bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dendronized Polymer‐Derived Nanomedicines for Mitochondrial Dynamics Regulation and Immune Modulation
Authors: Hou Xingyu , Pan Dayi , Zhong Dan , Gong Qiyong , Luo Kui 
Published: March 2024

AbstractThe effects of dendron side chains in polymeric conjugates on tumor penetration and antigen presentation are systematically examined. Three polymer‐gemcitabine (Gem) conjugates (pG0‐Gem, pG1‐Gem, pG2‐Gem) are designed and prepared. The pG2‐Gem conjugate uniquely binds to the mitochondria of tumor cells, thus regulating mitochondrial dynamics. The interaction between the pG2‐Gem conjugate and the mitochondria promotes great penetration and accumulation of the conjugate at the tumor site, resulting in pronounced antitumor effects in an animal model. Such encouraging therapeutic effects can be ascribed to immune modulation since MHC‐1 antigen presentation is significantly enhanced due to mitochondrial fusion and mitochondrial metabolism alteration after pG2‐Gem treatment. Crucially, the drug‐free dendronized polymer, pG2, is identified to regulate mitochondrial dynamics, and the regulation is independent of the conjugated Gem. Furthermore, the combination of pG2‐Gem with anti‐PD‐1 antibody results in a remarkable tumor clearance rate of 87.5% and a prolonged survival rate of over 150 days, demonstrating the potential of dendronized polymers as an innovative nanoplatform for metabolic modulation and synergistic tumor immunotherapy.
Spatiotemporal Reaction Dynamics Control in Two‐Photon Polymerization for Enhancing Writing Characteristics
Authors: Mao Aofei , Fess Sarah , Kraiem Nada , Li Peizi , Wu Zhipeng , Zhu Qiuchi , Huang Xi , Fan Peixun , Cui Bai , Silvain Jean‐Francois , Hu Suxing , Anthamatten Mitchell , Regan Sean P. , Harding David , Lu Yongfeng 
Published: March 2024

AbstractSince 2001, 3D microfabrication based on two‐photon polymerization (TPP) has drawn extensive attention and interest in biology, optics, photonics, material science, and high‐energy physics. The in‐volume fabrication capability due to the threshold behavior of two‐photon absorption enables TPP higher flexibility compared with other nanofabrication techniques. However, as determined by the in‐volume fabrication feature as well as various reaction dynamics, the writing characteristics of TPP, such as throughput, accuracy, surface quality, and fabrication capability, are still limited. Herein, a comprehensive study is performed on the spatiotemporal behavior of reaction dynamics during TPP fabrication, mainly focusing on spatiotemporal characteristics of radical diffusion, photothermal effect, microscale mechanics, and voxel stacking process. Based on the study, a nonsequential fabrication method is established to simultaneously improve key writing characteristics of TPP and realize sharp features, high speeds, large overhang structure, and smooth surfaces. The method established in this work can be applied to improve the performance of functional devices for various fields.
Mesenchymal Stem Cells‐Involved Strategies for Rheumatoid Arthritis Therapy
Authors: Li Chaoyang , Sun Yifu , Xu Weiguo , Chang Fei , Wang Yinan , Ding Jianxun 
Published: March 2024

AbstractRheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic inflammation of the joints and bone destruction. Because of systemic administration and poor targeting, traditional anti‐rheumatic drugs have unsatisfactory treatment efficacy and strong side effects, including myelosuppression, liver or kidney function damage, and malignant tumors. Consequently, mesenchymal stem cells (MSCs)‐involved therapy is proposed for RA therapy as a benefit of their immunosuppressive and tissue‐repairing effects. This review summarizes the progress of MSCs‐involved RA therapy through suppressing inflammation and promoting tissue regeneration and predicts their potential clinical application.
Gastrointestinal Dysmotility Predisposes to Colitis through Regulation of Gut Microbial Composition and Linoleic Acid Metabolism
Authors: Zhang Youhua , Song Feifei , Yang Muqing , Chen Chunqiu , Cui Jiaqu , Xing Mengyu , Dai Yuna , Li Man , Cao Yuan , Lu Ling , Zhu Huiyuan , Liu Ying , Ma Chunlian , Wei Qing , Qin Huanlong , Li Jiyu 
Published: March 2024

AbstractDisrupted gastrointestinal (GI) motility is highly prevalent in patients with inflammatory bowel disease (IBD), but its potential causative role remains unknown. Herein, the role and the mechanism of impaired GI motility in colitis pathogenesis are investigated. Increased colonic mucosal inflammation is found in patients with chronic constipation (CC). Mice with GI dysmotility induced by genetic mutation or chemical insult exhibit increased susceptibility to colitis, dependent on the gut microbiota. GI dysmotility markedly decreases the abundance of Lactobacillus animlalis and increases the abundance of Akkermansia muciniphila. The reduction in L. animlalis, leads to the accumulation of linoleic acid due to compromised conversion to conjugated linoleic acid. The accumulation of linoleic acid inhibits Treg cell differentiation and increases colitis susceptibility via inducing macrophage infiltration and proinflammatory cytokine expression in macrophage. Lactobacillus and A. muciniphila abnormalities are also observed in CC and IBD patients, and mice receiving fecal microbiota from CC patients displayed an increased susceptibility to colitis. These findings suggest that GI dysmotility predisposes host to colitis development by modulating the composition of microbiota and facilitating linoleic acid accumulation. Targeted modulation of microbiota and linoleic acid metabolism may be promising to protect patients with motility disorder from intestinal inflammation.
A Multifunctional Therapeutic Strategy Using P7C3 as A Countermeasure Against Bone Loss and Fragility in An Ovariectomized Rat Model of Postmenopausal Osteoporosis
Authors: Wei Fei , Hughes Megan , Omer Mahmoud , Ngo Christopher , Pugazhendhi Abinaya Sindu , Kolanthai Elayaraja , Aceto Matthew , Ghattas Yasmine , Razavi Mehdi , Kean Thomas J , Seal Sudipta , Coathup Melanie 
Published: March 2024

AbstractBy 2060, an estimated one in four Americans will be elderly. Consequently, the prevalence of osteoporosis and fragility fractures will also increase. Presently, no available intervention definitively prevents or manages osteoporosis. This study explores whether Pool 7 Compound 3 (P7C3) reduces progressive bone loss and fragility following the onset of ovariectomy (OVX)‐induced osteoporosis. Results confirm OVX‐induced weakened, osteoporotic bone together with a significant gain in adipogenic body weight. Treatment with P7C3 significantly reduced osteoclastic activity, bone marrow adiposity, whole‐body weight gain, and preserved bone area, architecture, and mechanical strength. Analyses reveal significantly upregulated platelet derived growth factor‐BB and leukemia inhibitory factor, with downregulation of interleukin‐1 R6, and receptor activator of nuclear factor kappa‐B (RANK). Together, proteomic data suggest the targeting of several key regulators of inflammation, bone, and adipose turnover, via transforming growth factor‐beta/SMAD, and Wingless‐related integration site/be‐catenin signaling pathways. To the best of the knowledge, this is first evidence of an intervention that drives against bone loss via RANK. Metatranscriptomic analyses of the gut microbiota show P7C3 increased Porphyromonadaceae bacterium, Candidatus Melainabacteria, and Ruminococcaceae bacterium abundance, potentially contributing to the favorable inflammatory, and adipo‐osteogenic metabolic regulation observed. The results reveal an undiscovered, and multifunctional therapeutic strategy to prevent the pathological progression of OVX‐induced bone loss.
NHC‐Au‐Catalyzed Isomerization of Propargylic B(MIDA)s to Allenes and Double Isomerization of Alkynes to 1,3‐Dienes
Authors: Liu Li‐Cai , Lin Shuang , Xu Kangwei , Qian Jiasheng , Wu Ruibo , Li Qingjiang , Wang Honggen 
Published: March 2024

AbstractThe synthesis of allenyl boronates is an important yet challenging topic in organic synthesis. Reported herein is an NHC‐gold‐catalyzed 1,3‐H shift toward allenyl boronates synthesis from simple propargylic B(MIDA)s. Mechanistic studies suggest dual roles of the boryl moiety in the reaction: to activate the substrate for isomerization and at the same time, to prevent the allene product from further isomerization. These effects should be a result of α‐anion stabilization and α‐cation destabilization conferred by the B(MIDA) moiety, respectively. The NHC‐Au catalyst, which is commercially available, is also found to be reactive in alkyne‐to‐1,3‐diene isomerization reactions in an atom‐economic and base‐free manner.
Photo‐Induced Charge State Dynamics of the Neutral and Negatively Charged Silicon Vacancy Centers in Room‐Temperature Diamond
Authors: Garcia‐Arellano G. , López‐Morales G. I. , Manson N. B. , Flick J. , Wood A. A. , Meriles C. A. 
Published: March 2024

AbstractThe silicon vacancy (SiV) center in diamond is drawing much attention due to its optical and spin properties, attractive for quantum information processing and sensing. Comparatively little is known, however, about the dynamics governing SiV charge state interconversion mainly due to challenges associated with generating, stabilizing, and characterizing all possible charge states, particularly at room temperature. Here, multi‐color confocal microscopy and density functional theory are used to examine photo‐induced SiV recombination — from neutral, to single‐, to double‐negatively charged — over a broad spectral window in chemical‐vapor‐deposition (CVD) diamond under ambient conditions. For the SiV0 to SiV‐ transition, a linear growth of the photo‐recombination rate with laser power at all observed wavelengths is found, a hallmark of single photon dynamics. Laser excitation of SiV‒, on the other hand, yields only fractional recombination into SiV2‒, a finding that is interpreted in terms of a photo‐activated electron tunneling process from proximal nitrogen atoms.
Easy but Efficient: Facile Approach to Molecule with Theoretically Justified Donor–Acceptor Structure for Effective Photothermal Conversion and Intravenous Photothermal Therapy
Authors: Zhong Yuan‐Hui , Huang Gui‐Feng , Zhao Sheng‐Yi , Chung Lai‐Hon , Zhang Hua‐Tang , Zheng Jin‐Hong , Yan Yi‐Lang , Ni Wen‐Xiu , He Jun 
Published: March 2024

AbstractTo accelerate the pace in the field of photothermal therapy (PTT), it is urged to develop easily accessible photothermal agents (PTAs) showing high photothermal conversion efficiency (PCE). As a proof‐of‐concept, hereby a conventional strategy is presented to prepare donor–acceptor (D–A) structured PTAs through cycloaddition‐retroelectrocyclization (CA–RE) reaction, and the resultant PTAs give high PCE upon near‐infrared (NIR) irradiation. By joint experimental‐theoretical study, these PTAs exhibit prominent D–A structure with strong intramolecular charge transfer (ICT) characteristics and significantly twisting between D and A units which account for the high PCEs. Among them, the DMA‐TCNQ exhibits the strongest absorption in NIR range as well as the highest PCE of 91.3% upon irradiation by 760‐nm LED lamp (1.2 W cm−2). In vitro and in vivo experimental results revealed that DMA‐TCNQ exhibits low dark toxicity and high phototoxicity after IR irradiation along with nude mice tumor inhibition up to 81.0% through intravenous therapy. The findings demonstrate CA–RE reaction as a convenient approach to obtain twisted D–A structured PTAs for effective PTT and probably promote the progress of cancer therapies.
Interface Modulation for the Heterointegration of Diamond on Si
Authors: Li Xing , Wan Li , Lin Chaonan , Huang Wen‐Tao , Zhou Jing , Zhu Jie , Yang Xun , Yang Xigui , Zhang Zhenfeng , Zhu Yandi , Ren Xiaoyan , Jin Ziliang , Dong Lin , Cheng Shaobo , Li Shunfang , Shan Chongxin 
Published: March 2024

AbstractAlong with the increasing integration density and decreased feature size of current semiconductor technology, heterointegration of the Si‐based devices with diamond has acted as a promising strategy to relieve the existing heat dissipation problem. As one of the heterointegration methods, the microwave plasma chemical vapor deposition (MPCVD) method is utilized to synthesize large‐scale diamond films on a Si substrate, while distinct structures appear at the Si‐diamond interface. Investigation of the formation mechanisms and modulation strategies of the interface is crucial to optimize the heat dissipation behaviors. By taking advantage of electron microscopy, the formation of the epitaxial β‐SiC interlayer is found to be caused by the interaction between the anisotropically sputtered Si and the deposited amorphous carbon. Compared with the randomly oriented β‐SiC interlayer, larger diamond grain sizes can be obtained on the epitaxial β‐SiC interlayer under the same synthesis condition. Moreover, due to the competitive interfacial reactions, the epitaxial β‐SiC interlayer thickness can be reduced by increasing the CH4/H2 ratio (from 3% to 10%), while further increase in the ratio (to 20%) can lead to the broken of the epitaxial relationship. The above findings are expected to provide interfacial design strategies for multiple large‐scale diamond applications.
Nucleation of Huntingtin Aggregation Proceeds via Conformational Conversion of Pre‐Formed, Sparsely‐Populated Tetramers
Authors: Torricella Francesco , Tugarinov Vitali , Clore G. Marius 
Published: March 2024

AbstractPathogenic huntingtin exon‐1 protein (httex1), characterized by an expanded polyglutamine tract located between the N‐terminal amphiphilic region and a C‐terminal polyproline‐rich domain, forms fibrils that accumulate in neuronal inclusion bodies, and is associated with a fatal, autosomal dominant neurodegenerative condition known as Huntington's disease. Here a complete kinetic model is described for aggregation/fibril formation of a httex1 construct with a 35‐residue polyglutamine repeat, httex1Q35. Using exchange NMR spectroscopy, it is previously shown that the reversible formation of a sparsely‐populated tetramer of the N‐terminal amphiphilic domain of httex1Q35, comprising a D2 symmetric four‐helix bundle, occurs on the microsecond time‐scale and is a prerequisite for subsequent nucleation and fibril formation on a time scale that is many orders of magnitude slower (hours). Here a unified kinetic model of httex1Q35 aggregation is developed in which fast, reversible tetramerization is directly linked to slow irreversible fibril formation via conversion of pre‐equilibrated tetrameric species to “active”, chain elongation‐capable nuclei by conformational re‐arrangement with a finite, monomer‐independent rate. The unified model permits global quantitative analysis of reversible tetramerization and irreversible fibril formation from a time series of 1H‐15N correlation spectra recorded during the course of httex1Q35 aggregation.
Innovative Arylimidazole‐Fused Phytovirucides via Carbene‐Catalyzed [3+4] Cycloaddition: Locking Viral Cell‐To‐Cell Movement by Out‐Competing Virus Capsid‐Host Interactions
Authors: Wei Chunle , Zhao Chunni , Li Jiao , Li Chunyi , Song Baoan , Song Runjiang 
Published: March 2024

AbstractThe control of potato virus Y (PVY) induced crop failure is a challengeable issue in agricultural chemistry. Although many anti‐PVY agents are designed to focus on the functionally important coat protein (CP) of virus, how these drugs act on CP to inactivate viral pathogenicity, remains largely unknown. Herein, a PVY CP inhibitor ‐3j (S) is disclosed, which is accessed by developing unusually efficient (up to 99% yield) and chemo‐selective (> 99:1 er in most cases) carbene‐catalyzed [3+4] cycloaddition reactions. Compound ‐3j bears a unique arylimidazole‐fused diazepine skeleton and shows chirality‐preferred performance against PVY. In addition, ‐3j (S) as a mediator allows ARG191 (R191) of CP to be identified as a key amino acid site responsible for intercellular movement of virions. R191 is further demonstrated to be critical for the interaction between PVY CP and the plant functional protein NtCPIP, enabling virions to cross plasmodesmata. This key step can be significantly inhibited through bonding with the ‐3j (S) to further impair pathogenic behaviors involving systemic infection and particle assembly. The study reveals the in‐depth mechanism of action of antiviral agents targeting PVY CP, and contributes to new drug structures and synthetic strategies for PVY management.
Nanowire Array Breath Acetone Sensor for Diabetes Monitoring
Authors: Wei Shiyu , Li Zhe , Murugappan Krishnan , Li Ziyuan , Lysevych Mykhaylo , Vora Kaushal , Tan Hark Hoe , Jagadish Chennupati , Karawdeniya Buddini I , Nolan Christopher J , Tricoli Antonio , Fu Lan 
Published: March 2024

AbstractDiabetic ketoacidosis (DKA) is a life‐threatening acute complication of diabetes characterized by the accumulation of ketone bodies in the blood. Breath acetone, a ketone, directly correlates with blood ketones. Therefore, monitoring breath acetone can significantly enhance the safety and efficacy of diabetes care. In this work, the design and fabrication of an InP/Pt/chitosan nanowire array‐based chemiresistive acetone sensor is reported. By incorporation of chitosan as a surface‐functional layer and a Pt Schottky contact for efficient charge transfer processes and photovoltaic effect, self‐powered, highly selective acetone sensing is achieved. The sensor has exhibited an ultra‐wide acetone detection range from sub‐ppb to >100 000 ppm level at room temperature, covering those in the exhaled breath from healthy individuals (300–800 ppb) to people at high risk of DKA (>75 ppm). The nanowire sensor has also been successfully integrated into a handheld breath testing prototype, the Ketowhistle, which can successfully detect different ranges of acetone concentrations in simulated breath samples. The Ketowhistle demonstrates the immediate potential for non‐invasive ketone monitoring for people living with diabetes, in particular for DKA prevention.
Injectable Hydrogel Delivery System with High Drug Loading for Prolonging Local Anesthesia
Authors: Li Yongchun , Chen You , Xue Yifan , Jin Jinlong , Xu Yixin , Zeng Weian , Liu Jie , Xie Jingdun 
Published: March 2024

AbstractPeripheral nerve block is performed for precise pain control and lesser side effects after surgery by reducing opioid consumption. Injectable hydrogel delivery systems with high biosafety and moisture content have good clinical application prospects for local anesthetic delivery. However, how to achieve high drug loading and long‐term controlled release of water‐soluble narcotic drugs remains a big challenge. In this study, heterogeneous microspheres and an injectable gel‐matrix composite drug delivery system are designed in two steps. First, heterogeneous hydrogel microspheres loaded with ropivacaine (HMS‐ROP) are prepared using a microfluidic chip and in situ alkalization. An injectable self‐healing hydrogel matrix (Gel) is then prepared from modified carboxymethylcellulose (CMC‐ADH) and oxidized hyaluronic acid (OHA). A local anesthetic delivery system, Gel/HMS‐ROP/dexmedetomidine (DEX), with long‐term retention and drug release in vivo is prepared by combining HMS‐ROP and Gel/DEX. The drug loading of HMS‐ROP reached 41.1%, with a drug release time of over 160 h in vitro, and sensory and motor blockade times in vivo of 48 and 36 h, respectively. In summary, the sequential release and synergistic analgesic effects of the two anesthetics are realized using core‐shell microspheres, DEX, and an injectable gel, providing a promising strategy for long‐acting postoperative pain management.
3D Printing of Anisotropic Piezoresistive Pressure Sensors for Directional Force Perception
Authors: Liu Jingfeng , Zhang Xuan , Liu Jintao , Liu Xingang , Zhang Chuhong 
Published: March 2024

AbstractAnisotropic pressure sensors are gaining increasing attention for next‐generation wearable electronics and intelligent infrastructure owing to their sensitivity in identifying different directional forces. 3D printing technologies have unparalleled advantages in the design of anisotropic pressure sensors with customized 3D structures for realizing tunable anisotropy. 3D printing has demonstrated few successes in utilizing piezoelectric nanocomposites for anisotropic recognition. However, 3D‐printed anisotropic piezoresistive pressure sensors (PPSs) remain unexplored despite their convenience in saving the poling process. This study pioneers the development of an aqueous printable ink containing waterborne polyurethane elastomer. An anisotropic PPS featuring tailorable flexibility in macroscopic 3D structures and microscopic pore morphologies is created by adopting direct ink writing 3D printing technology. Consequently, the desired directional force perception is achieved by programming the printing schemes. Notably, the printed PPS demonstrated excellent deformability, with a relative sensitivity of 1.22 (kPa*wt. %)−1 over a substantial pressure range (2.8 to 8.1 kPa), approximately fivefold than that of a state‐of‐the‐art carbon‐based PPS. This study underscores the versatility of 3D printing in customizing highly sensitive anisotropic pressure sensors for advanced sensing applications that are difficult to achieve using conventional measures.
Lineage‐Specific CYP80 Expansion and Benzylisoquinoline Alkaloid Diversity in Early‐Diverging Eudicots
Authors: An Zhoujie , Gao Ranran , Chen Shanshan , Tian Ya , Li Qi , Tian Lixia , Zhang Wanran , Kong Lingzhe , Zheng Baojiang , Hao Lijun , Xin Tianyi , Yao Hui , Wang Yu , Song Wei , Hua Xin , Liu Chengwei , Song Jingyuan , Fan Huahao , Sun Wei , Chen Shilin , Xu Zhichao 
Published: March 2024

AbstractMenispermaceae species, as early‐diverging eudicots, can synthesize valuable benzylisoquinoline alkaloids (BIAs) like bisbenzylisoquinoline alkaloids (bisBIAs) and sinomenines with a wide range of structural diversity. However, the evolutionary mechanisms responsible for their chemo‐diversity are not well understood. Here, a chromosome‐level genome assembly of Menispermum dauricum is presented and demonstrated the occurrence of two whole genome duplication (WGD) events that are shared by Ranunculales and specific to Menispermum, providing a model for understanding chromosomal evolution in early‐diverging eudicots. The biosynthetic pathway for diverse BIAs in M. dauricum is reconstructed by analyzing the transcriptome and metabolome. Additionally, five catalytic enzymes – one norcoclaurine synthase (NCS) and four cytochrome P450 monooxygenases (CYP450s) – from M. dauricum are responsible for the formation of the skeleton, hydroxylated modification, and C‐O/C‐C phenol coupling of BIAs. Notably, a novel leaf‐specific MdCYP80G10 enzyme that catalyzes C2′‐C4a phenol coupling of (S)‐reticuline into sinoacutine, the enantiomer of morphinan compounds, with predictable stereospecificity is discovered. Moreover, it is found that Menispermum‐specific CYP80 gene expansion, as well as tissue‐specific expression, has driven BIA diversity in Menispermaceae as compared to other Ranunculales species. This study sheds light on WGD occurrences in early‐diverging eudicots and the evolution of diverse BIA biosynthesis.