bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inflammation‐Responsive Hydrogel Accelerates Diabetic Wound Healing through Immunoregulation and Enhanced Angiogenesis
Authors: He Fang , Xu Pengqin , Zhu Zhikang , Zhang Ying , Cai Chenghao , Zhang Yuxiang , Shao Jiaming , Jin Fang , Li Qiong , You Jiahuan , Zhou Hanlei , Zhang Wei , Wei Jintao , Hong Xudong , Zhang Zhongtao , Han Chunmao , Zhang Yuqi , Gu Zhen , Wang Xingang 
Published: April 2024

AbstractAngiogenesis is a prominent component during the highly regulated process of wound healing. The application of exogenous vascular endothelial growth factor (VEGF) has shown considerable potential in facilitating angiogenesis. However, its effectiveness is often curtailed due to chronic inflammation and severe oxidative stress in diabetic wounds. Herein, an inflammation‐responsive hydrogel incorporating Prussian blue nanoparticles (PBNPs) is designed to augment the angiogenic efficacy of VEGF. Specifically, the rapid release of PBNPs from the hydrogel under inflammatory conditions effectively alleviates the oxidative stress of the wound, therefore reprogramming the immune microenvironment to preserve the bioactivity of VEGF for enhanced angiogenesis. In vitro and in vivo studies reveal that the PBNPs and VEGF co‐loaded hydrogel is biocompatible and possesses effective anti‐inflammatory properties, thereby facilitating angiogenesis to accelerate the wound healing process in a type 2 diabetic mouse model.
J‐Aggregate Promoting NIR‐II Emission for Fluorescence/Photoacoustic Imaging‐Guided Phototherapy
Authors: Ou Changjin , Zhao Ziqi , An Lei , Zheng Liangyu , Gao Fan , Zhu Qin , Wang Wenjun , Shao Jinjun , Xie Linghai , Dong Xiaochen 
Published: April 2024

AbstractJ‐aggregate is a promising strategy to enhance second near‐infrared window (NIR‐II) emission, while the controlled synthesis of J‐aggregated NIR‐II dyes is a huge challenge because of the lack of molecular design principle. Herein, bulk spiro[fluorene‐9,9′‐xanthene] functionalized benzobisthiadiazole‐based NIR‐II dyes (named BSFX‐BBT and OSFX‐BBT) are synthesized with different alkyl chains. The weak repulsion interaction between the donor and acceptor units and the S…N secondary interactions make the dyes to adopt a co‐planar molecular conformation and display a peak absorption >880 nm in solution. Importantly, BSFX‐BBT can form a desiring J‐aggregate in the condensed state, and femtosecond transient absorption spectra reveal that the excited states of J‐aggregate are the radiative states, and J‐aggregate can facilitate stimulated emission. Consequently, the J‐aggregated nanoparticles (NPs) display a peak emission at 1124 nm with a high relative quantum yield of 0.81%. The efficient NIR‐II emission, good photothermal effect, and biocompatibility make the J‐aggregated NPs demonstrate efficient antitumor efficacy via fluorescence/photoacoustic imaging‐guided phototherapy. The paradigm illustrates that tuning the aggregate states of NIR‐II dye via spiro‐functionalized strategy is an effective approach to enhance photo‐theranostic performance.
Selectivity Switch in Non‐Directed Palladium‐Catalyzed C−H Olefination of Chlorobenzene Derivatives
Authors: Fichez Jeanne , Lapuh Maria I. , Truong Lina , Oulyadi Hassan , Buttard Floris , Besset Tatiana 
Published: April 2024

AbstractA palladium(II)‐catalyzed oxidative C−H olefination of chlorobenzene derivatives, which favored the functionalization at the ortho‐to‐chlorine position, was reported. The catalytic system employed a commercially available quinoline ligand to access a wide panel of olefinated aryl chlorides in moderate to high yields from feedstock chemicals (42 examples, 28 to 93% yields). The synthetic utility of the method was further demonstrated by the coupling of various bio‐relevant acrylate partners offering straightforward access to structurally diverse complex molecules. A computational study of the reaction allowed us to confirm that the C−H activation step, occurring through a Concerted Metalation‐Deprotonation mechanism, determined the site‐selectivity of the transformation. The regioselectivity was controlled by the pKa of the C−H bond (more acidic position) and the lower distortion of chlorobenzene in the key transition structure.
Structural Pharmacology of TRPV4 Antagonists
Authors: Fan Junping , Guo Chang , Liao Daohong , Ke Han , Lei Jing , Xie Wenjun , Tang Yuliang , Tominaga Makoto , Huang Zhuo , Lei Xiaoguang 
Published: April 2024

AbstractThe nonselective calcium‐permeable Transient Receptor Potential Cation Channel Subfamily V Member4 (TRPV4) channel regulates various physiological activities. Dysfunction of TRPV4 is linked to many severe diseases, including edema, pain, gastrointestinal disorders, lung diseases, and inherited neurodegeneration. Emerging TRPV4 antagonists show potential clinical benefits. However, the molecular mechanisms of TRPV4 antagonism remain poorly understood. Here, cryo‐electron microscopy (cryo‐EM) structures of human TRPV4 are presented in‐complex with two potent antagonists, revealing the detailed binding pockets and regulatory mechanisms of TRPV4 gating. Both antagonists bind to the voltage‐sensing‐like domain (VSLD) and stabilize the channel in closed states. These two antagonists induce TRPV4 to undergo an apparent fourfold to twofold symmetry transition. Moreover, it is demonstrated that one of the antagonists binds to the VSLD extended pocket, which differs from the canonical VSLD pocket. Complemented with functional and molecular dynamics simulation results, this study provides crucial mechanistic insights into TRPV4 regulation by small‐molecule antagonists, which may facilitate future drug discovery targeting TRPV4.
Combination of a TGF‐β ligand trap (RAP‐GRL) and TMPRSS6‐ASO is superior for correcting β‐thalassemia
Authors: Guerra Amaliris , Hamilton Nolan , Rivera Ariel , Demsko Perry , Guo Shuling , Rivella Stefano 
Published: April 2024

AbstractA recently approved drug that induces erythroid cell maturation (luspatercept) has been shown to improve anemia and reduce the need for blood transfusion in non‐transfusion‐dependent as well as transfusion‐dependent β‐thalassemia (BT) patients. Although these results were predominantly positive, not all the patients showed the expected increase in hemoglobin (Hb) levels or transfusion burden reduction. Additional studies indicated that administration of luspatercept in transfusion‐dependent BT was associated with increased erythropoietic markers, decreased hepcidin levels, and increased liver iron content. Altogether, these studies suggest that luspatercept may necessitate additional drugs for improved erythroid and iron management. As luspatercept does not appear to directly affect iron metabolism, we hypothesized that TMPRSS6‐ASO could improve iron parameters and iron overload when co‐administered with luspatercept. We used an agent analogous to murine luspatercept (RAP‐GRL) and another novel therapeutic, IONIS TMPRSS6‐LRx (TMPRSS6‐ASO), a hepcidin inducer, to treat non‐transfusion‐dependent BT‐intermedia mice. Our study shows that RAP‐GRL alone improved red blood cell (RBC) production, with no or limited effect on splenomegaly and iron parameters. In contrast, TMPRSS6‐ASO improved RBC measurements, ameliorated splenomegaly, and improved iron overload most effectively. Our results provide pre‐clinical support for combining TMPRSS6‐ASO and luspatercept in treating BT, as these drugs together show potential for simultaneously improving both erythroid and iron parameters in BT patients.
Bifunctional Ligand Enables Gold‐Catalyzed Propargyl C−H Functionalization via Reactive Gold Allenylidene Intermediate
Authors: Wei Yongliang , Jiang Jingxing , Jing Yaru , Ke Zhuofeng , Zhang Liming 
Published: April 2024

AbstractGold allenylidene species have been seldom exploited as reactive intermediates in synthetically versatile catalytic reactions. By employing alkynylbenziodoxoles as the substrates and bifunctional WangPhos as the metal ligand, this work demonstrated ready catalytic access to these intermediates of general substitution patterns and their electrophilic reactivities at the γ‐carbon center with a diverse range of nucleophiles. The reaction is driven by the reductive decomposition of the benziodoxole moiety and achieves the replacement of a propargylic proton with an N/O/C‐based nucleophile, hence realizing reactivity umpolung. Corroborated by Density Functional Theory (DFT) calculations, the reaction mechanism involves a mild propargylic deprotonation. In contrast to prior works employing a tertiary amine functionality, a weakly BrØnsted‐basic amide group in WangPhos is surprisingly effective in deprotonation at the propargylic position under a gold‐ligand cooperation regime.
In‐Situ Cyclized Polyacrylonitrile as an Electron Selective Layer for n‐i‐p Perovskite Solar Cell with Enhanced Efficiency and Stability
Authors: Gu Wei‐Min , Jiang Ke‐Jian , Jiao Xinning , Gao Cai‐Yan , Fan Xin‐Heng , Yang Lian‐Ming , Song Yanlin 
Published: April 2024

AbstractIn situ cyclized polyacrylonitrile (CPAN) is developed to replace n‐type metal oxide semiconductors (TiO2 or SnO2) as an electron selective layer (ESL) for highly efficient and stable n‐i‐p perovskite solar cells (PSCs). The CPAN layer is fabricated via facile in situ cyclization reaction of polyacrylonitrile (PAN) coated on a conducting glass substrate. The CPAN layer is robust and insoluble in common solvents, and possesses n‐type semiconductor properties with a high electron mobility of 4.13×10−3 cm2 V−1 s−1. With the CPAN as an ESL, the PSC affords a power conversion efficiency (PCE) of 23.12 %, which is the highest for the n‐i‐p PSCs with organic ESLs. Moreover, the device with the CPAN layer holds superior operational stability, maintaining over 90 % of their initial efficiency after 500 h continuous light soaking. These results confirm that the CPAN layer would be a desirable low‐cost and efficient ESL for n‐i‐p PSCs and other photoelectronic devices with high performance and stability.
All‐organic shell–core PVDF/PMMA composite fiber films with enhanced piezoelectric performance for flexible sensing and energy harvesting
Authors: Li Xiao , Yuan ChongXiao , Gao Guoqi , Zhou Hengqing , Zhang Nannan , Yang Xinyue , Liu Xiaofang , Sun Huajun 
Published: April 2024

AbstractThe demand for self‐powered sensing technology and energy harvesting system necessitates high‐performance and flexible piezoelectric materials. This paper presents a novel approach utilizing coaxial electrospinning to fabricate all‐organic PVDF/PMMA piezoelectric fiber films with a shell–core structure. The resulting fiber films, cut into 2 × 2 cm2 square pieces and hot‐pressed every three pieces, demonstrate enhanced piezoelectric properties while retaining high flexibility. The interaction between the CO bonds in the PMMA polymer and the CH2 in PVDF promotes the arrangement of F atoms in PVDF, enhancing the content of the piezoelectric active phase. Additionally, the coaxial electrospinning process fosters vertically oriented hydrogen bonds between PVDF and PMMA, augmenting cross‐linking and improving mechanical properties. Notably, when the PVDF to PMMA layer volume ratio is 5:1, the piezoelectric coefficient (|d33|) of the composite fiber film exhibits a significant 60% increase from 10 pC N−1 in neat PVDF to 16 pC N−1. This research holds substantial promise for applications in self‐powered sensing and energy harvesting piezoelectric materials.
Isalo scorpion cytotoxic peptide‐strengthened immune function through the JAKs/STATs signaling pathway of the immune organ of grass carp (Ctenopharyngodon idella) challenged with Aeromonas hydrophila
Authors: He Yuanlin , Hu Qiyu , Zhou Xiaoqiu , Wu Pei , Jiang Weidan , Liu Yang , Jin Xiaowan , Ren Hongmei , Feng Lin 
Published: April 2024

AbstractTo investigate the impact of Isalo scorpion cytotoxic peptide (IsCT) on the immune function of immune organ (head kidney, spleen, and skin) of grass carp (Ctenopharyngodon idella), 540 fish (136.88 ± 0.72 g) were supplied with a different amount of IsCT (0, 0.6, 1.2, 1.8, 2.4, and 3.0 mg/kg diet) through a period of 60 days. Afterward, 24 fish were randomly selected from each group and were inoculated with Aeromonas hydrophila for a period of 6 days. Our findings suggested that appropriate IsCT complementation: (1) attenuated skin morbidity and histopathological structural changes in the head kidney and spleen (p < 0.05), which ensured the structural integrity of the immune organs; (2) increased the activity and expression of immune substances (p < 0.05), which in turn increased the function of the immune organs, promoting immune responses; (3) through the regulation of the Janus kinase/signal transducers and activators of transcription (JAKs/STATs) signaling pathway, the mRNA expression of anti‐inflammatory cytokines increased and the mRNA expression of pro‐inflammatory cytokines decreased, which in turn increased the function of the immune organs, reducing the inflammatory response (p < 0.05). However, the addition of IsCT did not affect the expression of IL‐12p35, STAT2, and STAT3a in the immune organ. Ultimately, this study provided evidence that IsCT enhanced immune function via the JAKs/STATs signaling pathway in the immune organ in grass carp after challenged with Aeromonas hydrophila.
High‐Density and Freestanding Porous Carbon Film for Compact Sodium‐Ion Storage
Authors: Lin Xiaomin , Zhang Weicai , Chen Jiaao , Lu Jiacong , Zheng Mingtao , Liu Yingliang , Liang Yeru 
Published: April 2024

AbstractPorous carbon materials are often difficult to achieve high density while possessing high porosity, which limits their application in compact energy storage. Here, a design of freestanding porous‐yet‐dense carbon films with a tunable density (1.08–1.33 g cm−3) and porosity (specific surface area of 0–423.8 m2 g−1) is presented through an assembly of porous carbon nanosheet with graphene oxide under vacuum filtration. The typical freestanding carbon films simultaneously deliver a high density of 1.08 g cm−3 and a high specific surface area of 423.8 m2 g−1 when the porous carbon nanosheet content is 75 wt.%. As anode materials for sodium‐ion batteries, the optimized freestanding carbon films deliver high volumetric capacity (270 mAh cm−3 at 20 mA g−1), high initial capacity efficiency (81 %) and superior long‐term cycling stability (1300 cycles with a capacity decay rate of 0.012 % per cycle). This study provides a promising direction for creating freestanding electrodes that meet both high‐porosity and high‐density requirements for compact sodium‐ion batteries.
Cholesterol transport and beyond: Illuminating the versatile functions of HDL apolipoproteins through structural insights and functional implications
Authors: Bhale Aishwarya Sudam , Meilhac Olivier , d'Hellencourt Christian Lefebvre , Vijayalakshmi Mookambeswaran A. , Venkataraman Krishnan 
Published: April 2024

AbstractHigh‐density lipoproteins (HDLs) play a vital role in lipid metabolism and cardiovascular health, as they are intricately involved in cholesterol transport and inflammation modulation. The proteome of HDL particles is indeed complex and distinct from other components in the bloodstream. Proteomics studies have identified nearly 285 different proteins associated with HDL; however, this review focuses more on the 15 or so traditionally named “apo” lipoproteins. Important lipid metabolizing enzymes closely working with the apolipoproteins are also discussed. Apolipoproteins stand out for their integral role in HDL stability, structure, function, and metabolism. The unique structure and functions of each apolipoprotein influence important processes such as inflammation regulation and lipid metabolism. These interactions also shape the stability and performance of HDL particles. HDLs apolipoproteins have multifaceted roles beyond cardiovascular diseases (CVDs) and are involved in various physiological processes and disease states. Therefore, a detailed exploration of these apolipoproteins can offer valuable insights into potential diagnostic markers and therapeutic targets. This comprehensive review article aims to provide an in‐depth understanding of HDL apolipoproteins, highlighting their distinct structures, functions, and contributions to various physiological processes. Exploiting this knowledge holds great potential for improving HDL function, enhancing cholesterol efflux, and modulating inflammatory processes, ultimately benefiting individuals by limiting the risks associated with CVDs and other inflammation‐based pathologies. Understanding the nature of all 15 apolipoproteins expands our knowledge of HDL metabolism, sheds light on their pathological implications, and paves the way for advancements in the diagnosis, prevention, and treatment of lipid and inflammatory‐related disorders.
Hydroxyapatite‐loaded macroporous calcium alginate hydrogels: Preparation, characterization, and in vitro evaluation
Authors: Drozdova Maria , Makhonina Alika , Gladkikh Daria , Artyukhov Alexander , Bryukhanov Leonid , Mezhuev Yaroslav , Lozinsky Vladimir , Markvicheva Elena 
Published: April 2024

AbstractHydrogels from natural polysaccharides are of great interest for tissue engineering. This study aims (1) to prepare hydroxyapatite‐loaded macroporous calcium alginate hydrogels by novel one‐step technique using internal gelation in water‐frozen solutions; (2) to evaluate their physicochemical properties; (3) to estimate their ability to support cell growth and proliferation in vitro. The structure of the hydrogel samples in a swollen state was studied by confocal laser scanning microscopy and was shown to represent a system of interconnected macropores with sizes of tens micron. The swelling behavior of the hydrogels, their mechanical properties (Young's moduli) in function of a hydroxyapatite content (5–30 mass%) were studied. All hydrogel samples loaded with hydroxyapatite were found to support growth and proliferation of mouse fibroblasts (L929) at long‐term cultivation for 7 days. The obtained macroporous composite Ca‐Alg‐HA hydrogels could be promising for tissue engineering.
Creating a sustainable future through Industry 4.0 technologies: Untying the role of circular economy practices and supply chain visibility
Authors: Junaid Muhammad , Du Jianguo , Mubarik Muhammad Shujaat , Shahzad Fakhar 
Published: April 2024

AbstractThe intersection of Industry 4.0 technology (I4.0‐Tech) with sustainability (SUS) remains largely unexplored, particularly due to its interactions with supply chain visibility (SCV) and circular economy practices (CEP). To fill this gap, our study empirically examines I4.0‐Tech's impact on SUS through SCV and CEP. We utilized structural equation modeling to test the hypothesized relationships using data from a survey of 344 medium and large Chinese firms. The empirical findings support the indirect role of I4.0 through SCV, and CEP. I4.0‐Tech enables real‐time material and product tracking for SCV. Optimizing material utilization, fostering closed‐loop supply chains, and allowing circular product design enhance CEP. Furthermore, our findings show a positive relationship between SCV, CEP, and SUS. This highlights the need for robust supply chain capabilities in enabling I4.0‐Tech to drive SUS. This paradigm emphasizes recalibrating approaches to SCV and CEP‐focused frameworks to easily include and exploit I4.0‐Tech. This study contributes to the literature and gives actionable insights for managers and policymakers wanting to synergize I4.0‐Tech, SCV, and CEP in industrial processes to promote sustainability goals and a sustainable future.
Association of leptin receptor polymorphisms with susceptibility of non‐small cell lung cancer: Evidence from 2249 subjects
Authors: Tang Weifeng , Wang Jian , Dai Ting , Qiu Hao , Liu Chao , Chen Shuchen , Hu Zhendong 
Published: April 2024

AbstractNon‐small cell lung cancer (NSCLC) is increasing dramatically. It is believed that energy metabolism‐related genes could play an important role in etiology of NSCLC. In this study, we sought to assess the correlation between three LEPR single nucleotide polymorphisms (rs1137101, rs1137100 and rs6588147) with NSCLS susceptibility. In total, 1193 NSCLC cases and 1056 controls were included. SNPscan™ genotyping method was used to analyze the genotypes of LEPR polymorphisms. Compared to rs6588147 GG in LEPR gene, this study identified a protective role of LEPR rs6588147 GA and GA/AA for the occurrence of NSCLC (GA vs. GG [p = 0.021] and GA/AA vs. GG [p = 0.030]). As well, we found that a protective role of LEPR rs6588147 for the occurrence of non‐SCC subgroup (p < 0.05). By logistic regression analysis, we found that the rs6588147 A allele related genotypes might play a protective role for the occurrence of NSCLC in drinking, BMI ≥24 kg/m2, smoking and male subgroups. We also found that the rs1137101 A allele related genotypes played a protective role for the occurrence of NSCLC in male, younger participants (under 59 years) and overweight/obesity (BMI ≥24 kg/m2) subgroups. We found that LEPR Ars1037100Ars1037101Ars6588147 haplotype might play a protective role for the occurrence of NSCLC (p = 0.013). In addition, our findings indicated that LEPR rs1137100 G>A SNP might increase the risk of lymph node metastases (p = 0.038). This study highlights that LEPR rs6588147, rs1137101 genotypes and LEPR Ars1037100Ars1037101Ars6588147 haplotype are correlated with the occurrence of NSCLC. LEPR rs1137100 G>A SNP increases the risk of lymph node metastases.
The efficiency and safety of low‐dose apatinib combined with oral vinorelbine in pretreated HER2‐negative metastatic breast cancer
Authors: Huang Jia‐Yi , Chen Xue‐Lian , Xie Xiao‐Feng , Song Lin , Chen Li‐Ping , Lan Xiao‐Feng , Bai Xue , Chen Xiao , Du Cai‐Wen 
Published: April 2024

AbstractBackgroundApatinib is an oral small‐molecule tyrosine kinase inhibitor that blocks vascular endothelial growth factor receptor‐2. Oral vinorelbine is a semisynthetic chemotherapeutic agent of vinorelbine alkaloids. Apatinib and oral vinorelbine have been proved to be effective in the treatment of metastatic breast cancer (mBC). At present, several small sample clinical trials have explored the efficacy of apatinib combined with oral vinorelbine in the treatment of mBC.MethodsThis retrospective study included 100 human epidermal growth factor receptor‐2 (HER2)‐negative mBC patients who received low‐dose apatinib (250 mg orally per day) plus oral vinorelbine until disease progression or intolerance during February 2017 and March 2023. The progression‐free survival (PFS), overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR), disease control rate (DCR), and safety were analyzed by SPSS 26.0 software and GraphPad Prism 8 software. Cox proportional hazards regression model for univariate and multivariate was used to identify factors significantly related to PFS and OS.ResultsThe median follow‐up time for this study was 38.1 months. Among 100 patients with HER2‐negative mBC, 66 were hormone receptor (HR)‐positive/HER2‐negative and 34 were triple‐negative breast cancer (TNBC). The median PFS and OS were 6.0 months (95% CI, 5.2–6.8 months) and 23.0 months (95% CI, 19.9–26.1 months). There were no statistical differences in PFS (p = 0.239) and OS (p = 0.762) between the HR‐positive /HER2‐negative and TNBC subgroups. The ORR, CBR, and DCR were 21.0%, 58.0%, and 78.0%, respectively. Ninety‐five patients (95.0%) experienced varying grades of adverse events (AEs) and 38.0% of patients for Grades 3–4. The most common Grades 3–4 AEs that we observed were neutropenia (30.0%) and leukopenia (25.0%).ConclusionLow‐dose apatinib combined with oral vinorelbine demonstrates potential efficacy and well tolerated for pretreated HER2‐negative mBC.