bluuebunny/crossref_metadata_2025_split huggingface dataset:
Light-triggered multi-joint microactuator fabricated by two-in-one femtosecond laser writing
Authors: Xin Chen , Ren Zhongguo , Zhang Leran , Yang Liang , Wang Dawei , Hu Yanlei , Li Jiawen , Chu Jiaru , Zhang Li , Wu Dong 
Published: July 2023

AbstractInspired by the flexible joints of humans, actuators containing soft joints have been developed for various applications, including soft grippers, artificial muscles, and wearable devices. However, integrating multiple microjoints into soft robots at the micrometer scale to achieve multi-deformation modalities remains challenging. Here, we propose a two-in-one femtosecond laser writing strategy to fabricate microjoints composed of hydrogel and metal nanoparticles, and develop multi-joint microactuators with multi-deformation modalities (>10), requiring short response time (30 ms) and low actuation power (<10 mW) to achieve deformation. Besides, independent joint deformation control and linkage of multi-joint deformation, including co-planar and spatial linkage, enables the microactuator to reconstruct a variety of complex human-like modalities. Finally, as a proof of concept, the collection of multiple microcargos at different locations is achieved by a double-joint micro robotic arm. Our microactuators with multiple modalities will bring many potential application opportunities in microcargo collection, microfluid operation, and cell manipulation.
Deep-profiling of phospholipidome via rapid orthogonal separations and isomer-resolved mass spectrometry
Authors: Xia Tian , Zhou Feng , Zhang Donghui , Jin Xue , Shi Hengxue , Yin Hang , Gong Yanqing , Xia Yu 
Published: July 2023

AbstractA lipidome comprises thousands of lipid species, many of which are isomers and isobars. Liquid chromatography-tandem mass spectrometry (LC-MS/MS), although widely used for lipidomic profiling, faces challenges in differentiating lipid isomers. Herein, we address this issue by leveraging the orthogonal separation capabilities of hydrophilic interaction liquid chromatography (HILIC) and trapped ion mobility spectrometry (TIMS). We further integrate isomer-resolved MS/MS methods onto HILIC-TIMS, which enable pinpointing double bond locations in phospholipids and sn-positions in phosphatidylcholine. This system profiles phospholipids at multiple structural levels with short analysis time (<10 min per LC run), high sensitivity (nM detection limit), and wide coverage, while data analysis is streamlined using a home-developed software, LipidNovelist. Notably, compared to our previous report, the system doubles the coverage of phospholipids in bovine liver and reveals uncanonical desaturation pathways in RAW 264.7 macrophages. Relative quantitation of the double bond location isomers of phospholipids and the sn-position isomers of phosphatidylcholine enables the phenotyping of human bladder cancer tissue relative to normal control, which would be otherwise indistinguishable by traditional profiling methods. Our research offers a comprehensive solution for lipidomic profiling and highlights the critical role of isomer analysis in studying lipid metabolism in both healthy and diseased states.
Akkermansia muciniphila inhibited the periodontitis caused by Fusobacterium nucleatum
Authors: Song Bingqing , Xian Wenpan , Sun Yan , Gou Lichen , Guo Qiang , Zhou Xuedong , Ren Biao , Cheng Lei 
Published: July 2023

AbstractPeriodontitis is the most important cause of tooth loss in adults and is closely related to various systemic diseases. Its etiologic factor is plaque biofilm, and the primary treatment modality is plaque control. Studies have confirmed that Fusobacterium nucleatum can cause periodontitis through its virulence factors and copolymerizing effects with other periodontal pathogens, such as the red complex. Inhibiting F. nucleatum is an essential target for preventing periodontitis. The time-consuming and costly traditional periodontal treatment, periodontal scaling, and root planing are a significant burden on individual and public health. Antibiotic use may lead to oral microbial resistance and microbiome imbalance, while probiotics regulate microbial balance. Akkermansia muciniphila is a critical probiotic isolated from the human intestine. It can protect the integrity of the epithelial barrier, regulate and maintain flora homeostasis, improve metabolism, and colonize the oral cavity. Its abundance is inversely correlated with various diseases. We hypothesized that A. muciniphila could inhibit the effects of F. nucleatum and alleviate periodontitis. Bacterial co-culture experiments showed that A. muciniphila could inhibit the expression of the virulence gene of F. nucleatum. After treating gingival epithelial cells (GECs) with F. nucleatum and A. muciniphila, transcriptome sequencing and ELISA experiments on medium supernatant showed that A. muciniphila inhibited the inflammatory effect of F. nucleatum on GECs by inhibiting TLR/MyD88/NF-κB pathway modulation and secretion of inflammatory factors. Finally, animal experiments demonstrated that A. muciniphila could inhibit F. nucleatum-induced periodontitis in BALB/c mice.
In vivo effects of the alpha-synuclein misfolding inhibitor minzasolmin supports clinical development in Parkinson’s disease
Authors: Price Diana L. , Khan Asma , Angers Rachel , Cardenas Alvaro , Prato Maria Key , Bani Massimo , Bonhaus Douglas W. , Citron Martin , Biere Anja-Leona 
Published: July 2023

AbstractDirect targeting of alpha-synuclein (ASYN) has emerged as a disease-modifying strategy for Parkinson’s disease and other synucleinopathies which is being approached using both small molecule compounds and ASYN-targeted biologics. Minzasolmin (UCB0599) is an orally bioavailable and brain-penetrant small molecule ASYN misfolding inhibitor in clinical development as a disease-modifying therapeutic for Parkinson’s disease. Herein the results of preclinical evaluations of minzasolmin that formed the basis for subsequent clinical development are described. Pharmacokinetic evaluations of intraperitoneal 1 and 5 mg/kg minzasolmin in wildtype mice revealed parallel and dose-proportional exposures in brain and plasma. Three-month administration studies in the Line 61 transgenic mouse model of PD were conducted to measure ASYN pathology and other PD-relevant endpoints including markers of CNS inflammation, striatal DAT labeling and gait. Reductions in ASYN pathology were correlated with improved aspects of gait and balance, reductions in CNS inflammation marker abundance, and normalized striatal DAT levels. These findings provide support for human dose determinations and have informed the translational strategy for clinical trial design and biomarker selection for the ongoing clinical studies of minzasolmin in patients living with early-stage Parkinson’s disease (ClinicalTrials.gov ID: NCT04658186; EudraCT Number 2020–003265).
Ablation of the gut microbiota alleviates high-methionine diet-induced hyperhomocysteinemia and glucose intolerance in mice
Authors: Li Wenqiang , Jia Yiting , Gong Ze , Dong Zhao , Yu Fang , Fu Yi , Jiang Changtao , Kong Wei 
Published: July 2023

AbstractA high-methionine (HM) diet leads to hyperhomocysteinemia (HHcy), while gastrointestinal tissue is an important site of net homocysteine (Hcy) production. However, the role of the gut microbiota in host HHcy remains obscure. This study aimed to determine whether gut microbiota ablation could alleviate host HHcy and glucose intolerance and reveal the underlying mechanism. The results showed that the HM diet-induced HHcy and glucose intolerance in mice, while antibiotic administration decreased the plasma level of Hcy and reversed glucose intolerance. HM diet increased intestinal epithelial homocysteine levels, while antibiotic treatment decreased intestinal epithelial homocysteine levels under the HM diet. Gut microbiota depletion had no effect on the gene expression and enzyme activity of CBS and BHMT in the livers of HM diet-fed mice. The HM diet altered the composition of the gut microbiota with marked increases in the abundances ofFaecalibaculumandDubosiella, which were also positively correlated with plasma Hcy concentrations. An in-depth analysis of the bacterial cysteine and methionine metabolism pathways showed that the abundances of two homocysteine biosynthesis-related KEGG orthologies (KOs) were markedly increased in the gut microbiota in HM diet-fed mice. Hcy was detected fromDubosiella newyorkensis-cultured supernatant by liquid chromatography–tandem mass spectrometry (LC‒MS) analysis. In conclusion, these findings suggested that the HM diet-induced HHcy and glucose intolerance in mice, by reshaping the composition of the gut microbiota, which might produce and secrete Hcy.
Conventional twin studies overestimate the environmental differences between families relevant to educational attainment
Authors: Wolfram Tobias , Morris Damien 
Published: July 2023

AbstractEstimates of shared environmental influence on educational attainment (EA) using the Classical Twin Design (CTD) have been enlisted as genetically sensitive measures of unequal opportunity. However, key assumptions of the CTD appear violated for EA. In this study we compared CTD estimates of shared environmental influence on EA with estimates from a Nuclear Twin and Family Design (NTFD) in the same 982 German families. Our CTD model estimated shared environmental influence at 43%. After accounting for assortative mating, our best fitting NTFD model estimated shared environmental influence at 26%, disaggregating this into twin-specific shared environments (16%) and environmental influences shared by all siblings (10%). Only the sibling shared environment captures environmental influences that reliably differ between families, suggesting the CTD substantially overestimates between-family differences in educational opportunity. Moreover, parental education was found to have no environmental effect on offspring education once genetic influences were accounted for.
Convergent resistance to GABA receptor neurotoxins through plant–insect coevolution
Authors: Guo Lei , Qiao Xiaomu , Haji Diler , Zhou Tianhao , Liu Zhihan , Whiteman Noah K. , Huang Jia 
Published: July 2023

AbstractThe molecular mechanisms of coevolution between plants and insects remain elusive. GABA receptors are targets of many neurotoxic terpenoids, which represent the most diverse array of natural products known. Over deep evolutionary time, as plant terpene synthases diversified in plants, so did plant terpenoid defence repertoires. Here we show that herbivorous insects and their predators evolved convergent amino acid changing substitutions in duplicated copies of theResistance to dieldrin(Rdl) gene that encodes the GABA receptor, and that the evolution of duplicatedRdland terpenoid-resistant GABA receptors is associated with the diversification of moths and butterflies. These same substitutions also evolved in pests exposed to synthetic insecticides that target the GABA receptor. We used in vivo genome editing inDrosophila melanogasterto evaluate the fitness effects of each putative resistance mutation and found that pleiotropy both facilitates and constrains the evolution of GABA receptor resistance. The same genetic changes that confer resistance to terpenoids across 300 Myr of insect evolution have re-evolved in response to synthetic analogues over one human lifespan.
Energy extraction, or lack thereof
Authors: Gudapati Nishanth 
Published: July 2023

AbstractThe problem of stability of rotating black holes is the subject of a long standing research program since the 1960s and remains an unresolved problem in general relativity. A major obstacle in the black hole stability problem is that the energy of waves propagating through rotating black holes spacetimes is not necessarily positive-definite, due to the so called ergo-region. This is a serious complication that limits the efficacy of most mathematical techniques. In this expository article, we report that, despite the ergo-region, there exists a positive-definite total energy for axisymmetric Maxwell, gravitational and electrovacuum perturbations of Kerr and Kerr–Newman black hole spacetimes.
Quantum correlation of microwave two-mode squeezed state generated by nonlinearity of InP HEMT
Authors: Salmanogli A. 
Published: July 2023

AbstractThis study significantly concentrates on cryogenic InP HEMT high-frequency circuit analysis using quantum theory to find how the transistor nonlinearity can affect the quantum correlation of the modes generated. Firstly, the total Hamiltonian of the circuit is derived, and the dynamic equation of the motion contributed is examined using the Heisenberg-Langevin equation. Using the nonlinear Hamiltonian, some components are attached to the intrinsic internal circuit of InP HEMT to address the circuit characteristics fully. The components attached are arisen due to the nonlinearity effects. As a result, the theoretical calculations show that the states generated in the circuit are mixed, and no pure state is produced. Accordingly, the modified circuit generates the two-mode squeezed thermal state, which means one can focus on calculating the Gaussian quantum discord to evaluate quantum correlation. It is also found that the nonlinearity factors (addressed as the nonlinear components in the circuit) can intensely influence the squeezed thermal state by which the quantum discord is changed. Finally, as the primary point, it is concluded that although it is possible to enhance the quantum correlation between modes by engineering the nonlinear components; however, attaining quantum discord greater than unity, entangled microwave photons, seems a challenging task since InP HEMT operates at 4.2 K.
Determining the structure of the bacterial voltage-gated sodium channel NaChBac embedded in liposomes by cryo electron tomography and subtomogram averaging
Authors: Chang Shih-Ying Scott , Dijkman Patricia M. , Wiessing Simon A. , Kudryashev Misha 
Published: July 2023

AbstractVoltage-gated sodium channels shape action potentials that propagate signals along cells. When the membrane potential reaches a certain threshold, the channels open and allow sodium ions to flow through the membrane depolarizing it, followed by the deactivation of the channels. Opening and closing of the channels is important for cellular signalling and regulates various physiological processes in muscles, heart and brain. Mechanistic insights into the voltage-gated channels are difficult to achieve as the proteins are typically extracted from membranes for structural analysis which results in the loss of the transmembrane potential that regulates their activity. Here, we report the structural analysis of a bacterial voltage-gated sodium channel, NaChBac, reconstituted in liposomes under an electrochemical gradient by cryo electron tomography and subtomogram averaging. We show that the small channel, most of the residues of which are embedded in the membrane, can be localized using a genetically fused GFP. GFP can aid the initial alignment to an average resulting in a correct structure, but does not help for the final refinement. At a moderate resolution of ˜16 Å the structure of NaChBac in an unrestricted membrane bilayer is 10% wider than the structure of the purified protein previously solved in nanodiscs, suggesting the potential movement of the peripheral voltage-sensing domains. Our study explores the limits of structural analysis of membrane proteins in membranes.
A tamper-resistant timed secure data transmission protocol based on smart contract
Authors: Yuan Ke , Cao Haowen , Zhang Suya , Zhai Chenxu , Du Xiaoyu , Jia Chunfu 
Published: July 2023

AbstractMany time-sensitive scenarios need to decrypt data at a specified time. The timed-release encryption (TRE) primitive can meet this requirement. However, in the single-time server TRE model, there is a single point of failure problem. Therefore, we propose a tamper-resistant timed secure data transmission protocol based on smart contracts. Firstly, by decomposing the ciphertext into ciphertext fragments, the amount of deposit that a single middleman needs to submit is reduced. Secondly, it provides the system with security redundancy that changes with the decomposition mode. Thirdly, the sender is required to submit the hash value of each ciphertext fragment to the blockchain network at the same time as sending data, so that the receiver can quickly verify the authenticity of the ciphertext to resist substitution attack. Security analysis shows that the proposed protocol model can resist interruption attacks, release-ahead attacks and replacement attacks. Finally, we conduct a monetary cost test on the Ethereum’s Rinkeby test network. The results show that our running cost is almost double compared with the existing similar scheme, but it is still very low and almost negligible compared with the value of the content and the expected profits it brings.
Benign nerve tumours in the upper limb: a registry-based study of symptoms and surgical outcome
Authors: Istefan Emanuel , Zimmerman Malin , Dahlin Lars B. , Nyman Erika 
Published: July 2023

AbstractSurgery for benign nerve tumours is performed for pathoanatomical diagnosis and symptomatic relief, but might cause residual problems. We aimed to assess patient-reported symptoms and disability before and after surgery at a national level. In total, 206 cases surgically treated for a benign peripheral nerve tumour 2010–2019 registered in the Swedish Quality Registry for Hand Surgery (HAKIR; response rates 22–34%) were analysed. Surgery reduced overall disability in the affected limb (QuickDASH 18/100 [IQR 5–36] preoperatively and 5/100 [IQR 0–22] 12 months postoperatively), improved ability to perform daily activities (HQ-8; 11/100 [IQR 0–50] preoperatively and 0/100 [IQR 0–20] 12 months postoperatively) and decreased three evaluated pain modalities: pain at rest (HQ-8; 20/100 [IQR 0–40] preoperatively and 0/100 [IQR 0–10] 12 months postoperatively), pain on motion without load (HQ-8; 20/100 [IQR 0–40] preoperatively and 0/100 [IQR 0–10] 12 months postoperatively), and pain on load (HQ-8; 24/100 [IQR 1–69] preoperatively and 1/100 [IQR 0–30] 12 months postoperatively). Cold sensitivity was a minor problem both before and after surgery (HQ-8; 0/100 [IQR 0–30] preoperatively and 1/100 [IQR 0–40] 12 months postoperatively). We conclude that surgery for benign peripheral nerve tumours provides good symptomatic relief with low risk for residual problems.
Iron oxide nanoparticles as positive T1 contrast agents for low-field magnetic resonance imaging at 64 mT
Authors: Oberdick Samuel D. , Jordanova Kalina V. , Lundstrom John T. , Parigi Giacomo , Poorman Megan E. , Zabow Gary , Keenan Kathryn E. 
Published: July 2023

AbstractWe have investigated the efficacy of superparamagnetic iron oxide nanoparticles (SPIONs) as positive T1 contrast agents for low-field magnetic resonance imaging (MRI) at 64 millitesla (mT). Iron oxide-based agents, such as the FDA-approved ferumoxytol, were measured using a variety of techniques to evaluate T1 contrast at 64 mT. Additionally, we characterized monodispersed carboxylic acid-coated SPIONs with a range of diameters (4.9–15.7 nm) in order to understand size-dependent properties of T1 contrast at low-field. MRI contrast properties were measured using 64 mT MRI, magnetometry, and nuclear magnetic resonance dispersion (NMRD). We also measured MRI contrast at 3 T to provide comparison to a standard clinical field strength. SPIONs have the capacity to perform well as T1 contrast agents at 64 mT, with measured longitudinal relaxivity (r1) values of up to 67 L mmol−1 s−1, more than an order of magnitude higher than corresponding r1 values at 3 T. The particles exhibit size-dependent longitudinal relaxivities and outperform a commercial Gd-based agent (gadobenate dimeglumine) by more than eight-fold at physiological temperatures. Additionally, we characterize the ratio of transverse to longitudinal relaxivity, r2/r1 and find that it is ~ 1 for the SPION based agents at 64 mT, indicating a favorable balance of relaxivities for T1-weighted contrast imaging. We also correlate the magnetic and structural properties of the particles with models of nanoparticle relaxivity to understand generation of T1 contrast. These experiments show that SPIONs, at low fields being targeted for point-of-care low-field MRI systems, have a unique combination of magnetic and structural properties that produce large T1 relaxivities.
Development of optimal sizing system for tactical gloves applying empirical loss coefficient ratio
Authors: Hong Yujin , Choi Hee Eun 
Published: July 2023

AbstractThis study aims to improve Korean male soldiers’ mission performance and protect them from safety accidents by establishing an optimal sizing system that considers the fit of tactical gloves and production and supply efficiency. First, the wearing condition of tactical gloves was investigated through in-depth interviews and surveys. The optimal glove fit and loss coefficient ratio was then analyzed through a glove size selection experiment. Finally, the sizing system was optimized and verified by comparing the coverage rate to the current sizing system. The empirically derived loss coefficient ratio was 0.075, and the optimal sizing system for tactical gloves was S-hand length: 168 mm, hand width: 81 mm, M-hand length: 177 mm, hand width: 83 mm, L-hand length: 184 mm, hand width: 86 mm, XL-hand length: 191 mm, and hand width: 89 mm. The coverage rate of the optimal sizing system proposed in this study was 86.4%, showing an improvement of approximately 21.1% compared to the current sizing system (65.3%). In conclusion, the optimal sizing system for tactical gloves proposed in this study can realistically solve current sizing issues, as it improved the coverage rate by 21.1% without incurring additional costs for production or hindering the supply efficiency.
Openable artificial intestinal tract device integrated with a permeable filter for evaluating drug permeation through cells
Authors: Konishi Satoshi , Ishibashi Shingo , Shimizu Shiho , Watanabe Keita , Abdalkader Rodi , Fujita Takuya 
Published: July 2023

AbstractOrgans-on-chips using cultured cells have been developed and applied for evaluating in vitro biological phenomena. We previously reported an openable artificial intestinal tract system, as an in vitro model of the small intestine, for in vitro drug screening. The intestinal tract device could be transformed using an integrated artificial muscle actuator. An initial flat state was suitable for cell culture, and the transformed tubular structure was used as a fluidic channel for perfusion tests. The previously developed intestinal tract system could be used to evaluate drug absorption by cells through perfusion testing. This study presents an improved artificial intestinal tract system for analysis of drug permeation, in addition to absorption. Permeable filters were integrated into the intestinal tract device. Integration of additional filters into the design of the existing artificial muscle actuator was accomplished by considering device performance and available filter locations. Filter permeability was evaluated by perfusion testing. MDCK-II cells were cultured on the device and visually and electrically evaluated. The openable device, equipped with new functions for further pharmacokinetic analysis, could perform and evaluate drug disposition using cultured cells. We anticipate that the improved, openable organ-on-a-chip device system will contribute to advances in in vitro drug screening technology.