bluuebunny/crossref_metadata_2025 huggingface dataset:
LncRNA-CCAT1/miR-152-5p is Involved in CSE-Induced Inflammation in HBE Cells Via Regulating ERK Signaling Pathway
Authors: Zong Dan-dan , Liu Xiang-ming , Li Jin-hua , Long Ying-jiao , Ouyang Ruo-yun , Chen Yan
Published: October 2021

Background: Emerging studies have noted that dysregulated long non-coding RNAs (lncRNAs) are implicated in the pathological processes of chronic obstructive pulmonary disease (COPD). LncRNA colon cancer-associated transcript 1 (CCAT1) plays well-defined roles in the inflammatory progression. The study aims to figure out the effect and regulatory mechanism of CCAT1 in the cigarette smoke induced inflammation in COPD. Methods: The expression levels of CCAT1 and miR-152-3p were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The inflammatory levels of IL-1β and IL-6 were evaluated by qRT-PCR and enzyme-linked immunosorbent assay (ELISA). Western blot was used for the measurement of ERK1/2, p-ERK1/2 protein levels. Luciferase reporter assay was performed for the target gene analysis.Results: CCAT1 was highly expressed in lung tissues of smokers with COPD compared with non-smokers without COPD samples. In human bronchial epithelial (HBE) cells, cigarette smoke extract (CSE) treatment led to an increase in CCAT1 expression in a dose- and time- dependent manner. Functional experiments showed that knockdown of CCAT1 ameliorated CSE-induced inflammation. Mechanistically, CCAT1 directly targeted miR-152-3p, and miR-197-3p overexpression reversed the pro-inflammatory effects of CCAT1 on HBE cells. Subsequently, miR-152-3p was found to regulate ERK signaling pathway. PD98059, ERK specific inhibitor, reversed miR-152-3p inhibition mediated inflammation in HBE cells. In addition, CCAT1 acted as a sponge for miR-152-3p to positively regulate ERK signaling pathway. Conclusion: Current findings suggest that CCAT1 promoted inflammation by activating ERK signal pathway via sponging miR‑152‑3p in CSE‑treated HBE cells. These results may provide a novel therapeutic target for alleviating cigarette smoke mediated airway inflammation.
Precise Design of Drill Structure Based on Cutting Force Distribution Alone Cutting Edge in CFRP Drilling
Authors: Qiu Xin-Yi , Li Peng-Nan , Li Chang-Ping , Niu Qiu-Lin , Li Shu-Jian , Ko Tae Jo
Published: October 2021

At present, the problems that need to be solved urgently in CFRP drilling are delamination and tool wear, which are closely related to the distribution of cutting force on the cutting edge. The aim of this paper is to present a method to analyze the cutting force distribution on the main cutting edge of the drill. This method applies to the analysis of the drilling performance of double point angle (DPA) drill and to optimize the step drill structure for CFRP drilling. Both of these applications prove the correctness of the analysis method. According to the calculation model of the rake angle of the main cutting edge of the twist drill and the cutting force prediction model, the distribution model of the cutting force on the main cutting edge is established. This method reveals the basic reason why the thrust force increases linearly when a single main cutting edge cuts into the workpiece. In the process of analyzing the drilling performance of the DPA drill, the edge force coefficient is used to represent the thrust force, and the application environment of the drill with a different structure is analyzed. Based on the distribution characteristics of the axial force on the main cutting edge, the step ratio of the step drill is optimized. This method can optimize the step ratio of the step drill. This method can be employed to optimize the step ratio of any structure step drill.
Jet Shape Analysis and Removal Function Optimization of Atmospheric Plasma Processing Applied in Optical Fabrication
Authors: Jin Yuan , Wang Bo , Ji Peng , Qiao Zheng , LI Duo , Ding Fei
Published: October 2021

When using Inductively Coupled Plasma (ICP) as a machining tool, its processing method based on the principle of chemical etching leads to no contact stress between the tool and the material, thereby generating no mechanical damage. In recent years, this issue has been widely concerned in the field of optical fabrication. However, there are many differences between low power ICP jet and conventional ICP jet, one of which is that the former does not easily form a rotation-symmetric removal function due to its obvious pinch effect. In this research, the electromagnetism principle of the plasma pinch effect was analyzed firstly, and the jet shape under the pinch effect was classified. Then, experimental study was carried out on the plasma jet shape under the pure Ar and mixed gas of CF4-Ar, and the influence law of the reaction gas on the jet propagation shape was analyzed. Finally, the rotational symmetry of the removal function of plasma jet processing was optimized, and the nozzle design criteria based on pinch effect were proposed.
Impact of Mg2+ and Zn2+ Addition on the Structural, Morphological, Physicochemical, Dielectric and Biological Properties of Hydroxyapatite
Authors: Narayanasamy Anandhan , Ramaswamy Panneerselvam , Ramaswamy Poonguzhali , Arockiam Amali Roselin , Issac Joseph Panneerdoss , Periannan Ganesan Karuppannan , Vasudevan Sugumar
Published: October 2021

In the present work, the wet-chemical precipitation technique is employed to prepare Zinc/Magnesium doped hydroxyapatite (HAP). In doped HAP, the X-ray diffraction peak shifts to a higher angle because of the contraction of the lattice parameters along a - axis. The Raman peaks at 519, 440, 1464 cm-1 indicate the presence of Mg, Zn and CO32- in doped HAP respectively. The Field Emission Scanning Electron Microscopy (FESEM) measures the grain size of pure, 5% Zn and 5% Mg doped HAP, as 275, 510, and 251 nm respectively. Transmission Electron Microscopy (TEM) confirmed the morphological change in HAP. The X-ray photoelectron spectroscopy (XPS) identifies the presence of Mg2+ and Zn2+ in doped HAP. The dopant elevates the hardness and dielectric constant, so the strength and the bone growth of HAP increases. All the doped samples show excellent antibacterial, antifungal and antibiofilm activities than the pure HAP.
Integrating Gene Mutation Mutual Exclusion Information Into Radiomics Algorithms to Improve Gene Mutation Prediction in Non-small Cell Lung Cancer
Authors: Wang Jingyi , Lv Xing , Cao Xin , Huang Weicheng , Quan Zhiyong , Li Guiyu , Zhao Xiaohu , Wang Yirong , Xie Zhaojuan , Yan Yuhao , Gao Yuhua , Li Xiang , Ma Wenhui , Yang Weidong , Kang Fei , Wang Jing
Published: October 2021

Purpose Gene mutations are mutually exclusive in non-small cell lung cancer (NSCLC). Using EGFR and KRAS as examples, this study aims to assess the significance of mutation mutual exclusion information in the optimization of radiomics algorithms for predicting gene mutation.Methods We retrospectively analyzed 161 NSCLC patients with 18F-FDG PET/CT scans and EGFR and KRAS gene mutation data. Patients were randomly divided into training and testing cohorts. The Pyradiomics toolkit was used for radiomics feature extraction. Based on these features, radiomics score (RS) models were developed for predicting KRAS mutations using the gradient boosting decision tree (GBDT) algorithm. Furthermore, to investigate the value of adding mutation mutual exclusion information, a composite model combining PET/CT RS and EGFR mutation status was developed using logistic regression. The area under the curve (AUC), specificity, sensitivity, and accuracy were calculated for model performance evaluation in the training and test cohorts. To test the generalizability of this optimization method, models for predicting EGFR mutation were established in parallel, with or without adding KRAS gene mutation information.Results Compared with CT, the PET/CT based RS model exhibited higher AUC (KRAS: 0.792 vs 0.426; EGFR: 0.786 vs 0.644). By integrating EGFR mutation information into the PET/CT RS model, the AUC, accuracy, and specificity for predicting KRAS mutations were all elevated in the test cohort (0.928, 0.857, 0.897 vs 0.792, 0.755, 0.769). Conversely, the composite model for predicting EGFR mutations could also be optimized by adding KRAS gene mutation information (AUC, accuracy, and specificity: 0.877, 0.776, 0.700 vs 0.786, 0.694, 0.567). By adding EGFR and KRAS exclusive mutation information, respectively, the composite model corrected 55.4% and 30.7% false positive cases produced by the PET/CT RS model in the test cohort, without sacrificing sensitivity.Conclusion Integrating the mutation status of a known gene is a potential method to optimize radiomics models for predicting another gene mutation. This method may help predict unconventional gene mutations when the second biopsy is clinically difficult to carry out.
Non-invasive in Vivo Assessment of 11β-hydroxysteroid Dehydrogenase type 1 Activity by 19 F-magnetic Resonance Spectroscopy
Authors: Naredo-Gonzalez Gregorio , Upreti Rita , Jansen Maurits A , Semple Scott , Sutcliffe Oliver B , Marshall Ian , Walker Brian R , Andrew Ruth
Published: October 2021

11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) amplifies tissue glucocorticoid levels and is a pharmaceutical target in diabetes and cognitive decline. Clinical translation of inhibitors is hampered by lack of in vivo pharmacodynamic biomarkers. Our goal was to monitor substrates and products of 11β-HSD1 non-invasively in liver via 19 Fluorine magnetic resonance spectroscopy (19 F-MRS). Interconversion of mono/poly-fluorinated substrate/product pairs was studied in Wistar rats (male, n=6) and healthy men (n=3) using 7 T and 3 T MRI scanners, respectively. Here we show that the limit of detection, as absolute fluorine content, was 0.625 μmol in blood. Mono-fluorinated steroids, dexamethasone and 11-dehydrodexamethasone, were detected in phantoms but not in vivo in human liver following oral dosing. A non-steroidal polyfluorinated tracer, 2-(phenylsulfonyl)-1-(4-(trifluoromethyl)phenyl)ethanone and its metabolic product were detected in vivo in rat liver after oral administration of the keto-substrate, giving a readout of reductase activity. Administration of a selective 11β-HSD1 inhibitor in vivo in rats altered total liver 19 F-MRS signal. We conclude that there is insufficient sensitivity to measure mono-fluorinated tracers in vivo in man with current dosage regimens and clinical scanners. However use of a poly-fluorinated tracer allowed detection of hepatic reductase activity in rats and could be developed for translation to man.
Genetic Identification and Diversity of Stocks of The African Bonytongue, Heterotis Niloticus (Osteoglossiformes: Arapaiminae), in Nigeria, West Africa
Authors: Oladimeji Tofunmi E. , Caballero Isabel C. , Mateos Mariana , Awodiran Michael O. , Winemiller Kirk O. , Adite Alphonse , Hurtado Luis A.
Published: October 2021

Inland fisheries are an important source of protein and income for people in Africa, and sustainable fisheries management requires knowledge of regional stocks. Presently, information regarding genetic diversity of African freshwater fishes is very limited. Here we present findings from a spatial analysis of genetic patterns in the African bonytongue, Heterotis niloticus, an important component of inland fisheries in West Africa. The species is common throughout Western and Central Africa and the Nile Basin; and has been introduced for aquaculture in locations across Africa. Nigeria has the largest fishery for African bonytongues, representing ~86% of the global total. Recent declines in yields at some Nigerian locations, however, suggest current levels of exploitation may be unsustainable. Habitat degradation also may be impacting some stocks. Despite its commercial and nutritional importance, the African bonytongue has been the subject of scant research to support management. We examined patterns of genetic diversity in natural populations of H. niloticus at four locations in Nigeria, including Kainji Lake, a reservoir on the Niger River in north-central Nigeria, and three southtern localities (Ethiope River, Igbokoda River, and Epe Lagoon), as well fish from the Ouémé River delta near Porto Novo, Benin. Eighty-five specimens were genotyped for nine microsatellite-loci. Genetic diversity estimates were highest at Kainji Lake, and substantially lower at southern localities. High levels of genetic differentiation were detected between samples from Kainji Lake and those from the southern localities. Low, yet significant FST values were observed among samples from southern Nigerian localities that were more differentiated from the sample from nearby coastal Benin. We thus recommend that African bonytongues from the five locations be considered distinct genetic stocks and managed accordingly.
Disarrangement and reorganization of the hippocampal functional connectivity during the spatial path adjustment of pigeons
Authors: Li Mengmeng
Published: October 2021

Background: The hippocampus plays an important role to support path planning and adjustment in goal-directed spatial navigation. While we still only have limited knowledge about how do the hippocampal neural activities, especially the functional connectivity patterns, change during the spatial path adjustment. In this study, we measured the behavioural indicators and local field potentials of the pigeon (Columba livia, male and female) during a goal-directed navigational task with the detour paradigm, exploring the changing patterns of the hippocampal functional network connectivity of the bird during the spatial path learning and adjustment. Results: Our study demonstrates that the pigeons progressively learned to solve the path adjustment task after the preferred path is blocked suddenly. Behavioural results show that both the total duration and the path lengths pigeons completed the task during the phase of adjustment are significantly longer than those during the acquisition and recovery phases. Furthermore, neural results show that hippocampal functional connectivity selectively changed during path adjustment. Specifically, we identified depressed connectivity in lower bands (delta and theta) and elevated connectivity in higher bands (slow-gamma and fast-gamma).Conclusions: These results feature both the behavioural response and neural representation of the avian spatial cognitive learning process, suggesting that the functional disarrangement and reorganization of the connectivity in the avian hippocampus during different phases may contribute to our further understanding of the potential mechanism of path learning and adjustment.
Deformation of the Nucleus by TGFβ1 Via the Remodeling of Nuclear Envelope and Histone Isoforms
Authors: Chi Ya-Hui , Wang Wan-Ping , Hung Ming-Chun , Liou Gunn-Guang , Wang Jing-Ya , Chao Pen-Hsiu Grace
Published: October 2021

The cause of nuclear shape abnormalities which are often seen in pre-neoplastic and malignant tissues is not clear. In this study we report that deformation of the nucleus can be induced by TGFb1 stimulation in several cell lines including Huh7. In our results, the upregulated histone H3.3 expression downstream of SMAD signaling contributed to TGFb1-induced nuclear deformation, a process of which requires incorporation of the nuclear envelope (NE) proteins lamin B1 and SUN1. During this process, the NE constitutively ruptured and reformed with no observable indications of DNA damage response. Contrast to lamin B1 which was relatively stationary around the nucleus, the upregulated lamin A was highly mobile, shuttling between the nucleus and cytoplasm, and clustering at the nuclear periphery. The chromatin regions that lost NE coverage formed a supra-nucleosomal structure characterized by elevated histone H3K27me3 and histone H1, the formation of which depended on the presence of lamin A. These results provide evidence that shape of the nucleus can be modulated through TGFb1-induced compositional changes in the chromatin and nuclear lamina.
Knockdown CD44 Promotes Amyloid-Beta Degradation in Ovarian Cancer Cells By Regulating CD36 Expression
Authors: Xu Ying , Gao Yunge , Qian Luomeng , Feng Wangyou , Song Tingting , Li Yuanfeng , Guo Fenfen , Zheng Jiao , Li Yu , Zhang Jianfang , Yang Hong
Published: October 2021

Background: CD44 is highly expressed in many cancers, including ovarian cancer. Its interactions with ligands are involved in tumor progression, prognosis, and metastasis. However, the function of CD44 in the advancement of ovarian cancer remains unclear. Methods and Results: RNA sequencing was used to investigate the possible molecules and pathways regulated by CD44 in ovarian cancer to compare gene expression in CD44-knockdown SKOV3 cells and control cells. Identify the differentially expressed genes and then proceed to functional enrichment analysis. The results showed that genes differentially expressed were enriched in ECM-receptor interaction, Protein digestion and absorption, Focal adhesion, Notch signaling pathway, microRNA in cancer, and TGF-beta signaling pathway. Furthermore, the analysis of the proteins interaction network revealed the interaction between CD44 and CD36 in SKOV3 cells. Further analysis showed that CD36, a molecule that may be involved in ECM-receptor interaction, was low expressed in CD44-knockdown SKOV3 cells. And the results showed that knockdown CD44 induces amyloid-beta degradation in ovarian cancer cells by regulating CD36 expression. The analyses of the public database demonstrated that the CD36 expression was related to the clinical survival of ovarian cancer. Conclusions: Our study showed that CD44 might up-regulate the CD36 expression in ovarian cancer, thereby exerting a cancer-promoting effect.
Biodegradable Reduce Expenditure Bioreactor For Augmented Sonodynamic Therapy Via Regulating Tumor Hypoxia And Inducing Pro-Death Autophagy
Authors: Zou Weijuan , Hao Junnian , Wu Jianrong , Cai Xiaojun , Hu Bing , Wang Zhigang , Zheng Yuanyi
Published: October 2021

Backgrounds: Sonodynamic therapy (SDT) as an emerging reactive oxygen species (ROS)-mediated antitumor means is still hampered by the rapid depletion of oxygen, as well as hypoxic tumor microenvironment. Instead of the currently coping strategies through amplifying endogenous O2 level, herein, a biodegradable O2 economizer is described as a reduce expenditure bioreactor for augmenting SDT efficacy. Results: We have successfully fabricated the O2 economizer (HMME@HMONs-3BP-PEG, HHBP) by the conjugation of respiration inhibitor 3-bromopyruvate (3BP) with hollow mesoporous organosilica nanoparticles (HMONs), followed by the loading of organic sonosensitizers (HMME) and further surface modification of poly(ethylene glycol) (PEG). The engineered HHBP features controllable pH/GSH/US-sensitive drug release. The exposed 3BP could effectively inhibit cell respiration for restraining the oxygen consumption, which could alleviate the tumor hypoxia. More interestingly, it could exorbitantly elevate the autophagy level, which in turn induce excessive activation of autophagy for promoting the therapeutic efficacy. As a result, accompanied with suppressing O2-consumption and triggering pro-death autophagy strategy, the HHBP achieves remarkable antitumor activity, which has been systematically validated both in vivo and in vitro assays. Conclusion: This work not only provides a reduce expenditure strategy for enduring SDT, but also represents an inquisitive strategy for tumor treatments via inducing pro-death autophagy.
Transdiagnostic Validation of the German Benefit Finding Scale (BFSC) for Youth With Chronic Conditions
Authors: von Rezori Roman , Buchallik Friederike , Warschburger Petra
Published: October 2021

We examined the psychometric properties of the 10-item Benefit Finding Scale (BFSC) in a transdiagnostic sample of German youth facing chronic conditions (N = 304; 12 – 21 years). Exploratory factor analysis with a first subsample revealed a one-dimensional factor structure. Confirmatory factor analysis with a second subsample verified the one-dimensionality with an acceptable fit. The BFSC exhibited acceptable internal consistency (α = .87 – .88). Benefit finding (BF) was positively correlated with age, disease severity, optimism, self-esteem, self-efficacy, sense of coherence, and support seeking. There were no correlations with avoidance, wishful thinking, emotional reaction, and health-related quality of life. Sex differences in BF were not consistent across subsamples. BF was negatively associated with social status. The BFSC is a psychometrically sound and transdiagnostic instrument to assess BF in youth and may facilitate further research on positive adaptation processes in response to chronic conditions.
Correlation between weather conditions and COVID-19 pandemic in the southeast area of Iran
Authors: Parvaz Najmeh , Amin Fatemeh , Nadimi Ali Esmaeili , Eslami Hadi
Published: October 2021

The Coronavirus disease 2019 (COVID-19) has influenced the live of all people around the world. This study analyzed the relationship between the weather elements (daily temperature, wind speed and humidity) and daily active, recovered and dead cases of covid-19 in Rafsanjan, in the southeast area of Iran. Covid-19 data and meteorological variables were obtained from 29 February 2020 to 20 March 2021 (386 days) from Rafsanjan University of Medical Sciences and Meteorological Organization of Iran, respectively. The results showed that there is a significant inverse association between daily average temperature with the number of daily active cases (r: -0.293, p<0.01), recovered cases (r: -0.301, p<0.01) and dead cases (r: -0.198, p<0.01). With decreasing the average wind speed, the number of daily active cases (r: -0.224, p<0.01), recovered cases (r: -0.232, p<0.01) and dead cases has been increased. A nonsignificant positive correlation between daily humidity average and daily active cases (r:0.033, p=0.518) and recovered cases (r:0.044, p=0.390), and significant positive correlation with the number of daily dead cases (r: 0.254, p<0.01) was observed. Therefore, temperature and wind speed can be considered as affective factors in COVID-19 as an auxiliary solution.
Same or Different? Perceptual Learning for Connected Speech Induced by Brief and Longer Experiences
Authors: Banai Karen , Karawani Hanin , Lavie Limor , Lavner Yizhar
Published: October 2021

Perceptual learning, defined as long-lasting changes in the ability to extract information from the environment, occurs following either brief exposure or prolonged practice. Whether these two types of experience yield qualitatively distinct patterns of learning is not clear. We used a time-compressed speech task to assess perceptual learning following either rapid exposure or additional training. We report that both experiences yielded robust and long-lasting learning. Individual differences in rapid learning explained unique variance in performance in independent speech tasks (natural-fast speech and speech-in-noise) with no additional contribution for training-induced learning (Experiment 1). Finally, it seems that similar factors influence the specificity of the two types of learning (Experiment 1 and 2). We suggest that rapid learning is key for understanding the role of perceptual learning in speech recognition under adverse conditions while longer learning could serve to strengthen and stabilize learning.
A Decentralized Framework for Patents and Intellectual Property as NFT in Blockchain Networks
Authors: Bamakan Seyed Mojtaba Hosseini , Nezhadsistani Nasim , Bodaghi Omid , Qu Qiang
Published: October 2021

With the explosive development of decentralized finance (DeFi), we witness a phenomenal growth in tokenization of all kinds of assets, including equity, funds, debt, and real estate. By taking advantage of blockchain technology, digital assets are broadly grouped into fungible and non-fungible tokens (NFT). Here non-fungible tokens refer to those with unique and non-substitutable properties. Although the application of NFT is currently limited to digital fantasy artwork, games, collectible, etc., due to its unique capabilities, protocols, and platforms, they could be utilized in more practical issues. The main objective of this paper is to examine the requirements of presenting intellectual property assets, specifically patents, as NFTs. Hence, we offer a layered conceptual NFT-based patent framework with a comprehensive discussion on each layer, including storage, decentralized authentication, decentralized verification, Blockchain, and application layer. Furthermore, a series of open challenges about NFT-based patents and the possible future directions are highlighted. The proposed framework provides fundamental elements and guidance for businesses in taking advantage of NFTs in real-world problems such as grant patents, funding, biotechnology, event ticketing, and so forth.
Regional Heterogeneity and an Unexpectedly High Abundance of Cooperia Punctata in Beef Cattle at Northern Latitude Were Revealed by ITS-2 rDNA Nemabiome Metabarcoding
Authors: De Seram Eranga Lakshitha , Redman Elizabeth Mary , Wills Felicity Kaye , de Queiroz Camila , Campbell John Ross , Waldner Cheryl Lynne , Parker Sarah Elizabeth , Avramenko Russell William , Gilleard John Stuart , Uehlinger Fabienne Dominique
Published: October 2021

BackgroundThe species composition of cattle gastrointestinal nematode (GIN) communities can vary greatly between regions. Despite this, there is remarkably little large-scale surveillance data for cattle GIN species which is due, at least in part, to a lack of scalable diagnostic tools. This lack of regional GIN species-level data represents a major knowledge gap for evidence-based parasite management and assessing the status and impact of factors such as climate change and anthelmintic drug resistance. MethodsThis paper presents a large-scale survey of GIN in beef herds across western Canada using ITS-2 rDNA nemabiome metabarcoding. Individual fecal samples were collected from 6–20 randomly selected heifers (n = 1665) from each of 85 herds between September 2016 and February 2017 and 10–25 first season calves (n = 824) from each of 42 herds between November 2016 and February 2017. ResultsGastrointestinal nematode communities in heifers and calves were similar in Alberta and Saskatchewan, with Ostertagia ostertagi and Cooperia oncophora being the predominant GIN species in all herds consistent with previous studies. However, in Manitoba, Cooperia punctata was the most predominant species overall and the most abundant GIN species in calves from 4/8 beef herds. ConclusionsThis study revealed a marked regional heterogenicity of GIN species in grazing beef herds in western Canada. The predominance of C. punctata in Manitoba is unexpected as although this parasite is often the most predominant cattle GIN species in more southerly latitudes, it is generally only a minor component of cattle GIN communities in northern temperate regions. We hypothesize that the unexpected predominance of C. punctata at such a northerly latitude represents a range expansion, likely associated with changes in climate, anthelmintic use, management, and/or animal movement. Whatever the cause, these results are of practical concern since C. punctata is more pathogenic than C. oncophora, the Cooperia species that typically predominates in cooler temperate regions. Finally, this study illustrates the value of ITS-2 rDNA nemabiome metabarcoding as a surveillance tool for ruminant GIN parasites.
Oxygen Nanocarrier Broke the Hypoxia Trap of Solid Tumors and Rescued Transfection Efficiency for Gene Therapy
Authors: Qin Bing , Jiang Mengshi , Li Xiang , Shi Yingying , Zhang Junlei , Luo Zhenyu , Luo Lihua , Lu Yichao , Liu Xu , Wang Sijie , Du Yongzhong , You Jian
Published: October 2021

Background: Gene therapy shows great promise for a broad array of diseases. However, we found that hypoxic tumor microenvironment (TME) exerted significant inhibitory effects on transfection efficiency of a variety of gene vectors (such as Lipo 2000 and PEI) in an oxygen-dependent manner. Solid tumors inevitably resulted in acute hypoxic areas due to the rapid proliferation of tumor cells and the aberrant structure of blood vessels. Thus, the hypoxic TME severely limited the efficiency and application of gene therapy. Methods: In our previous study, we constructed endoplasmic reticulum-targeted cationic liposomes, PAR-Lipo, which could effectively deliver genes and ensure high transfection efficiency under normoxia. Unsatisfactorily, the transfection efficiency of PAR-Lipo was rather poor under hypoxia. We believed that reoxygenation was the most direct and effective means to rescue the low transfection under hypoxia. Hence, we fabricated liposomes modified with perfluorooctyl bromide (PFOB@Lipo) to load oxygen and deliver it to tumor sites, which effectively alleviated the hypoxic nature of tumor. Then PAR-Lipo were applied to mediate high-efficiency delivery of tumor suppressor gene pTP53 to inhibit tumor progression. Results: The results showed that such staged strategy augmented the expression of P53 protein in tumors and extremely suppressed tumor growth. Conclusion:This work was the first attempt to utilize an oxygen nanocarrier to assist the therapeutic effect of gene therapy under hypoxia, providing a new reference for gene therapy in malignant tumors.
Cost and Cost-effectiveness of eLearning Interventions for Healthcare Workers in Low- and Middle-income Countries: a Protocol for a Systematic Review and Meta-analysis
Authors: Gwala Nonjabulo , Dlungwane Thembelihle Patricia , Nkambule Sphamandla , Mashamba-Thompson Tivani
Published: October 2021

BackgroundIn recent years, the shift from traditional face-to-face teaching methods to eLearning methods has shown to improve professional training, particularly for the health workers in achieving necessary specialised worker training. However, there is a insufficient evidence on the costs and cost-effectiveness of designing and deploying eLearning interventions for healthcare workers in low- and middle-income countries.MethodsThe study protocol was developed and reported following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P). The Cochrane Handbook for Systematic Reviews of Interventions will be used to guide the conduct of the proposed systematic review and meta-analysis. Systematic literature searches will be conducted using the EBSCOhost platform ( Academic Search Complete, ERIC, health source: nursing/academic edition, MEDLINE with Full Text, OpenDissertations), Google Scholar, and the following databases: Web of Science, PubMed and ProQuest databases, evaluating the cost and cost-effectiveness of e-learning interventions for healthcare workers in low- and middle-income countries. The searches will be open to peer-reviewed articles published in all languages and no restriction in publication year. We will further evaluate the cost-effectiveness by determining heterogeneity in the content, if feasible we will do a meta-analysis using Meta- Easy Excel software tools. We will use OR and 95% CIs as measures of effect for dichotomous outcomes. As for continuous outcomes, we will use standardised mean differences and 95% CIs. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach will be used to assess the certainty of the evidence across outcomes. PRISMA-P will be used to report the findings of this systematic review and meta-analysis.DiscussionThis systematic review target to deliver complete evidence of cost and the cost-effectiveness of eLearning interventions for healthcare worker training. The study will be disseminated through the publication of the manuscript and policy brief in an appropriate journal and shared with the relevant stakeholders through conference presentations, discussions and seminars.Protocol registrationPROSPERO ID: 271180
Lansoprazole-Induced Osteoporosis via IP3R and SOCE Mediated Calcium Signaling Pathway
Authors: Cheng Zi-Ping , Liu Jie-Yang , Ma Meng-Yuan , Sun Shi-Yu , Ma Zeng-qing , Wang Yu , Yu Li-Yuan , Qian Xu-Ping , Sun Lu-Ning , Zhang Xue-Hui , Liu Yun , Wang Yong-Qing
Published: October 2021

Background: Many clinical studies have shown a correlation between proton pump inhibitors (PPIs) and osteoporosis or fractures. The purposes of this study were to establish a murine model of chronic oral administration of PPIs to verify whether PPIs caused bone metabolic impairment, and to investigate the relevant molecular mechanism underlying the effects of PPIs on MC3T3-E1 mouse osteoblasts.Methods: Lansoprazole-induced bone loss model was employed to investigate the damage effects of PPIs. In vivo, immunohistochemistry and HE staining, micro-CT analysis, blood biochemical tests were used to evaluate the effect of lansoprazole on bone injury in mice. In vitro, the effects and related signaling pathway of lansoprazole on MC3T3-E1 cells were investigated by CCK8, EDU kit, flow cytometry, laser confocal, patch clamp, PCR and Western blotting, etc.Results: After 6 months of lansoprazole gavage in ICR mice, micro-CT results showed that compared with the vehicle group, the bone mineral density (BMD) of high-dose group was significantly decreased (P<0.05), and the bone microarchitecture gradually degraded. Biochemical assay of bone serum found that blood calcium and phosphorus were both decreased (P<0.01). We found that long-term administration of lansoprazole impairs skeletal function in mice. In vitro, we found that lansoprazole (LPZ) could cause calcium overload in MC3T3-E1 cells leading to apoptosis, and 2-APB, an inhibitor of IP3R calcium release channel and SOC pathway, efctively blocked calcium increase caused by LPZ, thus protecting cell viability.Conclusion: Long-term administration of LPZ induced osteoporotic symptoms in mice, and LPZ triggered calcium elevation in osteoblasts in a concentration dependent manner, intracellular calcium ([Ca2+] persisted at a high concentration thereby causing endoplasmic reticulum stress (ERS) and inducing osteoblasts apoptosis.
Loss of LKB1-NUAK1 Signalling Enhances NF-κB Activity in a Spheroid Model of High-Grade Serous Ovarian Cancer
Authors: Buensuceso Adrian , Fritz Jamie Lee , Collins Olga , Valdes Yudith Ramos , DiMattia Gabriel E. , Shepherd Trevor G.
Published: October 2021

High-grade serous ovarian cancer (HGSOC) is an aggressive malignancy often diagnosed at an advanced stage. Although most HGSOC patients respond initially to debulking surgery combined with cytotoxic chemotherapy, many ultimately relapse with platinum-resistant disease. Thus, improving outcomes requires new ways of limiting metastasis and eradicating residual disease. We identified previously that Liver kinase B1 (LKB1) and its substrate NUAK1 are implicated in EOC spheroid cell viability and are required for efficient metastasis in orthotopic mouse models. Here, we sought to identify additional signalling pathways altered in EOC cells due to LKB1 or NUAK1 loss-of-function. Transcriptome analysis revealed that inflammatory signalling mediated by NF-κB transcription factors is hyperactive due to LKB1-NUAK1 loss in HGSOC cells and spheroids. Upregulated NF-κB signalling due to NUAK1 loss suppresses reactive oxygen species (ROS) production and sustains cell survival in spheroids. NF-κB signalling is also activated in HGSOC precursor fallopian tube secretory epithelial cell spheroids, and is further enhanced by NUAK1 loss. Finally, immunohistochemical analysis of OVCAR8 xenograft tumors lacking NUAK1 displayed increased RelB expression and nuclear staining. Our results support the idea that NUAK1 and NF-κB signalling pathways together regulate ROS and inflammatory signalling, supporting cell survival during each step of HGSOC pathogenesis. We propose that their combined inhibition may be efficacious as a novel therapeutic strategy for advanced HGSOC.
The Clinicopathological Characteristics, Prognosis and Immune Microenvironment Mapping in MSI-H/MMR-D Endometrial Carcinomas
Authors: Guo Yu-e , Liu Yin , Luo Heng , Zhang Wei , Shu Ping , Chen Guofang , Li Yuping
Published: October 2021

Endometrial cancer had a relatively high prevalence of MMR deficiency. MMR-D/MSI-H endometrial cancer patients are suggested to be potential beneficiaries of PD-1/PD-L1 inhibitor therapy. Here, we explored the prognostic value of MSI subtype in endometrial cancer and its correlation with immune environment. Based on expression and clinical data of 78 POLE, 123 MSI and 299 Other EC samples from the TCGA-UCEC project, we found that the MSI tumors were identified more often in early stage, had a lower age, better patient survival, enriched CD8+ T cells, and regulatory T cells and less M2 macrophages and activated dendritic cells than the Other subgroup, and shared a relatively similar expression profile with POLE subgroup by differential analysis. In addition, we established the immune landscape of an MMR-D endometrial cancer tissue using unbiased single-cell RNA-seq analysis of 4518 cells. By immunohistochemistry analysis, we found that the MMR-D tumors showed a higher trend of CD20+ B cells infiltration. Our study might expand our understanding of the role of immune subsets in MSI endometrial carcinomas and provide guidance of immunotherapy for endometrial cancer.
WITHDRAWN: Particle Nature of Photons, Normal Diffraction Pattern and Curved Diffraction Pattern Emerging in Same Experiment --- Double-Slit Experiment Still Has Much to Offer
Authors: Peng Hui
Published: October 2021

The particle nature of the photons was experimentally confirmed. The static straight line diffraction pattern of the normal grating experiments has been shown experimentally. The phenomenon of the dynamic curved diffraction pattern of the grating experiment have been shown in separate experiments. In this article, the new experiments are proposed and performed, which show that the particle nature of the photons, the static straight line diffraction patterns, and the dynamic curved, expanded and inclined diffraction patterns co-exist in the same grating experiment simultaneously. The novel phenomena make the Feynman’s mystery of the normal double slit experiment more mysterious, violate Bohr’s complementarity principle, and provide comprehensive information/data for studying the wave-particle duality and developing new theoretical model. The double-slit experiment still has much to offer.
Noble Metal Alloy Thin Films by Atomic Layer Deposition & Rapid Joule Heating
Authors: Guo Yuanyuan , Zou Yiming , Cheng Chunyu , Wang Leyan , Made Riko I , Goei Ronn , Tan Kwan Wee , Li Shuzhou , Tok Alfred
Published: October 2021

Metal alloys are usually fabricated by melting constituent metals together or sintering metal alloy particles made by high energy ball milling (mechanical alloying). All these methods only allow for bulk alloys to be formed. This manuscript details a new method of fabricating Rhodium/Iridium (Rh/Ir) metal alloy films using atomic layer deposition (ALD) and rapid Joule heating induced alloying that gives functional thin film alloys, enabling conformal thin films with high aspect ratios on 3D nanostructured substrate. In this work, ALD was used to deposit Rh thin film on an Al2O3 substrate, followed by an Ir overlayer on top of the Rh film. The multilayered structure was then alloyed / sintered using rapid Joule heating. We can precisely control the thickness of the resultant alloy films down to the atomic scale. The Rh@Ir alloy thin films were characterized using scanning and transmission electron microscopy (SEM/TEM) and energy dispersive spectroscopy (EDS) to study their microstructural characteristics. Grazing-incidence X-ray diffraction (GIXRD) and X-ray photoelectron spectroscopy (XPS) were also carried out to confirm the composition and formation of Rh-Ir thin film alloys. All the characterization results reveal that the Rh-Ir alloy thin film was prepared successfully with one single phase and homogeneous distribution of Rh and Ir throughout the film. Molecular Dynamics simulation experiments of Rh/Ir alloys using Large-Scale Atomic/Molecular Massively Parallel Simulator (LAMMPS) were performed to elucidate the alloying mechanism during the rapid heating process, corroborating the experimental results.
The Assessment of a Novel Lower Body Resistance Garment As a Mechanism to Increase the Training Stimulus During Running: a Randomised Cross Over Study
Authors: Hoffmann Samantha M , Domenico Isaiah Di , Collins Paul K
Published: October 2021

Background: This study examined the physiological and perceived impact of wearing a novel lower body resistance garment during exercise and recovery.Methods: Using a randomised cross over design, 15 recreationally-active males performed 2x10-minute steady-state runs followed by a 10-minute passive recovery with concomitant monitoring of oxygen consumption (V̇O2), heart rate (HR) and rating of perceived exertion (RPE; exercise portion only), wearing either the resistance garment (experimental) or running shorts (control).Results: During exercise, V̇O2 and RPE were higher (4.5% and 7.7% respectively) in experimental than control (V̇O2: r=0.24, p>0.05; RPE: r=0.32, p>0.05) whilst HR was lower (-0.4%, r=-0.05, p>0.05). During recovery, V̇O2 and HR were lower (4.7% and 4.3% respectively) in experimental than control (V̇O2: r=‑0.32, p>0.05; HR: r=-0.27, p>0.05). Conclusions: Though effects were trivial to small, and not statistically significant, these findings provide proof of concept and suggest that this garment design may increase the training stimulus during running and aid post-exercise recovery.
Chiral Photochemistry of Achiral Molecules: The Emblematic Case of Stilbene and Stiff-Stilbene
Authors: Raucci Umberto , Weir Hayley , Bannwarth Christoph , Sanchez David , Martinez Todd
Published: October 2021

Chirality is a fundamental molecular property governed by the topography of the potential energy surface (PES). The barrier height between two enantiomers relative to the thermal energy dictates the timescale for their interconversion (and thus whether this can be observed). Thermally achiral molecules interconvert rapidly when the interconversion barrier is comparable to or lower than the thermal energy, in contrast to thermally stable chiral configurations. In principle, a change in the PES topography on the excited electronic state may diminish interconversion, leading to electronically prochiral molecules that can be converted from achiral to chiral by electronic excitation. We demonstrate that this is the case for two prototypical examples – cis-stilbene and cis-stiff stilbene. Both systems exhibit unidirectional photoisomerization for each enantiomer as a result of their electronic prochirality. We propose and simulate an experiment to demonstrate this effect in cis-stilbene based on its interaction with circularly polarized light. Our results highlight the drastic change in chiral behavior upon electronic excitation, opening up the possibility for asymmetric photochemistry from an effectively nonchiral starting point.
Desquamation Interstitial Pneumonia Presenting as a Solid Mass in the Lung: a Case Report.
Authors: Luo Wen , Wang Wanyu , Shi Yonghong , Lu Fang , Lin Yihua
Published: October 2021

Background: Desquamation interstitial pneumonia (DIP) is a rare type of idiopathic interstitial pneumonia. High resolution computed tomography (HRCT) shows ground glass opacities without the peripheral reticular opacities characteristic of usual interstitial pneumonia (UIP). Here we report a case of DIP presenting as a solid mass in the lung, which is rarely described in the literature.Case presentation: A 77-year-old man presented with dry cough and dyspnea on exertion for one month was admitted to our hospital. The lung CT scan showed there was a pulmonary mass in right lower lung and the patient was scheduled for surgery. He was a sculpture artist, non-smoker and the previous medical history included only mandatory spondylitis without other connective tissue diseases. Nine days post-last CT, the FDG PET/CT demonstrated the mass in the right lower lung was significantly hypermetabolic (SUV value=8.9) but inflammatory exudate could be observed around the mass. We gave antibiotics and performed CT-guided percutaneous lung biopsy. The result showed that there were a large number of macrophages in the alveolar cavity, alveolar epithelial type II cells hyperplasia in some areas and chronic inflammation was noted in the interstitium. Then the desquamative interstitial pneumonia was diagnosed. We gave the patient glucocorticoid therapy, then the patient's symptoms disappeared gradually and the lung CT showed that the pulmonary mass was disappeared.Conclusions: Our report illustrates the rare presentation of DIP. Furthermore, for the pulmonary mass, even if appeared hypermetabolic on PET/CT, it is still necessary to make a definite pathological diagnosis before operation, so as to reduce the damage to patients.
Improving company communication activity amidst the СOVID-19 restrictions
Authors: Kyslyy Volodymyr , Bondar Tetyana , Kabluchko Yevhen , Lieonov Hlib
Published: October 2021

This study aimed to consider the essence and significance of the company communication activities and identify modern communications tools amidst the COVID-19 quarantine restrictions. The study object is the Like Center LLC communication activity. In the study frameworks, the company organizational structure, the staff list, and the job responsibilities were analyzed. Besides, the SWOT analysis was conducted to disclose the company organization’s activities features. The authors examined the company’s competitive environment using the 4P concept, which allowed identifying the company’s main advantages and searches for solutions to existing problems in the communication activities. The methodology basis involved graphic and structural analysis, logical generalization to substantiate the goals, target audience, and communication strategy of Like Center LLC. The findings allowed developing the suggestions for forming a communication program of Like Center LLC under quarantine the COVID-19 restrictions. The authors emphasized the necessity to implement innovative communication tools for LLC «Like Center» such as 1) creating a chatbot, 2) launching a YouTube channel, 3) introducing educational activities (conferences and training on business education). In the study, the authors determined the main functions of the chatbot. The example of training for regular corporate customers was demonstrated. The feature of this training was using a smartphone as an assistant for quick access to information, control and register customers, a tool for evaluating the company efficiency, and a device for creating activities. After training, the clients could realize the received knowledge and skills into practice. The study proposed the topics for online conferences, determined the target audience. In the study, the authors suggested the YouTube channel action plan to expand the target audience. The obtained results indicated the possible prospects and the company’s efficiency through improving the company communication system.