bluuebunny/crossref_metadata_2025 huggingface dataset:
Peripheral HMGB1 is linked to O3 pathology of disease‐associated astrocytes and amyloid
Authors: Ahmed Chandrama , Greve Hendrik J. , Garza‐Lombo Carla , Malley Jamie A. , Johnson James A. , Oblak Adrian L. , Block Michelle L.
Published: April 2024

INTRODUCTION

Ozone (O3) is an air pollutant associated with Alzheimer's disease (AD) risk. The lung–brain axis is implicated in O3‐associated glial and amyloid pathobiology; however, the role of disease‐associated astrocytes (DAAs) in this process remains unknown.

METHODS

The O3‐induced astrocyte phenotype was characterized in 5xFAD mice by spatial transcriptomics and proteomics. Hmgb1fl/fl LysM‐Cre+ mice were used to assess the role of peripheral myeloid cell high mobility group box 1 (HMGB1).

RESULTS

O3 increased astrocyte and plaque numbers, impeded the astrocyte proteomic response to plaque deposition, augmented the DAA transcriptional fingerprint, increased astrocyte–microglia contact, and reduced bronchoalveolar lavage immune cell HMGB1 expression in 5xFAD mice. O3‐exposed Hmgb1fl/fl LysM‐Cre+ mice exhibited dysregulated DAA mRNA markers.

DISCUSSION

Astrocytes and peripheral myeloid cells are critical lung–brain axis interactors. HMGB1 loss in peripheral myeloid cells regulates the O3‐induced DAA phenotype. These findings demonstrate a mechanism and potential intervention target for air pollution–induced AD pathobiology.

Highlights

Astrocytes are part of the lung–brain axis, regulating how air pollution affects plaque pathology.

Ozone (O3) astrocyte effects are associated with increased plaques and modified by plaque localization.

O3 uniquely disrupts the astrocyte transcriptomic and proteomic disease‐associated astrocyte (DAA) phenotype in plaque associated astrocytes (PAA).

O3 changes the PAA cell contact with microglia and cell–cell communication gene expression.

Peripheral myeloid cell high mobility group box 1 regulates O3‐induced transcriptomic changes in the DAA phenotype.
Electrochemical Asymmetric Radical Functionalization of Aldehydes Enabled by a Redox Shuttle
Authors: Mazzarella Daniele , Qi Chun , Vanzella Michael , Sartorel Andrea , Pelosi Giorgio , Dell'Amico Luca
Published: April 2024

Aminocatalysis is a well‐established tool that enables the production of enantioenriched compounds under mild conditions. Its versatility is underscored by its seamless integration with various synthetic approaches. While the combination of aminocatalysis with metal catalysis, photochemistry, and stoichiometric oxidants has been extensively explored, its synergy with electrochemical activation remains largely unexplored. Herein, we present the successful merger of electrochemistry and aminocatalysis to perform SOMO‐type transformations, expanding the toolkit for asymmetric electrochemical synthesis. The methodology harnesses electricity to drive the oxidation of catalytically generated enamines, which ultimately partake in enantioselective radical processes, leading to α‐alkylated aldehydes. Crucially, mechanistic studies highlight how this electrochemical strategy is enabled by the use of a redox shuttle, 4,4′‐dimethoxybiphenyl, to prevent catalyst degradation and furnishing the coveted compounds in good yield and high enantioselectivity.
Alveoli‐Inspired Carbon Cathodes with Interconnected Porous Structure and Asymmetric Coordinated Vanadium Sites for Superior Li−S Batteries
Authors: Yan Rui , Zhao Zhenyang , Zhu Ran , Wu Min , Liu Xu , Adeli Mohsen , Yin Bo , Cheng Chong , Li Shuang
Published: April 2024

Accelerating sulfur conversion catalysis to alleviate the shuttle effect has become a novel paradigm for effective Li−S batteries. Although nitrogen‐coordinated metal single‐atom (M−N4) catalysts have been investigated, further optimizing its utilization rate and catalytic activities is urgently needed for practical applications. Inspired by the natural alveoli tissue with interconnected structure and well‐distributed enzyme catalytic sites on the wall for the simultaneously fast diffusion and in situ catalytic conversion of substrates, here, we proposed the controllable synthesis of bioinspired carbon cathode with interconnected porous structure and asymmetric coordinated V−S1N3 sites for efficient and stable Li−S batteries. The enzyme‐mimetic V−S1N3 shows asymmetric electronic distribution and high tunability, therefore enhancing in situ polysulfide conversion activities. Experimental and theoretical results reveal that the high charge asymmetry degree and large atom radius of S in V−S1N3 result in sloping adsorption for polysulfide, thereby exhibiting low thermodynamic energy barriers and long‐range stability (0.076 % decay over 600 cycles).
Breaking Highly Ordered PtPbBi Intermetallic with Disordered Amorphous Phase for Boosting Electrocatalytic Hydrogen Evolution and Alcohol Oxidation
Authors: Feng Fukai , Ma Chaoqun , Han Sumei , Ma Xiao , He Caihong , Zhang Huaifang , Cao Wenbin , Meng Xiangmin , Xia Jing , Zhu Lijie , Tian Yahui , Wang Qi , Yun Qinbai , Lu Qipeng
Published: April 2024

Constructing amorphous/intermetallic (A/IMC) heterophase structures by breaking the highly ordered IMC phase with disordered amorphous phase is an effective way to improve the electrocatalytic performance of noble metal‐based IMC electrocatalysts because of the optimized electronic structure and abundant heterophase boundaries as active sites. In this study, we report the synthesis of ultrathin A/IMC PtPbBi nanosheets (NSs) for boosting hydrogen evolution reaction (HER) and alcohol oxidation reactions. The resulting A/IMC PtPbBi NSs exhibit a remarkably low overpotential of only 25 mV at 10 mA cm−2 for the HER in an acidic electrolyte, together with outstanding stability for 100 h. In addition, the PtPbBi NSs show high mass activities for methanol oxidation reaction (MOR) and ethanol oxidation reaction (EOR), which are 13.2 and 14.5 times higher than those of commercial Pt/C, respectively. Density functional theory calculations demonstrate that the synergistic effect of amorphous/intermetallic components and multimetallic composition facilitate the electron transfer from the catalyst to key intermediates, thus improving the catalytic activity of MOR. This work establishes a novel pathway for the synthesis of heterophase two‐dimensional nanomaterials with high electrocatalytic performance across a wide range of electrochemical applications.
Ternary Complex‐Templated Dynamic Combinatorial Chemistry for the Selection and Identification of Homo‐PROTACs
Authors: Diehl Claudia J. , Salerno Alessandra , Ciulli Alessio
Published: April 2024

Dynamic combinatorial chemistry (DCC) leverages a reversible reaction to generate compound libraries from constituting building blocks under thermodynamic control. The position of this equilibrium can be biased by addition of a target macromolecule towards enrichment of bound ligands. While DCC has been applied to select ligands for a single target protein, its application to identifying chimeric molecules inducing proximity between two proteins is unprecedented. In this proof‐of‐concept study, we develop a DCC approach to select bifunctional proteolysis targeting chimeras (PROTACs) based on their ability to stabilize the ternary complex. We focus on VHL‐targeting Homo‐PROTACs as model system, and show that the formation of a VHL2 : Homo‐PROTAC ternary complex reversibly assembled using thiol‐disulfide exchange chemistry leads to amplification of potent VHL Homo‐PROTACs with degradation activities which correlated well with their biophysical ability to dimerize VHL. Ternary complex templated dynamic combinatorial libraries allowed identification of novel Homo‐PROTAC degraders. We anticipate future applications of ternary‐complex directed DCC to early PROTAC screenings and expansion to other proximity‐inducing modalities beyond PROTACs.
Ternary Rotational Polyanion Coupling Enables Fast Li Ion Dynamics in Tetrafluoroborate Ion Doped Antiperovskite Li2OHCl Solid Electrolyte
Authors: Bian Juncao , Ling Sifan , Deng Bei , Lin Haibin , Zhao Ruo , Kong Long , Yuan Huimin , Zhu Jinlong , Han Songbai , Wang Liping , Zhang Rui‐Qin , Zhao Yusheng , Lu Zhouguang
Published: April 2024

Li‐rich antiperovskite (LiRAP) hydroxyhalides are emerging as attractive solid electrolyte (SEs) for all‐solid‐state Li metal batteries (ASSLMBs) due to their low melting point, low cost, and ease of scaling‐up. The incorporation of rotational polyanions can reduce the activation energy and thus improve the Li ion conductivity of SEs. Herein, we propose a ternary rotational polyanion coupling strategy to fasten the Li ion conduction in tetrafluoroborate (BF4−) ion doped LiRAP Li2OHCl. Assisted by first‐principles calculation, powder X‐ray diffraction, solid‐state magnetic resonance and electrochemical impedance spectra, it is confirmed that Li ion transport in BF4− ion doped Li2OHCl is strongly associated with the rotational coupling among OH−, BF4− and Li2−O−H octahedrons, which enhances the Li ion conductivity for more than 1.8 times with the activation energy lowering 0.03 eV. This work provides a new perspective to design high‐performance superionic conductors with multi‐polyanions.
Anion‐Coordination Foldamer‐Based Polymer Network: from Molecular Spring to Elastomer
Authors: Qin Jiangping , Wang Yongming , Wang Tian , Wang Na , Xu Wenhua , Cheng Lin , Yu Wei , Yan Xuzhou , Gao Lingyan , Zheng Bo , Wu Biao
Published: April 2024

Foldamer is a scaled‐down version of coil spring, which can absorb and release energy by conformational change. Here, polymer networks with high density of molecular springs were developed by employing anion‐coordination‐based foldamers as the monomer. The coiling of the foldamer is controlled by oligo(urea) ligands coordinating to chloride ions; subsequently, the folding and unfolding of foldamer conformations endow the polymer network with excellent energy dissipation and toughness. The mechanical performance of the corresponding polymer networks shows a dramatic increase from P‐L2UCl (non‐folding), to P‐L4UCl (a full turn), and then to P‐L6UCl (1.5 turns), in terms of strength (2.62 MPa; 14.26 MPa; 22.93 MPa), elongation at break (70 %; 325 %; 352 %), Young's modulus (2.69 MPa; 63.61 MPa; 141.50 MPa), and toughness (1.12 MJ/m3; 21.39 MJ/m3; 49.62 MJ/m3), respectively, which is also better than those without anion centers and the non‐foldamer based counterparts. Moreover, P‐L6UCl shows enhanced strength and toughness than most of the molecular‐spring based polymer networks. Thus, an effective strategy for designing high‐performance anion‐coordination‐based materials is presented.
Fabrication of Large‐Area Multi‐Stimulus Responsive Thin Films via Interfacially Confined Irreversible Katritzky Reaction
Authors: Shu Yuanhong , Luo Yan , Wei Hexi , Peng Lingya , Liang Jingjing , Zhai Binbin , Ding Liping , Fang Yu
Published: April 2024

Fabrication of large‐area thin films through irreversible reactions remains a formidable task. This study reports a breakthrough strategy for in situ synthesis of large‐area, free‐standing, robust and multi‐stimulus responsive thin films through a catalyst‐free and irreversible Katritzky reaction at a liquid–liquid interface. The as resulted films are featured with adjustable thickness of 1–3 μm and an area up to 50 cm2. The thin films exhibit fast photo‐mechanical motions (a response time of ca 0.1 s), vapor‐mechanical motions, as well as photo‐chromic and solvato‐chromic behaviors. It was revealed that the reason behind the observable motions is proton transfer from the imine groups to the carbonyl structures within the film induced by photo‐ and/or dimethyl sulfoxide‐stimulus. In addition, the films can harvest anionic radicals and the radicals as captured can be efficiently degraded under UV light illumination. This study provides a new strategy for fabricating smart thin films via interfacially confined irreversible Katritzky reaction.
Regulating Sulfur Redox Kinetics by Coupling Photocatalysis for High‐Performance Photo‐Assisted Lithium‐Sulfur Batteries
Authors: Liu Yuhao , Wu Feng , Hu Zhengqiang , Zhang Fengling , Wang Ke , Li Li , Chen Renjie
Published: April 2024

Challenges such as shuttle effect have hindered the commercialization of lithium‐sulfur batteries (LSBs), despite their potential as high‐energy‐density storage devices. To address these issues, we explore the integration of solar energy into LSBs, creating a photo‐assisted lithium‐sulfur battery (PA‐LSB). The PA‐LSB provides a novel and sustainable solution by coupling the photocatalytic effect to accelerate sulfur redox reactions. Herein, a perovskite quantum dot‐loaded MOF material serves as a cathode for the PA‐LSB, creating built‐in electric fields at the micro‐interface to extend the lifetime of photo‐generated charge carriers. The band structure of the composite material aligns well with the electrochemical reaction potential of lithium‐sulfur, enabling precise regulation of polysulfides in the cathode of the PA‐LSB system. This is attributed to the selective catalysis of the liquid‐solid reaction stage in the lithium‐sulfur electrochemical process by photocatalysis. These contribute to the outstanding performance of PA‐LSBs, particularly demonstrating a remarkably high reversible capacity of 679 mAh g−1 at 5 C, maintaining stable cycling for 1500 cycles with the capacity decay rate of 0.022 % per cycle. Additionally, the photo‐charging capability of the PA‐LSB holds the potential to compensate for non‐electric energy losses during the energy storage process, contributing to the development of lossless energy storage devices.
Ethylenedioxythiophene‐Based Small Molecular Donor with Multiple Conformation Locks for Organic Solar Cells with Efficiency of 19.3 %
Authors: Xie Qian , Deng Xiangmeng , Zhao Chaowei , Fang Jie , Xia Dongdong , Zhang Yuefeng , Ding Feng , Wang Jiali , Li Mengdi , Zhang Zhou , Xiao Chengyi , Liao Xunfan , Jiang Lang , Huang Bin , Dai Runying , Li Weiwei
Published: April 2024

Ternary organic solar cells (T‐OSCs) represent an efficient strategy for enhancing the performance of OSCs. Presently, the majority of high‐performance T‐OSCs incorporates well‐established Y‐acceptors or donor polymers as the third component. In this study, a novel class of conjugated small molecules has been introduced as the third component, demonstrating exceptional photovoltaic performance in T‐OSCs. This innovative molecule comprises ethylenedioxythiophene (EDOT) bridge and 3‐ethylrhodanine as the end group, with the EDOT unit facilitating the creation of multiple conformation locks. Consequently, the EDOT‐based molecule exhibits two‐dimensional charge transport, distinguishing it from the thiophene‐bridged small molecule, which displays fewer conformation locks and provides one‐dimensional charge transport. Furthermore, the robust electron‐donating nature of EDOT imparts the small molecule with cascade energy levels relative to the electron donor and acceptor. As a result, OSCs incorporating the EDOT‐based small molecule as the third component demonstrate enhanced mobilities, yielding a remarkable efficiency of 19.3 %, surpassing the efficiency of 18.7 % observed for OSCs incorporating thiophene‐based small molecule as the third component. The investigations in this study underscore the excellence of EDOT as a building block for constructing conjugated materials with multiple conformation locks and high charge carrier mobilities, thereby contributing to elevated photovoltaic performance in OSCs.
Photoswitching Reagent for Super‐Resolution Fluorescence Microscopy
Authors: Go Ga‐eun , Jeong Uidon , Park Hyunbum , Go Seokran , Kim Doory
Published: April 2024

Single‐molecule localization microscopy (SMLM) has revolutionized optical microscopy by exceeding the diffraction limit and revealing previously unattainable nanoscale details of cellular structures and molecular dynamics. This super‐resolution imaging capability relies on fluorophore photoswitching, which is crucial for optimizing the imaging conditions and accurately determining the fluorophore positions. To understand the general on and off photoswitching mechanisms of single dye molecules, various photoswitching reagents were evaluated. Systematic measurement of the single‐molecule‐level fluorescence on and off rates (kon and koff) in the presence of various photoswitching reagents and theoretical calculation of the structure of the photoswitching reagent‐fluorophore pair indicated that the switch‐off mechanism is mainly determined by the nucleophilicity of the photoswitching reagent, and the switch‐on mechanism is a two‐photon‐induced dissociation process, which is related to the power of the illuminating laser and bond dissociation energy of this pair. This study contributes to a broader understanding of the molecular photoswitching mechanism in SMLM imaging and provides a basis for designing improved photoswitching reagents with potential applications extending to materials science and chemistry.
Biobased and biodegradable imine vitrimers from epoxidized soybean oil as packaging
Authors: Safarpour Milad , Zych Arkadiusz , Najafi Maedeh , Tedeschi Giacomo , Ceseracciu Luca , Marini Lara , Perotto Giovanni , Athanassiou Athanassia
Published: April 2024

A flexible and stretchable vitrimer was synthesized using exclusively biobased building blocks and following green chemistry principles. Epoxidized soybean oil (ESO), vanillin, the biobased diamine, Priamine®, and oleic acid were used to create a material that can replace fossil‐derived, non‐biodegradable packaging. Vanillin and Priamine® were used to develop a crosslinker that could react with the epoxide groups of ESO without the need for solvents, with a catalyst‐free synthesis that does not generate any waste or byproducts. Oleic acid was incorporated, to tune the properties of the final material, since it can react with ESO and control the crosslink density. The vitrimers produced in this work showed excellent reprocessability and recyclability. They possess the ability to be molded, and they can also strongly adhere on surfaces. Moreover, they exhibited oxygen and water vapor barrier comparable to low density polyethylene, while showing very low migration into food simulant, which position them as a promising material for flexible food and general packaging market. The vitrimers showed also the capability of biodegradation in seawater, providing a safe end of life in case of mismanagement.
Perceptions regarding the recreational cobia fishery in relation to manta ray conservation
Authors: Braun Raquel , Wester Julia , Macdonald Catherine , Pate Jessica H.
Published: April 2024

Understanding fisheries requires not only traditional modelling approaches but also the incorporation of local ecological knowledge (LEK) which can provide other types of essential contextualizing knowledge.

Recreational anglers within the cobia fishery on the east coast of central and northern Florida target cobia by seeking out the manta rays cobia often follow and associate with, and casting at or near them. Results suggest this fishery poses a threat of entanglement, injury and disturbance to mantas in the region, especially associated with the practices and behaviours of inexperienced anglers.

Expert angler responses in interviews described changes in manta and cobia habitat use and reductions in cobia abundance

Experienced anglers pointed to social media as a key driver of the expansion of this fishery and as an explanation for their perception of the growing presence of novice anglers engaged in these practices. Respondents proposed best practices and potential management interventions and generally supported conservation action, including through willingness to engage with researchers and support management and enforcement measures related to the fishery.
Identification of Suitable Mesh Size of Commercial Stainless‐Steel for Electrochemical Oxygen Evolution Reaction
Authors: Hardianto Yuda Prima , Aziz Md. Abdul , Mohamed Mostafa M. , Yamani Zain H.
Published: April 2024

The study examines the oxygen evolution reaction (OER) electrocatalytic efficiency of various stainless‐steel mesh (SSM) sizes in electrolytic cells. Stainless steel is chosen due to its widespread availability and stability, making it an economically viable option. The primary objective of this investigation is to determine the optimal stainless‐steel mesh size among those currently widely available on the market. The classification of stainless‐steel mesh sizes as SS304 is confirmed by the minimal compositional variations observed across all mesh sizes through electron dispersive X‐ray (EDX) spectra and X‐ray fluorescence (XRF) analyses. Remarkably, CV experiments carried out at different scan rates indicate that SSM 200 has the maximum specific electrochemical surface area (ECSA). As a result, SSM 200 demonstrates superior performance in terms of current density response and shows the lowest overpotential in the alkaline medium compared to other stainless‐steel mesh sizes. Furthermore, the SSM 200 exhibits a low overpotential of 337 mV at a current density of 10 mA/cm2 and a Tafel slope of 62.2 mV/decade, surpassing the performance of several previously reported electrodes for the OER. Stability tests conducted under constant voltage further confirm the remarkable stability of SSM 200, making it an ideal anode for electrolytic cell applications. These findings emphasize the cost‐effectiveness and high stability of SSM 200, presenting intriguing possibilities for future research and advancements in this field.
Stabilization of coupled delayed nonlinear time fractional reaction diffusion systems using sampled‐in‐space sensing and actuation
Authors: Chen Tiane , Chen Juan , Zhuang Bo
Published: April 2024

This paper is considered with the asymptotic stabilization of coupled delayed nonlinear time fractional reaction diffusion systems (FRDSs) governed by fractional parabolic partial differential equations (PDEs) with space‐dependent coefficients under sampled‐data in space control. It is assumed that state measurements can be averaged measurements (AMs) or point measurements (PMs), and a finite number of sensing and actuation devices are located in a spaced manner along the spatial domain of the interest. With the proposed sampled‐data in space controller, the closed‐loop
stability is obtained. Tuning rules of system parameters and control parameters are derived using the fractional Halanay's inequality and the fractional Lyapunov method. Subsequently, the dual problem of observer design is formulated. Fractional examples are used to valid the theoretical result. Discussions on the extension of sampled‐data boundary feedback stabilization are provided finally.
Fluid shear force and hydrostatic pressure jointly promote osteogenic differentiation of BMSCs by activating YAP1 and NFAT2
Authors: Zhou Yi , Guo Pan , Jin Ziyang , Chai Miaomiao , Zhang Shuhong , Wang Xianwei , Tan Wen‐Song , Zhou Yan
Published: April 2024

Natural bone tissue features a complex mechanical environment, with cells responding to diverse mechanical stimuli, including fluid shear stress (FSS) and hydrostatic pressure (HP). However, current in vitro experiments commonly employ a singular mechanical stimulus to simulate the mechanical environment in vivo. The understanding of the combined effects and mechanisms of multiple mechanical stimuli remains limited. Hence, this study constructed a mechanical stimulation device capable of simultaneously applying FSS and HP to cells. This study investigated the impact of FSS and HP on the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and examined the distinctions and interactions between the two mechanisms. The results demonstrated that both FSS and HP individually enhanced the osteogenic differentiation of BMSCs, with a more pronounced effect observed through their combined application. BMSCs responded to external FSS and HP stimulation through the integrin‐cytoskeleton and Piezo1 ion channel respectively. This led to the activation of downstream biochemical signals, resulting in the dephosphorylation and nuclear translocation of the intracellular transcription factors Yes Associated Protein 1 (YAP1) and nuclear factor of activated T cells 2 (NFAT2). Activated YAP1 could bind to NFAT2 to enhance transcriptional activity, thereby promoting osteogenic differentiation of BMSCs more effectively. This study highlights the significance of composite mechanical stimulation in BMSCs' osteogenic differentiation, offering guidance for establishing a complex mechanical environment for in vitro functional bone tissue construction.
Pediatric traumatic brain injury and early age multiple sclerosis in Finland: A nationwide register‐based cohort study
Authors: Laaksonen Juho , Ponkilainen Ville , Kuitunen Ilari , Möttönen Julius , Mattila Ville M.
Published: April 2024

Objective

Examine the link between pediatric traumatic brain injury (pTBI) and early‐onset multiple sclerosis in Finland.

Methods

Conducted nationwide register study (1998−2018) with 28,750 pTBI patients (< 18) and 38,399 pediatric references with extremity fractures. Multiple sclerosis diagnoses from Finnish Social Insurance Institution. Employed Kaplan−Meier and multivariable Cox regression for probability assessment, results presented with 95% CI.

Results

Of 66 post‐traumatic multiple sclerosis cases, 30 (0.10%) had pTBI, and 36 (0.09%) were in the reference group. Cumulative incidence rates (CIR) in the first 10 years were 46.5 per 100,000 (pTBI) and 33.1 per 100,000 (reference). Hazard ratio (HR) for pTBI was 1.10 (95% CI: 0.56−1.48).Stratified by gender, women's CIR was 197.9 per 100,000 (pTBI) and 167.0 per 100,000 (reference) after 15 years. For men, CIR was 44.6 per 100,000 (pTBI) and 34.7 per 100,000 (reference). In the initial 3 years, HR for female pTBI was 1.75 (95% CI: 0.05−6.32), and between years 3 and 20, it was 1.08 (95% CI: 0.51−1.67). For male patients, HR was 1.74 (95% CI: 0.69−4.39).

Significance

We did not find evidence of an association between pTBI and early‐onset multiple sclerosis 20 years post‐initial trauma.
MAPK4 facilitates angiogenesis by inhibiting the ERK pathway in non‐small cell lung cancer
Authors: Chen Jing , Yang Jing , Liu Yufang , Zhao Xu , Zhao Juanjuan , Tang Lin , Guo Mengmeng , Zhou Ya , Chen Chao , Li Dongmei , Wen Zhenke , Liang Guiyou , Xu Lin
Published: April 2024

Background

Angiogenesis plays an important role in the occurrence and development of non‐small cell lung cancer (NSCLC). The atypical mitogen‐activated protein kinase 4 (MAPK4) has been shown to be involved in the pathogenesis of various diseases. However, the potential role of MAPK4 in the tumor angiogenesis of NSCLC remains unclear.

Methods

Adult male C57BL/6 wild‐type mice were randomly divided into the control group and p‐siMAPK4 intervention group, respectively. The cell proliferation was analyzed with flow cytometry and immunofluorescence staining. The vascular density in tumor mass was analyzed by immunofluorescence staining. The expressions of MAPK4 and related signaling molecules were detected by western blot analysis and immunofluorescence staining, and so on.

Results

We found that the expression of MAPK4, which was dominantly expressed in local endothelial cells (ECs), was correlated with tumor angiogenesis of NSCLC. Furthermore, MAPK4 silencing inhibited the proliferation and migration abilities of human umbilical vein ECs (HUVECs). Global gene analysis showed that MAPK4 silencing altered the expression of multiple genes related to cell cycle and angiogenesis pathways, and that MAPK4 silencing increased transduction of the extracellular regulated protein kinases 1/2 (ERK1/2) pathway but not Akt and c‐Jun n‐terminal kinase pathways. Further analysis showed that MAPK4 silencing inhibited the proliferation and migration abilities of HUVECs cultured in tumor cell supernatant, which was accompanied with increased transduction of the ERK1/2 pathway. Clinical data analysis suggested that the higher expression of MAPK4 and CD34 were associated with poor prognosis of patients with NSCLC. Targeted silencing of MAPK4 in ECs using small interfering RNA driven by the CD34 promoter effectively inhibited tumor angiogenesis and growth of NSCLC in vivo.

Conclusion

Our results reveal that MAPK4 plays an important role in the angiogenesis and development of NSCLC. MAPK4 may thus represent a new target for NSCLC.
Identifying Potential SOS1 Inhibitors via Virtual Screening of Multiple Small Molecule Libraries against KRAS‐SOS1 Interaction
Authors: Ikram Saima , Sayyah Ehsan , Durdağı Serdar
Published: April 2024

The RAS‐MAPK signaling pathway, crucial for cell proliferation and differentiation, involves key proteins KRAS and SOS1. Mutations in the KRAS and SOS1 genes are implicated in various cancer types, including pancreatic, lung, and juvenile myelomonocytic leukemia. There is considerable interest in identifying inhibitors targeting KRAS and SOS1 to explore potential therapeutic strategies for cancer treatment. In this study, advanced in silico techniques were employed to screen small molecule libraries at this interface, leading to the identification of promising lead compounds as potential SOS1 inhibitors. Comparative analysis of the average binding free energies of these predicted potent compounds with known SOS1 small molecule inhibitors revealed that the identified compounds display similar or even superior predicted binding affinities compared to the known inhibitors. These findings offer valuable insights into the potential of these compounds as candidates for further development as effective anti‐cancer agents.
Monomeric Far‐red and Near‐infrared Fluorescent Biliproteins of Ultrahigh Brightness
Authors: Jiang Xiang‐Xiang , Hou Ya‐Nan , Lu Li‐Wen , Zhao Kai‐Hong
Published: April 2024

Far‐red and near‐infrared fluorescent proteins have regions of maximum transmission in most tissues and can be widely used as fluorescent biomarkers. We report that fluorescent phycobiliproteins originating from the phycobilisome core subunit ApcF2 can covalently bind biliverdin, named BDFPs. To further improve BDFPs, we conducted a series of studies. Firstly, we mutated K53Q and T144A of BDFPs to increase their effective brightness up to 190 % in vivo. Secondly, by homochromatic tandem fusion of high‐brightness BDFPs to achieve monomerization, which increases the effective brightness by up to 180 % in vivo, and can effectively improve the labeling effect. By combining the above two approaches, the brightness of the tandem BDFPs was much improved compared with that of the previously reported fluorescent proteins in a similar spectral range. The tandem BDFPs were expressed stably while maintaining fluorescence in mammalian cells and Caenorhabditis elegans. They were also photostable and resistant to high temperature, low pH, and chemical denaturation. The tandem BDFPs advantages were proved in applications as biomarkers for imaging in super‐resolution microscopy.
Chemometrics as a tool for monitoring corrosion degradation of the selected alloys in real conditions
Authors: Vastag Gyöngyi , Apostolov Suzana , Ivošević Špiro , Rudolf Rebeka
Published: April 2024

Monitoring of the corrosion process of alloys in real conditions often results in extensive data, which is characterized by complex interdependence, but by a large degree of mutual deviation. First of all, the large dispersion of the obtained results makes it very difficult to draw accurate conclusions about the real influence of the tested parameters on the corrosion behavior of alloys. On the other hand, in many cases, the high interdependence between the corrosion factors can also greatly burden the analyzed system and thus make it significantly difficult to recognize the main influence. Multivariate analysis, especially the principal component analysis, is becoming increasingly popular in processing of this type of data, due to its ability to recognize and eliminate redundant data. The aim of this study was to examine the possibility of using multivariate analysis methods in the processing of the corrosion test results obtained under real conditions. Based on the obtained results, it can be concluded that used multivariate method in combination with energy dispersive spectrometer analysis can be successfully used to identify the most important corrosion factors (type of corrosion environment, exposure time and technological production processes), as well as their influence on the degradation of the tested TiNi alloys under the given conditions.
Exploring the Magnetic Interactions in Two Novel Cyanide‐Bridged Homo‐ and Heterometallic Hexadecanuclear Complexes
Authors: Yadav Jyoti , Gupta Arindam , Mondal Arpan , Daumann Florian , Hörner Gerald , Weber Birgit , Konar Sanjit
Published: April 2024

Two novel isostructural cyanide‐bridged hexadecanuclear complexes with the general formula {[Fe(CN)6]6[M{en(Bn)py}]10}2+ [M=Fe (12+), Ni (22+)] have been synthesized. The structural analyses disclose the presence of multivalent Fe centres with different spin states in complex 12+ whereas all the Fe centres share a conserved oxidation state in complex 22+. The DC magnetic study revealed antiferromagnetic interactions between the adjacent metal centres and ferrimagnetic behaviour in 12+. On the other hand, ferromagnetic interactions were observed in complex 22+ due to nearly orthogonal orientation of the interacting orbitals and poor spatial overlap as observed in BS‐DFT calculations.
In Silico Design and Characterization of a New Molecular Electride: Li@Calix[3]Pyrrole
Authors: Saha Ranajit , Skjelstad Bastian Bjerkem , Pan Sudip
Published: April 2024

Electrides, in which anionic electrons are localized independently of the atoms in the compound, have shown promise, especially as catalysts and optoelectronic materials. Here, we present a new computationally designed molecular electride, Li@calix[3]pyrrole (Li@C3P). Electron density and electron localization function analyses unequivocally confirm the existence of localized electride electron density, outside the system, independent of any specific atoms. Non‐covalent interaction plots further validate the character of the isolated localized electron, suggesting that the system can be accurately represented by Li+@calix[3]pyrrole ⋅ e−, denoting its distinct charge separation. The remarkable non‐linear optical properties of Li@C3P, including average polarizability,
=412.4 au, first hyperpolarizability, β=4.46×104 au, and second hyperpolarizability,
=18.40×106 au, are unparalleled in the previously reported and similar Li@C4P molecular electride. Furthermore, energy decomposition analysis in combination with natural orbital for chemical valence theory sheds light on the mechanism of electron density transfer from Li to the C3P cage, yielding the charge‐separated Li@C3P complex. In addition to the electron transfer, a key factor to its electride nature is the electronic structure of the CnP cage, which has its lowest unoccupied molecular orbital located in the void adjacent to the N−H groups at the back of the bowl‐shaped CnP cage.
Multiple Bonding in AeN− (Ae=Ca, Sr, Ba)
Authors: Cui Li‐Juan , Liu Yu‐Qian , Wang Meng‐Hui , Yan Bing , Pan Sudip , Cui Zhong‐Hua , Frenking Gernot
Published: April 2024

Quantum chemical calculations using ab initio methods at the MRCI+Q(8,9)/def2‐QZVPPD and CCSD(T)/def2‐QZVPPD levels as well as using density functional theory are reported for the diatomic molecules AeN− (Ae=Ca, Sr, Ba). The anions CaN− and SrN− have electronic triplet (3Π) ground states with nearly identical bond dissociation energies De ~57 kcal/mol calculated at the MRCI+Q(8,9)/def2‐QZVPPD level. In contrast, the heavier homologue BaN− has a singlet (1Σ+) ground state, which is only 1.1 kcal/mol below the triplet (3Σ−) state. The computed bond dissociation energy of (1Σ+) BaN− is 68.4 kcal/mol. The calculations at the CCSD(T)‐full/def2‐QZVPPD and BP86‐D3(BJ)/def2‐QZVPPD levels are in reasonable agreement with the MRCI+Q(8,9)/def2‐QZVPPD data, except for the singlet (1Σ+) state, which has a large multireference character. The calculated atomic partial charges given by the CM5, Voronoi and Hirshfeld methods suggest small to medium‐sized Ae←N− charge donation for most electronic states. In contrast, the NBO method predicts for all species medium to large Ae→N− electronic charge donation, which is due to the neglect of the (n)p AOs of Ae atoms as genuine valence orbitals. Neither the bond orders nor the bond lengths correlate with the bond dissociation energies. The EDA−NOCV calculations show that the heavier alkaline earth atoms Ca, Sr, Ba use their (n)s and (n‐1)d orbitals for covalent bonding.
Engineering Modular DNA Reaction Networks for Signal Processing
Authors: Cui Shuang , Liu Xin , Zhang Xun , Shi Peijun , Zheng Yanfen , Wang Bin , Zhang Qiang
Published: April 2024

Diversified molecular information‐processing methods have significant implications for nanoscale manipulation and control, monitoring and disease diagnosis of organisms, and direct intervention in biological activities. However, as an effective approach for implementing multifunctional molecular information processing, DNA reaction networks (DRNs) with numerous functionally specialized molecular structures have challenged them on scale design, leading to increased network complexity, further causing problems such as signal leakage, attenuation, and cross‐talk in network reactions. Our study developed a strategy for performing various signal‐processing tasks through engineering modular DRNs. This strategy is based on a universal core unit with signal selection capability, and a time‐adjustable signal self‐resetting module is achieved by combing the core unit and self‐resetting unit, which improves the time controllability of modular DRNs. In addition, multi‐input and ‐output signal cross‐catalytic and continuously adjustable signal delay modules were realized by combining core and threshold units, providing a flexible, precise method for modular DRNs to process the signal. The strategy simplifies the design of DRNs, helps generate design ideas for large‐scale integrated DRNs with multiple functions, and provides prospects in biocomputing, gene regulation, and biosensing.
Selective Lattice Doping Enables a Low‐Cost, High‐Capacity and Long‐Lasting Potassium Layered Oxide Cathode for Potassium and Sodium Storage
Authors: Ai Ruopeng , Zhang Xinyuan , Li Shuyue , Wei Zhixuan , Chen Gang , Du Fei
Published: April 2024

Layered transition metal oxides are highly promising host materials for K ions, owing to their high theoretical capacities and appropriate operational potentials. To address the intrinsic issues of KxMnO2 cathodes and optimize their electrochemical properties, a novel P3‐type oxide doped with carefully chosen cost‐effective, electrochemically active and multi‐functional elements is proposed, namely K0.57Cu0.1Fe0.1Mn0.8O2. Compared to the pristine K0.56MnO2, its reversible specific is increased from 104 to 135 mAh g−1. In addition, the Cu and Fe co‐doping triples the capacity under high current densities, and contributes to long‐term stability over 500 cycles with a capacity retention of 68 %. Such endeavor holds the potential to make potassium‐ion batteries particularly competitive for application in sustainable, low‐cost, and large‐scale energy storage devices. In addition, the cathode is also extended for sodium storage. Facilitated by the interlayer K ions that protect the layered structure from collapsing and expand the diffusion pathway for sodium ions, the cathode shows a high reversible capacity of 144 mAh g−1, fast kinetics and a long lifespan over 1000 cycles. The findings offer a novel pathway for the development of high‐performance and cost‐effective sodium‐ion batteries.
14‐Membered Macrocyclic β‐Diiminato Gold(II) – A New Member for the Gold(II) Complex Family?
Authors: Sorge Lukas , Link Julian , Heinze Katja
Published: April 2024

The chemistry of molecular gold compounds is dominated by the oxidation states +I and +III. For the intermediate oxidation state +II with 5d9 electron configuration, dimerization or disproportionation of the gold(II) radicals is favored, so that only a few mononuclear gold(II) complexes have been isolated to date. The present study addresses the one‐electron reduction of the macrocyclic gold(III) complex [AuIIIL]+ of the innocent β‐diiminato ligand L2− with a 14‐membered macrocycle (L2−=5,7,12,14‐tetramethyl‐1,4,8,11‐tetraazacyclotetradeca‐5,7,12,14‐tetraenato). Electrochemistry, spectroelectrochemistry and chemical reduction of [AuIIIL]+ monitored by UV/Vis, NMR and EPR spectroscopy together with density functional theory calculations reveal disproportionation of the initially generated but elusive gold(II) complex AuIIL and provide guidelines for prospective stable mononuclear tetraazamacrocyclic gold(II) complexes.
Dynamics of Coordinated Phosphonate Group Directly Observed by 17O‐NMR in Lanthanide(iii) Complexes of a Mono(ethyl phosphonate) DOTA Analogue
Authors: Svítok Adam , Blahut Jan , Urbanovský Peter , Hermann Petr
Published: April 2024

Biological phosphates can coordinate metal ions and their complexes are common in living systems. Dynamics of mutual oxygen atom exchange in the tetrahedral group in complexes has not been investigated. Here, we present a direct experimental proof of exchange (“phosphonate rotation”) in model Ln(III) complexes of monophosphonate H4dota analogue which alters phosphorus atom chirality of coordinated phosphonate monoester. Combination of macrocycle‐based isomerism with P‐based chirality leads to several diastereoisomers. (Non)‐coordinated oxygen atoms were distinguished through 17O‐labelled phosphonate group and their mutual exchange was followed by various NMR techniques and DFT calculations. The process is sterically demanding and occurs through bulky bidentate (κ2‐PO2)− coordination and was observed only in twisted‐square antiprism (TSA) diastereoisomer of large Ln(III) ions. Its energy demands increase for smaller Ln(III) ions (298ΔG≠(exp./DFT)=51.8/52.1 and 61.0/71.5 kJ mol−1 for La(III) and Eu(III), respectively). These results are helpful in design of such complexes as MRI CA and for protein paramagnetic NMR probes. It demonstrates usefulness of 17O NMR to study solution dynamics in complexes involving phosphorus acid derivatives and it may inspire use of this method to study dynamics of phosphoric acid derivatives (as e. g. phosphorus acid‐based inhibitors of metalloenzymes) in different areas of chemistry.
Reductions of Arenes using a Magnesium‐Dinitrogen Complex
Authors: Evans Matthew J. , Mullins Jeremy , Mondal Rahul , Jones Cameron
Published: April 2024

In this contribution, we present “Birch‐type”, and other reductions of simple arenes by the potassium salt of an anionic magnesium dinitrogen complex, [{K(TCHPNON)Mg}2(μ‐N2)] (TCHPNON=4,5‐bis(2,4,6‐tricyclohexylanilido)‐2,7‐diethyl‐9,9‐dimethyl‐xanthene), which acts as a masked dimagnesium(I) diradical in these reactions. This reagent is non‐hazardous, easy‐to‐handle, and in some cases provides access to 1,4‐cyclohexadiene reduction products under relatively mild reaction conditions. This system works effectively to reduce benzene, naphthalene and anthracene through magnesium‐bound “Birch‐type” reduction intermediates. Cyclohexadiene products can be subsequently released from the magnesium centres by protonolysis with methanol. In contrast, the reduction of substituted arenes is less selective and involves competing reaction pathways. For toluene and 1,3,5‐triphenylbenzene, the structural authentication of “Birch‐type” reduction intermediates is conclusive, although the formation of corresponding 1,4‐cyclohexadiene derivatives was low yielding. Reduction of anisole did not yield an isolable “Birch‐type” intermediate, but instead gave a C−O activation product. Treating triphenylphosphine with [{K(TCHPNON)Mg}2(μ‐N2)] resulted in the extrusion of both biphenyl and dinitrogen to afford a magnesium(II) phosphanide [{K(TCHPNON)Mg(μ‐PPh2)}2]. Reduction of fluorobenzene proceeded via C−F activation of the arene, and isolation of the magnesium(II) fluoride [{K(TCHPNON)Mg(μ‐F)}2]. Finally, the two‐electron reduction of 1,3,5,7‐cyclooctatetraene (COT) with [{K(TCHPNON)Mg}2(μ‐N2)] yielded a complex, [{K(TCHPNON)Mg}2(μ‐COT)], incorporating the aromatic dianion (COT2−).
Effect of Co‐Adsorbed Guest Adsorbates on the Separation of Ethylene/Ethane Mixtures on Metal‐Organic Frameworks with Open Metal Sites
Authors: Xiao Yuqing , Li Shenhui , Jiang Bin , Liang Xinmiao , Chu Yueying , Deng Feng
Published: April 2024

Direct determination of the equilibrium adsorption and spectroscopic observation of adsorbent‐adsorbate interaction is crucial to evaluate the olefin/paraffin separation performance of porous adsorbents. However, the experimental characterization of competitive adsorption of various adsorbates at atomic‐molecular level in the purification of multicomponent gas mixtures is challenging and rarely conducted. Herein, solid‐state NMR spectroscopy is employed to examine the effect of co‐adsorbed guest adsorbates on the separation of ethylene/ethane mixtures on Mg‐MOF‐74, Zn‐MOF‐74 and UTSA‐74. 1H MAS NMR facilitates the determination of equilibrium uptake and adsorption selectivity of ethylene/ethane in ternary mixtures. The co‐adsorption of H2O and CO2 significantly leads to the degradation of ethylene uptake and ethylene/ethane selectivity. The detailed host‐guest and guest‐guest interactions are unraveled by 2D 1H−1H spin diffusion homo‐nuclear correlation and static 25Mg NMR experiments. The experimental results verify H2O coordinated on open metal sites can supply a new adsorption site for ethylene and ethane. The effects of guest adsorbates on the adsorption capacity and adsorption selectivity of ethylene/ethane mixtures are in the following order: H2O>CO2>O2. This work provides a direct approach for exploring the equilibrium adsorption and detailed separation mechanism of multicomponent gas mixtures using MOFs adsorbents.
Efficient Synthesis of Cyclohepta[b]indoles and Cyclohepta[b]indole‐Indoline Conjugates via RCM, Hydrogenation, and Acid‐Catalyzed Ring Expansion: A Biomimetic Approach
Authors: Parui Nabin , Mandal Tirtha , Maiti Sandip , Dash Jyotirmayee
Published: April 2024

Cyclohepta[b]indoles, prevalent in natural products and pharmaceuticals, are conventionally accessed via metal or Lewis acid‐mediated cycloadditions with prefunctionalized substrates. Our study introduces an innovative sequential catalytic assembly for synthesizing cyclohepta[b]indoles from readily available isatin derivatives. The process involves three catalytic sequences: ring‐closing metathesis, catalytic hydrogenation, and acid‐catalyzed ring expansion. The RCM of 2,2‐dialkene‐3‐oxindoles, formed by butenyl Grignard addition to 3‐allyl‐3‐hydroxy‐2‐oxindoles, yields versatile spirocyclohexene‐3‐oxindole derivatives. These derivatives undergo further transformations, including dibromination, dihydroxylation, epoxidation, Wacker oxidation at the double bond. Hydrogenation of spirocyclohexene‐3‐oxindole yields spirocyclohexane‐3‐oxindoles. Their subsequent acid‐catalyzed ring expansion/aromatization, dependent on the acid catalyst, results in either cyclohepta[b]indoles or cyclohepta[b]indole‐indoline conjugates, adding a unique synthetic dimension. The utility of this methodology is exemplified through the synthesis of an A‐FABP inhibitor, showcasing its potential in pharmaceutical applications.