing attention in recent years. In particular, platinum(II) metallacycle‐based host–guest systems provide opportunities for chemical scientists to prepare novel materials with various functions and structures due to the well‐defined shapes and cavity sizes of platinum(II) metallacycles. However, the research on platinum(II) metallacycle‐based host–guest systems has been given little attention. In this article, we demonstrate the host–guest complexation between a platinum(II) metallacycle and a polycyclic aromatic hydrocarbon molecule, naphthalene. Taking advantage of metallacycle‐based host–guest interactions and the dynamic property of reversible Pt coordination bonds, a [2]rotaxane is efficiently prepared by employing a template‐directed clipping procedure. The [2]rotaxane is further applied to the fabrication of an efficient light‐harvesting system with multi‐step energy transfer process. This work comprises an important supplement to macrocycle‐based host–guest systems and demonstrates a strategy for efficient production of well‐defined mechanically interlocked molecules with practical values.
Bismuth‐Catalyzed Amide Reduction
Authors: Yang Xiuxiu , Kuziola Jennifer , Béland Vanessa A. , Busch Julia , Leutzsch Markus , Burés Jordi , Cornella Josep
Published: June 2023

In this article we report that a cationic version of Akiba's BiIII complex catalyzes the reduction of amides to amines using silane as hydride donor. The catalytic system features low catalyst loadings and mild conditions, en route to secondary and tertiary aryl‐ and alkylamines. The system tolerates functional groups such as alkene, ester, nitrile, furan and thiophene. Kinetic studies on the reaction mechanism result in the identification of a reaction network with an important product inhibition that is in agreement with the experimental reaction profiles.
Tailoring Ion Ordering in Perovskite Oxide for High‐Temperature Oxygen Evolution Reaction
Authors: Liu Qingxue , Shen Feiran , Song Guohui , Liu Tianfu , Feng Weicheng , Li Rongtan , Zhang Xiaomin , Li Mingrun , He Lunhua , Zheng Xu , Yin Shuaishuai , Yin Guangzhi , Song Yuefeng , Wang Guoxiong , Bao Xinhe
Published: June 2023

Perovskites exhibit excellent high‐temperature oxygen evolution reaction (OER) activities as the anodes of solid oxide electrolysis cells (SOECs). However, the relationship between ion ordering and OER performances is rarely investigated. Herein, a series of PrBaCo2−xFexO5+δ perovskites with tailored ion orderings are constructed. Physicochemical characterizations and density functional theory calculations confirm that the oxygen bulk migration and surface transport capacities as well as the OER activities are promoted by the A‐site cation ordering, but weakened by the oxygen vacancy ordering. Hence, SOEC with the A‐site‐ordered and oxygen‐vacancy‐disordered PrBaCo2O5+δ anode exhibits the highest performance of 3.40 A cm−2 at 800 °C and 2.0 V. This work sheds light on the critical role of ion orderings in the high‐temperature OER performance and paves a new way for screening novel anode materials of SOECs.
Engineered Histidine‐Rich Peptides Enhance Endosomal Escape for Antibody‐Targeted Intracellular Delivery of Functional Proteins
Authors: Zhao Yan , Jiang Haolin , Yu Jiazhen , Wang Luyao , Du Juanjuan
Published: June 2023

Currently, the clinical application of protein/peptide therapeutics is mainly limited to the modulation of diseases in extracellular spaces. Intracellular targets are hardly accessed, owing largely to the endosomal entrapment of internalized proteins/peptides. Here, we report a strategy to design and construct peptides that enable endosome‐to‐cytosol delivery based on an extension of the “histidine switch” principle. By substituting the Arg/Lys residues in cationic cell‐penetrating peptides (CPPs) with histidine, we obtained peptides with pH‐dependent membrane‐perturbation activity. These peptides do not randomly penetrate cells like CPPs, but imitate the endosomal escape of CPPs following cellular uptake. Working with one such 16‐residue peptide (hsLMWP) with high endosomal escape capacity, we engineered modular fusion proteins and achieved antibody‐targeted delivery of diverse protein cargoes—including the pro‐apoptotic protein BID (BH3‐interacting domain death agonist) and Cre recombinase—into the cytosol of multiple cancer cell types. After extensive in vitro testing, an in vivo analysis with xenograft mice ultimately demonstrated that a trastuzumab‐hsLMWP‐BID fusion conferred strong anti‐tumor efficacy without apparent side effects. Notably, our fusion protein features a modular design, allowing flexible applications for any antibody/cargo combination of choice. Therefore, the potential applications extend throughout life science and biomedicine, including gene editing, cancer treatment, and immunotherapy.
Preparative Scale Applications of C−H Activation in Medicinal Chemistry
Authors: de Jesus Rita , Hiesinger Kerstin , van Gemmeren Manuel
Published: June 2023

C−H activation is an attractive methodology to increase molecular complexity without requiring substrate prefunctionalization. In contrast to well‐established cross‐coupling methods, C−H activation is less explored on large scales and its use in the production of pharmaceuticals faces substantial hurdles. However, the inherent advantages, such as shorter synthetic routes and simpler starting materials, motivate medicinal chemists and process chemists to overcome these challenges, and exploit C−H activation steps for the synthesis of pharmaceutically relevant compounds. In this review, we will cover examples of drugs/drug candidates where C−H activation has been implemented on a preparative synthetic scale (range between 355 mg and 130 kg). The optimization processes will be described, and each example will be examined in terms of its advantages and disadvantages, providing the reader with an in‐depth understanding of the challenges and potential of C−H activation methodologies in the production of pharmaceuticals.
Toughening of alicyclic epoxy resin by in situ polymerization of modifier vinyl monomers using alkylborane as a radical initiator
Authors: Kajihara Yuri , Oyama Toshiyuki
Published: June 2023

In this study, we attempted to improve the toughness of alicyclic epoxy cured resin using a vinyl polymer as a modifier which was generated with alkylborane as a radical initiator in parallel with the curing of the resin. Alkylborane has the ability to initiate radical polymerization around room temperature in the presence of oxygen, and the use of diethylmethoxyborane (DEMB) instead of a conventional peroxide radical initiator (DBPC) was found to allow copolymerization of styrene (St) and N‐phenylmaleimide (NPMI) in an alicyclic epoxy resin in the early stage of the multistep curing. As a result, only when DEMB was used as an initiator, a cured product with a phase‐separated structure at which ca. 50–100 nm St/NPMI copolymer phases were dispersed was obtained. The fracture toughness (KIC) of the modified cured resin with DEMB was 0.77 MN/m3/2, which was 30% higher than that of the modified resin with DBPC. Furthermore, the glass transition temperature of the modified cured resin with DEMB reached 247°C, which was 87 and 63°C higher than the unmodified rein and the modified resin with DBPC, respectively, since DEMB acted as a Lewis acid to promote cationic polymerization of the alicyclic epoxy resin.
Characterization of glutathione‐specific gamma glutamyl cyclotransferase (ChaC) in Bombyx mori
Authors: Afrin Wazifa , Yamada Naotaka , Furuya Shigeki , Yamamoto Kohji
Published: June 2023

Glutathione (GSH) contributes to redox maintenance and detoxification of various xenobiotic and endogenous substances. γ‐glutamyl cyclotransferase (ChaC) is involved in GSH degradation. However, the molecular mechanism underlying GSH degradation in silkworms (Bombyx mori) remains unknown. Silkworms are lepidopteran insects that are considered to be an agricultural pest model. We aimed to examine the metabolic mechanism underlying GSH degradation mediated by B. mori ChaC and successfully identified a novel ChaC gene in silkworms (herein, bmChaC). The amino acid sequence and phylogenetic tree revealed that bmChaC was closely related to mammalian ChaC2. We overexpressed recombinant bmChaC in Escherichia coli, and the purified bmChaC showed specific activity toward GSH. Additionally, we examined the degradation of GSH to 5‐oxoproline and cysteinyl glycine via liquid chromatography–tandem mass spectrometry. Quantitative real‐time polymerase chain reaction revealed that bmChaC mRNA expression was observed in various tissues. Our results suggest that bmChaC participates in tissue protection via GSH homeostasis. This study provides new insights into the activities of ChaC and the underlying molecular mechanisms that can aid the development of insecticides to control agricultural pests.
Inorganic polyphosphate's role in energy production and mitochondrial permeability transition pore opening in tick mitochondria
Authors: Domingues George , Moraes Jorge , Fonseca Rodrigo Nunes da , Campos Eldo
Published: June 2023

Inorganic polyphosphate (polyP) is a biopolymer composed of phosphoanhydride‐linked orthophosphate molecules. PolyP is engaged in a variety of cellular functions, including mitochondrial metabolism. Here, we examined the effects of polyP on electron transport chain enzymes and F1Fo ATP synthase in tick embryos during embryonic development. The study found that polyPs containing medium and long chains (polyP15 and polyP65) enhanced the activity of complex I, complex II, complex III, and F1Fo ATP synthase, while short polyP chains (polyP3) had no effect. The study also examined the activity of exopolyphosphatases (PPX) in various energy‐demand situations. PPX activity was stimulated when ADP concentrations are high, characterizing a low‐energy context. When complexes I–III and F1Fo ATP synthase inhibitors were added in energized mitochondria, PPX activity decreased, whereas the mitochondrial uncoupler FCCP had no impact on PPX activity. Additionally, the study investigated the effect of polyP on mitochondrial swelling, finding that polyP causes mitochondrial swelling by increasing calcium effects on the mitochondrial permeability transition pore. The findings presented here to increase our understanding of the function of polyP in mitochondrial metabolism and its relationship to mitochondrial permeability transition pore opening in an arthropod model.
Identification and characterization of Prx5 and Prx6 in Chilo suppressalis in response to environmental stress
Authors: Mo Wujia , Li Qiang , He Xiaochan , Lu Zhongxian , Xu Hongxing , Zheng Xusong , Guo Jiawen , Lu Yanhui , Wang Shuping
Published: June 2023

The antioxidant proteins, peroxiredoxins (Prxs), function to protect insects from reactive oxygen species‐induced toxicity. In this study, two Prx genes, CsPrx5, and CsPrx6, were cloned and characterized from the paddy field pest, Chilo suppressalis, containing open reading frames of 570 and 672 bp encoding 189 and 223 amino acid polypeptides, respectively. Then, we investigated the influence of various stresses on their expression levels using quantitative real‐time PCR (qRT‐PCR). The results showed expression of CsPrx5 and CsPrx6 in all developmental stages, with eggs having the highest level. CsPrx5 and CsPrx6 showed higher expression in the epidermis and fat body, and CsPrx6 also showed higher expression in midgut, fat body, and epidermis. Increasing concentrations of insecticides (chlorantraniliprole and spinetoram) and hydrogen peroxide (H2O2) increased the expression levels of CsPrx5 and CsPrx6. In addition, the expression levels of CsPrx5 and CsPrx6 were almost markedly upregulated in larvae under temperature stress or fed by vetiver. Thus, CsPrx5 and CsPrx6 upregulation might increase the C. suppressalis defense response by reducing the impact of environmental stress, providing a better understanding of the relationship between environmental stresses and insect defense systems.
Benzotriazole scaffold: An overview of antiproliferative potential, mechanisms of action, and structure–activity relationships
Authors: Kassab Asmaa E.
Published: June 2023

Being an isostere of the purine nucleus, which is found in naturally occurring nucleotides like ATP and other naturally available substances, benzotriazole is not surprising for its broad‐spectrum biological activity. Benzotriazole is widely used by medicinal chemists as a privileged scaffold for the identification and development of novel bioactive compounds and drug candidates. Additionally, benzotriazole is a structural motif of seven pharmaceuticals; some of these compounds are approved, commercially available medications, while others are experimental drugs still under investigation. This review highlights the defining role of benzotriazole derivatives in the search for potential anticancer agents published in the literature from 2008 to 2022; it also discusses their mechanisms of action and structure–activity relationship investigations.