bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis on Climate Literacy Capacity of Level XI High School Students in Surabaya
Authors: Nabilah Hasna’ , Hariyono Eko
Published: July 2021

The climate problem today caused damage to infrastructures and many other living elements among mankind. As the prospected future leaders, students need to understand and to respond the effects of climate change. A person with climate literacy may enhance their ability and capacity to face climate challenges in the future. Climate literacy is the understanding of the influence of self and society on the climate. This research is conducted to give a general picture of climate literacy among high school students in Surabaya and each indicator in climate competency aspects. The methodology used in this research is a descriptive qualitative method. The research instrument used in this research is a climate literacy test. The valuation of climate literacy capacity of the students being done by giving scores manually from the test answers according to the scoring guideline in the scoring rubric and achievement results with categories as very high, high, moderate, low, and very low. The research samples are 107 high school students at level XI in SMAN 22 Surabaya (Public High School 22 Surabaya). According to the research, the students’ indicator in scientific identifying is low with a score percentage of 48.9%. The students’ indicator in explaining the scientific phenomenon is moderate with a score of 74.5%, while students’ indicator score in using scientific evidence is moderate with 68.6%. It could be said that high school students in SMAN 22 Surabaya as a whole have a moderate climate literacy capacity with a percentage score of 64%.
Improving Students' Scientific Literacy: Learning Studies Using Science Teaching Materials on Circulatory System Materials
Authors: Karimah Karimah , Jufri A. Wahab , Ramdani Agus
Published: July 2021

Scientific literacy is very important in determining the quality of education in a country. The importance of scientific literacy for students because it can invite students to understand the environment, health, economy and many other problems facing modern society. This study aim to develop an integrated science teaching material with guided inquiry model that appropriate to improve students' scientific literacy. This research is a development research using the Dick & Carey model. In addition to developing science teaching materials, this research also develops syllabus, lesson plans, and scientific literacy instruments. This research was conducted in one of the NW MTs in West Lombok Regency. The validation of learning products was carried out by three validators, media experts and material experts. Expert validation data analysis was carried out using the Pearson validation formula. The results of the feasibility study of integrated science teaching materials using guided inquiry models obtained an average value of 94% with very valid criteria. The syllabus got an average score of 87%, lesson plans got an average score of 92%, and the scientific literacy instrument got an average score of 82%. In conclusion, the product of integrated science teaching materials with guided inquiry models is feasible to be implemented in learning process.
INNOVATIVE INFORMATION AND COMMUNICATION TECHNOLOGIES FOR ERGOTHERAPISTS APPLIED DURING ENGLISH LEARNING IN UKRAINE
Authors: KULICHENKO ALLA , POLYEZHAYEV YURIY
Published: July 2021

According to Ukrainian higher educational policy, there is an urgent need to combine general competencies. Thus, the article aims at highlighting the use of innovative information and communication technologies (ICTs) for ergotherapists when learning English in Ukrainian higher educational establishments as types of such competencies. To achieve the objective of research the authors have applied theoretical and empirical methods. Besides, the authors are convinced that content and language integrated learning (CLIL) is appropriate to apply with innovative information and communication technologies when teaching a foreign language. Moreover, the research describes how to use Lumowell, a YouTube channel, Quizlet, and Zoom, free online educational platforms.
Progress and paradigms in the search for the neural correlates of consciousness
Authors: Fink Sascha Benjamin , Lin Ying-Tung
Published: July 2021

An introduction to the second part of the special issue celebrating the neural correlates of consciousness. Here, we focus on progress and paradigms in the science of consciousness from the perspective of philosophy of science.
Identification of Biomarkers Controlling Cell Fate In Blood Cell Development
Authors: Nazarieh Maryam , Hoeppner Marc , Helms Volkhard
Published: July 2021

A blood cell lineage consists of several consecutive developmental stages starting from the pluri- or multipotent stem cell to a state of terminal differentiation. Despite their importance for human biology, the regulatory pathways and gene networks that govern these differentiation processes are not yet fully understood. This is in part due to challenges associated with delineating the interactions between transcription factors (TFs) and their corresponding target genes. A possible step forward in this case is provided by the increasing amount of expression data, as a basis for linking differentiation stages and gene activities. Here, we present a novel hierarchical approach to identify characteristic expression peak patterns that global regulators excert along the differentiation path of cell lineages. Based on such simple patterns, we identified cell state-specific marker genes and extracted TFs that likely drive their differentiation. Integration of the mean expression values of stage-specific “key player” genes yielded a distinct peaking pattern for each lineage that was used to identify further genes in the dataset which behave similarly. Incorporating the set of TFs that regulate these genes led to a set of stage-specific regulators that control the biological process of cell fate. As proof of concept, we considered two expression datasets covering key differentiation events in blood cell formation of mice.
A Smartphone-Fluidic Digital Imaging Analysis System for Pancreatic Islet Mass Quantification
Authors: Yu Xiaoyu , Zhang Pu , He Yi , Lin Emily , Ai Huiwang , Ramasubramanian Melur K. , Wang Yong , Xing Yuan , Oberholzer José
Published: July 2021

Islet beta-cell viability, function, and mass are three decisive attributes that determine the efficacy of human islet transplantation for type 1 diabetes mellitus (T1DM) patients. Islet mass is commonly assessed manually, which often leads to error and bias. Digital imaging analysis (DIA) system has shown its potential as an alternative, but it has some associated limitations. In this study, a Smartphone-Fluidic Digital Imaging Analysis (SFDIA) System, which incorporates microfluidic techniques and Python-based video processing software, was developed for islet mass assessment. We quantified islets by tracking multiple moving islets in a microfluidic channel using the SFDIA system, and we achieved a relatively consistent result. The counts from the SFDIA and manual counting showed an average difference of 2.91 ± 1.50%. Furthermore, our software can analyze and extract key human islet mass parameters, including quantity, size, volume, IEq, morphology, and purity, which are not fully obtainable from traditional manual counting methods. Using SFDIA on a representative islet sample, we measured an average diameter of 99.88 ± 53.91 µm, an average circularity of 0.591 ± 0.133, and an average solidity of 0.853 ± 0.107.Viaanalysis of dithizone-stained islets using SFDIA, we found that a higher islet tissue percentage is associated with top-layer islets as opposed to middle-layer islets (0.735 ± 0.213 and 0.576 ± 0.223, respectively). Our results indicate that the SFDIA system can potentially be used as a multi-parameter islet mass assay that is superior in accuracy and consistency, when compared to conventional manual techniques.
An Inhibitor of NF-κB and an Agonist of AMPK: Network Prediction and Multi-Omics Integration to Derive Signaling Pathways for Acteoside Against Alzheimer’s Disease
Authors: Li Ying-Qi , Chen Yi , Jiang Si-Qi , Shi Yuan-Yuan , Jiang Xiao-Li , Wu Shan-Shan , Zhou Ping , Wang Hui-Ying , Li Ping , Li Fei
Published: July 2021

Alzheimer’s disease (AD) is the most frequent type of dementia. Acteoside (ACT) is a compound isolated from Cistanche tubulosa, which possesses excellent neuroprotective properties. However, the underlying mechanism of ACT in regulating microglia polarization remains ill-defined. Therefore, a computational network model was established to identify the driving targets of ACT and predict its mechanism by integrating multiple available databases. The AlCl3-induced AD model in zebrafish larvae was successfully constituted to demonstrate the therapeutic efficacy of ACT. Subsequently, LPS-induced BV-2 cells uncovered the positive role of ACT in M1/M2 polarization. The NF-κB and AMPK pathways were further confirmed by transcriptomic analysis, metabolomics analysis, molecular biology techniques, and molecular docking. The research provided an infusive mechanism of ACT and revealed the connection between metabolism and microglia polarization from the perspective of mitochondrial function. More importantly, it provided a systematic and comprehensive approach for the discovery of drug targets, including the changes in genes, metabolites, and proteins.
Apatinib Suppresses Gastric Cancer Stem Cells Properties by Inhibiting the Sonic Hedgehog Pathway
Authors: Cao Wanshuang , Li Yuan , Sun Hongliang , Yang Chenying , Zhu Jianyun , Xie Chunfeng , Li Xiaoting , Wu Jieshu , Geng Shanshan , Wang Lu , Sun Liangfei , Geng Guozhu , Han Hongyu , Zhong Caiyun
Published: July 2021

The presence of gastric cancer stem cells (GCSCs) marks the onset of gastric carcinoma. The sonic hedgehog (SHH) pathway plays a vital role in the maintenance of GCSC characteristics. Apatinib has been approved in China for advanced gastric cancer (GC) treatment. However, whether apatinib can target GCSCs and affect the SHH pathway remains unclear. The present study aimed to investigate the underlying mechanism of apatinib’s antitumor effects on GC. The expression levels of GCSC markers and number of CD133+ cells were significantly elevated in the sphere-forming cells. Apatinib effectively suppressed GCSC traits by inhibiting tumorsphere formation and cell proliferation, suppressing GCSC markers expression and CD133+ cell number, and inducing apoptosis. Apatinib downregulated the activation of the SHH pathway; while upregulation of the SHH pathway attenuated the inhibitory effects of apatinib on GCSCs. Moreover, apatinib treatment significantly delayed tumor growth and inhibited GCSC characteristics in the xenograft model. Our data suggested that apatinib exhibited inhibitory effects on GCSCs by suppressing SHH pathway both in vitro and in vivo, thus providing new insights into the therapeutic application of apatinib in GCSC suppression and advanced gastric cancer treatment.
Quantitative Relationships Between Growth, Differentiation, and Shape That Control Drosophila Eye Development and Its Variation
Authors: Lobo-Cabrera Francisco Javier , Navarro Tomás , Iannini Antonella , Casares Fernando , Cuetos Alejandro
Published: July 2021

The size of organs is critical for their function and often a defining trait of a species. Still, how organs reach a species-specific size or how this size varies during evolution are problems not yet solved. Here, we have investigated the conditions that ensure growth termination, variation of final size and the stability of the process for developmental systems that grow and differentiate simultaneously. Specifically, we present a theoretical model for the development of theDrosophilaeye, a system where a wave of differentiation sweeps across a growing primordium. This model, which describes the system in a simplified form, predicts universal relationships linking final eye size and developmental time to a single parameter which integrates genetically-controlled variables, the rates of cell proliferation and differentiation, with geometrical factors. We find that the predictions of the theoretical model show good agreement with previously published experimental results. We also develop a new computational model that recapitulates the process more realistically and find concordance between this model and theory as well, but only when the primordium is circular. However, when the primordium is elliptical both models show discrepancies. We explain this difference by the mechanical interactions between cells, an aspect that is not included in the theoretical model. Globally, our work defines the quantitative relationships between rates of growth and differentiation and organ primordium size that ensure growth termination (and, thereby, specify final eye size) and determine the duration of the process; identifies geometrical dependencies of both size and developmental time; and uncovers potential instabilities of the system which might constraint developmental strategies to evolve eyes of different size.
A Small Molecule Inhibitor of Pex3–Pex19 Interaction Disrupts Glycosome Biogenesis and Causes Lethality in Trypanosoma brucei
Authors: Banerjee Hiren , LaPointe Paul , Eitzen Gary , Rachubinski Richard A.
Published: July 2021

Trypanosomatid parasites, including Trypanosoma and Leishmania, are infectious zoonotic agents for a number of severe diseases such as African sleeping sickness and American trypanosomiasis (Chagas disease) that affect millions of people, mostly in the emergent world. The glycosome is a specialized member of the peroxisome family of organelles found in trypanosomatids. These organelles compartmentalize essential enzymes of the glycolytic pathway, making them a prime target for drugs that can kill these organisms by interfering with either their biochemical functions or their formation. Glycosome biogenesis, like peroxisome biogenesis, is controlled by a group of proteins called peroxins (Pex). Pex3 is an early acting peroxin that docks Pex19, the receptor for peroxisomal membrane proteins, to initiate biogenesis of peroxisomes from the endoplasmic reticulum. Identification of Pex3 as the essential master regulator of glycosome biogenesis has implications in developing small molecule inhibitors that can impede Pex3–Pex19 interaction. Low amino acid sequence conservation between trypanosomatid Pex3 and human Pex3 (HsPex3) would aid in the identification of small molecule inhibitors that selectively interfere with the trypanosomatid Pex3–Pex19 interaction. We tested a library of pharmacologically active compounds in a modified yeast two-hybrid assay and identified a compound that preferentially inhibited the interaction of Trypanosoma brucei Pex3 and Pex19 versus HsPex3 and Pex19. Addition of this compound to either the insect or bloodstream form of T. brucei disrupted glycosome biogenesis, leading to mislocalization of glycosomal enzymes to the cytosol and lethality for the parasite. Our results show that preferential disruption of trypanosomal Pex3 function by small molecule inhibitors could help in the accelerated development of drugs for the treatment of trypanosomiases.
Using Dictyostelium to Develop Therapeutics for Acute Respiratory Distress Syndrome
Authors: Kirolos Sara A. , Rijal Ramesh , Consalvo Kristen M. , Gomer Richard H.
Published: July 2021

Acute respiratory distress syndrome (ARDS) involves damage to lungs causing an influx of neutrophils from the blood into the lung airspaces, and the neutrophils causing further damage, which attracts more neutrophils in a vicious cycle. There are ∼190,000 cases of ARDS per year in the US, and because of the lack of therapeutics, the mortality rate is ∼40%. Repelling neutrophils out of the lung airspaces, or simply preventing neutrophil entry, is a potential therapeutic. In this minireview, we discuss how our lab noticed that a protein called AprA secreted by growing Dictyostelium cells functions as a repellent for Dictyostelium cells, causing cells to move away from a source of AprA. We then found that AprA has structural similarity to a human secreted protein called dipeptidyl peptidase IV (DPPIV), and that DPPIV is a repellent for human neutrophils. In animal models of ARDS, inhalation of DPPIV or DPPIV mimetics blocks neutrophil influx into the lungs. To move DPPIV or DPPIV mimetics into the clinic, we need to know how this repulsion works to understand possible drug interactions and side effects. Combining biochemistry and genetics in Dictyostelium to elucidate the AprA signal transduction pathway, followed by drug studies in human neutrophils to determine similarities and differences between neutrophil and Dictyostelium chemorepulsion, will hopefully lead to the safe use of DPPIV or DPPIV mimetics in the clinic.
Vertical Transmission and Discordance of Cytomegalovirus in Twin Pregnancies
Authors: Hutton Jill , Rowan Paul J.
Published: July 2021

Objective

The objectives are to estimate the vertical transmission rate in twins relative to singleton pregnancies, to evaluate whether discordance within twin pairs is rare, and to characterize concordance within monozygotic and dizygotic twin pairs in relation to hereditability.

Methods

We first sought to estimate the vertical transmission rate of congenital CMV infection in twins by gathering cohort-based studies of congenital CMV in which vertical transmission in both singleton and twin pregnancies was reported. This also allowed us to compare singleton and twin infection rates. From the above studies and other large cohorts of congenitally infected infants, the percentage of discordantly infected twin pairs determined whether this is a rare phenomenon. Theorizing discordance is not rare, we then analyzed data from cases with twin outcomes for congenital CMV infection, according to whether the twins were monozygotic or dizygotic, and calculated their corresponding concordance rates to estimate the broad-sense heritability. Lastly, we described other factors that might affect vertical transmission.

Results

From five articles following at-risk pregnancies, the rate of vertical transmission in twin pregnancies is 58.7% (95% CI 43.3-72.3%) whereas in singleton pregnancies it is 31.4% (95% CI: 29.0-34.0%)p= 0.0002. Of ten studies of larger cohorts of infants with congenital CMV infection, 21 of 42 twin pairs with at least one twin infected were discordant for congenital CMV (50.0%, 95% CI: 34.4–65.6%) indicating discordance of congenital CMV infection in twin pairs is not rare. Of 28 studies covering 37 twin pairs where at least one twin had congenital CMV, and zygosity was known, eleven of thirteen monozygotic twin pairs (84.6%; 95% CI: 53.7-97.3%) were concordant for CMV infection, and nine of twenty-four dizygotic twin pairs (37.5%; 95% CI: 19.6-59.2%) were concordant for infection giving an estimated hereditability of 94.2%. Within these 37 twin pairs, factors such as primary or recurrent maternal infection, prematurity, growth discordance, and sex are described; however, in many of these cases these factors are unknown.

Conclusion

The rate of vertical transmission of congenital CMV is higher for twins than singletons. Discordance of congenital CMV in twins is not rare and suggests a possible genetic susceptibility to congenital CMV.
Helminth Coinfection Is Associated With Enhanced Plasma Levels of Matrix Metalloproteinases and Tissue Inhibitor of Metalloproteinases in Tuberculous Lymphadenitis
Authors: Kathamuthu Gokul Raj , Moideen Kadar , Thiruvengadam Kannan , Sridhar Rathinam , Baskaran Dhanaraj , Babu Subash
Published: July 2021

Matrix metalloproteinases (MMPs) are crucial for tissue remodeling and repair and are expressed in diverse infections, whereas tissue inhibitors of metalloproteinases (TIMPs) are endogenous inhibitors of MMPs. However, the interaction of MMPs and TIMPs in tuberculous lymphadenitis (TBL), an extra-pulmonary form of tuberculosis (EPTB) and helminth (Hel+) coinfection is not known. Therefore, this present study investigates the levels of circulating MMPs (1, 2, 3, 7, 8, 9, 12, 13) and TIMPs (1, 2, 3, 4) in TBL individuals with helminth (Strongyloides stercoralis [Ss], hereafter Hel+) coinfection and without helminth coinfection (hereafter, Hel-). In addition, we have also carried out the regression analysis and calculated the MMP/TIMP ratios between the two study groups. We describe that the circulating levels of MMPs (except MMP-8 and MMP-12) were elevated in TBL-Hel+ coinfected individuals compared to TBL-Hel- individuals. Similarly, the systemic levels of TIMPs (1, 2, 3, 4) were increased in TBL-Hel+ compared to TBL-Hel- groups indicating that it is a feature of helminth coinfection per se. Finally, our multivariate analysis data also revealed that the changes in MMPs and TIMPs were independent of age, sex, and culture status between TBL-Hel+ and TBL-Hel- individuals. We show that the MMP-2 ratio with all TIMPs were significantly associated with TBL-helminth coinfection. Thus, our results describe how helminth infection has a profound effect on the pathogenesis of TBL and that both MMPs and TIMPs could dampen the immunity against the TBL-Hel+ coinfected individuals.
CPI-637 as a Potential Bifunctional Latency-Reversing Agent That Targets Both the BRD4 and TIP60 Proteins
Authors: Zheng Tengyi , Chen Pei , Huang Yifan , Qiu Jiayin , Zhou Chenliang , Wu Ziyao , Li Lin
Published: July 2021

The failure of highly active antiretroviral therapy (HAART) has been largely responsible for the existence of latent human immunodeficiency virus type 1 (HIV-1) reservoirs. The “shock and kill” strategy was confirmed to reactivate HIV-1 latent reservoirs by latency-reversing agents (LRAs) for accelerated HIV-1 clearance. However, a single LRA might be insufficient to induce HIV-1 reactivation from latency due to the complexity of the multiple signaling regulatory pathways that establish the HIV-1 latent reservoir. Therefore, combinations of LRAs or dual-mechanism LRAs are urgently needed to purge the latent reservoirs. We demonstrate here for the first time that a dual-target inhibitor with a specific suppressive effect on both BRD4 and TIP60, CPI-637, could reactivate latent HIV-1 in vitro by permitting Tat to bind positive transcription elongation factor b (P-TEFb) and assembling Tat-super-elongation complex (SEC) formation. In addition, CPI-637-mediated TIP60 downregulation further stimulated BRD4 dissociation from the HIV-1 long terminal repeat (LTR) promoter, allowing Tat to more effectively bind P-TEFb compared to BRD4 inhibition alone. Much more importantly, CPI-637 exerted a potent synergistic effect but alleviated global T cell activation and blocked viral spread to uninfected bystander CD4+ T cells with minimal cytotoxicity. Our results indicate that CPI-637 opens up the prospect of novel dual-target inhibitors for antagonizing HIV-1 latency and deserves further investigation for development as a promising LRA with a “shock and kill” strategy.
Feasibility of Transcatheter Caval Valve Implantation to Improve Sleep-Disordered Breathing in Patients With Severe Tricuspid Regurgitation—A Pilot Study
Authors: Wang Youmeng , Fernandes Branco Roberto , Fietzeck Andrea , Penzel Thomas , Schöbel Christoph
Published: July 2021

Transcatheter caval valve implantation (CAVI) has been evaluated as a treatment option for inoperable patients with severe symptomatic tricuspid regurgitation (TR). We studied the effect of CAVI on sleep disorder breathing (SDB) in patients with right heart failure and TR. Twenty right heart failure patients with severe symptomatic TR who underwent portable monitoring of SDB (ApneaLink), echocardiography, cardiopulmonary exercise (CPET), and laboratory testing were enrolled. This was a single-center, nonblinded study. There were no significant changes in sleep variables, echocardiographic parameters, laboratory results, lung function, and CPET after CAVI. In conclusion, these data suggest that CAVI may not have an effect on SDB; however, additional follow-up fully powered studies with appropriate statistical analyses are needed.
Strain Transformation Adjacent to the West Qinling Orogen: Implications for the Growth of the Northeastern Tibetan Plateau
Authors: Li Zhangjun , Cheng Feng , Hao Ming , Young Zachary M. , Song Shangwu , Yang Fan , Zhuang Wenquan
Published: July 2021

The West Qinling orogen has played an important role in accommodating the deformation in the northeastern Tibetan Plateau induced by the India-Eurasia convergence. Here we construct a vertical land motion (VLM) model based on the latest leveling observations adjacent to the West Qinling orogen. Combined with the horizontal deformation field, the crustal deformation pattern in this area is investigated. Additionally, slip rate and coupling coefficients of the West Qinling fault, the longest fault separating the West Qinling orogen from the Lanzhou (Longxi) block, are inverted and constrained with GPS and VLM observations. Results show that the West Qinling fault slips slowly at a rate of 1–2 mm/yr and is strongly coupled with a moment magnitude deficit of Mw7.4. The crustal uplift rates adjacent to the West Qinling orogen are 0–3 mm/yr; which combined with 0–12.5 × 10−9/yr contraction rates, suggests that strain transformation plays a key role in controlling the tectonic uplift in the West Qinling orogen, and furthers our understanding of the contemporary geomorphic and topographic features. We identify a significant deformation transition belt at longitudes of 105°–106°E, which indicates that crustal deformation, induced from the northeastern expansion of the Tibetan Plateau, is mainly constrained to the plateau, rather than accommodated by crustal materials escaping eastward along the Qinling Mountains.
Reliabilities of Genomic Prediction for Young Stock Survival Traits Using 54K SNP Chip Augmented With Additional Single-Nucleotide Polymorphisms Selected From Imputed Whole-Genome Sequencing Data
Authors: Gebreyesus Grum , Lund Mogens Sandø , Sahana Goutam , Su Guosheng
Published: July 2021

This study investigated effects of integrating single-nucleotide polymorphisms (SNPs) selected based on previous genome-wide association studies (GWASs), from imputed whole-genome sequencing (WGS) data, in the conventional 54K chip on genomic prediction reliability of young stock survival (YSS) traits in dairy cattle. The WGS SNPs included two groups of SNP sets that were selected based on GWAS in the Danish Holstein for YSS index (YSS_SNPs, n = 98) and SNPs chosen as peaks of quantitative trait loci for the traits of Nordic total merit index in Denmark–Finland–Sweden dairy cattle populations (DFS_SNPs, n = 1,541). Additionally, the study also investigated the possibility of improving genomic prediction reliability for survival traits by modeling the SNPs within recessive lethal haplotypes (LET_SNP, n = 130) detected from the 54K chip in the Nordic Holstein. De-regressed proofs (DRPs) were obtained from 6,558 Danish Holstein bulls genotyped with either 54K chip or customized LD chip that includes SNPs in the standard LD chip and some of the selected WGS SNPs. The chip data were subsequently imputed to 54K SNP together with the selected WGS SNPs. Genomic best linear unbiased prediction (GBLUP) models were implemented to predict breeding values through either pooling the 54K and selected WGS SNPs together as one genetic component (a one-component model) or considering 54K SNPs and selected WGS SNPs as two separate genetic components (a two-component model). Across all the traits, inclusion of each of the selected WGS SNP sets led to negligible improvements in prediction accuracies (0.17 percentage points on average) compared to prediction using only 54K. Similarly, marginal improvement in prediction reliability was obtained when all the selected WGS SNPs were included (0.22 percentage points). No further improvement in prediction reliability was observed when considering random regression on genotype code of recessive lethal alleles in the model including both groups of the WGS SNPs. Additionally, there was no difference in prediction reliability from integrating the selected WGS SNP sets through the two-component model compared to the one-component GBLUP.
Comprehensive Analysis of Differentially Expressed lncRNAs miRNAs and mRNA and Their ceRNA Network of Patients With Rare-Earth Pneumoconiosis
Authors: Shi Xue-min , Bai Yu-chao , Gao Yan-rong , Bu Ning , Song Hai-yan , Huang Li-hua , Zhao Yu-hang , Wang Su-hua
Published: July 2021

Rare-earth pneumoconiosis (REP) is the main occupational disease of rare earth exposed workers and there is no specific treatment. In this study, we performed high-throughput sequencing on the plasma of nine REP to describe and analyze the expression profiles of long non-coding RNA (lncRNA), micro RNA (miRNA) and mRNA and investigate their regulatory networks. Our results identified a total of 125 lncRNAs, 5 miRNAs, and 82 mRNAs were differentially expressed in the plasma of patients with REP. Furthermore, Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were used to analyze the differentially expressed non-coding RNAs (ncRNA). We found the differential expression of ncRNA are mainly related to the response of cells to stimulation, Hedgehog signaling pathway and so on. We also constructed lncRNA-miRNA-mRNA networks to further explore their underlying mechanism and possible relationships in REP. We found that in the competitive endogenous RNA (ceRNA) networks, lncRNA acts as a sponge of miRNA to regulate the target gene. The expression results were verified by qRT-PCR and the protein interaction networks of differentially expressed genes were constructed via the STRING database. OncoLnc online platform was used to do the lung cancer survival analysis among the top five mRNA analyzed by Protein-protein interaction (PPI) network analysis. We found miR-16-2-3p may used as biomarker for REP, because it is closely related to the occurrence and prognosis of REP through inflammatory reaction and in lung squamous cell carcinoma, its expression levels were positively correlated with the overall survival rate of patients.
Identification of Candidate Blood mRNA Biomarkers in Intracerebral Hemorrhage Using Integrated Microarray and Weighted Gene Co-expression Network Analysis
Authors: Jin Feng , Li Lei , Hao Yuehan , Tang Ling , Wang Yuye , He Zhiyi
Published: July 2021

Purpose

Intracerebral hemorrhage (ICH) is a serious public health hazard due to its high morbidity, disability, and mortality. Currently, the exact molecular mechanisms of ICH are unknown. We tried to identify the ICH-related candidate blood messenger RNA (mRNA) biomarkers by microarray analysis and weighted gene co-expression network analysis (WGCNA).

Materials and Methods

We collected the blood samples from patients with ICH (n = 4) and from vascular risk factor (VRF) controls (n = 4) and analyzed the mRNA expression profiles by competitive endogenous RNA (ceRNA) microarray. Differentially expressed genes (DEGs) were identified and then a weighted gene co-expression network was constructed. Modules with clinical significance were distinguished. Then, we downloaded two Gene Expression Omnibus (GEO) datasets (GSE24265 and GSE125512). Candidate mRNAs were identified by taking the intersection of the DEGs in our microarray, the interesting genes in the key module, and the DEGs in GSE24265. Functional analysis involving Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) and construction of a protein–protein interaction (PPI) network were conducted.

Results

A total of 340 DEGs in our microarray were identified between the ICH group and the control group. Among the eight gene modules established by WGCNA, the yellow module containing 191 genes was the most strongly associated with ICH. Four candidate mRNAs (C3AR1, PAWR, ARNTL2, and LDLRAD4) were identified. In the early stage of ICH (within 24 h), C3AR1, PAWR, and ARNTL2 were highly expressed in the perihematomal tissue, but with low expressions in peripheral blood; in the late stage (72 h after the first blood draw), an obvious upward trend of C3AR1 and PAWR in peripheral blood was seen. Functional analysis showed that candidate mRNAs were concerned with multiple pathways, such as the Wnt signaling pathway and calcium signaling pathway. They might affect the process of ICH through neuroinflammation, cell apoptosis, and pyroptosis.

Conclusion

We identified four candidate blood mRNAs (C3AR1, PAWR, ARNTL2, and LDLRAD4) related to ICH. They showed different expression patterns in peripheral blood and perihematomal tissues and changed with time. They might play important roles in ICH through neuroinflammation, cell apoptosis, and pyroptosis and might shed new light to novel biomarkers or therapeutic targets in ICH.
Multi-Omics Profiling Identifies Risk Hypoxia-Related Signatures for Ovarian Cancer Prognosis
Authors: Chen Xingyu , Lan Hua , He Dong , Xu Runshi , Zhang Yao , Cheng Yaxin , Chen Haotian , Xiao Songshu , Cao Ke
Published: July 2021

Background

Ovarian cancer (OC) has the highest mortality rate among gynecologic malignancy. Hypoxia is a driver of the malignant progression in OC, which results in poor prognosis. We herein aimed to develop a validated model that was based on the hypoxia genes to systematically evaluate its prognosis in tumor immune microenvironment (TIM).

Results

We identified 395 hypoxia-immune genes using weighted gene co-expression network analysis (WGCNA). We then established a nine hypoxia-related genes risk model using least absolute shrinkage and selection operator (LASSO) Cox regression, which efficiently distinguished high-risk patients from low-risk ones. We found that high-risk patients were significantly related to poor prognosis. The high-risk group showed unique immunosuppressive microenvironment, lower antigen presentation, and higher levels of inhibitory cytokines. There were also significant differences in somatic copy number alterations (SCNAs) and mutations between the high- and low-risk groups, indicating immune escape in the high-risk group. Tumor immune dysfunction and exclusion (TIDE) and SubMap algorithms showed that low-risk patients are significantly responsive to programmed cell death protein-1 (PD-1) inhibitors.

Conclusions

In this study, we highlighted the clinical significance of hypoxia in OC and established a hypoxia-related model for predicting prognosis and providing potential immunotherapy strategies.
Neoadjuvant Programmed Cell Death 1 (PD-1) Inhibitor Treatment in Patients With Hepatocellular Carcinoma Before Liver Transplant: A Cohort Study and Literature Review
Authors: Qiao Zi-yun , Zhang Zi-jie , Lv Zi-cheng , Tong Huan , Xi Zhi-feng , Wu Hao-xiang , Chen Xiao-song , Xia Lei , Feng Hao , Zhang Jian-jun , Xia Qiang
Published: July 2021

Programmed cell death 1 (PD-1) blockade is considered contraindicated in liver transplant (LT) recipients due to potentially lethal consequences of graft rejection and loss. Though post-transplant PD-1 blockade had already been reported, pre-transplant use of PD-1 blockade has not been thoroughly investigated. This study explores the safety and efficacy of neoadjuvant PD-1 blockade in patients with hepatocellular carcinoma (HCC) after registration on the waiting list. Seven transplant recipients who underwent neoadjuvant PD-1 blockade combined with lenvatinib and subsequent LT were evaluated. The objective response rate (ORR) and disease control rate (DCR) was 71% and 85% according to the mRECIST criteria. Additionally, a literature review contained 29 patients were conducted to summarize the PD-1 blockade in LT for HCC. Twenty-two LT recipients used PD-1 inhibitors for recurrent HCC. 9.1% (2/22) and 4.5% (1/22) recipients achieved complete remission (CR) and partial remission (PR), respectively; 40.9% (9/22) recipients had progressive disease (PD). Allograft rejection occurred in 45% of patients. In total, seven patients from our center and three from the literature used pretransplant anti-PD-1 antibodies, eight patients (80%) had a PR, and the disease control rate was 100%. Biopsy-proven acute rejection (BPAR) incidence was 30% (3 in 10 patients), two patients died because of BPAR. This indicated that neoadjuvant PD-1-targeted immunotherapy plus tyrosine kinase inhibitors (TKI) exhibited promising efficacy with tolerable mortality in transplant recipients under close clinical monitoring.
Structure-Function Relationships of Covalent and Non-Covalent BTK Inhibitors
Authors: Zain Rula , Vihinen Mauno
Published: July 2021

Low-molecular weight chemical compounds have a longstanding history as drugs. Target specificity and binding efficiency represent major obstacles for small molecules to become clinically relevant. Protein kinases are attractive cellular targets; however, they are challenging because they present one of the largest protein families and share structural similarities. Bruton tyrosine kinase (BTK), a cytoplasmic protein tyrosine kinase, has received much attention as a promising target for the treatment of B-cell malignancies and more recently autoimmune and inflammatory diseases. Here we describe the structural properties and binding modes of small-molecule BTK inhibitors, including irreversible and reversible inhibitors. Covalently binding compounds, such as ibrutinib, acalabrutinib and zanubrutinib, are discussed along with non-covalent inhibitors fenebrutinib and RN486. The focus of this review is on structure-function relationships.
ZBTB Transcription Factors: Key Regulators of the Development, Differentiation and Effector Function of T Cells
Authors: Cheng Zhong-Yan , He Ting-Ting , Gao Xiao-Ming , Zhao Ying , Wang Jun
Published: July 2021

The development and differentiation of T cells represents a long and highly coordinated, yet flexible at some points, pathway, along which the sequential and dynamic expressions of different transcriptional factors play prominent roles at multiple steps. The large ZBTB family comprises a diverse group of transcriptional factors, and many of them have emerged as critical factors that regulate the lineage commitment, differentiation and effector function of hematopoietic-derived cells as well as a variety of other developmental events. Within the T-cell lineage, several ZBTB proteins, including ZBTB1, ZBTB17, ZBTB7B (THPOK) and BCL6 (ZBTB27), mainly regulate the development and/or differentiation of conventional CD4/CD8 αβ+ T cells, whereas ZBTB16 (PLZF) is essential for the development and function of innate-like unconventional γδ+ T & invariant NKT cells. Given the critical role of T cells in host defenses against infections/tumors and in the pathogenesis of many inflammatory disorders, we herein summarize the roles of fourteen ZBTB family members in the development, differentiation and effector function of both conventional and unconventional T cells as well as the underlying molecular mechanisms.
The Three-Dimensional Structure of Mediterranean Shallow Rocky Reefs: Use of Photogrammetry-Based Descriptors to Assess Its Influence on Associated Teleost Assemblages
Authors: Monfort Tiffany , Cheminée Adrien , Bianchimani Olivier , Drap Pierre , Puzenat Arthur , Thibaut Thierry
Published: July 2021

In the Mediterranean Sea, shallow rocky reefs and the associated three-dimensional (3D) structure support rich and abundant communities; they are therefore of functional importance, in particular for the renewal of fish stocks. However, these habitats and their functions are likely to be altered by anthropogenic pressures inducing habitat transformations. It is therefore necessary to assess their 3D structure, their transformations and relationship to communities, especially for management and conservation purposes. In this article we aimed (i) to compare two methods that quantify the metrics of the 3D structure (rugosity) of shallow rocky reefs (chain-and-tape method and photogrammetry), and (ii) to quantify the possible links between this habitat structure and the fish assemblages. We found that photogrammetry and the chain-and-tape method yielded a similar estimate of rugosity, but photogrammetry was the most efficient method in terms of measurement quality and time (when considering in-water acquisition). This method also displayed the best repeatability. The 3D habitat descriptors (mean surface rugosity, variation of surface rugosity, and depth) differed significantly between the studied sites and were therefore included as covariables. Total fish abundance and species richness increased with higher mean surface rugosity. In addition, the composition of fish assemblages was significantly influenced by surface rugosity, although this effect was modulated by depth. When focusing on specific taxa, neither density patterns nor size class distributions displayed clear patterns in relation to rugosity metrics. However, this study demonstrated that spatial variability of teleost fish assemblages can be explained by habitat rugosity which probably increases the number of shelters and food resources, and therefore improves chances of survival. In addition, our study has shown that photogrammetry is an appropriate method to assess 3D structure metrics in a temperate rocky reef.
Aggregation and Degradation of Dispersants and Oil by Microbial Exopolymers (ADDOMEx): Toward a Synthesis of Processes and Pathways of Marine Oil Snow Formation in Determining the Fate of Hydrocarbons
Authors: Quigg Antonietta , Santschi Peter H. , Xu Chen , Ziervogel Kai , Kamalanathan Manoj , Chin Wei-Chun , Burd Adrian B. , Wozniak Andrew , Hatcher Patrick G.
Published: July 2021

Microbes (bacteria, phytoplankton) in the ocean are responsible for the copious production of exopolymeric substances (EPS) that include transparent exopolymeric particles. These materials act as a matrix to form marine snow. After the Deepwater Horizon oil spill, marine oil snow (MOS) formed in massive quantities and influenced the fate and transport of oil in the ocean. The processes and pathways of MOS formation require further elucidation to be better understood, in particular we need to better understand how dispersants affect aggregation and degradation of oil. Toward that end, recent work has characterized EPS as a function of microbial community and environmental conditions. We present a conceptual model that incorporates recent findings in our understanding of the driving forces of MOS sedimentation and flocculent accumulation (MOSSFA) including factors that influence the scavenging of oil into MOS and the routes that promote decomposition of the oil post MOS formation. In particular, the model incorporates advances in our understanding of processes that control interactions between oil, dispersant, and EPS in producing either MOS that can sink or dispersed gels promoting microbial degradation of oil compounds. A critical element is the role of protein to carbohydrate ratios (P/C ratios) of EPS in the aggregation process of colloid and particle formation. The P/C ratio of EPS provides a chemical basis for the “stickiness” factor that is used in analytical or numerical simulations of the aggregation process. This factor also provides a relative measure for the strength of attachment of EPS to particle surfaces. Results from recent laboratory experiments demonstrate (i) the rapid formation of microbial assemblages, including their EPS, on oil droplets that is enhanced in the presence of Corexit-dispersed oil, and (ii) the subsequent rapid oil oxidation and microbial degradation in water. These findings, combined with the conceptual model, further improve our understanding of the fate of the sinking MOS (e.g., subsequent sedimentation and preservation/degradation) and expand our ability to predict the behavior and transport of spilled oil in the ocean, and the potential effects of Corexit application, specifically with respect to MOS processes (i.e., formation, fate, and half-lives) and Marine Oil Snow Sedimentation and Flocculent Accumulation.
Seasonal and Ontogenetic Variation in Depth Use by a Critically Endangered Benthic Elasmobranch and Its Implications for Spatial Management
Authors: Thorburn James , Wright Peter J. , Lavender Edward , Dodd Jane , Neat Francis , Martin Julien G. A. , Lynam Caroline , James Mark
Published: July 2021

Seasonal and ontogenetic variations in depth use by benthic species are often concomitant with changes in their spatial distribution. This has implications for the efficacy of spatial conservation measures such as marine protected areas (MPAs). The critically endangered flapper skate (Dipturus intermedius) is the designation feature of an MPA in Scotland. This species is generally associated with deeper waters >100 m; however, little is known about its seasonal or ontogenetic variation in habitat use. This study used archival depth data from 25 immature and mature flapper skate tagged in the MPA over multiple years. Time series ranged from 3 to 772 (mean = 246) days. Generalised additive mixed models and highest density intervals were used to identify home (95%) and core (50%) highest density depth regions (HDDRs) to quantify depth use in relation to time of year and body size. Skate used a total depth range of 1–312 m, but home HDDRs typically occurred between 20 and 225 m. Core HDDRs displayed significant seasonal and ontogenetic variations. Summer core HDDRs (100–150 m) suggest high occupancy of the deep trenches in the region by skate of most size classes. There was an inverse relationship between body size and depth use and a seasonal trend of skate moving into shallow water over winter months. These results suggest that flapper skate are not solely associated with deep water, as skate, especially large females, are frequently found in shallow waters (25–75 m). The current management, which protects the entire depth range, is appropriate for the protection of flapper skate through much of its life history. This research demonstrates why collecting data across seasonal scales and multiple ontogenetic stages is needed to assess the effectiveness of spatial management.
Predicted Shifts in the Distributions of Atlantic Reef-Building Corals in the Face of Climate Change
Authors: Principe Silas C. , Acosta André L. , Andrade João E. , Lotufo Tito M. C.
Published: July 2021

Many species drive the diversity of ecosystems by adding structural complexity to the environment. In coral reefs, stony corals act as habitat-forming species, increasing niche availability for other organisms. Some coral species play key roles as reef builders due to their abundance or morpho-functional characteristics. Thus, changes in the distributions of these species can entail cascading effects in entire ecosystems. With climate change, many coral species are experiencing shifts in their distributions, threatening the preservation of coral reefs. Here, we projected the current and future distributions of three key reef builders of the Atlantic (Mussismilia hispida, Montastraea cavernosa, and the Siderastrea complex) under three relative concentration pathway scenarios: the most optimistic, the most pessimistic and one moderate scenario (RCP2.6, 4.5, and 8.5). Our models revealed that all the above species will undergo habitat loss in the future (2100) in the most pessimistic scenario, although new areas could become suitable, including regions in the eastern Atlantic Ocean. Additionally, when considering only its actual range of occurrence, M. hispida will lose habitats under all future scenarios. Moreover, in some regions of both the Tropical Northwestern Atlantic (TNA) and the Brazilian coast, these three species could disappear, with detrimental consequences for the associated communities. We highlight the need for an urgent change of course to guarantee functional reefs in the Atlantic in the future.