bluuebunny/crossref_metadata_2025 huggingface dataset:
AraC interacts with p75NTR transmembrane domain to induce cell death of mature neurons
Authors: Lopes-Rodrigues Vanessa , Boxy Pia , Sim Eunice , Park Dong Ik , Habeck Michael , Carbonell Josep , Andersson Annika , Fernández-Suárez Diana , Nissen Poul , Nykjær Anders , Kisiswa Lilian
Published: July 2023

Cytosine arabinoside (AraC) is one of the main therapeutic treatments for several types of cancer, including acute myeloid leukaemia. However, after a high-dose AraC chemotherapy regime, patients develop severe neurotoxicity and cell death in the central nervous system leading to cerebellar ataxia, dysarthria, nystagmus, somnolence and drowsiness. AraC induces apoptosis in dividing cells. However, the mechanism by which it leads to neurite degeneration and cell death in mature neurons remains unclear. We hypothesise that the upregulation of the death receptor p75NTRis responsible for AraC-mediated neurodegeneration and cell death in leukaemia patients undergoing AraC treatment. To determine the role of AraC-p75NTRsignalling in the cell death of mature neurons, we used mature cerebellar granule neurons’ primary cultures from p75NTRknockout andp75NTRCys259mice. Evaluation of neurite degeneration, cell death and p75NTRsignalling was done by immunohistochemistry and immunoblotting. To assess the interaction between AraC and p75NTR, we performed cellular thermal shift and AraTM assays as well as Homo-FRET anisotropy imaging. We show that AraC induces neurite degeneration and programmed cell death of mature cerebellar granule neurons in a p75NTR-dependent manner. Mechanistically, Proline 252 and Cysteine 256 residues facilitate AraC interaction with the transmembrane domain of p75NTRresulting in uncoupling of p75NTRfrom the NFκB survival pathway. This, in turn, exacerbates the activation of the cell death/JNK pathway by recruitment of TRAF6 to p75NTR. Our findings identify p75NTRas a novel molecular target to develop treatments for counteract AraC-mediated cell death of mature neurons.
The checkpoint inhibitor PD-1H/VISTA controls osteoclast-mediated multiple myeloma bone disease
Authors: Fu Jing , Li Shirong , Ma Huihui , Yang Jun , Pagnotti Gabriel M. , Brown Lewis M. , Weiss Stephen J. , Mapara Markus Y. , Lentzsch Suzanne
Published: July 2023

Multiple myeloma bone disease is characterized by the development of osteolytic bone lesions. Recent work identified matrix metalloproteinase 13 as a myeloma-derived fusogen that induces osteoclast activation independent of its proteolytic activity. We now identify programmed death-1 homolog, PD-1H, as the bona fide MMP-13 receptor on osteoclasts. Silencing PD-1H or usingPd-1h-/-bone marrow cells abrogates the MMP-13-enhanced osteoclast fusion and bone-resorptive activity. Further, PD-1H interacts with the actin cytoskeleton and plays a necessary role in supporting c-Src activation and sealing zone formation. The critical role of PD-1H in myeloma lytic bone lesions was confirmed using aPd-1h-/-myeloma bone disease mouse model wherein myeloma cells injected intoPd-1h-/-Rag2-/-results in attenuated bone destruction. Our findings identify a role of PD-1H in bone biology independent of its known immunoregulatory functions and suggest that targeting the MMP-13/PD-1H axis may represent a potential approach for the treatment of myeloma associated osteolysis.
Optimal reactive nitrogen control pathways identified for cost-effective PM2.5 mitigation in Europe
Authors: Liu Zehui , Rieder Harald E. , Schmidt Christian , Mayer Monika , Guo Yixin , Winiwarter Wilfried , Zhang Lin
Published: July 2023

Excess reactive nitrogen (Nr), including nitrogen oxides (NOx) and ammonia (NH3), contributes strongly to fine particulate matter (PM2.5) air pollution in Europe, posing challenges to public health. Designing cost-effective Nr control roadmaps for PM2.5 mitigation requires considering both mitigation efficiencies and implementation costs. Here we identify optimal Nr control pathways for Europe by integrating emission estimations, air quality modeling, exposure-mortality modeling, Nr control experiments and cost data. We find that phasing out Nr emissions would reduce PM2.5 by 2.3 ± 1.2 μg·m−3 in Europe, helping many locations achieve the World Health Organization (WHO) guidelines and reducing PM2.5-related premature deaths by almost 100 thousand in 2015. Low-ambition NH3 controls have similar PM2.5 mitigation efficiencies as NOx in Eastern Europe, but are less effective in Western Europe until reductions exceed 40%. The efficiency for NH3 controls increases at high-ambition reductions while NOx slightly decreases. When costs are considered, strategies for both regions uniformly shift in favor of NH3 controls, as NH3 controls up to 50% remain 5-11 times more cost-effective than NOx per unit PM2.5 reduction, emphasizing the priority of NH3 control policies for Europe.
Atlas-scale single-cell multi-sample multi-condition data integration using scMerge2
Authors: Lin Yingxin , Cao Yue , Willie Elijah , Patrick Ellis , Yang Jean Y. H.
Published: July 2023

The recent emergence of multi-sample multi-condition single-cell multi-cohort studies allows researchers to investigate different cell states. The effective integration of multiple large-cohort studies promises biological insights into cells under different conditions that individual studies cannot provide. Here, we present scMerge2, a scalable algorithm that allows data integration of atlas-scale multi-sample multi-condition single-cell studies. We have generalized scMerge2 to enable the merging of millions of cells from single-cell studies generated by various single-cell technologies. Using a large COVID-19 data collection with over five million cells from 1000+ individuals, we demonstrate that scMerge2 enables multi-sample multi-condition scRNA-seq data integration from multiple cohorts and reveals signatures derived from cell-type expression that are more accurate in discriminating disease progression. Further, we demonstrate that scMerge2 can remove dataset variability in CyTOF, imaging mass cytometry and CITE-seq experiments, demonstrating its applicability to a broad spectrum of single-cell profiling technologies.
Molecular basis of β-lactam antibiotic resistance of ESKAPE bacterium E. faecium Penicillin Binding Protein PBP5
Authors: Hunashal Yamanappa , Kumar Ganesan Senthil , Choy Meng S. , D’Andréa Éverton D. , Da Silva Santiago Andre , Schoenle Marta V. , Desbonnet Charlene , Arthur Michel , Rice Louis B. , Page Rebecca , Peti Wolfgang
Published: July 2023

Penicillin-binding proteins (PBPs) are essential for the formation of the bacterial cell wall. They are also the targets of β-lactam antibiotics. In Enterococcus faecium, high levels of resistance to β-lactams are associated with the expression of PBP5, with higher levels of resistance associated with distinct PBP5 variants. To define the molecular mechanism of PBP5-mediated resistance we leveraged biomolecular NMR spectroscopy of PBP5 – due to its size (>70 kDa) a challenging NMR target. Our data show that resistant PBP5 variants show significantly increased dynamics either alone or upon formation of the acyl-enzyme inhibitor complex. Furthermore, these variants also exhibit increased acyl-enzyme hydrolysis. Thus, reducing sidechain bulkiness and expanding surface loops results in increased dynamics that facilitates acyl-enzyme hydrolysis and, via increased β-lactam antibiotic turnover, facilitates β-lactam resistance. Together, these data provide the molecular basis of resistance of clinical E. faecium PBP5 variants, results that are likely applicable to the PBP family.
Two-dimensional Kβ-Kα fluorescence spectrum by nonlinear resonant inelastic X-ray scattering
Authors: Tamasaku Kenji , Taguchi Munetaka , Inoue Ichiro , Osaka Taito , Inubushi Yuichi , Yabashi Makina , Ishikawa Tetsuya
Published: July 2023

High sensitivity of the Kβ fluorescence spectrum to electronic state is widely used to investigate spin and oxidation state of first-row transition-metal compounds. However, the complex electronic structure results in overlapping spectral features, and the interpretation may be hampered by ambiguity in resolving the spectrum into components representing different electronic states. Here, we tackle this difficulty with a nonlinear resonant inelastic X-ray scattering (RIXS) scheme, where we leverage sequential two-photon absorption to realize an inverse process of the Kβ emission, and measure the successive Kα emission. The nonlinear RIXS reveals two-dimensional (2D) Kβ-Kα fluorescence spectrum of copper metal, leading to better understanding of the spectral feature. We isolate 3d-related satellite peaks in the 2D spectrum, and find good agreement with our multiplet ligand field calculation. Our work not only advances the fluorescence spectroscopy, but opens the door to extend RIXS into the nonlinear regime.
Revealing broken valley symmetry of quantum emitters in WSe2 with chiral nanocavities
Authors: Yang Longlong , Yuan Yu , Fu Bowen , Yang Jingnan , Dai Danjie , Shi Shushu , Yan Sai , Zhu Rui , Han Xu , Li Hancong , Zuo Zhanchun , Wang Can , Huang Yuan , Jin Kuijuan , Gong Qihuang , Xu Xiulai
Published: July 2023

Single photon emission of quantum emitters (QEs) carrying internal degrees of freedom such as spin and angular momentum plays an important role in quantum optics. Recently, QEs in two-dimensional semiconductors have attracted great interest as promising quantum light sources. However, whether those QEs are characterized by the same valley physics as delocalized valley excitons is still under debate. Moreover, the potential applications of such QEs still need to be explored. Here we show experimental evidence of valley symmetry breaking for neutral QEs in WSe2 monolayer by interacting with chiral plasmonic nanocavities. The anomalous magneto-optical behaviour of the coupled QEs suggests that the polarization state of emitted photon is modulated by the chiral nanocavity instead of the valley-dependent optical selection rules. Calculations of cavity quantum electrodynamics further show the absence of intrinsic valley polarization. The cavity-dependent circularly polarized single-photon output also offers a strategy for future applications in chiral quantum optics.
Topological nodal line in superfluid 3He and the Anderson theorem
Authors: Kamppinen T. , Rysti J. , Volard M.-M. , Volovik G. E. , Eltsov V. B.
Published: July 2023

Superconductivity and superfluidity with anisotropic pairing—such as d-wave in cuprates and p-wave in superfluid 3He—are strongly suppressed by impurities. Meanwhile, for applications, the robustness of Cooper pairs to disorder is highly desired. Recently, it has been suggested that unconventional systems become robust if the impurity scattering mixes quasiparticle states only within individual subsystems obeying the Anderson theorem that protects conventional superconductivity. Here, we experimentally verify this conjecture by measuring the temperature dependence of the energy gap in the polar phase of superfluid 3He. We show that oriented columnar non-magnetic defects do not essentially modify the energy spectrum, which has a Dirac nodal line. Although the scattering is strong, it preserves the momentum along the length of the columns and forms robust subsystems according to the conjecture. This finding may stimulate future experiments on the protection of topological superconductivity against disorder and on the nature of topological fermionic flat bands.
Proteogenomics of clear cell renal cell carcinoma response to tyrosine kinase inhibitor
Authors: Zhang Hailiang , Bai Lin , Wu Xin-Qiang , Tian Xi , Feng Jinwen , Wu Xiaohui , Shi Guo-Hai , Pei Xiaoru , Lyu Jiacheng , Yang Guojian , Liu Yang , Xu Wenhao , Anwaier Aihetaimujiang , Zhu Yu , Cao Da-Long , Xu Fujiang , Wang Yue , Gan Hua-Lei , Sun Meng-Hong , Zhao Jian-Yuan , Qu Yuanyuan , Ye Dingwei , Ding Chen
Published: July 2023

The tyrosine kinase inhibitor (TKI) Sunitinib is one the therapies approved for advanced renal cell carcinoma. Here, we undertake proteogenomic profiling of 115 tumors from patients with clear cell renal cell carcinoma (ccRCC) undergoing Sunitinib treatment and reveal the molecular basis of differential clinical outcomes with TKI therapy. We find that chromosome 7q gain-induced mTOR signaling activation is associated with poor therapeutic outcomes with Sunitinib treatment, whereas the aristolochic acid signature and VHL mutation synergistically caused enhanced glycolysis is correlated with better prognosis. The proteomic and phosphoproteomic analysis further highlights the responsibility of mTOR signaling for non-response to Sunitinib. Immune landscape characterization reveals diverse tumor microenvironment subsets in ccRCC. Finally, we construct a multi-omics classifier that can detect responder and non-responder patients (receiver operating characteristic–area under the curve, 0.98). Our study highlights associations between ccRCC molecular characteristics and the response to TKI, which can facilitate future improvement of therapeutic responses.
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

Inspired 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

A 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

Periodontitis 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

Direct 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

A 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

Estimates 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

The 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

The 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

This 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

Voltage-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

Many 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

Surgery 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

We 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

This 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

Organs-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.
A new validated facile HPLC analysis method to determine methylprednisolone including its derivatives and practical application
Authors: Al-Hakkani Mostafa F.
Published: July 2023

Methylprednisolone sodium succinate (MPSS) is a parenteral water-soluble corticosteroid ester. It gives three peaks methylprednisolone (MP), 17-methylprednisolone hemisuccinate (17-MPHS), and methylprednisolone hemisuccinate (MPHS) that share in the assay determination as total MP. It is used on a wide scale in prescribed anti-inflammatory drugs as a common use. The current study aimed to find a rapid RP-HPLC method of MP and its derivatives analysis with high linearity, repeatability, sensitivity, selectivity, and inexpensive to use without the need for any special chemical reagents. The use of the current method achieved a satisfactory result to detect, determine and separate the MP, 17-MPHS, and MPHS in a short time. The chromatographic system consists of RP-HPLC using the BDS column (250 mm × 4.6 mm × 5 μm). The mobile phase was prepared by mixing the WFI: glacial acetic acid: acetonitrile in a volume ratio (63:2:35) at a flow rate of 2.0 mL/min with detection wavelength at 254 nm at room temperature and injection volume 20 μL. The method manifested a satisfied linearity regression R2 (0.9998–0.99999) with LOD 143.97 ng/mL and 4.49 µg/mL; and LOQ 436.27 ng/mL and 13.61 µg/mL for MP and MPHS respectively. The method proved its efficiency via system suitability achievement in the robustness and ruggedness conduction according to the validation guidelines. High sensitivity according to its LOD and LOQ. So, the current method could be considered in the pharmaceutical industry. The suggested method has been successfully implemented in the Egyptian local market for the quantitative assessment of the assay of the finished product.
Enhanced light focusing inside scattering media with shaped ultrasound
Authors: Mestre-Torà Blanca , Duocastella Martí
Published: July 2023

Light focusing is the primary enabler of various scientific and industrial processes including laser materials processing and microscopy. However, the scattering of light limits the depth at which current methods can operate inside heterogeneous media such as biological tissue, liquid emulsions, and composite materials. Several approaches have been developed to address this issue, but they typically come at the cost of losing spatial or temporal resolution, or increased invasiveness. Here, we show that ultrasound waves featuring a Bessel-like profile can locally modulate the optical properties of a turbid medium to facilitate light guiding. Supported by wave optics and Monte Carlo simulations, we demonstrate how ultrasound enhances light focusing a factor of 7 compared to conventional methods based on placing optical elements outside the complex medium. Combined with point-by-point scanning, images of samples immersed in turbid media with an optical density up to 15, similar to that of weakly scattering biological tissue, can be reconstructed. The quasi-instantaneous generation of the shaped-ultrasound waves, together with the possibility to use transmission and reflection architectures, can pave the way for the real-time control of light inside living tissue.
Relationships of rapid eating with visceral and subcutaneous fat mass and plasma adiponectin concentration
Authors: Tsumura Hideki , Fukuda Mari , Hisamatsu Takashi , Sato Rie , Tsuchie Rina , Kanda Hideyuki
Published: July 2023

Rapid eating has been demonstrated to be associated with obesity and overweight. However, few studies have characterized the separate relationships of eating speed with visceral and subcutaneous fat mass or circulating adiponectin concentration. We hypothesized that rapid eating is associated with the larger visceral fat tissue (VFT) area and lower adiponectin concentration, but not with the subcutaneous fat tissue (SFT) area in men and women. We performed a cross-sectional study of 712 adults aged 20–86 years (528 men and 184 women; mean ± SD age 59.36 ± 13.61 years). The participants completed a self-reported questionnaire, and underwent anthropometric and laboratory measurements and computed tomographic imaging of the abdomen as a part of annual medical check-ups. Multivariate linear regression analyses revealed that rapid eating was associated with larger visceral (B = 24.74; 95% CI 8.87–40.61, p = 0.002) and subcutaneous fat areas (B = 31.31; 95% CI 12.23–50.38, p = 0.001), lower adiponectin concentration (B =  − 2.92; 95% CI − 4.39– − 1.46, p < 0.001), higher body mass index (BMI) (B = 2.13; 95% CI 1.02–3.25, p < 0.001), and larger waist circumference (B = 5.23; 95% CI 2.16–8.30, p < 0.001) in men, which is partially consistent with the hypothesis. In contrast, rapid eating was found to be associated only with BMI, and not with abdominal adipose area or adiponectin concentration in women, which is a result that is not consistent with the hypothesis. These results suggest that there is no difference in the association of rapid eating with VFT and SFT areas.
Cross-mating between the alien bumblebee Bombus terrestris and two native Japanese bumblebees, B. hypocrita sapporensis and B. cryptarum florilegus, in the Nemuro Peninsula, Japan
Authors: Kubo Ryohei , Asanuma Yuine , Fujimoto Erina , Okuyama Hisashi , Ono Masato , Takahashi Jun-ichi
Published: July 2023

The rapid naturalization of Bombus terrestris across the Nemuro Peninsula has led to a decline in two closely related native Japanese species, namely Bombus hypocrita sapporensis and Bombus cryptarum florilegus, both belonging to the common subgenus Bombus. Although it is widely believed that cross-mating of native and non-native species is influenced by the common male sex pheromone in this region, no study has been conducted to substantiate this claim. Thus, we investigated the cross-activities of male sex pheromones between native and non-native bumblebees, as well as the frequencies of cross-mating, using chemical and DNA assays. Our gas chromatography–electroantennographic detector analyses and behavioral tests revealed the presence of sex pheromonal cross-activities between B. terrestris and the two Japanese bumblebees species. Furthermore, DNA analyses revealed the occurrence of cross-mating between native and non-native species in the Nemuro Peninsula. Overall, these results indicate the immediate need for conservation measures to safeguard Japanese bumblebee populations in the Nemuro Peninsula.
Open quantum system violates generalized Pauli constraints on quantum device
Authors: Avdic Irma , Sager-Smith LeeAnn M. , Mazziotti David A.
Published: July 2023

The Pauli exclusion principle governs the fundamental structure and function of fermionic systems from molecules to materials. Nonetheless, when such a fermionic system is in a pure state, it is subject to additional restrictions known as the generalized Pauli constraints (GPCs). Here we verify experimentally the violation of the GPCs for an open quantum system using data from a superconducting-qubit quantum computer. We prepare states of systems with three-to-seven qubits directly on the quantum device and measure the one-fermion reduced density matrix (1-RDM) from which we can test the GPCs. We find that the GPCs of the 1-RDM are sufficiently sensitive to detect the openness of the 3-to-7 qubit systems in the presence of a single-qubit environment. Results confirm experimentally that the openness of a many-fermion quantum system can be decoded from only a knowledge of the 1-RDM with potential applications from quantum computing and sensing to noise-assisted energy transfer.
Symmetry-protected Bose-Einstein condensation of interacting hardcore bosons
Authors: Wilke Reja H. , Köhler Thomas , Palm Felix A. , Paeckel Sebastian
Published: July 2023

The large practical potential of exotic quantum states is often precluded by their notorious fragility against external perturbations or temperature. Here, we introduce a mechanism stabilizing a one-dimensional quantum many-body phase exploiting an emergent $${{\mathbb{Z}}}_{2}$$

Z

2

-symmetry based on a simple geometrical modification, i.e. a site that couples to all lattice sites. We illustrate this mechanism by constructing the solution of the full quantum many-body problem of hardcore bosons on a wheel geometry, which are known to form Bose-Einstein condensates. The robustness of the condensate against interactions is shown numerically by adding nearest-neighbor interactions, which typically destroy Bose-Einstein condensates. We discuss further applications such as geometrically inducing finite-momentum condensates. Since our solution strategy is based on a generic mapping, our findings are applicable in a broader context, in which a particular state should be protected, by introducing an additional center site.
Development of a bioactive tunable hyaluronic-protein bioconjugate hydrogel for tissue regenerative applications
Authors: Kasper Mary , Cydis Madison , Afridi Abdullah , Smadi Bassam M. , Li Yuan , Charlier Alban , Barnes Brooke E. , Hohn Julia , Cline Michael J. , Carver Wayne , Matthews Michael , Savin Daniel , Rinaldi-Ramos Carlos M. , Schmidt Christine E.
Published: July 2023

Hyaluronic acid-based hydrogels conjugated with a fibrinogen linker were found to contribute to faster scaffold degradationviaactive enzymatic breakdown, paving the pathway for use in a variety of multi-purpose tissue engineering applications.
Intracellular regulation of zinc by metal–organic framework-mediated genome editing for prostate cancer therapy
Authors: Xue Yanan , Tang Honglin , Chen Guangpeng , Pan Yubin , Li Da , Ping Yuan
Published: July 2023

The preparation process of Cas9@ZIF8-DUPA nanoparticles and the anti-tumour mechanism for PCa.
Membrane interaction and selectivity of novel alternating cationic lipid-nanodisc assembling polymers
Authors: Farrelly Michelle D. , Zhai Jiali , Tiong Alice Y. J. , van ‘t Hag Leonie , Yu Heidi H. , Li Jian , Martin Lisandra L. , Thang San H.
Published: July 2023

The polymer–lipid nanodisc forming ability of a novel class of amphipathic copolymer comprised of an alternating sequence was established. Selective membrane disruption was shown to be tuneable in relation to polymer hydrophobicity.
Efficient additive-free formic acid dehydrogenation with a NNN–ruthenium complex
Authors: Knörr Pascal , Lentz Nicolas , Albrecht Martin
Published: July 2023

A new phosphine-free N,N,N-coordinated ruthenium complex featuring a pyridylidene amine (PYE) ligand catalyzes the dehydrogenation of formic acid with high activity; mechanistic studies reveal a critical role of the central N-donor of the NNN ligand.
Biomass to energy: a machine learning model for optimum gasification pathways
Authors: Gil María Victoria , Jablonka Kevin Maik , Garcia Susana , Pevida Covadonga , Smit Berend
Published: July 2023

Machine learning model to identify the optimal gasification-based biomass conversion route from biomass properties. It allows us to connect the wide diversity of biomass feedstocks with the most suitable application.
Topological quantum devices: a review
Authors: Jin Kyung-Hwan , Jiang Wei , Sethi Gurjyot , Liu Feng
Published: July 2023

This review discusses recent advancements in topological quantum devices, focusing on topological spintronic, electronic, and quantum optoelectronic devices.
Controllably modulated asymmetrical photoresponse with a nonvolatile memory effect in a single CH3NH3PbI3 micro/nanowire for photorectifiers and photomemory
Authors: Hong Zhen , Quan Hongying , Ke Changying , Ouyang Zhiyong , Cheng Baochang
Published: July 2023

By clarifying electrode interface photoresponse of CH3NH3PbI3 micro/nanowires, multifunction photorectifier and self-powered photodetector are achieved. Precise modulation of electrode interface states with voltage and illumination enables realization of nonvolatile photomemory.