bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhanced radiosensitivity and chemoradiation efficacy in nasopharyngeal carcinoma via a dual-targeted SPION@polymer hybrid nanosensitizer
Authors: Ding Yuxun , Xiao Xiaohui , Bai Lu , Yang Bowen , Lin Guanghui , Zeng Lingli , Xie Lisi , Li Lei , Duan Xiaohui , Shen Jun , Zhou Jianhua , Pan Yue 
Published: June 2023

AbstractCisplatin-based nanoparticles show good potential in enhancing the effect of nasopharynx carcinoma (NPC) therapy but are still limited by their low radiation sensitization and poor tumor targeting ability. Herein, an ingenious design of multifunctional superparamagnetic iron oxide nanoparticle (SPION)@polymer hybrid nanosensitizer (SPHN) with enhanced radiosensitization and dual-targeting capability is described. SPHN have a core-shell structure, in which radiosensitizer superparamagnetic iron oxide particle (SPION) and cis-platinum (CDDP) are encapsulated in RGD-conjugated amphiphilic block copolymers. These unique structures endow SPHN with outstanding radiosensitization and tumor targeting abilities. When combined with X-rays, SPHN showed strong promotion of the apoptosis of CNE-1 cells in vitro. In addition, RNA-seq and KEGG enrichment analyses indicated that the PI3K-Akt and TNF signaling pathways were closely related to the molecular mechanism of SPHN in chemoradiotherapy. Furthermore, gene set enrichment analysis (GSEA) revealed that SPHN + X-rays treatment decreased translation initiation pathways and the cytoplasmic translation pathway. Through a combination of radiation and chemotherapy, SPHN can achieve remarkable inhibition of tumor growth in vivo, making this nanotechnology a general platform for the chemoradiation therapy of NPC in the future.
Development of electroresponsive functional soft materials by electroresponsive dopants
Authors: Itoh Yoshimitsu , Morishita Daiki 
Published: June 2023

AbstractIn this Focus Review, we summarize our new strategy to create electroresponsive soft materials using electroresponsive dopants. Liquid crystals (LCs) are representative electroresponsive soft functional materials that have been utilized for various applications, including LC display devices. The response to the applied electric field (E-field) is generally realized by the direct coupling between the E-field and the LC molecules. Thus, LC molecules must simultaneously exhibit electroresponsiveness and LC properties. As a new concept to create electroresponsive soft materials, we came up with an idea of using electroresponsive dopants. Dopants can change the property of the LC material only with a minute amount and do not need to have an LC property by itself, thus allows more freedom for the molecular design. Based on this new concept, we developed several intriguing materials, such as cholesteric displays with rewritable color memory functions and quick color modulation functions, which are both unprecedented. We also utilized this concept to columnar LC systems and realized multiresponsive columnar LC materials, which are usually rigid and poorly responsive to applied external perturbations.
Eagle eyed or bird brained?
Authors: Williams David 
Published: June 2023

AbstractThe importance of the visual system to birds for behaviours from feeding, mate choice, flying, navigation and determination of seasons, together with the presence of photoreceptors in the retina, the pineal and the brain, render the avian visual system a particularly fruitful model for understanding of eye-brain interactions. In this review we will particularly focus on the pigeon, since here we have a brain stereotactically mapped and a genome fully sequenced, together with a particular bird, the homing pigeon, with remarkable ability to navigate over hundreds of miles and return to exactly the same roosting site with exceptional precision. We might denigrate the avian species by the term bird brained, but here are animals with phenomenal abilities to use their exceptional vision, their eagle eyedness, to best advantage.
The role of mechano-regulated YAP/TAZ in erectile dysfunction
Authors: Ji Mintao , Chen Dongsheng , Shu Yinyin , Dong Shuai , Zhang Zhisen , Zheng Haimeng , Jin Xiaoni , Zheng Lijun , Liu Yang , Zheng Yifei , Zhang Wensheng , Wang Shiyou , Zhou Guangming , Li Bingyan , Ji Baohua , Yang Yong , Xu Yongde , Chang Lei 
Published: June 2023

AbstractPhosphodiesterase type 5 inhibitors (PDE5is) constitute the primary therapeutic option for treating erectile dysfunction (ED). Nevertheless, a substantial proportion of patients, approximately 30%, do not respond to PDE5i treatment. Therefore, new treatment methods are needed. In this study, we identified a pathway that contributes to male erectile function. We show that mechano-regulated YAP/TAZ signaling in smooth muscle cells (SMCs) upregulates adrenomedullin transcription, which relaxed the SMCs to maintain erection. Using single-nucleus RNA sequencing, we investigated how penile erection stretches the SMCs, inducing YAP/TAZ activity. Subsequently, we demonstrate that YAP/TAZ plays a role in erectile function and penile rehabilitation, using genetic lesions and various animal models. This mechanism relies on direct transcriptional regulation of adrenomedullin by YAP/TAZ, which in turn modulates penile smooth muscle contraction. Importantly, conventional PDE5i, which targets NO-cGMP signaling, does not promote erectile function in YAP/TAZ-deficient ED model mice. In contrast, by activating the YAP/TAZ-adrenomedullin cascade, mechanostimulation improves erectile function in PDE5i nonrespondent ED model rats and mice. Furthermore, using clinical retrospective observational data, we found that mechanostimulation significantly promotes erectile function in patients irrespective of PDE5i use. Our studies lay the groundwork for exploring the mechano-YAP/TAZ-adrenomedullin axis as a potential target in the treatment of ED.
Systems-level analyses of protein-protein interaction network dysfunctions via epichaperomics identify cancer-specific mechanisms of stress adaptation
Authors: Rodina Anna , Xu Chao , Digwal Chander S. , Joshi Suhasini , Patel Yogita , Santhaseela Anand R. , Bay Sadik , Merugu Swathi , Alam Aftab , Yan Pengrong , Yang Chenghua , Roychowdhury Tanaya , Panchal Palak , Shrestha Liza , Kang Yanlong , Sharma Sahil , Almodovar Justina , Corben Adriana , Alpaugh Mary L. , Modi Shanu , Guzman Monica L. , Fei Teng , Taldone Tony , Ginsberg Stephen D. , Erdjument-Bromage Hediye , Neubert Thomas A. , Manova-Todorova Katia , Tsou Meng-Fu Bryan , Young Jason C. , Wang Tai , Chiosis Gabriela 
Published: June 2023

AbstractSystems-level assessments of protein-protein interaction (PPI) network dysfunctions are currently out-of-reach because approaches enabling proteome-wide identification, analysis, and modulation of context-specific PPI changes in native (unengineered) cells and tissues are lacking. Herein, we take advantage of chemical binders of maladaptive scaffolding structures termed epichaperomes and develop an epichaperome-based ‘omics platform, epichaperomics, to identify PPI alterations in disease. We provide multiple lines of evidence, at both biochemical and functional levels, demonstrating the importance of these probes to identify and study PPI network dysfunctions and provide mechanistically and therapeutically relevant proteome-wide insights. As proof-of-principle, we derive systems-level insight into PPI dysfunctions of cancer cells which enabled the discovery of a context-dependent mechanism by which cancer cells enhance the fitness of mitotic protein networks. Importantly, our systems levels analyses support the use of epichaperome chemical binders as therapeutic strategies aimed at normalizing PPI networks.
TRPV4-Rho GTPase complex structures reveal mechanisms of gating and disease
Authors: Kwon Do Hoon , Zhang Feng , McCray Brett A. , Feng Shasha , Kumar Meha , Sullivan Jeremy M. , Im Wonpil , Sumner Charlotte J. , Lee Seok-Yong 
Published: June 2023

AbstractCrosstalk between ion channels and small GTPases is critical during homeostasis and disease, but little is known about the structural underpinnings of these interactions. TRPV4 is a polymodal, calcium-permeable cation channel that has emerged as a potential therapeutic target in multiple conditions. Gain-of-function mutations also cause hereditary neuromuscular disease. Here, we present cryo-EM structures of human TRPV4 in complex with RhoA in the ligand-free, antagonist-bound closed, and agonist-bound open states. These structures reveal the mechanism of ligand-dependent TRPV4 gating. Channel activation is associated with rigid-body rotation of the intracellular ankyrin repeat domain, but state-dependent interaction with membrane-anchored RhoA constrains this movement. Notably, many residues at the TRPV4-RhoA interface are mutated in disease and perturbing this interface by introducing mutations into either TRPV4 or RhoA increases TRPV4 channel activity. Together, these results suggest that RhoA serves as an auxiliary subunit for TRPV4, regulating TRPV4-mediated calcium homeostasis and disruption of TRPV4-RhoA interactions can lead to TRPV4-related neuromuscular disease. These insights will help facilitate TRPV4 therapeutics development.
Targeting neddylation sensitizes colorectal cancer to topoisomerase I inhibitors by inactivating the DCAF13-CRL4 ubiquitin ligase complex
Authors: Sun Yilun , Baechler Simone A. , Zhang Xiaohu , Kumar Suresh , Factor Valentina M. , Arakawa Yasuhiro , Chau Cindy H. , Okamoto Kanako , Parikh Anup , Walker Bob , Su Yijun P. , Chen Jiji , Ting Tabitha , Huang Shar-yin N. , Beck Erin , Itkin Zina , McKnight Crystal , Xie Changqing , Roper Nitin , Nijhawan Deepak , Figg William Douglas , Meltzer Paul S. , Yang James C. , Thomas Craig J. , Pommier Yves 
Published: June 2023

AbstractColorectal cancers (CRCs) are prevalent worldwide, yet current treatments remain inadequate. Using chemical genetic screens, we identify that co-inhibition of topoisomerase I (TOP1) and NEDD8 is synergistically cytotoxic in human CRC cells. Combination of the TOP1 inhibitor irinotecan or its bioactive metabolite SN38 with the NEDD8-activating enzyme inhibitor pevonedistat exhibits synergy in CRC patient-derived organoids and xenografts. Mechanistically, we show that pevonedistat blocks the ubiquitin/proteasome-dependent repair of TOP1 DNA-protein crosslinks (TOP1-DPCs) induced by TOP1 inhibitors and that the CUL4-RBX1 complex (CRL4) is a prominent ubiquitin ligase acting on TOP1-DPCs for proteasomal degradation upon auto-NEDD8 modification during replication. We identify DCAF13, a DDB1 and Cullin Associated Factor, as the receptor of TOP1-DPCs for CRL4. Our study not only uncovers a replication-coupled ubiquitin-proteasome pathway for the repair of TOP1-DPCs but also provides molecular and translational rationale for combining TOP1 inhibitors and pevonedistat for CRC and other types of cancers.
A reconfigurable binary/ternary logic conversion-in-memory based on drain-aligned floating-gate heterojunction transistors
Authors: Lee Chungryeol , Lee Changhyeon , Lee Seungmin , Choi Junhwan , Yoo Hocheon , Im Sung Gap 
Published: June 2023

AbstractA new type of heterojunction non-volatile memory transistor (H-MTR) has been developed, in which the negative transconductance (NTC) characteristics can be controlled systematically by a drain-aligned floating gate. In the H-MTR, a reliable transition between N-shaped transfer curves with distinct NTC and monolithically current-increasing transfer curves without apparent NTC can be accomplished through programming operation. Based on the H-MTR, a binary/ternary reconfigurable logic inverter (R-inverter) has been successfully implemented, which showed an unprecedentedly high static noise margin of 85% for binary logic operation and 59% for ternary logic operation, as well as long-term stability and outstanding cycle endurance. Furthermore, a ternary/binary dynamic logic conversion-in-memory has been demonstrated using a serially-connected R-inverter chain. The ternary/binary dynamic logic conversion-in-memory could generate three different output logic sequences for the same input signal in three logic levels, which is a new logic computing method that has never been presented before.
Light-driven self-assembly of spiropyran-functionalized covalent organic framework
Authors: Das Gobinda , Prakasam Thirumurugan , Alkhatib Nour , AbdulHalim Rasha G. , Chandra Falguni , Sharma Sudhir Kumar , Garai Bikash , Varghese Sabu , Addicoat Matthew A. , Ravaux Florent , Pasricha Renu , Jagannathan Ramesh , Saleh Na’il , Kirmizialtin Serdal , Olson Mark A. , Trabolsi Ali 
Published: June 2023

AbstractControlling the number of molecular switches and their relative positioning within porous materials is critical to their functionality and properties. The proximity of many molecular switches to one another can hinder or completely suppress their response. Herein, a synthetic strategy involving mixed linkers is used to control the distribution of spiropyran-functionalized linkers in a covalent organic framework (COF). The COF contains a spiropyran in each pore which exhibits excellent reversible photoswitching behavior to its merocyanine form in the solid state in response to UV/Vis light. The spiro-COF possesses an urchin-shaped morphology and exhibits a morphological transition to 2D nanosheets and vesicles in solution upon UV light irradiation. The merocyanine-equipped COFs are extremely stable and possess a more ordered structure with enhanced photoluminescence. This approach to modulating structural isomerization in the solid state is used to develop inkless printing media, while the photomediated polarity change is used for water harvesting applications.
Ordering of room-temperature magnetic skyrmions in a polar van der Waals magnet
Authors: Meisenheimer Peter , Zhang Hongrui , Raftrey David , Chen Xiang , Shao Yu-Tsun , Chan Ying-Ting , Yalisove Reed , Chen Rui , Yao Jie , Scott Mary C. , Wu Weida , Muller David A. , Fischer Peter , Birgeneau Robert J. , Ramesh Ramamoorthy 
Published: June 2023

AbstractControl and understanding of ensembles of skyrmions is important for realization of future technologies. In particular, the order-disorder transition associated with the 2D lattice of magnetic skyrmions can have significant implications for transport and other dynamic functionalities. To date, skyrmion ensembles have been primarily studied in bulk crystals, or as isolated skyrmions in thin film devices. Here, we investigate the condensation of the skyrmion phase at room temperature and zero field in a polar, van der Waals magnet. We demonstrate that we can engineer an ordered skyrmion crystal through structural confinement on the μm scale, showing control over this order-disorder transition on scales relevant for device applications.
Colloid driven low supersaturation crystallization for atomically thin Bismuth halide perovskite
Authors: Li Lutao , Yao Junjie , Zhu Juntong , Chen Yuan , Wang Chen , Zhou Zhicheng , Zhao Guoxiang , Zhang Sihan , Wang Ruonan , Li Jiating , Wang Xiangyi , Lu Zheng , Xiao Lingbo , Zhang Qiang , Zou Guifu 
Published: June 2023

AbstractIt is challenging to grow atomically thin non-van der Waals perovskite due to the strong electronic coupling between adjacent layers. Here, we present a colloid-driven low supersaturation crystallization strategy to grow atomically thin Cs3Bi2Br9. The colloid solution drives low-concentration solute in a supersaturation state, contributing to initial heterogeneous nucleation. Simultaneously, the colloids provide a stable precursor source in the low-concentration solute. The surfactant is absorbed in specific crystal nucleation facet resulting in the anisotropic growth of planar dominance. Ionic perovskite Cs3Bi2Br9 is readily grown from monolayered to six-layered Cs3Bi2Br9 corresponding to thicknesses of 0.7, 1.6, 2.7, 3.6, 4.6 and 5.7 nm. The atomically thin Cs3Bi2Br9 presents layer-dependent nonlinear optical performance and stacking-induced second harmonic generation. This work provides a concept for growing atomically thin halide perovskite with non-van der Waal structures and demonstrates potential application for atomically thin single crystals’ growth with strong electronic coupling between adjacent layers.
Practical intelligent diagnostic algorithm for wearable 12-lead ECG via self-supervised learning on large-scale dataset
Authors: Lai Jiewei , Tan Huixin , Wang Jinliang , Ji Lei , Guo Jun , Han Baoshi , Shi Yajun , Feng Qianjin , Yang Wei 
Published: June 2023

AbstractCardiovascular disease is a major global public health problem, and intelligent diagnostic approaches play an increasingly important role in the analysis of electrocardiograms (ECGs). Convenient wearable ECG devices enable the detection of transient arrhythmias and improve patient health by making it possible to seek intervention during continuous monitoring. We collected 658,486 wearable 12-lead ECGs, among which 164,538 were annotated, and the remaining 493,948 were without diagnostic. We present four data augmentation operations and a self-supervised learning classification framework that can recognize 60 ECG diagnostic terms. Our model achieves an average area under the receiver-operating characteristic curve (AUROC) and average F1 score on the offline test of 0.975 and 0.575. The average sensitivity, specificity and F1-score during the 2-month online test are 0.736, 0.954 and 0.468, respectively. This approach offers real-time intelligent diagnosis, and detects abnormal segments in long-term ECG monitoring in the clinical setting for further diagnosis by cardiologists.
An integrative mathematical model for timing treatment toxicity and Zeitgeber impact in colorectal cancer cells
Authors: Hesse Janina , Müller Tim , Relógio Angela 
Published: June 2023

AbstractIncreasing evidence points to a role of the circadian clock in the regulation of cancer hallmarks with a strong impact on the understanding and treatment of this disease. Anti-cancer treatment can be personalized considering treatment timing. Here we present a new mathematical model based on data from three colorectal cancer cell lines and core-clock knock-outs, which couples the circadian and drug metabolism network, and that allows to determine toxicity profiles for a given drug and cell type. Moreover, this model integrates external Zeitgebers and thus may be used to fine-tune toxicity by using external factors, such as light, and therefore, to a certain extent, help fitting the endogenous rhythms of the patients to a defined clinic routine facilitating the implementation of time-dependent treatment in clinical practice.
Medium-throughput image-based phenotypic siRNA screen to unveil the molecular basis of B cell polarization
Authors: Obino Dorian , Maurin Mathieu , Dingli Florent , Loew Damarys , Lescure Aurianne , Terriac Emmanuel , Goudot Christel , Malbec Odile , Lankar Danielle , Yuseff Maria-Isabel , Lennon-Duménil Ana-Maria , Moreau Hélène D. 
Published: June 2023

AbstractCell polarity is an essential and highly conserved process governing cell function. Cell polarization is generally triggered by an external signal that induces the relocation of the centrosome, thus defining the polarity axis of the cell. Here, we took advantage of B cells as a model to study cell polarity and perform a medium-throughput siRNA-based imaging screen to identify new molecular regulators of polarization. We first identified candidates based on a quantitative proteomic analysis of proteins differentially associated with the centrosome of resting non-polarized and stimulated polarized B cells. We then targeted 233 candidates in a siRNA screen and identified hits regulating the polarization of the centrosome and/or lysosomes in B cells upon stimulation. Our dataset of proteomics, images, and polarity indexes provides a valuable source of information for a broad community of scientists interested in the molecular mechanisms regulating cell polarity.
Vitamin C injection improves antioxidant stress capacity through regulating blood metabolism in post-transit yak
Authors: Zhang Li , Chen Yi , Zhou Ziyao , Wang Zhiyu , Fu Lin , Zhang Lijun , Xu Changhui , Loor Juan J. , Wang Gaofu , Zhang Tao , Dong Xianwen 
Published: June 2023

AbstractTransportation stress is one of the most serious issues in the management of yak. Previous studies have demonstrated that transport stress is caused by a pro-oxidant state in the animal resulting from an imbalance between pro-oxidant and antioxidant status. In this context, vitamin C has the ability to regulate reactive oxygen species (ROS) synthesis and alleviate oxidative stress. Although this effect of vitamin C is useful in pigs, goats and cattle, the effect of vitamin C on the mitigation of transport stress in yaks is still unclear. The purpose of this study was to better assess the metabolic changes induced by the action of vitamin C in yaks under transportation stress, and whether these changes can influence antioxidant status. After the yaks arrived at the farm, control or baseline blood samples were collected immediately through the jugular vein (VC_CON). Then, 100 mg/kg VC was injected intramuscularly, and blood samples were collected on the 10th day before feeding in the morning (VC). Relative to the control group, the VC injection group had higher levels of VC. Compared with VC_CON, VC injection significantly (P < 0.05) decreased the blood concentrations of ALT, AST, T-Bil, D-Bil, IDBIL, UREA, CRP and LDH. However, VC injection led to greater (P < 0.05) AST/ALT and CREA-S relative to VC_CON. There was no difference (P > 0.05) in GGT, ALP, TBA, TP, ALBII, GLO, A/G, TC, TG, HDL-C, LDL-C, GLU and l-lactate between VC_CON and VC. The injection of VC led to greater (P < 0.05) concentration of MDA, but did not alter (P > 0.05) the serum concentrations of LPO and ROS. The injection of VC led to greater (P < 0.05) serum concentrations of POD, CAT and GSH-PX. In contrast, lower (P < 0.05) serum concentrations of SOD, POD and TPX were observed in VC relative to VC_CON. No difference (P > 0.05) in GSH, GSH-ST and GR was observed between VC_CON and VC. Compared with the control group, metabolomics using liquid chromatography tandem–mass spectrometry identified 156 differential metabolites with P < 0.05 and a variable importance in projection (VIP) score > 1.5 in the VC injection group. The injection of VC resulted in significant changes to the intracellular amino acid metabolism of glutathione, glutamate, cysteine, methionine, glycine, phenylalanine, tyrosine, tryptophan, alanine and aspartate. Overall, our study indicated that VC injections were able to modulate antioxidant levels by affecting metabolism to resist oxidative stress generated during transport.