bluuebunny/crossref_metadata_2025 huggingface dataset:
MSI2 promotes translation of multiple IRES-containing oncogenes and virus to induce self-renewal of tumor initiating stem-like cells
Authors: Yeh Da-Wei , Zhao Xuyao , Siddique Hifzur R. , Zheng Mengmei , Choi Hye Yeon , Machida Tatsuya , Narayanan Padmini , Kou Yi , Punj Vasu , Tahara Stanley M. , Feldman Douglas E. , Chen Lin , Machida Keigo
Published: April 2023

RNA-binding protein Musashi 2 (MSI2) is elevated in several cancers and is linked to poor prognosis. Here, we tested if MSI2 promotes MYC and viral mRNA translation to induce self-renewal via an internal ribosome entry sequence (IRES). We performed RIP-seq using anti-MSI2 antibody in tumor-initiating stem-like cells (TICs). MSI2 binds the internal ribosome entry site (IRES)-containing oncogene mRNAs including MYC, JUN and VEGFA as well as HCV IRES to increase their synthesis and promote self-renewal and tumor-initiation at the post-transcriptional level. MSI2 binds a lncRNA to interfere with processing of a miRNA that reduced MYC translation in basal conditions. Deregulation of this integrated MSI2-lncRNA-MYC regulatory loop drives self-renewal and tumorigenesis through increased IRES-dependent translation of MYC mRNA. Overexpression of MSI2 in TICs promoted their self-renewal and tumor-initiation properties. Inhibition of MSI2-RNA binding reduced HCV IRES activity, viral replication and liver hyperplasia in humanized mice predisposed by virus infection and alcohol high-cholesterol high-fat diet. Together MSI2, integrating the MYC oncogenic pathway, can be employed as a therapeutic target in the treatment of HCC patients.
Macrophages mediate psoriasis via Mincle-dependent mechanism in mice
Authors: Tan Rui-zhi , Zhong Xia , Han Rang-yue , Xie Ke-huan , Jia Jian , Yang Ye , Cheng Mei , Yang Chun-yan , Lan Hui-yao , Wang Li
Published: April 2023

Psoriasis is currently considered to be an immune and inflammatory disease characterized by massive immune cells infiltration including macrophages. It has been reported that macrophage-inducible C-type lectin (Mincle) is essential to maintain the pro-inflammatory phenotype of M1 macrophages, however, its role and mechanisms in psoriasis remain largely unknown. A model of psoriasis was induced in mice by a daily topical application of imiquimod for 7 days. Role and mechanisms of Mincle in macrophage-mediated psoriasis were investigated in clodronate liposomes induced macrophage depletion mice followed by adoptively transferring with Mincle-expressing or -knockout (KO) macrophages, and in macrophage specific Mincle knockout mice (Mincleloxp/loxp/Lyz2-cre+/+). Finally, a Mincle neutralizing antibody was employed to the psoriasis mice to reveal the therapeutic potential for psoriasis by targeting Mincle. Mincle was highly expressed by M1 macrophages in the skin lesions of patients and mice with psoriasis. Clodronate liposomes-induced macrophage depletion inhibited psoriasis in mice, which was restored by adoptive transfer with Mincle-expressing macrophages but not by Mincle-KO macrophages. This was further confirmed in macrophage-specific Mincle-KO mice. Mechanistically, macrophages mediated psoriasis via the Mincle-Syk-NF-κB pathway as blocking macrophage Mincle inhibited Syk/NF-κB-driven skin lesions and epidermal injury in vivo and in vitro. We also found that LPS induced Mincle expression by M1 macrophages via the PU.1-dependent mechanism. Most importantly, we revealed that targeting Mincle with a neutralizing antibody significantly improved psoriasis in mice. In summary, our findings demonstrated that macrophages mediate psoriasis in mice via the Mincle-dependent mechanism, targeting Mincle may represent as a novel therapy for psoriasis.
An aptamer-based depot system for sustained release of small molecule therapeutics
Authors: Wang Dali , Li Yang , Deng Xiaoran , Torre Matthew , Zhang Zipei , Li Xiyu , Zhang Wei , Cullion Kathleen , Kohane Daniel S. , Weldon Christopher B.
Published: April 2023

Delivery of hydrophilic small molecule therapeutics by traditional drug delivery systems is challenging. Herein, we have used the specific interaction between DNA aptamers and drugs to create simple and effective drug depot systems. The specific binding of a phosphorothioate-modified aptamer to drugs formed non-covalent aptamer/drug complexes, which created a sustained release system. We demonstrated the effectiveness of this system with small hydrophilic molecules, the site 1 sodium channel blockers tetrodotoxin and saxitoxin. The aptamer-based delivery system greatly prolonged the duration of local anesthesia and reduced systemic toxicity. The beneficial effects of the aptamers were restricted to the compounds they were specific to. These studies establish aptamers as a class of highly specific, modifiable drug delivery systems, and demonstrate potential usefulness in the management of postoperative pain.
PeakDecoder enables machine learning-based metabolite annotation and accurate profiling in multidimensional mass spectrometry measurements
Authors: Bilbao Aivett , Munoz Nathalie , Kim Joonhoon , Orton Daniel J. , Gao Yuqian , Poorey Kunal , Pomraning Kyle R. , Weitz Karl , Burnet Meagan , Nicora Carrie D. , Wilton Rosemarie , Deng Shuang , Dai Ziyu , Oksen Ethan , Gee Aaron , Fasani Rick A. , Tsalenko Anya , Tanjore Deepti , Gardner James , Smith Richard D. , Michener Joshua K. , Gladden John M. , Baker Erin S. , Petzold Christopher J. , Kim Young-Mo , Apffel Alex , Magnuson Jon K. , Burnum-Johnson Kristin E.
Published: April 2023

Multidimensional measurements using state-of-the-art separations and mass spectrometry provide advantages in untargeted metabolomics analyses for studying biological and environmental bio-chemical processes. However, the lack of rapid analytical methods and robust algorithms for these heterogeneous data has limited its application. Here, we develop and evaluate a sensitive and high-throughput analytical and computational workflow to enable accurate metabolite profiling. Our workflow combines liquid chromatography, ion mobility spectrometry and data-independent acquisition mass spectrometry with PeakDecoder, a machine learning-based algorithm that learns to distinguish true co-elution and co-mobility from raw data and calculates metabolite identification error rates. We apply PeakDecoder for metabolite profiling of various engineered strains ofAspergillus pseudoterreus, Aspergillus niger, Pseudomonas putidaandRhodosporidium toruloides. Results, validated manually and against selected reaction monitoring and gas-chromatography platforms, show that 2683 features could be confidently annotated and quantified across 116 microbial sample runs using a library built from 64 standards.
Pain-causing stinging nettle toxins target TMEM233 to modulate NaV1.7 function
Authors: Jami Sina , Deuis Jennifer R. , Klasfauseweh Tabea , Cheng Xiaoyang , Kurdyukov Sergey , Chung Felicity , Okorokov Andrei L. , Li Shengnan , Zhang Jiangtao , Cristofori-Armstrong Ben , Israel Mathilde R. , Ju Robert J. , Robinson Samuel D. , Zhao Peng , Ragnarsson Lotten , Andersson Åsa , Tran Poanna , Schendel Vanessa , McMahon Kirsten L. , Tran Hue N. T. , Chin Yanni K.-Y. , Zhu Yifei , Liu Junyu , Crawford Theo , Purushothamvasan Saipriyaa , Habib Abdella M. , Andersson David A. , Rash Lachlan D. , Wood John N. , Zhao Jing , Stehbens Samantha J. , Mobli Mehdi , Leffler Andreas , Jiang Daohua , Cox James J. , Waxman Stephen G. , Dib-Hajj Sulayman D. , Neely G. Gregory , Durek Thomas , Vetter Irina
Published: April 2023

Voltage-gated sodium (NaV) channels are critical regulators of neuronal excitability and are targeted by many toxins that directly interact with the pore-forming α subunit, typically via extracellular loops of the voltage-sensing domains, or residues forming part of the pore domain. Excelsatoxin A (ExTxA), a pain-causing knottin peptide from the Australian stinging tree Dendrocnide excelsa, is the first reported plant-derived NaV channel modulating peptide toxin. Here we show that TMEM233, a member of the dispanin family of transmembrane proteins expressed in sensory neurons, is essential for pharmacological activity of ExTxA at NaV channels, and that co-expression of TMEM233 modulates the gating properties of NaV1.7. These findings identify TMEM233 as a previously unknown NaV1.7-interacting protein, position TMEM233 and the dispanins as accessory proteins that are indispensable for toxin-mediated effects on NaV channel gating, and provide important insights into the function of NaV channels in sensory neurons.
Navigating surface reconstruction of spinel oxides for electrochemical water oxidation
Authors: Sun Yuanmiao , Wang Jiarui , Xi Shibo , Shen Jingjing , Luo Songzhu , Ge Jingjie , Sun Shengnan , Chen Yubo , Hanna John V. , Li Shuzhou , Wang Xin , Xu Zhichuan J.
Published: April 2023

Understanding and mastering the structural evolution of water oxidation electrocatalysts lays the foundation to finetune their catalytic activity. Herein, we demonstrate that surface reconstruction of spinel oxides originates from the metal-oxygen covalency polarity in the MT–O–MO backbone. A stronger MO–O covalency relative to MT–O covalency is found beneficial for a more thorough reconstruction towards oxyhydroxides. The structure-reconstruction relationship allows precise prediction of the reconstruction ability of spinel pre-catalysts, based on which the reconstruction degree towards the in situ generated oxyhydroxides can be controlled. The investigations of oxyhydroxides generated from spinel pre-catalysts with the same reconstruction ability provide guidelines to navigate the cation selection in spinel pre-catalysts design. This work reveals the fundamentals for manipulating the surface reconstruction of spinel pre-catalysts for water oxidation.
A point mutation in recC associated with subclonal replacement of carbapenem-resistant Klebsiella pneumoniae ST11 in China
Authors: Zhou Kai , Xue Chun-Xu , Xu Tingting , Shen Ping , Wei Sha , Wyres Kelly L. , Lam Margaret M. C. , Liu Jinquan , Lin Haoyun , Chen Yunbo , Holt Kathryn E. ,   the BRICS Working Group, Chen Yunbo , Ding Hui , Liu Yongyun , Mao Haifeng , Huang Ying , Yang Zhenghai , Dai Yuanyuan , Liao Guolin , Zhu Lisha , Zhang Liping , Li Yanhong , Xu Hongyun , Cao Junmin , Zhang Baohua , Guo Liang , Dong Haixin , Hu Shuyan , Man Sijin , Wang Lu , Liao Zhixiang , Xu Rong , Liu Dan , Jin Yan , Zhou Yizheng , Liao Yiqun , Chen Fenghong , Gu Beiqing , Wang Jiliang , Liang Jinhua , Zheng Lin , Li Aiyun , Shen Jilu , Dong Yinqiao , Zhang Lixia , Hu Hongxia , Quan Bo , Zhu Wencheng , Liang Kunpeng , Liu Qiang , Wang Shifu , Yan Xiaoping , Kang Jiangbang , Xia Xiusan , Ma Lan , Sun Li , Luan Liang , Wang Jianzhong , Lin Haoyun , Li Zhuo , Qiao Dengyan , Zhang Lin , Wan Chuandan , Qi Xiaoyan , Du Fei , Xiao Yonghong
Published: April 2023

Adaptation to selective pressures is crucial for clinically important pathogens to establish epidemics, but the underlying evolutionary drivers remain poorly understood. The current epidemic of carbapenem-resistant Klebsiella pneumoniae (CRKP) poses a significant threat to public health. In this study we analyzed the genome sequences of 794 CRKP bloodstream isolates collected in 40 hospitals in China between 2014 and 2019. We uncovered a subclonal replacement in the predominant clone ST11, where the previously prevalent subclone OL101:KL47 was replaced by O2v1:KL64 over time in a stepwise manner. O2v1:KL64 carried a higher load of mobile genetic elements, and a point mutation exclusively detected in the recC of O2v1:KL64 significantly promotes recombination proficiency. The epidemic success of O2v1:KL64 was further associated with a hypervirulent sublineage with enhanced resistance to phagocytosis, sulfamethoxazole-trimethoprim, and tetracycline. The phenotypic alterations were linked to the overrepresentation of hypervirulence determinants and antibiotic genes conferred by the acquisition of an rmpA-positive pLVPK-like virulence plasmid and an IncFII-type multidrug-resistant plasmid, respectively. The dissemination of the sublineage was further promoted by more frequent inter-hospital transmission. The results collectively demonstrate that the expansion of O2v1:KL64 is correlated to a repertoire of genomic alterations convergent in a subpopulation with evolutionary advantages.
Single-atomic platinum on fullerene C60 surfaces for accelerated alkaline hydrogen evolution
Authors: Zhang Ruiling , Li Yaozhou , Zhou Xuan , Yu Ao , Huang Qi , Xu Tingting , Zhu Longtao , Peng Ping , Song Shuyan , Echegoyen Luis , Li Fang-Fang
Published: April 2023

The electrocatalytic hydrogen evolution reaction (HER) is one of the most studied and promising processes for hydrogen fuel generation. Single-atom catalysts have been shown to exhibit ultra-high HER catalytic activity, but the harsh preparation conditions and the low single-atom loading hinder their practical applications. Furthermore, promoting hydrogen evolution reaction kinetics, especially in alkaline electrolytes, remains as an important challenge. Herein, Pt/C60 catalysts with high-loading, high-dispersion single-atomic platinum anchored on C60 are achieved through a room-temperature synthetic strategy. Pt/C60-2 exhibits high HER catalytic performance with a low overpotential (η10) of 25 mV at 10 mA cm−2. Density functional theory calculations reveal that the Pt-C60 polymeric structures in Pt/C60-2 favors water adsorption, and the shell-like charge redistribution around the Pt-bonding region induced by the curved surfaces of two adjacent C60 facilitates the desorption of hydrogen, thus favoring fast reaction kinetics for hydrogen evolution.
An interactive murine single-cell atlas of the lung responses to radiation injury
Authors: Curras-Alonso Sandra , Soulier Juliette , Defard Thomas , Weber Christian , Heinrich Sophie , Laporte Hugo , Leboucher Sophie , Lameiras Sonia , Dutreix Marie , Favaudon Vincent , Massip Florian , Walter Thomas , Mueller Florian , Londoño-Vallejo José-Arturo , Fouillade Charles
Published: April 2023

Radiation Induced Lung Injury (RILI) is one of the main limiting factors of thorax irradiation, which can induce acute pneumonitis as well as pulmonary fibrosis, the latter being a life-threatening condition. The order of cellular and molecular events in the progression towards fibrosis is key to the physiopathogenesis of the disease, yet their coordination in space and time remains largely unexplored. Here, we present an interactive murine single cell atlas of the lung response to irradiation, generated from C57BL6/J female mice. This tool opens the door for exploration of the spatio-temporal dynamics of the mechanisms that lead to radiation-induced pulmonary fibrosis. It depicts with unprecedented detail cell type-specific radiation-induced responses associated with either lung regeneration or the failure thereof. A better understanding of the mechanisms leading to lung fibrosis will help finding new therapeutic options that could improve patients’ quality of life.
USP7 controls NGN3 stability and pancreatic endocrine lineage development
Authors: Manea Teodora , Nelson Jessica Kristine , Garrone Cristina Maria , Hansson Karin , Evans Ian , Behrens Axel , Sancho Rocio
Published: April 2023

Understanding the factors and mechanisms involved in beta-cell development will guide therapeutic efforts to generate fully functional beta cells for diabetes. Neurogenin 3 (NGN3) is the key transcription factor that marks endocrine progenitors and drives beta-cell differentiation. Here we screen for binding partners of NGN3 and identify the deubiquitylating enzyme USP7 as a key regulator of NGN3 stability. Mechanistically, USP7 interacts with, deubiquitinates and stabilizes NGN3. In vivo, conditional knockout of Usp7 in the mouse embryonic pancreas causes a dramatic reduction in islet formation and hyperglycemia in adult mice, due to impaired NGN3-mediated endocrine specification during pancreatic development. Furthermore, pharmacological inhibition of USP7 during endocrine specification in human iPSC models of beta-cell differentiation decreases NGN3 expressing progenitor cell numbers and impairs beta cell differentiation. Thus, the USP7-NGN3 axis is an essential mechanism for driving endocrine development and beta-cell differentiation, which can be therapeutically exploited.
Quantum microscopy of cells at the Heisenberg limit
Authors: He Zhe , Zhang Yide , Tong Xin , Li Lei , Wang Lihong V.
Published: April 2023

Entangled biphoton sources exhibit nonclassical characteristics and have been applied to imaging techniques such as ghost imaging, quantum holography, and quantum optical coherence tomography. The development of wide-field quantum imaging to date has been hindered by low spatial resolutions, speeds, and contrast-to-noise ratios (CNRs). Here, we present quantum microscopy by coincidence (QMC) with balanced pathlengths, which enables super-resolution imaging at the Heisenberg limit with substantially higher speeds and CNRs than existing wide-field quantum imaging methods. QMC benefits from a configuration with balanced pathlengths, where a pair of entangled photons traversing symmetric paths with balanced optical pathlengths in two arms behave like a single photon with half the wavelength, leading to a two-fold resolution improvement. Concurrently, QMC resists stray light up to 155 times stronger than classical signals. The low intensity and entanglement features of biphotons in QMC promise nondestructive bioimaging. QMC advances quantum imaging to the microscopic level with significant improvements in speed and CNR toward the bioimaging of cancer cells. We experimentally and theoretically prove that the configuration with balanced pathlengths illuminates an avenue for quantum-enhanced coincidence imaging at the Heisenberg limit.
A visual opsin from jellyfish enables precise temporal control of G protein signalling
Authors: van Wyk Michiel , Kleinlogel Sonja
Published: April 2023

Phototransduction is mediated by distinct types of G protein cascades in different animal taxa: bilateral invertebrates typically utilise the Gαq pathway whereas vertebrates typically utilise the Gαt(i/o) pathway. By contrast, photoreceptors in jellyfish (Cnidaria) utilise the Gαs intracellular pathway, similar to olfactory transduction in mammals1. How this habitually slow pathway has adapted to support dynamic vision in jellyfish remains unknown. Here we study a light-sensing protein (rhodopsin) from the box jellyfish Carybdea rastonii and uncover a mechanism that dramatically speeds up phototransduction: an uninterrupted G protein-coupled receptor – G protein complex. Unlike known G protein-coupled receptors (GPCRs), this rhodopsin constitutively binds a single downstream Gαs partner to enable G-protein activation and inactivation within tens of milliseconds. We use this GPCR in a viral gene therapy to restore light responses in blind mice.
Liquid sculpture and curing of bio-inspired polyelectrolyte aqueous two-phase systems
Authors: Zhang Chongrui , Liu Xufei , Gong Jiang , Zhao Qiang
Published: April 2023

Aqueous two-phase systems (ATPS) provide imperative interfaces and compartments in biology, but the sculpture and conversion of liquid structures to functional solids is challenging. Here, inspired by phase evolution of mussel foot proteins ATPS, we tackle this problem by designing poly(ionic liquids) capable of responsive condensation and phase-dependent curing. When mixed with poly(dimethyl diallyl ammonium chloride), the poly(ionic liquids) formed liquid condensates and ATPS, which were tuned into bicontinuous liquid phases under stirring. Selective, rapid curing of the poly(ionic liquids)-rich phase was facilitated under basic conditions (pH 11), leading to the liquid-to-gel conversion and structure sculpture, i.e., the evolution from ATPS to macroporous sponges featuring bead-and-string networks. This mechanism enabled the selective embedment of carbon nanotubes in the poly(ionic liquids)-rich phase, which showed exceptional stability in harsh conditions (10 wt% NaCl, 80 oC, 3 days) and high (2.5 kg/m2h) solar thermal desalination of concentrated salty water under 1-sun irradiation.
Rational engineering of lung alveolar epithelium
Authors: Leiby Katherine L. , Yuan Yifan , Ng Ronald , Raredon Micha Sam Brickman , Adams Taylor S. , Baevova Pavlina , Greaney Allison M. , Hirschi Karen K. , Campbell Stuart G. , Kaminski Naftali , Herzog Erica L. , Niklason Laura E.
Published: April 2023

Engineered whole lungs may one day expand therapeutic options for patients with end-stage lung disease. However, the feasibility of ex vivo lung regeneration remains limited by the inability to recapitulate mature, functional alveolar epithelium. Here, we modulate multimodal components of the alveolar epithelial type 2 cell (AEC2) niche in decellularized lung scaffolds in order to guide AEC2 behavior for epithelial regeneration. First, endothelial cells coordinate with fibroblasts, in the presence of soluble growth and maturation factors, to promote alveolar scaffold population with surfactant-secreting AEC2s. Subsequent withdrawal of Wnt and FGF agonism synergizes with tidal-magnitude mechanical strain to induce the differentiation of AEC2s to squamous type 1 AECs (AEC1s) in cultured alveoli, in situ. These results outline a rational strategy to engineer an epithelium of AEC2s and AEC1s contained within epithelial-mesenchymal-endothelial alveolar-like units, and highlight the critical interplay amongst cellular, biochemical, and mechanical niche cues within the reconstituting alveolus.
Dataset of theoretical multinary perovskite oxides
Authors: Bare Zachary J. L. , Morelock Ryan J. , Musgrave Charles B.
Published: April 2023

Perovskite oxides (ternary chemical formula ABO3) are a diverse class of materials with applications including heterogeneous catalysis, solid-oxide fuel cells, thermochemical conversion, and oxygen transport membranes. However, their multicomponent (chemical formula$${A}_{x}{A}_{1-x}^{\text{'}}{B}_{y}{B}_{1-y}^{\text{'}}{O}_{3}$$AxA1−x'ByB1−y'O3) chemical space is underexplored due to the immense number of possible compositions. To expand the number of computed$${A}_{x}{A}_{1-x}^{{\prime} }{B}_{y}{B}_{1-y}^{{\prime} }{O}_{3}$$AxA1−x′ByB1−y′O3compounds we report a dataset of 66,516 theoretical multinary oxides, 59,708 of which are perovskites. First, 69,407$${A}_{0.5}{A}_{0.5}^{{\prime} }{B}_{0.5}{B}_{0.5}^{{\prime} }{O}_{3}$$A0.5A0.5′B0.5B0.5′O3compositions were generated in thea−b+a−Glazer tilting mode using the computationally-inexpensive Structure Prediction and Diagnostic Software (SPuDS) program. Next, we optimized these structures with density functional theory (DFT) using parameters compatible with the Materials Project (MP) database. Our dataset contains these optimized structures and their formation (ΔHf) and decomposition enthalpies (ΔHd) computed relative to MP tabulated elemental references and competing phases, respectively. This dataset can be mined, used to train machine learning models, and rapidly and systematically expanded by optimizing more SPuDS-generated$${A}_{0.5}{A}_{0.5}^{{\prime} }{B}_{0.5}{B}_{0.5}^{{\prime} }{O}_{3}$$A0.5A0.5′B0.5B0.5′O3perovskite structures using MP-compatible DFT calculations.
Gene sequencing and result analysis of balanced translocation carriers by third-generation gene sequencing technology
Authors: Zeng Xiaoqi , Lin Dandan , Liang Danhong , Huang Jingwen , Yi Jinsong , Lin Dianliang , Zhang Zhengmian
Published: April 2023

Because the total gene copy number remains constant and all genes are normally expressed, carriers of balanced chromosomal translocations usually have a normal phenotype but are able to produce many different types of gametes during meiosis, and unbalanced gametes lead to increased risks of infertility, recurrent spontaneous abortion, stillbirth, neonatal death or malformations and intellectual abnormalities in offspring. The key to balanced translocations lies in finding the breakpoints, but current genetic testing techniques are all short-read sequencing, with the disadvantage of procedural complexity and imprecision for precisely identifying the breakpoints. The latest third-generation sequencing technology overcomes these drawbacks and uses robust long-read sequencing to accurately and rapidly detect genome-wide information and identify breakpoint locations. In this paper, we performed whole genome long-read sequencing using an Oxford Nanopore sequencer to detect the breakpoints of 4 balanced chromosomal translocation carriers. The results showed that employing about ~ 10× coverage confirmed 6 of the 8 breakpoints, of which, 2 had microdeletions/insertions identified near the breakpoints and 4 had breakpoints that disrupted the normal gene structure and were simultaneously tested for genome-wide structural variation (SV). The results show that whole genome long-read sequencing is an efficient method for pinpointing translocation breakpoints and providing genome-wide information, which is essential for medical genetics and preimplantation genetic testing.
Establishing the root causes of unsafe behaviors among construction workers: an integrative interpretive structural modeling analysis
Authors: Sathvik S. , Krishnaraj L. , Awuzie Bankole Ostia
Published: April 2023

There has been a significant decline in worker productivity at construction sites globally owing to the increase in accidents and fatalities due to unsafe behavior among workers. Although many studies have explored the incidence of unsafe behaviors among construction workers, limited studies have attempted to evaluate the causal factors and to determine the root causes. An integrative interpretive structural modeling analysis of the interrelationships that exist between these causal factors established from relevant literature was conducted in this study to determine the root factors hence bridging this gap. Fifteen causal factors were identified through literature review, and the nature of interrelationships between them was determined using interpretive structural modeling (ISM) and a Cross-impact matrix multiplication applied to classification (MICMAC) analysis. Data was obtained from a purposively selected cohort of experts using semi-structured interviews. The emergent data was subsequently analyzed using the ISM and MICMAC analysis to ascertain the interrelationships between the causal factors. The results of the study showed that age, sleep quality, degree of interaction and workers’ skillsets were the root causes of unsafe behavior among construction workers. Besides engendering the establishment of the root causes of unsafe behavior among construction workers, the results of this study will facilitate the prioritization of appropriate solutions for tackling the menace.
MasitinibL shows promise as a drug-like analog of masitinib that elicits comparable SARS-Cov-2 3CLpro inhibition with low kinase preference
Authors: Durojaye Olanrewaju Ayodeji , Okoro Nkwachukwu Oziamara , Odiba Arome Solomon , Nwanguma Bennett Chima
Published: April 2023

SARS-CoV-2 infection has led to several million deaths worldwide and ravaged the economies of many countries. Hence, developing therapeutics against SARS-CoV-2 remains a core priority in the fight against COVID-19. Most of the drugs that have received emergency use authorization for treating SARS-CoV-2 infection exhibit a number of limitations, including side effects and questionable efficacy. This challenge is further compounded by reinfection after vaccination and the high likelihood of mutations, as well as the emergence of viral escape mutants that render SARS-CoV-2 spike glycoprotein-targeting vaccines ineffective. Employing de novo drug synthesis or repurposing to discover broad-spectrum antivirals that target highly conserved pathways within the viral machinery is a focus of current research. In a recent drug repurposing study, masitinib, a clinically safe drug against the human coronavirus OC43 (HCoV-OC43), was identified as an antiviral agent with effective inhibitory activity against the SARS-CoV-2 3CLpro. Masitinib is currently under clinical trial in combination with isoquercetin in hospitalized patients (NCT04622865). Nevertheless, masitinib has kinase-related side effects; hence, the development of masitinib analogs with lower anti–tyrosine kinase activity becomes necessary. In this study, in an attempt to address this limitation, we executed a comprehensive virtual workflow in silico to discover drug-like compounds matching selected pharmacophore features in the SARS-CoV-2 3CLpro-bound state of masitinib. We identified a novel lead compound, “masitinibL”, a drug-like analog of masitinib that demonstrated strong inhibitory properties against the SARS-CoV-2 3CLpro. In addition, masitinibL further displayed low selectivity for tyrosine kinases, which strongly suggests that masitinibL is a highly promising therapeutic that is preferable to masitinib.
Prognostic value of soluble PD-L1 and exosomal PD-L1 in advanced gastric cancer patients receiving systemic chemotherapy
Authors: Shin Kabsoo , Kim Joori , Park Se Jun , Lee Myung Ah , Park Jae Myung , Choi Myung-Gyu , Kang Donghoon , Song Kyo Young , Lee Han Hong , Seo Ho Seok , Lee Sung Hak , Kim Bohyun , Kim Okran , Park Juyeon , Kang Nahyeon , Kim In-Ho
Published: April 2023

The prognostic role of soluble PD-L1 (sPD-L1) and exosomal PD-L1 (exoPD-L1) in patients with gastric cancer (GC) receiving systemic chemotherapy remains unelucidated. Thus, we examined their prognostic significance in patients with advanced GC. Blood samples were obtained from 99 patients with advanced GC receiving first-line chemotherapy. Serum-derived exosomes were isolated by centrifugation and polymer precipitation. The correlation between serum-derived exoPD-L1, plasma sPD-L1, immune-related markers, and circulating immune cells was evaluated. Patients were divided into two groups according to pretreatment sPD-L1 and exoPD-L1 levels: low sPD-L1 and high sPD-L1 groups, low exoPD-L1 and high exoPD-L1 groups. Patients with low sPD-L1 level before treatment (< 9.32 pg/mL) showed significantly better overall survival (OS) and progression-free survival (PFS) than those with high sPD-L1 level (≥ 9.32 pg/mL). The low exoPD-L1 group (< 10.21 pg/mL) showed a tendency of longer PFS than the high exoPD-L1 group (≥ 10.21 pg/mL). Pretreatment sPD-L1 was an independent prognostic factor for OS in multivariate analysis. exoPD-L1 was associated with systemic inflammation markers, immunomodulatory cytokines, and T cells, while sPD-L1 was associated with tumor markers. Pretreatment plasma-derived sPD-L1 level could be used as a prognostic marker for patients receiving cytotoxic chemotherapy. Serum-derived exoPD-L1 may reflect the immunosuppressive state of patients with advanced GC.
Rapid short-pulses of focused ultrasound and microbubbles deliver a range of agent sizes to the brain
Authors: Lim Kee Chang William , Chan Tiffany G. , Raguseo Federica , Mishra Aishwarya , Chattenton Dani , de Rosales Rafael T. M. , Long Nicholas J. , Morse Sophie V.
Published: April 2023

Focused ultrasound and microbubbles can non-invasively and locally deliver therapeutics and imaging agents across the blood–brain barrier. Uniform treatment and minimal adverse bioeffects are critical to achieve reliable doses and enable safe routine use of this technique. Towards these aims, we have previously designed a rapid short-pulse ultrasound sequence and used it to deliver a 3 kDa model agent to mouse brains. We observed a homogeneous distribution in delivery and blood–brain barrier closing within 10 min. However, many therapeutics and imaging agents are larger than 3 kDa, such as antibody fragments and antisense oligonucleotides. Here, we evaluate the feasibility of using rapid short-pulses to deliver higher-molecular-weight model agents. 3, 10 and 70 kDa dextrans were successfully delivered to mouse brains, with decreasing doses and more heterogeneous distributions with increasing agent size. Minimal extravasation of endogenous albumin (66.5 kDa) was observed, while immunoglobulin (~ 150 kDa) and PEGylated liposomes (97.9 nm) were not detected. This study indicates that rapid short-pulses are versatile and, at an acoustic pressure of 0.35 MPa, can deliver therapeutics and imaging agents of sizes up to a hydrodynamic diameter between 8 nm (70 kDa dextran) and 11 nm (immunoglobulin). Increasing the acoustic pressure can extend the use of rapid short-pulses to deliver agents beyond this threshold, with little compromise on safety. This study demonstrates the potential for deliveries of higher-molecular-weight therapeutics and imaging agents using rapid short-pulses.
Impact of small boat sound on the listening space of Pempheris adspersa, Forsterygion lapillum, Alpheus richardsoni and Ovalipes catharus
Authors: Wilson Louise , Constantine Rochelle , Pine Matthew K. , Farcas Adrian , Radford Craig A.
Published: April 2023

Anthropogenic stressors, such as plastics and fishing, are putting coastal habitats under immense pressure. However, sound pollution from small boats has received little attention given the importance of sound in the various life history strategies of many marine animals. By combining passive acoustic monitoring, propagation modelling, and hearing threshold data, the impact of small-boat sound on the listening spaces of four coastal species was determined. Listening space reductions (LSR) were greater for fishes compared to crustaceans, for which LSR varied by day and night, due to their greater hearing abilities. Listening space also varied by sound modality for the two fish species, highlighting the importance of considering both sound pressure and particle motion. The theoretical results demonstrate that boat sound hinders the ability of fishes to perceive acoustic cues, advocating for future field-based research on acoustic cues, and highlighting the need for effective mitigation and management of small-boat sound within coastal areas worldwide.
Association between school environment with sedentary behavior and physical activity intensity in children
Authors: Sales Diego , da Silva Junior João Pedro , Bergamo Raiany Rosa , de Oliveira Luis Carlos , Ferrari Gerson , Matsudo Victor
Published: April 2023

We examined the association between indicators of the school environment with sedentary behavior and different intensities of physical activity in children. The study that included 515 children (265 boys) aged 9–11 years old from public and private schools in the city of São Caetano do Sul. Sedentary behavior and different intensities of physical activity were evaluated with an accelerometer. Inside school environment (policies, supervision committee, extracurricular activities, breaks, and access to school facilities) was evaluated using a questionnaire. Policies and practice (β: 8.49; 95% CI: 3.62–13.36), supervision committee (5.42; 0.64–10.19), inter-school competitions (2.40, 2.25–2.55), breaks of 15–29 min/day (6.87; 2.20–10.75), and outdoor sports field (5.40; 0.37–10.44), were positively associated with moderate-to-vigorous-intensity physical activity. Furthermore, crossing guards (7.65; 3.00–12.30) were positively associated with moderate-to-vigorous-intensity physical activity. We concluded that an association was found between school environment indicators with higher levels of physical activity and greater odds of meeting physical activity guidelines.
Enhancement of quasi-static compression strength for aluminum closed cell foam blocks shielded by aluminum tubes
Authors: Dadoura Mohamed H. , Farahat Ahmed Ismail Zaky , Taha M. R. , Elshaer Ramadan N.
Published: April 2023

Aluminum closed cell foam blocks are created with a volume of 1 inch3 which consist of aluminum foam parts shielded with part of aluminum tube and in some types reinforced with inner aluminum tubes. Blocks have been made to overcome some existing problems in metallic foam used to protect some applications parts from impacts as a sacrificial part. Metallic foam has three main categories sandwich panels, filled tubes and corrugated sheets. Quasi-static compression tests have been applied on 12 blocks with different shapes and compared with pure aluminum foam blocks as a reference. Results display the enhancement of mechanical properties of blocks like yield strength (SY), crushing strength (Sc) and densification strength (Sd), compression at strain 70%, as well as absorbed energy (area of compression under the curve). The highest value for yield strength (5.87 MPa) was registered for Finger phalanxes cube block (FP—0.1 Sq.). While the highest value for densification strength (21.7 MPa) was registered for spine cylinder block (SV8—0.17 C25). The registered results for samples apparent the highest value for energy dissipation density (Edd) is 40.52 J/in3 (91% enhancement) and crushing strength (8.61 MPa) was registered for Finger phalanx cylinder block (FP—0.17 C25). The lowest value for Edd is 14.16 J/in3 (less than pure aluminum foam block value by 33%), SY = 0.42 MPa, Sc = 3.21 MPa, and Sd = 4.46 MPa, registered for thin wall Ear canal cylinder block (EC8—0.075 C26.5). Best mechanical properties had been achieved for Finger phalanx cylinder block (FP—0.17 C25) and spine cylinder block (SV8—0.17 C25).
Smoking induces increased apoptosis in osteoblasts: changes in bone matrix organic components
Authors: Kohler Júlia Benini , da Silva Alex Ferreira , Farias Walleson Alves , Sampaio Barbara Fialho Carvalho , Neves Marco Aurélio Silveiro , Lima Leandro Gregorut , Lourenço Juliana Dias , Moreira Alyne Riani , Barbosa Alexandre Póvoa , de Fátima Lopes Calvo Tibério Iolanda , Teodoro Walcy Rosolia , dos Santos Lopes Fernanda Degobbi Tenorio Quirino
Published: April 2023

Clinical studies demonstrate the impact of smoking on bone tissue fragility and higher incidence of fractures. However, it is not totally understood which physiological mechanisms could be involved in these events. Previously, we showed important changes in bone tissue components in experimental model of cigarette smoke (CS) exposure. CS exposure induces worsening in bone mineralization and a decrease in collagen type I deposition, leading to bone fragility. Considering that the majority of clinical studies described bone structural changes by radiographic images, in this study we performed analyses “in situ” using tissue samples from smokers, former smokers and non-smokers to better understand how the increase in inflammatory mediators induced by smoking exposure could interfere in bone cells activity leading bone structural changes. We observed increased levels of IL-1β, IL-6 and TNF-α in bone tissue homogenates with a concomitant increase in osteoblast apoptosis in smokers and former smokers compared with non-smokers. Histological changes in both smokers and former smokers were characterized by reduction in collagen type I. Only in smokers, it was observed decrease in trabecular area, suggesting increased bone resorption and increase in collagen type V. These results showed that osteoblasts apoptosis in association with increased bone resorption leads bone structural changes in smokers.
Psychopharmacological treatment of disruptive behavior in youths: systematic review and network meta-analysis
Authors: Seok Ji-Woo , Soltis-Vaughan Brigette , Lew Brandon J. , Ahmad Aatiya , Blair R. J. R. , Hwang Soonjo
Published: April 2023

To conduct a systematic review of the comparative efficacy of various psychotropic medications for the treatment of disruptive behavior (DBs) in youths. To this aim, we systematically reviewed randomized clinical trials (RCTs) of various psychotropic medications targeting symptoms of DBs and applied network meta-analysis to investigate their relative efficacy. Fifty-five RCTs meeting the inclusion criteria were selected. To predict and interpret relative treatment efficacy, we compared the efficacy of various psychotropic medications prescribed for DB symptoms based on their mechanism of action. Network meta-analysis revealed that for reducing DBs, second-generation antipsychotics, stimulants, and non-stimulant ADHD medications were more efficacious than placebo, and second-generation antipsychotics were the most efficacious. The dopaminergic modulation of top-down inhibitory process by these medications is discussed in this review. This study offers information on the relative efficacy of various psychotropic medications for the treatment of DB, and insight into a potential neurobiological underpinning for those symptoms. It also illustrates the potential utility of these neurobiological mechanisms as a target for future treatment studies.
The prognostic value and immunological role of CD44 in pan-cancer study
Authors: Chen Shaoyong , Zhang Siqin , Chen Shaohua , Ma Fei
Published: April 2023

To investigate the correlation between cluster of differentiation-44 (CD44) expression and immunotherapy response and identify its possible predictive value in pan-cancer. Datasets of 33 cancer types from The Cancer Genome Atlas (TCGA) database were applied to investigate the relationship of CD44 expression with prognosis, tumor mutational burden (TMB), and microsatellite instability (MSI), and determine its potential prognostic value in pan-cancer. Patients were split into high-risk and low-risk cancer groups based on the survival outcomes of various cancer types. Additionally, the underlying mechanisms of CD44 in the tumor microenvironment (TME) were analyzed using ESTIMATE and CIBERSORT algorithms and Gene Set Enrichment Analysis (GSEA). Subsequently, the biological role of CD44 at single-cell level was investigated using CancerSEA database. Variable expression levels of CD44 between tumor and adjacent normal tissues were identified in pan-cancer datasets, further survival analysis revealed that CD44 expression was associated with multiple clinical annotations and survival indicators. Besides, the expression of CD44 was significantly associated with TMB and MSI in 10 types and 6 types of cancer, respectively, indicating it could be exploited as a potential biomarker predicting immunotherapy outcomes. Meanwhile, CD44 could influence several crucial immune cell-related pathways. and the results revealed by CancerSEA database denoted the correlation of CD44 with malignant phenotype and functional states, further indicating it can serve as a potential therapeutic target in cancer management. Our study demonstrated that CD44 shows great promise as a prognostic biomarker in numerous cancers, which will assist in developing new strategies in cancer management.
Change in skeletal muscle mass is associated with hepatic steatosis in nonalcoholic fatty liver disease
Authors: Jo Ik Hyun , Song Do Seon , Chang U Im , Yang Jin Mo
Published: April 2023

The association between nonalcoholic fatty liver disease (NAFLD) and sarcopenia is known. We aimed to determine the association between skeletal muscle mass changes and NAFLD status. This retrospective single-center study analyzed patients who underwent health screening twice between November 2009 and December 2017, with a temporal gap of 6 ± 0.5 years. The degree of sarcopenia was assessed using appendicular skeletal muscle mass (ASM) adjusted for weight and body mass index (BMI). Changes in hepatic steatosis and fibrosis status were evaluated using noninvasive serum markers. Patients with a decrease in ASM/BMI (n = 353) had increased hepatic steatosis index (HSI) and fatty liver index (FLI) scores during 6 years (p < 0.05). The baseline sarcopenia group had a greater elevation in NAFLD fibrosis score (NFS) over 6 years than those without baseline sarcopenia. ASM changes over 6 years showed a negative correlation with variations in HSI (β = − 0.96 in ASM/Weight and -28.93 in ASM/BMI) and FLI (β = − 5.44 in ASM/Weight and − 167.12 in ASM/BMI). Subgroup analyses showed similar results according to sex and age. Sarcopenia may worsen steatosis and vice versa. Skeletal muscle status can be used to predict the course of NAFLD and establish individualized treatment strategies.
Prognostic value of adjuvant external beam radiotherapy for papillary thyroid cancer based on competitive risk model and propensity score matching
Authors: Zhou Jiani , Wu Chaoqun , Fan Shihong , Zhao Miaohui
Published: April 2023

This study aimed to assess the impact of adjuvant external beam radiotherapy (EBRT) on the survival of patients with locally invasive papillary thyroid carcinoma. This retrospective study used data from the Surveillance, Epidemiology, and End Results database for the diagnosis of papillary thyroid carcinoma, using Cox models to screen for adverse prognostic factors. The prognostic value of using adjuvant external beam radiotherapy in papillary thyroid carcinoma was further evaluated, based on the competing risk model and propensity score matching. Based on the competitive risk model, the sub-distribution hazard ratio (SHR) of the multivariate analysis of patients receiving EBRT alone versus those receiving radioiodine-131 alone was 9.301 (95% CI 5.99–14.44) (P < 0.001), and the SHR of the univariate analysis was 1.97 (95% CI 1.03–3.78) (P = 0.042). In the propensity score-matched Kaplan–Meier analysis, patients who received EBRT still had worse OS (6-year OS, 59.62% vs 74.6%; P < 0.001) and DSS (6-year DSS, 66.6% vs 78.2%; P < 0.001) than patients who did not receive EBRT. Patients who received EBRT had a higher cumulative risk of death due to thyroid cancer after PSM (P < 0.001). Adjuvant EBRT was not associated with survival benefit in the initial management of locally invasive papillary thyroid cancer.
Binder-free NiO/CuO hybrid structure via ULPING (Ultra-short Laser Pulse for In-situ Nanostructure Generation) technique for supercapacitor electrode
Authors: Khot Mayuresh , Shaik Rahaman Sharif , Touseef Wania , Kiani Amirkianoosh
Published: April 2023

Developing a cost-effective pseudocapacitor electrode manufacturing process incorporating binder-free, green synthesis methods and single-step fabrication is crucial in advancing supercapacitor research. This study aims to address this pressing issue and contribute to the ongoing efforts in the field by introducing ULPING (Ultra-short Laser Pulse for In-situ Nanostructure Generation) technique for effective design. Laser irradiation was conducted in ambient conditions to form a CuO/NiO hybrid structure providing a synergistic contribution to the electrical behavior of the electrode. Mainly, the effects of surface morphology and electrochemical surface because of tuning laser intensity were analyzed. The samples demonstrated high oxide formation, fiber generation, excellent porosity, and ease of ion accessibility. Owing to a less than 10-min binder-free fabrication method, the electrochemical performance of the as-fabricated electrode was 25.8 mC cm−2at a current density of 1 mA cm−2proved to be excellent. These excellent surface properties were possible by the simple working principle of pulsed laser irradiation in ambient conditions and smart tuning of the important laser parameters. The CuO/NiO electrode demonstrates excellent conductivity and rewarding cyclic stability of 83.33% after 8000 cycles. This study demonstrates the potential of the ULPING technique as a green and simple method for fabricating high-performance pseudocapacitor electrodes.