bluuebunny/crossref_metadata_2025 huggingface dataset:
Ciclopirox drives growth arrest and autophagic cell death through STAT3 in gastric cancer cells
Authors: Chen Lingyan , Chen Dejian , Li Jiwei , He Lipeng , Chen Ting , Song Dandan , Shan Shuang , Wang Jiaxin , Lu Xiaoang , Lu Bin
Published: November 2022

Ciclopirox (CPX), an antifungal drug, has recently been identified as a promising agent for cancer treatment. However, the effects and underlying mechanism of CPX as an antitumor agent of gastric cancer (GC) remain largely unknown. Here, we found that CPX dramatically suppresses GC xenograft growth in vitro via inhibiting proliferation and stimulating autophagic cell death rather than apoptosis. Moreover, CPX (20 mg/kg, intraperitoneally) substantially inhibits GC xenograft tumor growth in vivo. Mechanistically, CPX promotes growth arrest and autophagic cell death through suppressing the phosphorylation of signal transducers and activators of transcription 3 (STAT3) at tyrosine 705 (Tyr705) and serine 727 (Ser727) sites, respectively. Additionally, CPX induces STAT3 ubiquitination, which subsequently leads to a decrease in the p-STAT3 (Ser727) level. On the other hand, CPX represses the p-STAT3 (Tyr705) level via p-Src (Tyr416) inhibition. Collectively, our findings unmask a novel mechanism by which CPX regulates growth and autophagic cell death in GC cells via regulating the phosphorylation of STAT3 both at Tyr705 and Ser727 residues, and suggest that CPX may be a potential treatment for GC.
Low-dose IL-2 reduces IL-21+ T cell frequency and induces anti-inflammatory gene expression in type 1 diabetes
Authors: Zhang Jia-Yuan , Hamey Fiona , Trzupek Dominik , Mickunas Marius , Lee Mercede , Godfrey Leila , Yang Jennie H. M. , Pekalski Marcin L. , Kennet Jane , Waldron-Lynch Frank , Evans Mark L. , Tree Timothy I. M. , Wicker Linda S. , Todd John A. , Ferreira Ricardo C.
Published: November 2022

Despite early clinical successes, the mechanisms of action of low-dose interleukin-2 (LD-IL-2) immunotherapy remain only partly understood. Here we examine the effects of interval administration of low-dose recombinant IL-2 (iLD-IL-2) in type 1 diabetes using high-resolution single-cell multiomics and flow cytometry on longitudinally-collected peripheral blood samples. Our results confirm that iLD-IL-2 selectively expands thymic-derived FOXP3+HELIOS+regulatory T cells and CD56brightNK cells, and show that the treatment reduces the frequency of IL-21-producing CD4+T cells and of two innate-like mucosal-associated invariant T and Vγ9Vδ2CD8+T cell subsets. The cellular changes induced by iLD-IL-2 associate with an anti-inflammatory gene expression signature, which remains detectable in all T and NK cell subsets analysed one month after treatment. These findings warrant investigations into the potential longer-term clinical benefits of iLD-IL-2 in immunotherapy.
Secreted EMC10 is upregulated in human obesity and its neutralizing antibody prevents diet-induced obesity in mice
Authors: Wang Xuanchun , Li Yanliang , Qiang Guifen , Wang Kaihua , Dai Jiarong , McCann Maximilian , Munoz Marcos D. , Gil Victoria , Yu Yifei , Li Shengxian , Yang Zhihong , Xu Shanshan , Cordoba-Chacon Jose , De Jesus Dario F. , Sun Bei , Chen Kuangyang , Wang Yahao , Liu Xiaoxia , Miao Qing , Zhou Linuo , Hu Renming , Ding Qiang , Kulkarni Rohit N. , Gao Daming , Blüher Matthias , Liew Chong Wee
Published: November 2022

Secreted isoform of endoplasmic reticulum membrane complex subunit 10 (scEMC10) is a poorly characterized secreted protein of largely unknown physiological function. Here we demonstrate that scEMC10 is upregulated in people with obesity and is positively associated with insulin resistance. Consistent with a causal role for scEMC10 in obesity, Emc10-/- mice are resistant to diet-induced obesity due to an increase in energy expenditure, while scEMC10 overexpression decreases energy expenditure, thus promoting obesity in mouse. Furthermore, neutralization of circulating scEMC10 using a monoclonal antibody reduces body weight and enhances insulin sensitivity in obese mice. Mechanistically, we provide evidence that scEMC10 can be transported into cells where it binds to the catalytic subunit of PKA and inhibits its stimulatory action on CREB while ablation of EMC10 promotes thermogenesis in adipocytes via activation of the PKA signalling pathway and its downstream targets. Taken together, our data identify scEMC10 as a circulating inhibitor of thermogenesis and a potential therapeutic target for obesity and its cardiometabolic complications.
Active DNA damage response signaling initiates and maintains meiotic sex chromosome inactivation
Authors: Abe Hironori , Yeh Yu-Han , Munakata Yasuhisa , Ishiguro Kei-Ichiro , Andreassen Paul R. , Namekawa Satoshi H.
Published: November 2022

Meiotic sex chromosome inactivation (MSCI) is an essential process in the male germline. While genetic experiments have established that the DNA damage response (DDR) pathway directs MSCI, due to limitations to the experimental systems available, mechanisms underlying MSCI remain largely unknown. Here we establish a system to study MSCI ex vivo, based on a short-term culture method, and demonstrate that active DDR signaling is required both to initiate and maintain MSCI via a dynamic and reversible process. DDR-directed MSCI follows two layers of modifications: active DDR-dependent reversible processes and irreversible histone post-translational modifications. Further, the DDR initiates MSCI independent of the downstream repressive histone mark H3K9 trimethylation (H3K9me3), thereby demonstrating that active DDR signaling is the primary mechanism of silencing in MSCI. By unveiling the dynamic nature of MSCI, and its governance by active DDR signals, our study highlights the sex chromosomes as an active signaling hub in meiosis.
mTORC1 links pathology in experimental models of Still’s disease and macrophage activation syndrome
Authors: Huang Zhengping , You Xiaomeng , Chen Liang , Du Yan , Brodeur Kailey , Jee Hyuk , Wang Qiang , Linder Grace , Darbousset Roxane , Cunin Pierre , Chang Margaret H. , Wactor Alexandra , Wauford Brian M. , Todd Marc J. C. , Wei Kevin , Li Ying , Levescot Anais , Iwakura Yoichiro , Pascual Virginia , Baldwin Nicole E. , Quartier Pierre , Li Tianwang , Gianatasio Maria T. , Hasserjian Robert P. , Henderson Lauren A. , Sykes David B. , Mellins Elizabeth D. , Canna Scott W. , Charles Julia F. , Nigrovic Peter A. , Lee Pui Y.
Published: November 2022

Still’s disease is a severe inflammatory syndrome characterized by fever, skin rash and arthritis affecting children and adults. Patients with Still’s disease may also develop macrophage activation syndrome, a potentially fatal complication of immune dysregulation resulting in cytokine storm. Here we show that mTORC1 (mechanistic target of rapamycin complex 1) underpins the pathology of Still’s disease and macrophage activation syndrome. Single-cell RNA sequencing in a murine model of Still’s disease shows preferential activation of mTORC1 in monocytes; both mTOR inhibition and monocyte depletion attenuate disease severity. Transcriptomic data from patients with Still’s disease suggest decreased expression of the mTORC1 inhibitors TSC1/TSC2 and an mTORC1 gene signature that strongly correlates with disease activity and treatment response. Unrestricted activation of mTORC1 by Tsc2 deletion in mice is sufficient to trigger a Still’s disease-like syndrome, including both inflammatory arthritis and macrophage activation syndrome with hemophagocytosis, a cellular manifestation that is reproduced in human monocytes by CRISPR/Cas-mediated deletion of TSC2. Consistent with this observation, hemophagocytic histiocytes from patients with macrophage activation syndrome display prominent mTORC1 activity. Our study suggests a mechanistic link of mTORC1 to inflammation that connects the pathogenesis of Still’s disease and macrophage activation syndrome.
Thiocarbazate building blocks enable the construction of azapeptides for rapid development of therapeutic candidates
Authors: Altiti Ahmad , He Mingzhu , VanPatten Sonya , Cheng Kai Fan , Ahmed Umair , Chiu Pui Yan , Mughrabi Ibrahim T. , Jabari Bayan Al , Burch Ronald M. , Manogue Kirk R. , Tracey Kevin J. , Diamond Betty , Metz Christine N. , Yang Huan , Hudson LaQueta K. , Zanos Stavros , Son Myoungsun , Sherry Barbara , Coleman Thomas R. , Al-Abed Yousef
Published: November 2022

Peptides, polymers of amino acids, comprise a vital and expanding therapeutic approach. Their rapid degradation by proteases, however, represents a major limitation to their therapeutic utility and chemical modifications to native peptides have been employed to mitigate this weakness. Herein, we describe functionalized thiocarbazate scaffolds as precursors of aza-amino acids, that, upon activation, can be integrated in a peptide sequence to generate azapeptides using conventional peptide synthetic methods. This methodology facilitates peptide editing—replacing targeted amino acid(s) with aza-amino acid(s) within a peptide—to form azapeptides with preferred therapeutic characteristics (extending half-life/bioavailability, while at the same time typically preserving structural features and biological activities). We demonstrate the convenience of this azapeptide synthesis platform in two well-studied peptides with short half-lives: FSSE/P5779, a tetrapeptide inhibitor of HMGB1/MD-2/TLR4 complex formation, and bradykinin, a nine-residue vasoactive peptide. This bench-stable thiocarbazate platform offers a robust and universal approach to optimize peptide-based therapeutics.
The fate of early perichondrial cells in developing bones
Authors: Matsushita Yuki , Chu Angel Ka Yan , Tsutsumi-Arai Chiaki , Orikasa Shion , Nagata Mizuki , Wong Sunny Y. , Welch Joshua D. , Ono Wanida , Ono Noriaki
Published: November 2022

In endochondral bone development, bone-forming osteoblasts and bone marrow stromal cells have dual origins in the fetal cartilage and its surrounding perichondrium. However, how early perichondrial cells distinctively contribute to developing bones remain unidentified. Here we show using in vivo cell-lineage analyses that Dlx5+ fetal perichondrial cells marked by Dlx5-creER do not generate cartilage but sustainably contribute to cortical bone and marrow stromal compartments in a manner complementary to fetal chondrocyte derivatives under the regulation of Hedgehog signaling. Postnatally, Dlx5+ fetal perichondrial cell derivatives preferentially populate the diaphyseal marrow stroma with a dormant adipocyte-biased state and are refractory to parathyroid hormone-induced bone anabolism. Therefore, early perichondrial cells of the fetal cartilage are destined to become an adipogenic subset of stromal cells in postnatal diaphyseal bone marrow, supporting the theory that the adult bone marrow stromal compartments are developmentally prescribed within the two distinct cells-of-origins of the fetal bone anlage.
PCGF1-PRC1 links chromatin repression with DNA replication during hematopoietic cell lineage commitment
Authors: Takano Junichiro , Ito Shinsuke , Dong Yixing , Sharif Jafar , Nakajima-Takagi Yaeko , Umeyama Taichi , Han Yong-Woon , Isono Kyoichi , Kondo Takashi , Iizuka Yusuke , Miyai Tomohiro , Koseki Yoko , Ikegaya Mika , Sakihara Mizuki , Nakayama Manabu , Ohara Osamu , Hasegawa Yoshinori , Hashimoto Kosuke , Arner Erik , Klose Robert J. , Iwama Atsushi , Koseki Haruhiko , Ikawa Tomokatsu
Published: November 2022

Polycomb group proteins (PcG), polycomb repressive complexes 1 and 2 (PRC1 and 2), repress lineage inappropriate genes during development to maintain proper cellular identities. It has been recognized that PRC1 localizes at the replication fork, however, the precise functions of PRC1 during DNA replication are elusive. Here, we reveal that a variant PRC1 containing PCGF1 (PCGF1-PRC1) prevents overloading of activators and chromatin remodeling factors on nascent DNA and thereby mediates proper deposition of nucleosomes and correct downstream chromatin configurations in hematopoietic stem and progenitor cells (HSPCs). This function of PCGF1-PRC1 in turn facilitates PRC2-mediated repression of target genes such asHmga2and restricts premature myeloid differentiation. PCGF1-PRC1, therefore, maintains the differentiation potential of HSPCs by linking proper nucleosome configuration at the replication fork with PcG-mediated gene silencing to ensure life-long hematopoiesis.
SOTIP is a versatile method for microenvironment modeling with spatial omics data
Authors: Yuan Zhiyuan , Li Yisi , Shi Minglei , Yang Fan , Gao Juntao , Yao Jianhua , Zhang Michael Q.
Published: November 2022

The rapidly developing spatial omics generated datasets with diverse scales and modalities. However, most existing methods focus on modeling dynamics of single cells while ignore microenvironments (MEs). Here we present SOTIP (Spatial Omics mulTIPle-task analysis), a versatile method incorporating MEs and their interrelationships into a unified graph. Based on this graph, spatial heterogeneity quantification, spatial domain identification, differential microenvironment analysis, and other downstream tasks can be performed. We validate each module’s accuracy, robustness, scalability and interpretability on various spatial omics datasets. In two independent mouse cerebral cortex spatial transcriptomics datasets, we reveal a gradient spatial heterogeneity pattern strongly correlated with the cortical depth. In human triple-negative breast cancer spatial proteomics datasets, we identify molecular polarizations and MEs associated with different patient survivals. Overall, by modeling biologically explainable MEs, SOTIP outperforms state-of-art methods and provides some perspectives for spatial omics data exploration and interpretation.
Correlation driven near-flat band Stoner excitations in a Kagome magnet
Authors: Nag Abhishek , Peng Yiran , Li Jiemin , Agrestini S. , Robarts H. C. , García-Fernández Mirian , Walters A. C. , Wang Qi , Yin Qiangwei , Lei Hechang , Yin Zhiping , Zhou Ke-Jin
Published: November 2022

Among condensed matter systems, Mott insulators exhibit diverse properties that emerge from electronic correlations. In itinerant metals, correlations are usually weak, but can also be enhanced via geometrical confinement of electrons, that manifest as ‘flat’ dispersionless electronic bands. In the fast developing field of topological materials, which includes Dirac and Weyl semimetals, flat bands are one of the important components that can result in unusual magnetic and transport behaviour. To date, characterisation of flat bands and their magnetism is scarce, hindering the design of novel materials. Here, we investigate the ferromagnetic Kagomé semimetal Co3Sn2S2 using resonant inelastic X-ray scattering. Remarkably, nearly non-dispersive Stoner spin excitation peaks are observed, sharply contrasting with the featureless Stoner continuum expected in conventional ferromagnetic metals. Our band structure and dynamic spin susceptibility calculations, and thermal evolution of the excitations, confirm the nearly non-dispersive Stoner excitations as unique signatures of correlations and spin-polarized electronic flat bands in Co3Sn2S2. These observations serve as a cornerstone for further exploration of band-induced symmetry-breaking orders in topological materials.
Extensive germline-somatic interplay contributes to prostate cancer progression through HNF1B co-option of TMPRSS2-ERG
Authors: Giannareas Nikolaos , Zhang Qin , Yang Xiayun , Na Rong , Tian Yijun , Yang Yuehong , Ruan Xiaohao , Huang Da , Yang Xiaoqun , Wang Chaofu , Zhang Peng , Manninen Aki , Wang Liang , Wei Gong-Hong
Published: November 2022

Genome-wide association studies have identified 270 loci conferring risk for prostate cancer (PCa), yet the underlying biology and clinical impact remain to be investigated. Here we observe an enrichment of transcription factor genes including HNF1B within PCa risk-associated regions. While focused on the 17q12/HNF1B locus, we find a strong eQTL for HNF1B and multiple potential causal variants involved in the regulation of HNF1B expression in PCa. An unbiased genome-wide co-expression analysis reveals PCa-specific somatic TMPRSS2-ERG fusion as a transcriptional mediator of this locus and the HNF1B eQTL signal is ERG fusion status dependent. We investigate the role of HNF1B and find its involvement in several pathways related to cell cycle progression and PCa severity. Furthermore, HNF1B interacts with TMPRSS2-ERG to co-occupy large proportion of genomic regions with a remarkable enrichment of additional PCa risk alleles. We finally show that HNF1B co-opts ERG fusion to mediate mechanistic and biological effects of the PCa risk-associated locus 17p13.3/VPS53/FAM57A/GEMIN4. Taken together, we report an extensive germline-somatic interaction between TMPRSS2-ERG fusion and genetic variations underpinning PCa risk association and progression.
Hydrophobicity of arginine leads to reentrant liquid-liquid phase separation behaviors of arginine-rich proteins
Authors: Hong Yuri , Najafi Saeed , Casey Thomas , Shea Joan-Emma , Han Song-I , Hwang Dong Soo
Published: November 2022

Intrinsically disordered proteins rich in cationic amino acid groups can undergo Liquid-Liquid Phase Separation (LLPS) in the presence of charge-balancing anionic counterparts. Arginine and Lysine are the two most prevalent cationic amino acids in proteins that undergo LLPS, with arginine-rich proteins observed to undergo LLPS more readily than lysine-rich proteins, a feature commonly attributed to arginine’s ability to form stronger cation-π interactions with aromatic groups. Here, we show that arginine’s ability to promote LLPS is independent of the presence of aromatic partners, and that arginine-rich peptides, but not lysine-rich peptides, display re-entrant phase behavior at high salt concentrations. We further demonstrate that the hydrophobicity of arginine is the determining factor giving rise to the reentrant phase behavior and tunable viscoelastic properties of the dense LLPS phase. Controlling arginine-induced reentrant LLPS behavior using temperature and salt concentration opens avenues for the bioengineering of stress-triggered biological phenomena and drug delivery systems.
High antibody levels and reduced cellular response in children up to one year after SARS-CoV-2 infection
Authors: Jacobsen Eva-Maria , Fabricius Dorit , Class Magdalena , Topfstedt Fernando , Lorenzetti Raquel , Janowska Iga , Schmidt Franziska , Staniek Julian , Zernickel Maria , Stamminger Thomas , Dietz Andrea N. , Zellmer Angela , Hecht Manuel , Rauch Peter , Blum Carmen , Ludwig Carolin , Jahrsdörfer Bernd , Schrezenmeier Hubert , Heeg Maximilian , Mayer Benjamin , Seidel Alina , Groß Rüdiger , Münch Jan , Kirchhoff Frank , Bode Sebastian F. N. , Strauss Gudrun , Renk Hanna , Elling Roland , Stich Maximillian , Voll Reinhard E. , Tönshof Burkhard , Franz Axel R. , Henneke Philipp , Debatin Klaus-Michael , Rizzi Marta , Janda Ales
Published: November 2022

The COVID-19 course and immunity differ in children and adults. We analyzed immune response dynamics in 28 families up to 12 months after mild or asymptomatic infection. Unlike adults, the initial response is plasmablast-driven in children. Four months after infection, children show an enhanced specific antibody response and lower but detectable spike 1 protein (S1)-specific B and T cell responses than their parents. While specific antibodies decline, neutralizing antibody activity and breadth increase in both groups. The frequencies of S1-specific B and T cell responses remain stable. However, in children, one year after infection, an increase in the S1-specific IgA class switch and the expression of CD27 on S1-specific B cells and T cell maturation are observed. These results, together with the enhanced neutralizing potential and breadth of the specific antibodies, suggest a progressive maturation of the S1-specific immune response. Hence, the immune response in children persists over 12 months but dynamically changes in quality, with progressive neutralizing, breadth, and memory maturation. This implies a benefit for booster vaccination in children to consolidate memory formation.
Paired electrolysis-enabled nickel-catalyzed enantioselective reductive cross-coupling between α-chloroesters and aryl bromides
Authors: Liu Dong , Liu Zhao-Ran , Wang Zhen-Hua , Ma Cong , Herbert Simon , Schirok Hartmut , Mei Tian-Sheng
Published: November 2022

Electrochemical asymmetric catalysis has emerged as a sustainable and promising approach to the production of chiral compounds and the utilization of both the anode and cathode as working electrodes would provide a unique approach for organic synthesis. However, precise matching of the rate and electric potential of anodic oxidation and cathodic reduction make such idealized electrolysis difficult to achieve. Herein, asymmetric cross-coupling between α-chloroesters and aryl bromides is probed as a model reaction, wherein alkyl radicals are generated from the α-chloroesters through a sequential oxidative electron transfer process at the anode, while the nickel catalyst is reduced to a lower oxidation state at the cathode. Radical clock studies, cyclic voltammetry analysis, and electron paramagnetic resonance experiments support the synergistic involvement of anodic and cathodic redox events. This electrolytic method provides an alternative avenue for asymmetric catalysis that could find significant utility in organic synthesis.
Limited carbon cycling due to high-pressure effects on the deep-sea microbiome
Authors: Amano Chie , Zhao Zihao , Sintes Eva , Reinthaler Thomas , Stefanschitz Julia , Kisadur Murat , Utsumi Motoo , Herndl Gerhard J.
Published: November 2022

Deep-sea microbial communities are exposed to high-pressure conditions, which has a variable impact on prokaryotes depending on whether they are piezophilic (that is, pressure-loving), piezotolerant or piezosensitive. While it has been suggested that elevated pressures lead to higher community-level metabolic rates, the response of these deep-sea microbial communities to the high-pressure conditions of the deep sea is poorly understood. Based on microbial activity measurements in the major oceanic basins using an in situ microbial incubator, we show that the bulk heterotrophic activity of prokaryotic communities becomes increasingly inhibited at higher hydrostatic pressure. At 4,000 m depth, the bulk heterotrophic prokaryotic activity under in situ hydrostatic pressure was about one-third of that measured in the same community at atmospheric pressure conditions. In the bathypelagic zone—between 1,000 and 4,000 m depth—~85% of the prokaryotic community was piezotolerant and ~5% of the prokaryotic community was piezophilic. Despite piezosensitive-like prokaryotes comprising only ~10% (mainly members of Bacteroidetes,Alteromonas) of the deep-sea prokaryotic community, the more than 100-fold metabolic activity increase of these piezosensitive prokaryotes upon depressurization leads to high apparent bulk metabolic activity. Overall, the heterotrophic prokaryotic activity in the deep sea is likely to be substantially lower than hitherto assumed, with major impacts on the oceanic carbon cycling.
Feedback-controlled hydrogels with homeostatic oscillations and dissipative signal transduction
Authors: Zhang Hang , Zeng Hao , Eklund Amanda , Guo Hongshuang , Priimagi Arri , Ikkala Olli
Published: November 2022

Driving systems out of equilibrium under feedback control is characteristic for living systems, where homeostasis and dissipative signal transduction facilitate complex responses. This feature not only inspires dissipative dynamic functionalities in synthetic systems but also poses great challenges in designing novel pathways. Here we report feedback-controlled systems comprising two coupled hydrogels driven by constant light, where the system can be tuned to undergo stable homeostatic self-oscillations or damped steady states of temperature. We demonstrate that stable temperature oscillations can be utilized for dynamic colours and cargo transport, whereas damped steady states enable signal transduction pathways. Here mechanical triggers cause temperature changes that lead to responses such as bending motions inspired by the single-touch mechanoresponse in Mimosa pudica and the frequency-gated snapping motion inspired by the plant arithmetic in the Venus flytrap. The proposed concepts suggest generalizable feedback pathways for dissipative dynamic materials and interactive soft robotics.
Distinct changes in endosomal composition promote NLRP3 inflammasome activation
Authors: Zhang Zhirong , Venditti Rossella , Ran Li , Liu Zengzhen , Vivot Karl , Schürmann Annette , Bonifacino Juan S. , De Matteis Maria Antonietta , Ricci Romeo
Published: November 2022

Inflammasome complexes are pivotal in the innate immune response. The NLR family pyrin domain containing protein 3 (NLRP3) inflammasome is activated in response to a broad variety of cellular stressors. However, a primary and converging sensing mechanism by the NLRP3 receptor initiating inflammasome assembly remains ill defined. Here, we demonstrate that NLRP3 inflammasome activators primarily converge on disruption of endoplasmic reticulum–endosome membrane contact sites (EECS). This defect causes endosomal accumulation of phosphatidylinositol 4-phosphate (PI4P) and a consequent impairment of endosome-to-trans-Golgi network trafficking (ETT), necessary steps for endosomal recruitment of NLRP3 and subsequent inflammasome activation. Lowering endosomal PI4P levels prevents endosomal association of NLRP3 and inhibits inflammasome activation. Disruption of EECS or ETT is sufficient to enhance endosomal PI4P levels, to recruit NLRP3 to endosomes and to potentiate NLRP3 inflammasome activation. Mice with defects in ETT in the myeloid compartment are more susceptible to lipopolysaccharide-induced sepsis. Our study thus identifies a distinct cellular mechanism leading to endosomal NLRP3 recruitment and inflammasome activation.
Tribotronic control of an ionic boundary layer in operando extends the limits of lubrication
Authors: Reddy Akepati Bhaskar , Pilkington Georgia A. , Rutland Mark W. , Glavatskih Sergei
Published: November 2022

The effect of electric potential on the lubrication of a non-halogenated phosphonium orthoborate ionic liquid used as an additive in a biodegradable oil was studied. An in-house tribotronic system was built around an instrument designed to measure lubricant film thickness between a rolling steel ball and a rotating silica-coated glass disc. The application of an electric field between the steel ball and a set of customized counter-electrodes clearly induced changes in the thickness of the lubricant film: a marked decrease at negative potentials and an increase at positive potentials. Complementary neutron reflectivity studies demonstrated the intrinsic electroresponsivity of the adsorbate: this was performed on a gold-coated silicon block and made possible in the same lubricant system by deuterating the oil. The results indicate that the anions, acting as anchors for the adsorbed film on the steel surface, are instrumental in the formation of thick and robust lubricating ionic boundary films. The application of a high positive potential, outside the electrochemical window, resulted in an enormous boost to film thickness, implicating the formation of ionic multi-layers and demonstrating the plausibility of remote control of failing contacts in inaccessible machinery, such as offshore wind and wave power installations.
Mechanical properties and acoustic emission analysis of desert sand concrete reinforced with steel fiber
Authors: Qu Changwei , Qin Yongjun , Luo Ling , Zhang Liangliang
Published: November 2022

In this study, to reduce the consumption of natural sand and improve the utilization rate of desert sand in western China, while preparing 14 groups of samples, desert sand is used to replace natural sand by the ratio of 20%, 40%, and 60%, and steel fiber is mixed with volume fraction 0.5%, 1.0%, 1.5%, and 2.0%. The mechanical properties of the specimens, including compressive strength, splitting tensile strength, and axial compressive strength were tested. Besides, the microstructures of the samples were analyzed by SEM, XRD, and acoustic emission detection technologies to identify the damage process. The results show that the desert sand can refine the microstructure and fill the pores, and it has good comprehensive properties at a 40% substitution rate. The compression properties of specimens are not apparently improved, but the tensile strength and deformation properties are significantly improved. The steel fiber with 1.5 vol% content behaves better, and the 28d compressive strength of the optimized group reaches 58.7 MPa. As a result, the polynomial fitting degree of total AE hits and stress level receives a more incredible goodness (R2) value than 0.96. The strength characteristics of steel fiber-desert sand concrete (SFDSC) can meet the demands of C40 concrete, and this research can provide a reference for engineers using desert sand in their designs.
Physics inspired compact modelling of $$\hbox {BiFeO}_3$$ based memristors
Authors: Yarragolla Sahitya , Du Nan , Hemke Torben , Zhao Xianyue , Chen Ziang , Polian Ilia , Mussenbrock Thomas
Published: November 2022

With the advent of the Internet of Things, nanoelectronic devices or memristors have been the subject of significant interest for use as new hardware security primitives. Among the several available memristors, BiFe$$\mathrm{O}_{3}$$

O
3

 (BFO)-based electroforming-free memristors have attracted considerable attention due to their excellent properties, such as long retention time, self-rectification, intrinsic stochasticity, and fast switching. They have been actively investigated for use in physical unclonable function (PUF) key storage modules, artificial synapses in neural networks, nonvolatile resistive switches, and reconfigurable logic applications. In this work, we present a physics-inspired 1D compact model of a BFO memristor to understand its implementation for such applications (mainly PUFs) and perform circuit simulations. The resistive switching based on electric field-driven vacancy migration and intrinsic stochastic behaviour of the BFO memristor are modelled using the cloud-in-a-cell scheme. The experimental current–voltage characteristics of the BFO memristor are successfully reproduced. The response of the BFO memristor to changes in electrical properties, environmental properties (such as temperature) and stress are analyzed and consistant with experimental results.
Novice-performed point-of-care ultrasound for home-based imaging
Authors: Duggan Nicole M. , Jowkar Nick , Ma Irene W. Y. , Schulwolf Sara , Selame Lauren A. , Fischetti Chanel E. , Kapur Tina , Goldsmith Andrew J.
Published: November 2022

Patient-performed point-of-care ultrasound (POCUS) may be feasible for use in home-based healthcare. We investigated whether novice users can obtain lung ultrasound (LUS) images via self-scanning with similar interpretability and quality as experts. Adult participants with no prior medical or POCUS training, who were capable of viewing PowerPoint slides in their home and who could hold a probe to their chest were recruited. After training, volunteers self-performed 8-zone LUS and saved images using a hand-held POCUS device in their own home. Each 8-zone LUS scan was repeated by POCUS experts. Clips were independently viewed and scored by POCUS experts blinded to performing sonographers. Quality and interpretability scores of novice- and expert-obtained LUS images were compared. Thirty volunteers with average age of 42.8 years (Standard Deviation (SD) 15.8), and average body mass index of 23.7 (SD 3.1) were recruited. Quality of novice and expert scans did not differ (median score 2.6, interquartile range (IQR) 2.3–2.9 vs. 2.8, IQR 2.3–3.0, respectively p = 0.09). Individual zone quality also did not differ (P > 0.05). Interpretability of LUS was similar between expert and novice scanners (median 7 zones interpretable, IQR 6–8, for both groups, p = 0.42). Interpretability of novice-obtained scans did not differ from expert scans (median 7 out of 8 zones, IQR 6–8, p = 0.42). Novice-users can self-obtain interpretable, expert-quality LUS clips with minimal training. Patient-performed LUS may be feasible for outpatient home monitoring.
Perceived safety in human–cobot interaction for fixed-path and real-time motion planning algorithms
Authors: Tusseyeva Inara , Oleinikov Artemiy , Sandygulova Anara , Rubagotti Matteo
Published: November 2022

This study investigates how different motion planning algorithms, implemented on a collaborative robot (cobot), are perceived by 48 human subjects. The four implemented algorithms ensure human safety based on the concept ofspeed and separation monitoring, but differ based on the following characteristics: (a) the cobot motion happens either along a fixed path or with a trajectory that is continuously planned in real time via nonlinear model predictive control, to increase cobot productivity; (b) the cobot speed is further reduced—or not—in real time based on heart rate measurements, to increase perceived safety. We conclude that (1) using a fixed path—compared to real-time motion planning—may reduce productivity and, at least when heart rate measurements are not used to modify the cobot speed, increases perceived safety; (2) reducing cobot speed based on heart rate measurements reduces productivity but does not improve perceived safety; (3) perceived safety is positively affected by habituation during the experiment, and unaffected by previous experience.
Characterization of a new potent and long-lasting single chain peptide agonist of RXFP1 in cells and in vivo translational models
Authors: Illiano Stephane , Poirier Bruno , Minoletti Claire , Pasquier Olivier , Riva Laurence , Chenede Xavier , Menguy Isabelle , Guillotel Michel , Prigent Philippe , Le Claire Stéphane , Gillot Florence , Thill Gilbert , Lo Presti François , Corbier Alain , Le Bail Jean-Christophe , Grailhe Patrick , Monteagudo Edith , Ingenito Raffaele , Bianchi Elisabetta , Philippo Christophe , Duclos Olivier , Mallart Sergio , Bathgate Ross , Janiak Philip
Published: November 2022

Despite beneficial effects in acute heart failure, the full therapeutic potential of recombinant relaxin-2 has been hampered by its short half-life and the need for intravenous administration limiting its use to intensive care units. A multiparametric optimization of the relaxin B-chain led to the identification of single chain lipidated peptide agonists of RXFP1 like SA10SC-RLX with subcutaneous bioavailability and extended half-life. SA10SC-RLX has sub nanomolar activity on cells expressing human RXFP1 and molecular modeling associated with the study of different RXFP1 mutants was used to decipher the mechanism of SA10SC-RLX interaction with RXFP1. Telemetry was performed in rat where SA10SC-RLX was able to engage RXFP1 after subcutaneous administration without tachyphylaxis after repeated dosing. Renal blood flow was then used as a translational model to evaluate RXFP1 activation. SA10SC-RLX increased renal blood flow and decreased renal vascular resistance in rats as reported for relaxin in humans. In conclusion, SA10SC-RLX mimics relaxin activity in in vitro and in vivo models of acute RXFP1 engagement. SA10SC-RLX represents a new class of long-lasting RXFP1 agonist, suitable for once daily subcutaneous administration in patients and potentially paving the way to new treatments for chronic fibrotic and cardiovascular diseases.
Exposing intracellular molecular changes during the differentiation of human-induced pluripotent stem cells into erythropoietin-producing cells using Raman spectroscopy and imaging
Authors: Ishigaki Mika , Hitomi Hirofumi , Ozaki Yukihiro , Nishiyama Akira
Published: November 2022

The objective of this study was to explore intracellular molecular changes during the differentiation of human-induced pluripotent stem cells (iPSCs) into erythropoietin (EPO)-producing cells using Raman spectroscopy and imaging. Raman imaging data of fixed cells at four stages of cell differentiation were analyzed by a partial least squares (PLS) regression model, and the variations in the intracellular molecular compositions with cell differentiation were investigated. As a result, three biomarkers characterizing the cell phases were identified: dimethyl sulfoxide (DMSO), fatty acids with a low grade of unsaturation, and glycoproteins. The uptake of DMSO by EPO-producing cells, which was added into a culture medium as an inducer for cell differentiation, was detected, and the increase in unsaturated fatty acid concentrations was revealed that lipid metabolism changed over the course of cell differentiation. The decrease in the glycoprotein concentration after the cell phase during which iPSCs differentiated into EPO-producing cells was also made clear. Raman imaging successfully visualized chemical images of these three biomarkers in two dimensions, where the biomarker concentrations independently varied during cell differentiation. These results demonstrated the application potential of the proposed method to regenerative medicine for monitoring cell differentiation and discriminating cell maturation in situ at the molecular level.
Double-layer polarization-independent achromatic metasurface array for optical fiber bundle coupling in microendoscope
Authors: Sun Yan , Wang Chang , Zheng Shuhang , Tao Xiao , Liu Xinyu , Li Yong , Wu Fei , Zheng Zhenrong
Published: November 2022

Optical fiber bundle-based microendoscope, which is significant in clinical diagnosis and industrial detection, calls for miniaturization of the probe and high-resolution observation. Here, we propose a double-layer metasurface array borrowing the structures of insect compound eyes to meet both requirements instead of traditional optical components. Each unit in the array aims for an incident field of view, focusing light at the center of the fiber end face with no chromatic aberration at the wavelengths of 470 nm, 530 nm and 630 nm. The metasurface array is composed of a series of isotropic TiO2 nanopillars which are special selected after considering resonance mode and angular dispersion characteristics, etched on both sides of a silica substrate, with the individual functions of deflecting and focusing. In image space, numerical aperture (NA) is 0.287 and the particular layout of two layers achieve zero telecentricity theoretically, which meet the requirements of optical fiber bundle coupling. A unit for incident angle of 20° is shown to validate our design approach numerically, which obtains a focused spot close to the diffraction limit. The compact and ultrathin metasurface could greatly reduce the size of the probe in optical fiber bundle based microendoscope while ensuring the imaging quality.
A draft chromosome-scale genome assembly of a commercial sugarcane
Authors: Shearman Jeremy R. , Pootakham Wirulda , Sonthirod Chutima , Naktang Chaiwat , Yoocha Thippawan , Sangsrakru Duangjai , Jomchai Nukoon , Tongsima Sissades , Piriyapongsa Jittima , Ngamphiw Chumpol , Wanasen Nanchaya , Ukoskit Kittipat , Punpee Prapat , Klomsa-ard Peeraya , Sriroth Klanarong , Zhang Jisen , Zhang Xingtan , Ming Ray , Tragoonrung Somvong , Tangphatsornruang Sithichoke
Published: November 2022

Sugarcane accounts for a large portion of the worlds sugar production. Modern commercial cultivars are complex hybrids ofS. officinarum,S. spontaneum, and several otherSaccharumspecies, resulting in an auto-allopolyploid with 8–12 copies of each chromosome. The current genome assembly gold standard is to generate a long read assembly followed by chromatin conformation capture sequencing to scaffold. We used the PacBio RSII and chromatin conformation capture sequencing to sequence and assemble the genome of a South East Asian commercial sugarcane cultivar, known as Khon Kaen 3. The Khon Kaen 3 genome assembled into 104,477 contigs totalling 7 Gb, which scaffolded into 56 pseudochromosomes containing 5.2 Gb of sequence. Genome annotation produced 242,406 genes from 30,927 orthogroups. Aligning the Khon Kaen 3 genome sequence toS. officinarumandS. spontaneumrevealed a high level of apparent recombination, indicating a chimeric assembly. This assembly error is explained by high nucleotide identity betweenS. officinarumandS. spontaneum, where 91.8% ofS. spontaneumaligns toS. officinarumat 94% identity. Thus, the subgenomes of commercial sugarcane are so similar that using short reads to correct long PacBio reads produced chimeric long reads. Future attempts to sequence sugarcane must take this information into account.
Phylogeny and biogeography of Indochinese freshwater mussels in the genus Pilsbryoconcha Simpson, 1900 (Bivalvia: Unionidae) with descriptions of four new species
Authors: Jeratthitikul Ekgachai , Paphatmethin Siwanon , Sutcharit Chirasak , Ngor Peng Bun , Inkhavilay Khamla , Prasankok Pongpun
Published: November 2022

The body of knowledge regarding the classification and evolution of freshwater mussels in the family Unionidae (Bivalvia) in Indochina has recently increased. However, the taxonomic revision of all extant taxa in the region is still ongoing. In this study, the genus Pilsbryoconcha was revised based on an integrative analysis of shell morphology, biogeography, and molecular data. Multi-locus phylogeny indicated the availability of eight species within the genus. Four previously recognized species are P. exilis (Lea, 1838), P. schomburgki (Martens, 1860) stat. rev., P. linguaeformis (Morelet, 1875), and P. carinifera (Conrad, 1837), while four other species are described herein as P. acuta sp. nov., P. mekongiana sp. nov., P. kittitati sp. nov., and P. hoikaab sp. nov. In addition, the neotype of P. carinifera is also designated to clarify its long taxonomic ambiguity. Divergent time estimation and historical biogeography analysis revealed that Pilsbryoconcha originated in the area now called the Khorat Plateau around the middle of the Eocene (mean age = 43.12 Mya), before its range was expanded across Indochina through a series of complex geomorphological changes of river systems, which also led to diversification of the genus.
The causal relationship between psoriasis, psoriatic arthritis, and inflammatory bowel diseases
Authors: Sun Yang , Li Yue , Zhang Jiting
Published: November 2022

Psoriasis is more common in patients with inflammatory bowel disease (IBD) than in the general population. Similarly, patients with psoriasis or psoriatic arthritis (PsA) have a higher incidence of IBD. However, whether this association is causal remains unknown. Therefore, we used a two-sample bidirectional Mendelian randomization (MR) analysis to identify this relationship. According to MR analysis, psoriasis and PsA causally increased the odds of developing Crohn’s disease (OR = 1.350 (1.066–1.709)P = 0.013; OR = 1.319 (1.166–1.492)P < 0.001). In contrast, MR estimates gave little support to a possible causal effect of psoriasis, PsA, on ulcerative colitis (OR = 1.101 (0.905–1.340)P = 0.335; OR = 1.007 (0.941–1.078)P = 0.831). Similarly, the reverse analysis suggested the Crohn’s disease causally increased the odds of psoriasis and PsA (OR = 1.425 (1.174–1.731)P < 0.001; OR = 1.448 (1.156–1.182)P = 0.001), whereas there are no causal association between ulcerative colitis and psoriasis, PsA (OR = 1.192 (0.921–1.542)P = 0.182; OR = 1.166 (0.818–1.664)P = 0.396). In summary, our MR analysis strengthens the evidence for the bidirectional dual causality between psoriasis (including PsA) and Crohn’s disease.
Hypertension and associated factors in HIV-infected patients receiving antiretroviral treatment in Burundi: a cross-sectional study
Authors: Harimenshi Déo , Niyongabo Théodore , Preux Pierre-Marie , Aboyans Victor , Desormais Ileana
Published: November 2022

Currently, the life expectancy of people living with the human immunodeficiency virus (HIV) and the general population are similar. Hypertension is a major public health issue in Africa and is largely underdiagnosed. Most HIV-infected individuals, especially those on Anti-Retroviral Therapy (ART) have hypertension. Our project aims to determine the prevalence of hypertension and associated factors amongst HIV-infected adults treated by ART in Burundi. A cross-sectional study was conducted among HIV-infected subjects over the age of 20, managed in five healthcare centers for people living with HIV (PLWH). The World Health Organization STEPWISE survey and anthropometric measurements were employed. Blood pressure was measured according to the ESC 2018 recommendations. 1 250 HIV-infected patients aged between 35.4 and 50.2 years were included (18.4% men). The prevalence of hypertension was 17.4% (95% CI 13.2–22.1). Approximately 47.25% of HIV patients with hypertension were previously undiagnosed. Other factors were associated with HTN, such as being overweight (OR 2.88; 95% CI 1.46–5.62), obesity (OR 2.65; 95% CI 1.27–5.55), longer duration of HIV infection: ≥ 10 years (OR 1.04; 95% CI 1.14–3.20), diabetes (OR 2.1; 95% CI 1.37–3.32) and age (OR 1.13; 95% CI 1.09–1.14). Despite their young age, almost 20% of HIV-ART treated patients had hypertension, 50% of these were undiagnosed. Blood pressure monitoring is crucial in these patients, especially those identified as high-risk, with prompt life and disability-saving interventions.
High-performance parallel tandem MoTe2/perovskite solar cell based on reduced graphene oxide as hole transport layer
Authors: Gholipoor Mohammad , Solhtalab Nasrin , Mohammadi Mohammad Hosein
Published: November 2022

Recently, the impressive achievements accomplished in multijunction (tandem) perovskite solar cells have triggered a huge research effort to boost their performance. Here, using a three-dimensional (3D) finite element method (FEM) technique, we propose and investigate a parallel tandem PSCs consisting of two absorbing layers of MoTe2 and CH3NH3PbI3 with cascaded bandgaps to more efficiently use the near-infrared (NIR) solar spectrum. Endowed with a bandgap of about 1 eV, the MoTe2 layer in conjunction with a CH3NH3PbI3 layer is able to broaden the light absorption range of structure beyond the wavelength of 800 nm, up to 1200 nm. In addition to this, the MoTe2 material can not only appreciably harvest light even with a thickness as low as 20 nm due to their high absorption coefficient, but also make a perfect band alignment with the CH3NH3PbI3 layer. As a result, the proposed multijunction PCS yields a high power conversion efficiency (PCE) of 18.52% with a VOC of 0.83 V, Jsc of 26.25 mA/cm2, and FF of 0.84, which is considerably greater than its corresponding single-junction PSCs with PCE, VOC, Jsc, and FF of, 14.01%, 1.14 V, 15.20 mA/cm2, and 0.81, respectively. Furthermore, to mitigate the VOC loss caused by the low bandgap of MoTe2, we demonstrate an increase in VOC from 0.84 to 0.928 V and in PCE from 18.52% to 20.32%, when we replace a reduced graphene oxide (rGO) layer with Spiro-OMeTAD layer as a hole transport layer (HTL).