bluuebunny/crossref_metadata_2025_split huggingface dataset:
Botulinum Neurotoxin Induces Neurotoxic Microglia Mediated by Exogenous Inflammatory Responses
Authors: Ambrin Ghuncha , Kang You Jung , Van Do Khanh , Lee Charles , Singh Bal Ram , Cho Hansang 
Published: February 2024

AbstractBotulinum neurotoxin serotype A (BoNT/A) is widely used in therapeutics and cosmetics. The effects of multi‐dosed BoNT/A treatment are well documented on the peripheral nervous system (PNS), but much less is known on the central nervous system (CNS). Here, the mechanism of multi‐dosed BoNT/A leading to CNS neurodegeneration is explored by using the 3D human neuron‐glia model. BoNT/A treatment reduces acetylcholine, triggers astrocytic transforming growth factor beta, and upregulates C1q, C3, and C5 expression, inducing microglial proinflammation. The disintegration of the neuronal microtubules is escorted by microglial nitric oxide, interleukin 1β, tumor necrosis factor α, and interleukin 8. The microglial proinflammation eventually causes synaptic impairment, phosphorylated tau (pTau) aggregation, and the loss of the BoNT/A‐treated neurons. Taking a more holistic approach, the model will allow to assess therapeutics for the CNS neurodegeneration under the prolonged use of BoNT/A.
High Intensity Focused Ultrasound‐Driven Nanomotor for Effective Ferroptosis‐Immunotherapy of TNBC
Authors: Yu Xiangrong , Li Xuejing , Chen Qingwang , Wang Siyu , Xu Ruizhe , He Ying , Qin Xifeng , Zhang Jun , Yang Wuli , Shi Leming , Lu Ligong , Zheng Yuanting , Pang Zhiqing , Peng Shaojun 
Published: February 2024

AbstractThe heterogeneity of triple‐negative breast cancers (TNBC) remains challenging for various treatments. Ferroptosis, a recently identified form of cell death resulting from the unrestrained peroxidation of phospholipids, represents a potential vulnerability in TNBC. In this study, a high intensity focused ultrasound (HIFU)‐driven nanomotor is developed for effective therapy of TNBC through induction of ferroptosis. Through bioinformatics analysis of typical ferroptosis‐associated genes in the FUSCCTNBC dataset, gambogic acid is identified as a promising ferroptosis drug and loaded it into the nanomotor. It is found that the rapid motion of nanomotors propelled by HIFU significantly enhanced tumor accumulation and penetration. More importantly, HIFU not only actuated nanomotors to trigger effective ferroptosis of TNBC cells, but also drove nanomotors to activate ferroptosis‐mediated antitumor immunity in primary and metastatic TNBC models, resulting in effective tumor regression and prevention of metastases. Overall, HIFU‐driven nanomotors show great potential for ferroptosis‐immunotherapy of TNBC.
Deciphering Membrane‐Protein Interactions and High‐Throughput Antigen Identification with Cell Doublets
Authors: Wang Yuqian , Wang Zhe , Yang Juan , Lei Xiaobo , Liu Yisu , Frankiw Luke , Wang Jianwei , Li Guideng 
Published: February 2024

AbstractDeciphering cellular interactions is essential to both understand the mechanisms underlying a broad range of human diseases, but also to manipulate therapies targeting these diseases. Here, the formation of cell doublets resulting from specific membrane ligand‐receptor interactions is discovered. Based on this phenomenon, the study developed DoubletSeeker, a novel high‐throughput method for the reliable identification of ligand‐receptor interactions. The study shows that DoubletSeeker can accurately identify T cell receptor (TCR)‐antigen interactions with high sensitivity and specificity. Notably, DoubletSeeker effectively captured paired TCR‐peptide major histocompatibility complex (pMHC) information during a highly complex library‐on‐library screening and successfully identified three mutant TCRs that specifically recognize the MART‐1 epitope. In turn, DoubletSeeker can act as an antigen discovery platform that allows for the development of novel immunotherapy targets, making it valuable for investigating fundamental tumor immunology.
Self‐Reinforced Bimetallic Mito‐Jammer for Ca2+ Overload‐Mediated Cascade Mitochondrial Damage for Cancer Cuproptosis Sensitization
Authors: Du Chier , Guo Xun , Qiu Xiaoling , Jiang Weixi , Wang Xiaoting , An Hongjin , Wang Jingxue , Luo Yuanli , Du Qianying , Wang Ruoyao , Cheng Chen , Guo Yuan , Teng Hua , Ran Haitao , Wang Zhigang , Li Pan , Zhou Zhiyi , Ren Jianli 
Published: February 2024

AbstractOverproduction of reactive oxygen species (ROS), metal ion accumulation, and tricarboxylic acid cycle collapse are crucial factors in mitochondria‐mediated cell death. However, the highly adaptive nature and damage‐repair capabilities of malignant tumors strongly limit the efficacy of treatments based on a single treatment mode. To address this challenge, a self‐reinforced bimetallic Mito‐Jammer is developed by incorporating doxorubicin (DOX) and calcium peroxide (CaO2) into hyaluronic acid (HA) ‐modified metal‐organic frameworks (MOF). After cellular, Mito‐Jammer dissociates into CaO2 and Cu2+ in the tumor microenvironment. The exposed CaO2 further yields hydrogen peroxide (H2O2) and Ca2+ in a weakly acidic environment to strengthen the Cu2+‐based Fenton‐like reaction. Furthermore, the combination of chemodynamic therapy and Ca2+ overload exacerbates ROS storms and mitochondrial damage, resulting in the downregulation of intracellular adenosine triphosphate (ATP) levels and blocking of Cu‐ATPase to sensitize cuproptosis. This multilevel interaction strategy also activates robust immunogenic cell death and suppresses tumor metastasis simultaneously. This study presents a multivariate model for revolutionizing mitochondria damage, relying on the continuous retention of bimetallic ions to boost cuproptosis/immunotherapy in cancer.
Myofibrillogenesis Regulator‐1 Regulates the Ubiquitin Lysosomal Pathway of Notch3 Intracellular Domain Through E3 Ubiquitin‐Protein Ligase Itchy Homolog in the Metastasis of Non‐Small Cell Lung Cancer
Authors: Zhao Wenxia , Li Yang , Cheng Hanzeng , Wang Mengyan , Zhang Zhishuo , Cai Meilian , Zhao Cong , Xi Xiaoming , Zhao Xiaojun , Zhao Wuli , Yang Yajun , Shao Rongguang 
Published: February 2024

AbstractMyofibrillogenesis regulator‐1 (MR‐1) is a multifunctional protein involved in the development of various human tumors. The study is the first to report the promoting effect of MR‐1 on the development and metastasis of non‐small cell lung cancer (NSCLC). MR‐1 is upregulated in NSCLC and positively associated with poor prognosis. The overexpression of MR‐1 promotes the metastasis of NSCLC cells by stabilizing the expression of Notch3‐ICD (NICD3) in the cytoplasm through enrichment analysis, in vitro and in vivo experimental researches. And Notch3 signaling can upregulate many genes related to metastasis. The stabilizing effect of MR‐1 on NICD3 is achieved through the mono‐ubiquitin lysosomal pathway and the specific E3 ubiquitin ligase is Itchy homolog (ITCH). There is a certain interaction between MR‐1 and NICD3. Elevated MR‐1 can affect the level of ITCH phosphorylation, reduce its E3 enzyme activity, and thus lead to reduce the ubiquitination and degradation of NICD3. Interference with the interaction between MR‐1 and NICD3 can increase the degradation of NICD3 and impair the metastatic ability of NSCLC cells, which is a previously overlooked treatment option in NSCLC. In summary, interference with the interaction between MR‐1 and NICD3 in the progression of lung cancer may be a promising therapeutic target.
Targeting C21orf58 is a Novel Treatment Strategy of Hepatocellular Carcinoma by Disrupting the Formation of JAK2/C21orf58/STAT3 Complex
Authors: Jiang Hao , Wang Yang , Wen Doudou , Yu Rongji , Esa Sayed S , Lv Kefeng , Feng Qing , Liu Jing , Li Faxiang , He Lan , Di Xiaotang , Zhang Shubing 
Published: February 2024

AbstractHepatocellular carcinoma (HCC) is the third leading cause of cancer‐related death worldwide. Functionally uncharacterized genes are an attractive repository to explore candidate oncogenes. It is demonstrated that C21orf58 displays an oncogenic role in promoting cell growth, tumorigenesis and sorafenib resistance of HCC cells by abnormal activation of STAT3 signaling. Mechanistically, a novel manner to regulate STAT3 signaling that adaptor C21orf58 forms a ternary complex is reveal with N‐terminal domain of STAT3 and SH2 domain of JAK2, by which C21orf58 overactivates wild‐type STAT3 by facilitating its phosphorylation mediated by JAK2, and hyper‐activates of constitutively mutated STAT3 due to preferred binding with C21orf58 and JAK2. Moreover, it is validated that inhibition of C21orf58 with drug alminoprofen, selected by virtual screening, could effectively repress the viability and tumorigenesis of HCC cells. Therefore, it is identified that C21orf58 functions as an oncogenic adaptor, reveal a novel regulatory mechanism of JAK2/STAT3 signaling, explain the cause of abnormal activity of activated mutants of STAT3, and explore the attractive therapeutic potential by targeting C21orf58 in HCC.
An Integrated Arterial Remodeling Hydrogel for Preventing Restenosis After Angioplasty
Authors: Fu Chenxing , Li Qiu , Li Minghui , Zhang Jiexin , Zhou Feiran , Li Zechuan , He Dongyue , Hu Xinyi , Ning Xiaodong , Guo Wenjie , Li Weirun , Ma Jing , Chen Guoqin , Xiao Yafang , Ou Caiwen , Guo Weisheng 
Published: February 2024

AbstractThe high incidence of restenosis after angioplasty has been the leading reason for the recurrence of coronary heart disease, substantially increasing the mortality risk for patients. However, current anti‐stenosis drug‐eluting stents face challenges due to their limited functions and long‐term safety concerns, significantly compromising their therapeutic effect. Herein, a stent‐free anti‐stenosis drug coating (denoted as Cur‐NO‐Gel) based on a peptide hydrogel is proposed. This hydrogel is formed by assembling a nitric oxide (NO) donor‐peptide conjugate as a hydrogelator and encapsulating curcumin (Cur) during the assembly process. Cur‐NO‐Gel has the capability to release NO upon β‐galactosidase stimulation and gradually release Cur through hydrogel hydrolysis. The in vitro experiments confirmed that Cur‐NO‐Gel protects vascular endothelial cells against oxidative stress injury, inhibits cellular activation of vascular smooth muscle cells, and suppresses adventitial fibroblasts. Moreover, periadventitial administration of Cur‐NO‐Gel in the angioplasty model demonstrate its ability to inhibit vascular stenosis by promoting reendothelialization, suppressing neointima hyperplasia, and preventing constrictive remodeling. Therefore, the study provides proof of concept for designing a new generation of clinical drugs in angioplasty.
Light Color‐Controlled pH‐Adjustment of Aqueous Solutions Using Engineered Proteoliposomes
Authors: Harder Daniel , Ritzmann Noah , Ucurum Zöhre , Müller Daniel J. , Fotiadis Dimitrios 
Published: February 2024

AbstractControlling the pH at the microliter scale can be useful for applications in research, medicine, and industry, and therefore represents a valuable application for synthetic biology and microfluidics. The presented vesicular system translates light of different colors into specific pH changes in the surrounding solution. It works with the two light‐driven proton pumps bacteriorhodopsin and blue light‐absorbing proteorhodopsin Med12, that are oriented in opposite directions in the lipid membrane. A computer‐controlled measuring device implements a feedback loop for automatic adjustment and maintenance of a selected pH value. A pH range spanning more than two units can be established, providing fine temporal and pH resolution. As an application example, a pH‐sensitive enzyme reaction is presented where the light color controls the reaction progress. In summary, light color‐controlled pH‐adjustment using engineered proteoliposomes opens new possibilities to control processes at the microliter scale in different contexts, such as in synthetic biology applications.
A Polymer Nanocomposite with Strong Full‐Spectrum Solar Absorption and Infrared Emission for All‐Day Thermal Energy Management and Conversion
Authors: Li Xiangxin , Zhang Zipeng , Zhang Xueting , Cao Yanxia , Yang Yanyu , Wang Wanjie , Wang Jianfeng 
Published: February 2024

AbstractRealizing efficient energy utilization from the heat source of the sun and the cold source of outer space is of great significance for addressing the global energy and environmental crisis. Materials with ideal full‐spectrum solar absorption and infrared emission are highly desirable for adapting to the continuous weather dynamic throughout the day, nonetheless, their development remains challenging. Here, a polymer nanocomposite with full‐spectrum strong solar (280–2500 nm) absorption ranging from 88.8% to 94.8% with an average value of 93.2% and full‐spectrum high infrared (8–13 µm) emission ranging from 81.3% to 90.0% with an average value of 84.2%, is reported by melt‐processing polypropylene and uniformly dispersed low‐loading MXene nanosheets (1.9 vol%). The nanocomposite can achieve daytime photothermal enhancement of ≈50 °C and nighttime radiative cooling of 8 °C. The temperature difference throughout the day ensures all‐day uninterrupted thermoelectric generation, yielding a power density output of 1.5 W m−2 (daytime) and 7.9 mW m−2 (nighttime) in real outdoor environment without any additional energy consumption. This work provides an impressive polymer nanocomposite with ideal full‐spectrum solar absorption and infrared emission for all‐day uninterrupted thermal energy management and conversion.
Fabrication of Interface Engineered S‐Scheme Heterojunction Nanocatalyst for Ultrasound‐Triggered Sustainable Cancer Therapy
Authors: Yuan Meng , Yang Ling , Yang Zhuang , Ma Zhizi , Ma Jie , Liu Zhendong , Ma Ping'an , Cheng Ziyong , Maleki Aziz , Lin Jun 
Published: February 2024

AbstractIn order to establish a set of perfect heterojunction designs and characterization schemes, step‐scheme (S‐scheme) BiOBr@Bi2S3 nanoheterojunctions that enable the charge separation and expand the scope of catalytic reactions, aiming to promote the development and improvement of heterojunction engineering is developed. In this kind of heterojunction system, the Fermi levels mediate the formation of the internal electric field at the interface and guide the recombination of the weak redox carriers, while the strong redox carriers are retained. Thus, these high‐energy electrons and holes are able to catalyze a variety of substrates in the tumor microenvironment, such as the reduction of oxygen and carbon dioxide to superoxide radicals and carbon monoxide (CO), and the oxidation of H2O to hydroxyl radicals, thus achieving sonodynamic therapy and CO combined therapy. Mechanistically, the generated reactive oxygen species and CO damage DNA and inhibit cancer cell energy levels, respectively, to synergistically induce tumor cell apoptosis. This study provides new insights into the realization of high efficiency and low toxicity in catalytic therapy from a unique perspective of materials design. It is anticipated that this catalytic therapeutic method will garner significant interest in the sonocatalytic nanomedicine field.
Solar Thermal Energy Storage Systems Based on Discotic Nematic Liquid Crystals That Can Efficiently Charge and Discharge below 0 °C
Authors: Gupta Monika , Ashy  
Published: February 2024

AbstractSolid‐state solar thermal fuels (SSTFs) serve as efficient means of storing solar energy as chemical potential energy in a closed loop system and releasing it as heat on‐demand. An ideal SSTF requires photoswitchability in visible‐region without any external heating as well as extended storage times. However, existing systems often rely on ultraviolet (UV) light or heating for photoswitching, or suffer from low storage times. Addressing this, a novel strategy is presented to obtain visible‐light responsive SSTFs designed to operate effectively at room‐temperature or sub‐zero temperatures by innovatively integrating a tetra‐ortho‐fluoro/chloro azobenzene arm in triphenylene based liquid crystal (LC) moiety. The resulting compounds exhibit discotic nematic (ND) mesophases till −6.5 °C. These compounds exhibit excellent photocyclability, photostability, and sufficient half‐lives of cis states. Achieving up to 77% charging under sunlight with a bandpass filter and 62.4% without it, these systems uniquely demonstrate efficient chargeability and dischargeability at sub‐zero temperatures. Upon discharging, temperature rise of up to 6.5 and 29.5 °C occur at room‐temperature (25 °C) and sub‐zero temperatures (around −6 to −7 °C), respectively. This efficacy is attributed to less‐ordered ND phases providing conformational freedom for photoisomerization at low temperatures.
How Solvation Energetics Dampen the Hydrogen Evolution Reaction to Maximize Zinc Anode Stability
Authors: Roy Kingshuk , Rana Ashutosh , Ghosh Tushar K , Heil Joseph N , Roy Sayan , Vannoy Kathryn J , Tackett Brian M. , Chen Ming , Dick Jeffrey E. 
Published: February 2024

AbstractAqueous zinc metal batteries (AZMB) are emerging as a promising alternative to the prevailing existing Lithium‐ion battery technology. However, the development of AZMBs is hindered due to challenges including dendrite formation, hydrogen evolution reaction (HER), and ZnO passivation on the anode. Here, a tetraalkylsulfonamide (TAS) additive for suppressing HER, dendrite formation, and enhancing cyclability is rationally designed. Only 1 mm TAS is found that can effectively displace water molecules from the Zn2+ solvation shell, thereby altering the solvation matrix of Zn2+ and disrupting the hydrogen bond network of free water, as demonstrated through 67 Zn and 1H nuclear magnetic resonance spectroscopy, high‐resolution mass spectrometry (HRMS), and density functional theory (DFT) studies. Voltammetry synchronized with in situ monitoring of the electrode surface reveals suppressed dendritic growth and HER in the presence of TAS. Electrochemical mass spectrometry (ECMS) captures real‐time HER suppression during Zn electrodeposition, revealing the ability of TAS to suppress the HER by an order of magnitude. A ≈25‐fold cycle life improvement from ≈100 h to over 2500 h in coin cells cycled in the presence of TAS. Furthermore, by suppressing passivation product formation, it is demonstrated that strategy robustly maximizes the stability of Zn metal anodes.
Hydrodynamics, mass transfer, and hydrogenation performance of a HiGee‐aided fixed bed reactor
Authors: Liao Hai‐Long , Jiang Lan , Wang Li‐Hua , Luo Yong , Tan Qing‐Feng , Ma Shou‐Tao , Chen Jian‐Feng 
Published: February 2024

AbstractMicrobubble shows great potential for hydrogenation reaction in fixed bed reactors (FBRs). However, the lack of understanding of the hydrodynamic behaviors of microbubble swarm in FBR limits the reactor design. In this work, a pilot‐scale HiGee‐aided fixed bed reactor (HFBR), including a HiGee microbubble generator (HMG) and a catalyst bed, has been developed and then applied for poly alpha olefin 4 (PAO 4) hydrogenation. An empirical correlation of Sauter mean diameter (d32) of microbubbles at the inlet and outlet of catalyst bed was established. The gas holdup (φb) of catalyst bed with HMG was 5–10 times higher than that without HMG. Based on d32 and φb, the effective interfacial area in HFBR was calculated as 2000–6000 m2/m3. Compared with static mixer‐aided fixed bed reactor, the aromatic content of PAO 4 hydrogenated in the HFBR was 56%–69% lower, which shows bright future for industrial application.
Clinical outcomes of hypomethylating agents plus Venetoclax as frontline treatment in patients 75 years and older with acute myeloid leukemia: Real‐world data from eight US academic centers
Authors: Abaza Yasmin , Winer Eric S. , Murthy Guru Subramanian Guru , Shallis Rory M. , Matthews Andrew H. , Badar Talha , Geramita Emily M. , Kota Vamsi K. , Swaroop Alok , Doukas Peter , Bradshaw Danielle , Helenowski Irene B. , Liu Yingzhe , Zhang Hui , Im Annie , Litzow Mark R. , Perl Alexander E. , Atallah Ehab , Altman Jessica K. 
Published: February 2024

AbstractVenetoclax (VEN) combined with hypomethylating agents (HMAs) is the standard of care for the treatment of patients with newly diagnosed acute myeloid leukemia (AML) unfit for intensive chemotherapy. To date, real‐world data published on HMAs plus VEN have been either single‐center studies or using community‐based electronic databases with limited details on mutational landscape, tolerability, and treatment patterns in elderly patients. Therefore, we conducted a multicenter retrospective study to assess the real‐world experience of 204 elderly patients (≥75 years) with newly diagnosed AML treated with HMAs plus VEN from eight academic centers in the United States. Overall, 64 patients achieved complete remission (CR; 38%) and 43 CR with incomplete count recovery (CRi; 26%) for a CR/CRi rate of 64%, with a median duration of response of 14.2 months (95% CI: 9.43, 22.1). Among responders, 63 patients relapsed (59%) with median overall survival (OS) after relapse of 3.4 months (95% CI, 2.4, 6.7). Median OS for the entire population was 9.5 months (95% CI, 7.85–13.5), with OS significantly worse among patients with TP53‐mutated AML (2.5 months) and improved in patients harboring NPM1, IDH1, and IDH2 mutations (13.5, 18.3, and 21.1 months, respectively). The 30‐day and 60‐day mortality rates were 9% and 19%, respectively. In conclusion, HMAs plus VEN yielded high response rates in elderly patients with newly diagnosed AML. The median OS was inferior to that reported in the VIALE‐A trial. Outcomes are dismal after failure of HMAs plus VEN, representing an area of urgent unmet clinical need.
Excess prenatal loss and respiratory illnesses of infant macaques living outdoors and exposed to wildfire smoke
Authors: Berns Kathryn , Haertel Andrew J. 
Published: February 2024

AbstractGlobal climate change has transformed predictions of fire seasons in the near future, and record‐breaking wildfire events have had catastrophic consequences in recent years. In September 2020, multiple wildfires subjected Oregon to hazardous air quality for several days. In this retrospective cohort study, we aimed to examine prenatal loss, morbidity, and mortality of rhesus (Macaca mulatta) and Japanese macaques (Macaca fuscata) exposed to poor air quality from the nearby wildfires. Detailed medical records from 2014 to 2020 of 580 macaques housed outdoors at a research facility in Beaverton, Oregon were used to evaluate the association between these health outcomes and wildfire smoke exposure. Logistic regression models estimated excess prenatal loss, hospitalization rates, respiratory problems, and mortality during and following the wildfire event, and Kruskal–Wallis statistics were used to determine if infant growth was affected by wildfire smoke exposure. Risk of pregnancy loss (relative risk = 4.1; p < 0.001) and odds of diagnosis with a respiratory problem (odds ratio = 4.47; p = 0.003) were higher in exposed infant macaques compared to nonexposed infants. Infant growth was not affected by poor air quality exposure. Our findings suggest wildfire smoke exposure poses a risk to the health of infants and pregnant individuals and should be monitored more closely in the future.