bluuebunny/crossref_metadata_2025_split huggingface dataset:
E3 Ubiquitin Ligase RNF13 Suppresses TLR Lysosomal Degradation by Promoting LAMP‐1 Proteasomal Degradation
Authors: Liu Wei , Wang Yuyang , Liu Shuo , Zhang Xuan , Cao Xuetao , Jiang Minghong 
Published: June 2024

AbstractAs a highly organized system, endo‐lysosomes play a crucial role in maintaining immune homeostasis. However, the mechanisms involved in regulating endo‐lysosome progression and subsequent inflammatory responses are not fully understood. By screening 103 E3 ubiquitin ligases in regulating endo‐lysosomal acidification, it is discovered that lysosomal RNF13 inhibits lysosome maturation and promotes inflammatory responses mediated by endosomal Toll‐like receptors (TLRs) in macrophages. Mechanistically, RNF13 mediates K48‐linked polyubiquitination of LAMP‐1 at residue K128 for proteasomal degradation. Upon TLRs activation, LAMP‐1 promotes lysosomes maturation, which accelerates lysosomal degradation of TLRs and reduces TLR signaling in macrophages. Furthermore, peripheral blood mononuclear cells (PBMCs) from patients with rheumatoid arthritis (RA) show increased RNF13 levels and decreased LAMP‐1 expression. Accordingly, the immunosuppressive agent hydroxychloroquine (HCQ) can increase the polyubiquitination of RNF13. Taken together, the study establishes a linkage between proteasomal and lysosomal degradation mechanisms for the induction of appropriate innate immune response, and offers a promising approach for the treatment of inflammatory diseases by targeting intracellular TLRs.
A Glucose‐Responsive Hydrogel Inhibits Primary and Secondary BRB Injury for Retinal Microenvironment Remodeling in Diabetic Retinopathy
Authors: Zhou Yue , Zhao Chan , Shi Zhiyuan , Heger Zbynek , Jing HuaQing , Shi Zhengming , Dou Yunsheng , Wang Siyu , Qiu Zitong , Li Nan 
Published: June 2024

AbstractCurrent diabetic retinopathy (DR) treatment involves blood glucose regulation combined with laser photocoagulation or intravitreal injection of vascular endothelial growth factor (VEGF) antibodies. However, due to the complex pathogenesis and cross‐interference of multiple biochemical pathways, these interventions cannot block disease progression. Recognizing the critical role of the retinal microenvironment (RME) in DR, it is hypothesized that reshaping the RME by simultaneously inhibiting primary and secondary blood–retinal barrier (BRB) injury can attenuate DR. For this, a glucose‐responsive hydrogel named Cu‐PEI/siMyD88@GEMA‐Con A (CSGC) is developed that effectively delivers Cu‐PEI/siMyD88 nanoparticles (NPs) to the retinal pigment epithelium (RPE). The Cu‐PEI NPs act as antioxidant enzymes, scavenging ROS and inhibiting RPE pyroptosis, ultimately blocking primary BRB injury by reducing microglial activation and Th1 differentiation. Simultaneously, MyD88 expression silence in combination with the Cu‐PEI NPs decreases IL‐18 production, synergistically reduces VEGF levels, and enhances tight junction proteins expression, thus blocking secondary BRB injury. In summary, via remodeling the RME, the CSGC hydrogel has the potential to disrupt the detrimental cycle of cross‐interference between primary and secondary BRB injury, providing a promising therapeutic strategy for DR.
Allicin‒Decorated FeO1‐xOH Nanocatalytic Medicine for Fe2+/Fe3+ Cycling‒Promoted Efficient and Sustained Tumor Regression
Authors: Jie Zhongming , Xiong Bingyan , Shi Jianlin 
Published: June 2024

AbstractIn the tumor treatment by Fenton reaction‒based nanocatalytic medicines, the gradual consumption of Fe(II) ions greatly reduces the production of hydroxyl radicals, one of the most active reactive oxygen species (ROS), leading to much deteriorated therapeutic efficacy. Meanwhile, the ROS consumption caused by the highly expressed reduced glutathione (GSH) in the tumor microenvironment further prevents tumor apoptosis. Therefore, using the highly expressed GSH in tumor tissue to promote the Fe(III) reduction to Fe(II) can not only weaken the resistance of tumor to ROS attack, but also generate enough Fe(II) to accelerate the Fenton reaction. In view of this, an allicin‒modified FeO1‐xOH nanocatalyst possessing varied valence states (II, III) has been designed and synthesized. The coexistence of Fe(II)/Fe(III) enables the simultaneous occurrence of Fenton reaction and GSH oxidation, and the Fe(III) reduction by GSH oxidation results in the promoted cyclic conversion of Fe ions in tumor and positive catalytic therapeutic effects. Moreover, allicin capable of regulating cell cycle and suppressing tumor growth is loaded on FeO1‐xOH nanosheets to activate immune response against tumors and inhibit tumor recurrence, finally achieving the tumor regression efficiently and sustainably. This therapeutic strategy provides an innovative approach to formulate efficient antitumor nanomedicine for enhanced tumor treatment.
Enhancing 2D Photonics and Optoelectronics with Artificial Microstructures
Authors: Song Haizeng , Chen Shuai , Sun Xueqian , Cui Yichun , Yildirim Tanju , Kang Jian , Yang Shunshun , Yang Fan , Lu Yuerui , Zhang Linglong 
Published: June 2024

AbstractBy modulating subwavelength structures and integrating functional materials, 2D artificial microstructures (2D AMs), including heterostructures, superlattices, metasurfaces and microcavities, offer a powerful platform for significant manipulation of light fields and functions. These structures hold great promise in high‐performance and highly integrated optoelectronic devices. However, a comprehensive summary of 2D AMs remains elusive for photonics and optoelectronics. This review focuses on the latest breakthroughs in 2D AM devices, categorized into electronic devices, photonic devices, and optoelectronic devices. The control of electronic and optical properties through tuning twisted angles is discussed. Some typical strategies that enhance light‐matter interactions are introduced, covering the integration of 2D materials with external photonic structures and intrinsic polaritonic resonances. Additionally, the influences of external stimuli, such as vertical electric fields, enhanced optical fields and plasmonic confinements, on optoelectronic properties is analysed. The integrations of these devices are also thoroughly addressed. Challenges and future perspectives are summarized to stimulate research and development of 2D AMs for future photonics and optoelectronics.
Phase Transformations Driving Biaxial Stress Reduction During Wake‐Up of Ferroelectric Hafnium Zirconium Oxide Thin Films
Authors: Jaszewski Samantha T. , Fields Shelby S. , Calderon Sebastian , Aronson Benjamin L. , Beechem Thomas E. , Kelley Kyle P. , Zhang Casey , Lenox Megan K. , Brummel Ian A. , Dickey Elizabeth C. , Ihlefeld Jon F. 
Published: June 2024

AbstractBiaxial stress is identified to play an important role in the polar orthorhombic phase stability in hafnium oxide‐based ferroelectric thin films. However, the stress state during various stages of wake‐up has not yet been quantified. In this work, the stress evolution with field cycling in hafnium zirconium oxide capacitors is evaluated. The remanent polarization of a 20 nm thick hafnium zirconium oxide thin film increases from 9.80 to 15.0 µC cm−2 following 106 field cycles. This increase in remanent polarization is accompanied by a decrease in relative permittivity that indicates that a phase transformation has occurred. The presence of a phase transformation is supported by nano‐Fourier transform infrared spectroscopy measurements and scanning transmission electron microscopy that show an increase in ferroelectric phase content following wake‐up. The stress of individual devices field cycled between pristine and 106 cycles is quantified using the sin2(ψ) technique, and the biaxial stress is observed to decrease from 4.3 ± 0.2 to 3.2 ± 0.3 GPa. The decrease in stress is attributed, in part, to a phase transformation from the antipolar Pbca phase to the ferroelectric Pca21 phase. This work provides new insight into the mechanisms controlling and/or accompanying polarization wake‐up in hafnium oxide‐based ferroelectrics.
Scaffold‐free three‐dimensional cartilage regeneration based on cartilaginous organoids bioassembly technology
Authors: Huo Yingying , Ci Zheng , Wu Shiqi , Feng Shaoqing , Sun Yuyan , Li Genke , Liu Yu , Hua Yujie , Zhang Yixin , Zhou Guangdong 
Published: June 2024

AbstractCartilage tissue engineering is a promising strategy to repair damaged tissue and reconstruct organ function, but the scaffold‐free cartilage regeneration technology is currently limited in its ability to construct three‐dimensional (3D) shapes, maintain the chondrogenic phenotype, and express cartilage‐specific extracellular matrix (ECM). Recently, cartilaginous organoids (COs), multicellular aggregates with spheroid architecture, have shown great potential in miniaturized cartilage developmental models in vitro. However, high‐efficiency and transferable in vivo organoid‐based 3D cartilage regeneration technology for preclinical research needs further exploration. In this study, we develop novel cartilaginous organoids bioassembly (COBA) strategy to achieve scaffold‐free 3D cartilage regeneration, which displays batch‐to‐batch efficiency, structural integration, and functional reconstruction. For underlying molecule mechanism, cellular adhesion proteins significantly regulate cell aggregation and cytoskeleton reorganization to form cartilaginous spheroids, and the hypoxic microenvironment created by high‐density cell aggregates synergistically activates hypoxia‐inducible factor‐1α‐mediated glycolytic metabolism reprogramming to maintain the chondrogenic phenotype and promote cartilage‐specific ECM deposition. Furthermore, separated COs can integrate into a complete and continuous cartilage tissue through the COBA approach, and thus facilitate raising the nasal dorsa in goats after minimally invasive injection. This study thus demonstrates the promise of COBA technology to achieve scaffold‐free 3D cartilage regeneration for organoid‐based translational applications.
Optimized design of macro‐microreactor for scale‐up of liquid–liquid chemical processes
Authors: Zhao Shuangfei , Hu Xin , Wang Huiyue , Liu Yihuan , Fang Zheng , Guo Kai , Zhu Ning 
Published: June 2024

AbstractThe scale‐up of microreactor‐based flow chemical process represents a grand challenge in chemical engineering. The small characteristic size (<1000 μm) of a typical microreactor leads to not only microscale effect (process intensification) but also low throughput. Here, we report macro‐microreactor to achieve scale‐up of liquid–liquid chemical operation with process intensification. By incorporating the designed internals based on computational fluid dynamics, the characteristic size of the macro‐microreactor is expanded into 3000–4000 μm. The optimized design of macro‐microreactor with helical‐shaped internal exhibits both similar or even stronger microscale effect and high throughput in contrast to the typical microreactor. For the liquid–liquid chemical process, seven times higher mass transfer coefficient and about half reduction of the pressure drop are realized. These macro‐microreactors would find further applications in industrial chemical manufacturing.
Experimental and molecular insights on the regulatory effects of solvent on CaC2 reaction activity
Authors: Chen Zhengrun , Xu Hui , Zang Xiaoteng , Meng Hong , Fan Hongwei , Lu Yingzhou , Li Chunxi 
Published: June 2024

AbstractCalcium carbide (CaC2) is a valuable carbanion resource, but the reactivity is highly restricted by its insolubility and super‐basicity. For this, the effect of solvent and mechanical forces on its reactivity is investigated extensively here via quantum chemistry calculation, molecular dynamic simulation, and experiments. The dissolution free energy of CaC2 in over 100 solvents has been evaluated. DMSO, CH3CN, and DMF can enhance the negative potential and reactivity of CaC2, especially DMSO. The electrostatic interaction of CaC2‐solvent mainly originates from the interaction between Ca2+ and O or N atom. The increased electron density around is mainly ascribed to the electron transfer from solvent. DMSO can change the ionic orientation of CaC2 interface. The solvent may be deprotonated by , compromising the solvent stability. The interface interaction of CaC2 with DMF and DMSO is verified through FT‐IR, and the lattice structure of CaC2 is lost virtually after 0.5 h mechanical milling.
Catalytic Aerobic Carbooxygenation for the Construction of Vicinal Tetrasubstituted Centers: Application to the Synthesis of Hexasubstituted γ‐Lactones
Authors: Pünner Florian , Sohtome Yoshihiro , Lyu Yanzong , Hashizume Daisuke , Akakabe Mai , Yoshimura Mami , Yashiroda Yoko , Yoshida Minoru , Sodeoka Mikiko 
Published: June 2024

AbstractStrategic design for the construction of contiguous tetrasubstituted carbon centers represents a daunting challenge in synthetic organic chemistry. Herein, we report a combined experimental and computational investigation aimed at developing catalytic aerobic carbooxygenation, involving the intramolecular addition of tertiary radicals to geminally disubstituted alkenes, followed by aerobic oxygenation. This reaction provides a straightforward route to various α,α,β,β‐tetrasubstituted γ‐lactones, which can be readily transformed into hexasubstituted γ‐lactones through allylation/translactonization. Computational analysis reveals that the key mechanistic foundation for achieving the developed aerobic carbooxygenation involves the design of endothermic (energetically uphill) C−C bond formation followed by exothermic (energetically downhill) oxygenation. Furthermore, we highlight a unique fluorine‐induced stereoelectronic effect that stabilizes the endothermic stereodetermining transition state.
A Double Twisted Nanographene with a Contorted Pyrene Core
Authors: Dong Yanping , Zhang Zhiyu , Hashikawa Yoshifumi , Meng He , Bai Fenghua , Itami Kenichiro , Chaolumen  
Published: June 2024

AbstractThe mature synthetic methodologies enable us to rationally design and produce chiral nanographenes (NGs), most of which consist of multiple helical motifs. However, inherent chirality originating from twisted geometry has just emerged to be employed in chiral NGs. Herein, we report a red‐emissive chiral NG constituted of orthogonally arranged two‐fold twisted π‐skeletons at a contorted pyrene core which contributes to optical transitions of S0→S1 and vice versa. The thus‐obtained NG exhibited a robustness on its redox properties through 2e− uptake/release. The chemical oxidation generated stable radical cation whose absorption covers near‐infrared I and II regions. Overall, the contorted pyrene core governs electronic nature of the chiral NG. The twist operation on NGs would be, therefore, a design strategy to alter conventional chirality induction on NGs.
Closed‐Loop Recyclable Poly(ester‐disulfide)s for Potential Alternatives to Engineering Plastic
Authors: Chen Meng , Yang Rulin , Wu Huiping , Wang Qian , Shi Chenyu , Zhou Shang‐Wu , Yang Ding , Liu Fang‐Yu , Tian He , Qu Da‐Hui 
Published: June 2024

AbstractFacile fabrication, low material complexity and closed‐loop recycling are essential for polymer plastics to alter their linear product economy towards a cradle‐to‐cradle one. Covalent adaptable networks (CANs) are one way to achieve that, which intrinsically exhibit decent mechanical properties like the thermosets but could also be easily recycled like the thermoplastics. In this work, we introduce rigid ester structural motifs into dynamic poly(disulfide)s to form a series of dual polymer networks. Owning to the coherence of soft/rigid segments and the reversible sacrificial crosslinking, they exhibit tailorable mechanical properties and good resistance towards different chemicals. Their closed‐loop recycling is achieved via mild solvolysis, maintaining materials’ mechanical integrities. It offers a solution as a sustainable replacement for engineering plastics which are massively under production but hard to be recycled.
Solvent Effects in Hyperpolarization of 15N Nuclei in [15N3]Metronidazole and [15N3]Nimorazole Antibiotics via SABRE‐SHEATH**
Authors: Yi Anna P. , Salnikov Oleg G. , Burueva Dudari B. , Chukanov Nikita V. , Chekmenev Eduard Y. , Koptyug Igor V. 
Published: June 2024

AbstractMetronidazole and nimorazole are antibiotics of a nitroimidazole group which also may be potentially utilized as hypoxia radiosensitizers for the treatment of cancerous tumors. Hyperpolarization of 15N nuclei in these compounds using SABRE‐SHEATH (Signal Amplification By Reversible Exchange in SHield Enables Alignment Transfer to Heteronuclei) approach provides dramatic enhancement of detection sensitivity of these analytes using magnetic resonance spectroscopy and imaging. Methanol‐d4 is conventionally employed as a solvent in SABRE hyperpolarization process. Herein, we investigate SABRE‐SHEATH hyperpolarization of isotopically labeled [15N3]metronidazole and [15N3]nimorazole in nondeuterated methanol and ethanol solvents. Optimization of such hyperpolarization parameters as polarization transfer magnetic field, temperature, parahydrogen flow rate and pressure allowed us to obtain an average 15N polarization of up to 7.2–7.4 % for both substrates. The highest 15N polarizations were observed in methanol‐d4 for [15N3]metronidazole and in ethanol for [15N3]nimorazole. At a clinically relevant magnetic field of 1.4 T the 15N nuclei of these substrates possess long characteristic hyperpolarization lifetimes (T1) of ca. 1 to ca. 7 min. This study represents a major step toward SABRE in more biocompatible solvents, such as ethanol, and also paves the way for future utilization of these hyperpolarized nitroimidazoles as molecular contrast agents for MRI visualization of tumors.
Bringing genomics to the field: An integrative approach to seed sourcing for forest restoration
Authors: Prakash Anoob , Capblancq Thibaut , Shallows Kathryn , Saville David , Landau Deborah , Landress Chad , Jacobs Tal , Keller Stephen 
Published: June 2024

AbstractPremiseGlobal anthropogenic change threatens the health and productivity of forest ecosystems. Assisted migration and reforestation are tools to help mitigate these impacts. However, questions remain about how to approach sourcing seeds to ensure high establishment and future adaptability.MethodsUsing exome‐capture sequencing, we demonstrate a computational approach to finding the best n‐sets from a candidate list of seed sources that collectively achieve high genetic diversity (GD) and minimal genetic load (GL), while also increasing evolvability in quantitative traits. The benefits of this three‐part strategy (diversity‐load‐evolvability) are to increase near‐term establishment success while also boosting evolutionary potential to respond to future stressors. Members of The Nature Conservancy and the Central Appalachian Spruce Restoration Initiative planted 58,000 seedlings across 255 acres. A subset of seedlings was monitored for establishment success and variation in growth.ResultsThe results show gains in GD relative to GL and increases in quantitative genetic variation in seedling growth for pooled vs. single‐source restoration. No single “super source” was observed across planting sites; rather, monitoring results demonstrate that pooling of multiple sources helps achieve higher GD:GL and evolvability.DiscussionOur study shows the potential for integrating genomics into local‐scale restoration and the importance of building partnerships between academic researchers and applied conservation managers.
Design, synthesis, and antiproliferative activity of new indole/1,2,4‐triazole/chalcone hybrids as EGFR and/or c‐MET inhibitors
Authors: Mahmoud Esraa , Abdelhamid Dalia , Youssif Bahaa G. M. , Gomaa Hesham A. M. , Hayallah Alaa M. , Abdel‐Aziz Mohamad 
Published: June 2024

AbstractA novel group of indolyl‐1,2,4‐triazole‐chalcone hybrids was designed, synthesized, and assessed for their anticancer activity. The synthesized compounds exhibited significant antiproliferative activity. Compounds 9a and 9e exhibited significant cancer inhibition with GI50 ranging from 3.69 to 20.40 µM and from 0.29 to >100 µM, respectively. Both compounds displayed a broad spectrum of anticancer activity with selectivity ratios ranging between 0.50–2.78 and 0.25–2.81 at the GI50 level, respectively. The synthesized compounds were also screened for their cytotoxicity by 3‐(4,5‐dimethylthiazole‐2‐yl)‐2,5‐diphenyltetrazol (MTT) assay and for inhibition of epidermal growth factor receptor (EGFR) and c‐MET (mesenchymal‐epithelial transition factor). Some of the tested compounds exhibited significant inhibition against EGFR and/or c‐MET. Compound 9b showed the highest c‐MET inhibition (IC50 = 4.70 nM) compared to foretinib (IC50 = 2.5 nM). Compound 9d showed equipotent activity compared with erlotinib against EGFR (IC50 = 0.052 µM) and displayed significant c‐MET inhibition with an IC50 value of 4.90 nM.
Investigation of an Industrially Scalable Production of Sulfur‐Polyacrylonitrile Based Cathodes
Authors: Moschner Robin , Cavers Heather , Michalowski Peter , Kwade Arno 
Published: June 2024

AbstractSulfur‐polyacrylonitrile (SPAN) is a sulfur‐based active material for next‐generation lithium‐sulfur battery cathodes. Due to the covalent bonding between sulfur chains and the polymeric backbone, the shuttle effect degrading classical sulfur‐based cathodes can be suppressed while also achieving a high active material content in the cathode. In this paper, we investigate the processability of an industrially scalable SPAN active material with 38 wt.‐% of sulfur in a water‐based and scalable process route. The potential of the SPAN material for industrial adoption and the impact of the process route on the cell performance are discussed. We show that when processed correctly, the SPAN material delivers exceptional cycling stability and good C‐rate performance with ether‐based electrolytes. However, the performance of the SPAN cathode is influenced by the mixing characteristic. Using higher mixing intensities during the slurry preparation leads to deterioration of the electrochemical performance. This can be attributed to a decreasing carbon black percolation with increasing tip speed in combination with the kinetic limitation of sulfur cathodes during Li2S2 and Li2S oxidation.