bluuebunny/crossref_metadata_2025_split huggingface dataset:
Retinal thinning differentiates treatment effects in relapsing multiple sclerosis below the clinical threshold
Authors: Bsteh Gabriel , Hegen Harald , Krajnc Nik , Föttinger Fabian , Altmann Patrick , Auer Michael , Berek Klaus , Kornek Barbara , Leutmezer Fritz , Macher Stefan , Monschein Tobias , Ponleitner Markus , Rommer Paulus , Schmied Christiane , Zebenholzer Karin , Zulehner Gudrun , Zrzavy Tobias , Deisenhammer Florian , Di Pauli Franziska , Pemp Berthold , Berger Thomas 
Published: December 2024

AbstractObjectiveTo investigate retinal layer thinning as a biomarker of disease‐modifying treatment (DMT) effects in relapsing multiple sclerosis (RMS).MethodsFrom an ongoing prospective observational study, we included patients with RMS, who (i) had an optical coherence tomography (OCT) scan within 6 to 12 months after DMT start (rebaseline) and ≥1 follow‐up OCT ≥12 months after rebaseline and (ii) adhered to DMT during follow‐up. Differences between DMT in thinning of peripapillary‐retinal‐nerve‐fiber‐layer (pRNFL) and macular ganglion cell‐plus‐inner plexiform‐layer (GCIPL) were analyzed using mixed‐effects linear regression. Eyes suffering optic neuritis during follow‐up were excluded.ResultsWe included 291 RMS patients (mean age 30.8 years [SD 7.9], 72.9% female, median disease duration 9 months [range 6–94], median rebaseline‐to‐last‐follow‐up‐interval 32 months [12–82]).Mean annualized rates of retinal layer thinning (%/year) in reference to DMF (n = 84, GCIPL 0.28, pRNFL 0.53) were similar under TERI (n = 18, GCIPL 0.34, pRNFL 0.59), GLAT (n = 24, GCIPL 0.32, pRNFL 0.56), and IFNb (n = 13, GCIPL 0.33, pRNFL 0.60) were slightly lower under S1PM (n = 27, GCIPL 0.19, pRNFL 0.42) and CLA (n = 23, GCIPL 0.20, pRNFL 0.42), and were significantly lower under NTZ (n = 47, GCIPL 0.09, pRNFL 0.24; both p < 0.001) and antiCD20 (n = 55, GCIPL 0.10, pRNFL 0.23; both p < 0.001). In patients achieving NEDA‐2, observed thinning rates were lower overall, but still significantly lower under NTZ and antiCD20.InterpretationApplying a rebaselining concept, retinal layer thinning differentiates DMT effects even in clinically stable patients and, thus, might be a useful biomarker to monitor DMT efficacy on subclinical neuroaxonal degeneration—at least on a group level.
Theoretical Design and Synthesis of Metal–Inorganic Frameworks Using Host Atom‐Centered Building Blocks for Efficient Catalysis with Diverse Reactive Sites
Authors: He Chao , Dong Xingxing , Zhang Junqiu , Xu Shaogang , Huang Xiang , Wang Hui , He Changchun , Liang Xiaowei , Xie Maohai , Xu Hu 
Published: December 2024

AbstractThe modular assembly of organic molecules commonly guides the design of metal–organic frameworks (MOFs), yet the systematic exploration of inorganic building blocks remains limited. Given the promising applications in catalytic reactions and topological materials, the study of metal–inorganic frameworks (MIFs)—which fundamentally differ from the well‐established MOFs—has become urgent. This study introduces a strategy for designing MIFs using host atom‐centered building blocks, applied to the platinum–Phosphorus (Pt–P) system. By combining experimental observations with theoretical calculations, a Pt18P18 framework utilizing PtP3 building blocks, demonstrating significant energetic benefits is proposed. PtP3 units are employed to characterize Pt3P6 clusters within the pores, leading to a “compass” model that aligns with experimental findings. To address computational challenges associated with the large periodicity of the superstructure, a robust machine learning force field is developed. The analysis, combining surface nucleation studies, first‐principles calculations, and machine learning techniques, provides a comprehensive understanding of MIF structure. This validated Pt–P MIF exhibits exceptional catalytic properties with diverse reaction sites, significantly outperforming Pt(111) in the hydrogen evolution reaction. The findings not only present additional candidates for practical applications of metal phosphides but also highlight the vast potential of MIFs, paving the way for the discovery of numerous promising materials.
Anion‐Selective Ion Conductor Boosting Highly Flexible All‐In‐One Electrochromic Fabrics
Authors: Li Wanzhong , Li Ang , Wang Yuhao , Ding Mingyu , Liu Jingbing , Wang Hao , Zheng Zilong , Zhang Qianqian 
Published: December 2024

AbstractFlexible all‐in‐one electrochromic fabrics (AECF) have attracted attention for application in wearable intelligent electronics. However, undifferentiated and disordered ion transport within the AECFs usually cause a slow transfer kinetics of reactive ions and thus restrict their electrochromic performance. Here, a new strategy is proposed to optimize active ion transport based on a well‐designed anion‐selective ion conductor (ASIC) for boosting the anionic AECF. The ASIC is developed by the interaction difference between ions and electronegative functional groups in the fabric substrate. Benefiting from cation immobilization and free anion transport, the ASIC exhibits both high anion transference number (0.75) and ionic conductivity (2.41 × 10−3 S cm−1) at room temperature. Such optimization of anion transport dynamics enhances the efficiency of the electrochromic redox reaction in the polyaniline‐based anionic AECF, contributing to a significant improvement of the overall electrochromic performance. Based on the switchable earth yellow and dark green discoloration, the AECF is further integrated into a camouflage uniform, achieving dynamic environment adaptation in deserts or forests. This work is anticipated to provide some fresh ideas for developing functional ion conductors of electrochromic fabrics toward applications in wearable intelligent electronics.
Glutathione Induced In Situ Activation of Dual‐Locked Cuproptosis Nanoamplifier with Glycolysis Metabolism Inhibition to Boost Cancer Immunotherapy
Authors: Wu Xiaomei , Zhang Shuo , Feng Mei , Sun Haoya , Lan Xiaopeng , Liang Wenlong , Liu Chunzhao , Li Yongxin 
Published: December 2024

AbstractInterference with glycolysis metabolism not only promotes the efficient sensitization of cuproptosis, but also amplifies cytotoxic T cell functions and proliferations, thus contributing to relieve immunosuppressive tumor microenvironment. However, the synergistic mechanism and the design of multicomponent nanoformulations involving these three pathways have not yet been explored. a copper‐coordinated nanoassembly (designated as Cu‐GM) is reported here that integrates a lactate dehydrogenase inhibitor, galloflavin (GF), with an immune checkpoint inhibitor, myricetin (MY), to boost cancer cuproptosis‐immunotherapy. These results suggest that Cu‐GM can be activated by the endogenous overexpressed glutathione to release Cu+, leading to the abnormal aggregation of lipoylated proteins and iron‐sulfur cluster proteins loss, which triggers proteotoxic stress and cell cuproptosis. Meanwhile, the released GF not only inhibits the glycolysis to amplify cuproptosis efficacy but also achieves effective lactate depletion, thus alleviating immunosuppressive effects of lactate. Notably, the killed tumor cells can induce immunogenic cell death to evoke the anti‐tumor immunity, which further augmented by the MY‐mediated immune checkpoint blockade. Taken together, the first anticancer synergy of glycolysis metabolism, cuproptosis, and immunotherapy is presented, showcasing remarkable in vivo antitumor effects and encouraging further exploration of a rational multimodal treatment approach.
Matrix Viscoelasticity Controls Differentiation of Human Blood Vessel Organoids into Arterioles and Promotes Neovascularization in Myocardial Infarction
Authors: Sun Dayu , Zhang Kunyu , Zheng Feiyang , Yang Guanyuan , Yang Mingcan , Xu Youqian , Qin Yinhua , Lin Mingxin , Li Yanzhao , Tan Ju , Li Qiyu , Qu Xiaohang , Li Gang , Bian Liming , Zhu Chuhong 
Published: December 2024

AbstractStem cell‐derived blood vessel organoids are embedded in extracellular matrices to stimulate vessel sprouting. Although vascular organoids in 3D collagen I‐Matrigel gels are currently available, they are primarily capillaries composed of endothelial cells (ECs), pericytes, and mesenchymal stem‐like cells, which necessitate mature arteriole differentiation for neovascularization. In this context, the hypothesis that matrix viscoelasticity regulates vascular development is investigated in 3D cultures by encapsulating blood vessel organoids within viscoelastic gelatin/β‐CD assembly dynamic hydrogels or methacryloyl gelatin non‐dynamic hydrogels. The vascular organoids within the dynamic hydrogel demonstrate enhanced angiogenesis and differentiation into arterioles containing smooth muscle cells. The dynamic hydrogel mechanical microenvironment promotes vascular patterning and arteriolar differentiation by elevating notch receptor 3 signaling in mesenchymal stem cells and downregulating platelet‐derived growth factor B expression in ECs. Transplantation of vascular organoids in vivo, along with the dynamic hydrogel, leads to the reassembly of arterioles and restoration of cardiac function in infarcted hearts. These findings indicate that the viscoelastic properties of the matrix play a crucial role in controlling the vascular organization and differentiation processes, suggesting an exciting potential for its application in regenerative medicine.
Polyphenol Mediated Assembly: Tailored Nano‐Dredger Unblocks Axonal Autophagosomes Retrograde Transport Traffic Jam for Accelerated Alzheimer's Waste Clearance
Authors: Meng Ran , Li Yixian , Yang Xiyu , Cheng Yunlong , Xu Minjun , Zhou LingLing , Wu Chengqin , Yu Shuai , Huang Wenyi , Wang Tianying , Zhang Qizhi 
Published: December 2024

AbstractClear‐cut evidence has linked defective autophagy to Alzheimer's disease (AD). Recent studies underscore a unique hurdle in AD neuronal autophagy: impaired retrograde axonal transport of autophagosomes, potent enough to induce autophagic stress and neurodegeneration. Nonetheless, pertinent therapy is unavailable. Here, a novel combinational therapy composed of siROCK2 and lithospermic acid B (LA) is introduced, tailored to dredge blocked axonal autophagy by multi‐mitigating microtubule disruption, ATP depletion, oxidative stress, and autophagy initiation impediments in AD. Leveraging the recent discovery of multi‐interactions between polyphenol LA and siRNA, ε‐Poly‐L‐lysine, and anionic lipid nanovacuoles, LA and siROCK2 are successfully co‐loaded into a fresh nano‐drug delivery system, LIP@PL‐LA/siRC, via a ratio‐flexible and straightforward fabrication process. Further modification with the TPL peptide onto LIP@PL‐LA/siRC creates a brain‐neuron targeted, biocompatible, and pluripotent nanomedicine, named “Nano‐dredger” (T‐LIP@PL‐LA/siRC). Nano‐dredger efficiently accelerates axonal retrograde transport and lysosomal degradation of autophagosomes, thereby facilitating the clearance of neurotoxic proteins, improving neuronal complexity, and alleviating memory defects in 3×Tg‐AD transgenic mice. This study provides a fresh and flexible polyphenol/siRNA co‐delivery paradigm and furnishes conceptual proof that dredging axonal autophagy represents a promising AD therapeutic avenue.
Single‐Nucleus and Spatial Transcriptome Profiling Delineates the Multicellular Ecosystem in Hepatocellular Carcinoma After Hepatic Arterial Infusion Chemotherapy
Authors: Huang YeXing , Du ZeFeng , Lai ZhiCheng , Wen DongSheng , Huang LiChang , He MinKe , Wu ZiChao , Li HuiFang , OuYang HanYue , Wu WenChao , Kan Anna , Shi Ming 
Published: December 2024

AbstractHepatic arterial infusion chemotherapy (HAIC) has emerged as a promising treatment strategy for hepatocellular carcinoma (HCC), but a detailed understanding of the multicellular ecosystem after HAIC treatment is lacking. Here, we collected tumor samples from treatment‐naïve primary and post‐HAIC HCC, and integrated single‐nucleus RNA sequencing with spatial transcriptomics to characterize the tumor ecosystem in the post‐HAIC HCC. Increased fractions and enhanced cellular communication of CD4+ T, CD20+ B, and dendritic cell subtypes were identified in post‐HAIC tumors. Moreover, it is substantiated that HAIC promoted tertiary lymphoid structures (TLS) formation, and addressed the roles of TLSs as spatial niches of cellular communication. Specifically, intermediate exhausted CD8+ T cells expressing Granzyme‐K and PD‐1 (PD‐1+CD8+ Tex‐int) expanded following HAIC and exhibited a functionally antitumor phenotype. PD‐1+CD8+ Tex‐int accumulated in the TLS vicinity and disseminated throughout the tumor microenvironment, demonstrating potential as an effective biomarker for HAIC‐based treatment in HCC. This study provides valuable resources and biological insights in the cellular underpinnings of HAIC treatment.
Consumption of Endogenous Caspase‐3 Activates Molecular Theranostic Nanoplatform against Inflammation‐Induced Profibrotic Positive Feedback in Pulmonary Fibrosis
Authors: Li Qiu‐Ling , Chang Xin , Han Yu‐Mo , Guo Zi‐Chao , Liu Yi‐Na , Guo Bin , Liu Chang , Yang Bin‐Rong , Fan Zhong‐Kai , Jiang Hu‐Lin , Chang Xin 
Published: December 2024

AbstractThe limited and backward diagnostic approaches elicit high mortality associated with pulmonary fibrosis (PF) because they fail to identify injury phase of PF. Developing a precisely theranostic nanoplatform presents a promising shortcut to reverse PF. Herein, a specific molecular nanotheranostic (Casp‐GNMT), which is triggered by endogenous cysteinyl aspartate specific proteinase‐3 (caspase‐3), boosts antifibrotic efficacy through bioimaging synergistic with chemotherapy at molecular level, facilitating by ionizable lipid and reactive oxygen species sensitive lipid for precise and manageable therapy. The activation of molecular imaging probe (pCY‐pairs) by consumption of endogenous caspase‐3 initiates fluorescence resonance energy transfer‐guided theranostic pattern, aiming to restore mitochondrial dysfunction‐induced oxidative stress and inflammatory responses in alveolar epithelial cells II (AECs II). This process sequentially resists the expression of interleukin‐1β and vascular endothelial growth factor receptor through combined with nintedanib, further suppressing abnormal injury of AECs II and persistent migration and proliferation of inflammatory cells. Especially, the homeostasis of injured AECs II diminishes excessive accumulation of transforming growth factor‐β to restrain myofibroblasts proliferation and collagen deposition, thereby amplifying the possibility of reversing PF. This theranostic nanoplatform is proposed to provide a prompt and exact approach to enhance diagnostic authenticity and treating efficiency through harnessing endogenous indicator for PF reversal.
Reversible Carrier Modulation in InP Nanolasers by Ionic Liquid Gating with Low Energy Consumption
Authors: Wu Chia‐Hung , Chen Chi‐Wen , Shen Hung‐Jung , Chuang Hsiang‐Yu , Tan Hark Hoe , Jagadish Chennupati , Lu Tien‐Chang , Ishii Satoshi , Chen Kuo‐Ping 
Published: December 2024

AbstractNanoscale light sources are demanded vigorously due to rapid development in photonic integrated circuits (PICs). III‐V semiconductor nanowire (NW) lasers have manifested themselves as indispensable components in this field, associated with their extremely compact footprint and ultra‐high optical gain within the 1D cavity. In this study, the carrier concentrations of indium phosphide (InP) NWs are actively controlled to modify their emissive properties at room temperature. The InP NW lasers can achieve repetitive switching between photoluminescence (PL) and lasing with an extinction ratio of 22‐fold by applying a gate voltage of 3 V using ionic liquid (IL) as a dielectric layer. IL brings forth ultra‐high capacitance due to the nanometer‐wide electric double layer (EDL) between interfaces, mapping out gating efficiency of ≈100‐fold compared to the conventional bottom gate configurations. This IL‐embedded nanolaser device can be a promising platform for the advanced integrated nanophotonic system.
Pulse Dynamics in Reduced Graphene Oxide Electrolyte‐Gated Transistors: Charge Memory Effects and Mechanisms Governing the Ion‐To‐Electron Transduction
Authors: Selmi Guilherme Segolin , Lourenço Neto Eduardo Rodrigues , Lelis Gabrielle Coelho , Okazaki Anderson Kenji , Riul Antonio , Braunger Maria Luisa , de Oliveira Rafael Furlan 
Published: December 2024

AbstractElectrolyte‐gated transistors (EGTs) are widely employed in bioelectronics due to their ability to bridge ionic and electronic phenomena in a single device. Among potential materials, reduced graphene oxide (rGO) has gained significant attention due to its ambipolar current response, quantum capacitance, and tunable conductivity. However, the rGO EGT dynamic behavior remains significantly unexplored. Here, the time‐dependent response of rGO EGTs is systematically investigated under gate voltage pulsing across different time scales (10 ms to 40 s) and amplitudes (up to |±0.8 V|). Significant charge memory is observed, particularly for long (40 s) pulses at 0.8 V, with effects also evident for shorter (1 s) and weaker stimuli (0.6 V). Multiple low‐level (0.1 V) fast pulsing (100 ms) further demonstrate charge retention post‐stimulation. All these characteristics are attributed to a complex interplay between ion entrapment within the rGO film, electrical double‐layer formation, and charge transfer processes. The stability of rGO EGTs under prolonged bias stress is also examined, aiming to contribute to the development of more robust devices. These findings revealed the complex role of electrolyte ions and electronic carriers governing the ion‐to‐electron transduction and charge memory effects in rGO EGTs, contributing to the advancement of the next‐generation bioelectronic devices.
A Homozygous MYH1 Variant Underlies Autosomal Recessive Isolated Recurrent Rhabdomyolysis
Authors: Uctepe Eyyup , Mancılar Hanifenur , Esen Fatma Nisa , Unverengil Gokcen Gundogdu , Vona Barbara , Yesilyurt Ahmet 
Published: December 2024

ABSTRACTRhabdomyolysis is a severe condition involving the breakdown of skeletal muscle fibers, leading to the release of muscle components into the bloodstream, which can lead to potential complications such as acute kidney injury and electrolyte imbalances. The etiology of rhabdomyolysis is multifactorial, encompassing traumatic, exertional, metabolic, infectious, toxic, and genetic causes. Genetic causes, including variants in LPIN1, RYR1, and CACNA1S, are increasingly recognized as significant contributors to recurrent rhabdomyolysis. MYH1 has recently been identified as a candidate gene for recurrent rhabdomyolysis with limited evidence originating from a single patient. In this report, we describe a 35‐year‐old male, born to consanguineous parents, who presented with recurrent rhabdomyolysis attacks, beginning at age 28, characterized by muscle pain, weakness, and episodes of acute kidney injury requiring dialysis. During attacks, the patient exhibited remarkably elevated markers of muscle breakdown and mildly elevated creatine kinase levels between episodes. A muscle biopsy revealed non‐specific myopathic changes. Exome sequencing analysis was carried out and revealed a novel homozygous variant (NM_005963.4: c.1825G>A [p.Val609Met]) in MYH1 segregating in a manner compatible with an autosomal recessive pattern. In summary, this case provides confirmatory support for the role of pathogenic MYH1 variants in the pathogenesis of recurrent rhabdomyolysis and emphasizes the importance of comprehensive genetic testing in patients with unexplained recurrent episodes of muscle breakdown. Further cases are necessary to fully elucidate the genotypic and phenotypic spectrum of MYH1‐related muscle disorders.
C−H Methylthiolation/d3‐Methylthiolation of Pyrazole Skeleton via Interrupted Pummerer Reaction
Authors: Shi Haofeng , Sun Fengxia , Wu Jialiang , He Jiaxin , Sun Yuli , Du Yunfei 
Published: December 2024

AbstractThe reaction of a series of pyrazole derivatives with DMSO/ ‐DMSO‐d6 and thionyl chloride conveniently afforded the 4‐thiolated pyrazole products under metal‐free conditions. This C−H functionalization/elelctrophilic thiolation process is postulated to involve the in situ generation of the electrophilic hypochlorothioite via interrupted Pummerer reaction, followed with the electrophilic methylthiolation of pyrazole skeleton.
An Unconventional Redox‐Neutral Regioselective Iodoamination of Allenamides
Authors: Tian Zhe , Zeng Zhaoxuan , Xie Hongqiang , Liu Qing , Yan Fachao , Liu Hui 
Published: December 2024

AbstractA novel unconventional redox‐neutral regioselective iodoamination of allenamides was developed. In the absence of metal catalyst, base and oxidant, the selective iodoamination of allenamides was achieved by using iodide salt in combination with morpholine/imidazole. The Iodide‐substituted Z‐enamides were synthesized under mild reaction conditions, and the products were stable and highly amenable to further modification.
Linker Installation in a Metal–Organic Framework for Enhanced Quantitative Redox Species Recognition
Authors: Han Zongsu , Wang Kun‐Yu , Liang Rong‐Ran , Yang Yihao , Huo Jiatong , Zhou Hong‐Cai 
Published: December 2024

AbstractLinker installation has proven to be an effective strategy for introducing diverse functional groups into metal–organic frameworks (MOFs). Reductants and oxidants are found in various environments, but their accumulation poses a danger due to their high reactivity, necessitating prompt monitoring instantly, particularly in natural environments and industrial processes. In this study, a series of redox‐active dyes were successfully incorporated into a flexible Zr‐based MOF, PCN‐700, through linker installation strategy. Notably, both the reduction of PCN‐700‐Resazurin towards oxidants and oxidation of PCN‐700‐Amplex Red towards reductants result in the formation of PCN‐700‐Resorufin, which exhibit visible color changes and largely elevated luminescent intensities, giving rise to the quantitative recognition of reductants and oxidants. This work presents a straightforward approach to developing efficient luminescent sensors for the rapid qualitative and quantitative detection of reductants and oxidants, extending the sensing mechanism from common energy transfer to electron transfer and demonstrating the MOF's versability as a highly designable sensing material for target analytes.
Recent Applications of the Sonogashira Reaction in the Synthesis of Drugs and Their Derivatives: A Review
Authors: Yan Fang , Zhang Xiyu , Li Daliang , Zhu Nengbo , Bao Hongli 
Published: December 2024

ABSTRACTMetal‐catalyzed cross‐coupling reactions are essential tools for constructing C–C bonds in organic synthesis. Among these prominent approaches, the Sonogashira reaction stands out as a key player and is widely utilized in medicinal chemistry. This versatile method enables the creation of complex C (sp2)–C (sp) bonds by linking aryl or vinyl halides with terminal alkynes, facilitating the efficient construction of molecular structures crucial for drug development. A notable application of the Sonogashira reaction is its ability to incorporate aromatic and alkynyl functionalities into pharmaceutical compounds. Depending on the impactful catalytic system evolved gradually, the Sonogashira reaction can involve either double‐metal catalysis or single‐metal catalysis. This review sheds light on the diverse applications of the Sonogashira coupling approach in drug synthesis and the generation of their derivatives.