bluuebunny/crossref_metadata_2025 huggingface dataset:
The Stressful Effects of Microplastics Associated With Chromium (VI) on the Microbiota of Daphnia Magna
Authors: Varg Javier Edo , Bergvall Christoffer , Svanbäck Richard
Published: May 2022

Contamination by microplastics (particles < 1 mm) is a growing and alarming environmental problem in freshwater systems. Evidence suggests that industrial effluents could be one of the critical point sources of microplastics and other pollutants, and their interaction can cause organismal stress and affect host and environmental microbial communities. We tested the individual and combined effects of microplastics and other pollutants on host survival and host associated (commensal) bacterial diversity. We exposed Daphnia magna to 1 µm microplastic beads with a concentration of approximately 1820 particles/ml and chromium (VI) simultaneously with treatments of 2 and 5 ppm for 72 h. DNA extraction was done to amplify and sequence the ribosomal Bacterial 16S from both the water and the Daphnia. Daphnia experienced low mortality in treatments microplastics (13.3%) and 2 ppm chromium VI (30%) individually. However, the combination of microplastics and 2 ppm chromium (VI) increased the mortality to 74.4%. In the treatments with 5 ppm of chromium (VI) mortality rose to 100% after 30 h of exposure. Microbial diversity changed in response to microplastics, chromium (VI), and both combined exposure. Microplastics and toxic metals can cause dysbiosis of freshwater environmental microbiota, whole host microbiota, and host survival. This work stresses the importance to assess how pollutants’ individual and joint effects could affect organisms including their microbiome.
The Relationship Between Rail Transit and Industrial Agglomeration: Mediating Effect of Labor Agglomeration
Authors: Sun Jing , Cherian Jacob , Deng Dasong , Yucel Ali Gokhan , Sial Muhammad Safdar , Fu Qinghua , Cismas Laura Mariana
Published: May 2022

The urban transit system is considered the backbone of any society as it heavily depends on economic progress. The railway transit system is crucial for any urban transit system. Based on this notion, the present research explores the industrial agglomeration in China’s prefecture-level and cities from 2010 to 2020. The research analyses the processes of urban rail transit building, industrial agglomeration, and labor agglomeration due to the railway’s transit network development. The findings are summarized in three main points; first, the agglomeration of the labor force is positively affected by the construction of urban rail transit infrastructure. Secondly, the development of railways infrastructure stimulates the agglomeration of manufacturing industries in and near urban population centers leading to the development of services industries. Third, the development and integration of railways networks with other transportation networks also optimize the allocation of capital in these areas as well. In the present research Preacher and Hayes, Behavior research methods, 2008, 40 (3), 879–891 methodology has been applied to determine the relationship between the development of railways transit system and concentration of industries, by taking into account the mediating effects of labor agglomeration. The development of railways network tends to bring economic and industrial development to these regions resulting in overall social development.
A Spatial Patterns Identification Method of Rural Residential Land Change Integrating Dynamic and Multi-Scale Information
Authors: Jiang Guanghui , Chen Tianqian , Zhang Ruijuan , Tian Yaya , Wu Siduo
Published: May 2022

Affected by rapid urbanization, the spatial layout of rural residential land (RRL) is facing urgent reconstruction and adjustment. The study of spatial change patterns of RRL can provide a basis for optimization and adjustment. The Pinggu of Beijing was chosen as the study area. Taking into account the layout characteristics of RRL from 2005 to 2015, a combination matrix method was developed to identify the spatial change patterns. The distribution characteristics of the change patterns under different environmental gradients were further analyzed. The study shows that the layout types of RRL in Pinggu in 2015 were dominated by the dispersion-regular-large scale cluster type and concentration-regular-large scale cluster type. The area of RRL patches in Pinggu increased by 686.89 hm2 from 2005 to 2015, which was approximately 12%. The main spatial change patterns of the RRL are the cluster leapfrog dispersion change pattern and cluster edge-expansion concentration change pattern. The distribution of the pattern of RRL shows a decreasing trend under the topography and location gradients set in this paper. And the spatial patterns of RRL are changing at an accelerated rate due to the advanced production environment represented. Our study analyzes the changing pattern of RRL from multiple environmental gradients and provides a basis for the formulation of RRL layout optimization strategies.
Exploring Evolved Multicellular Life Histories in a Open-Ended Digital Evolution System
Authors: Moreno Matthew Andres , Ofria Charles
Published: May 2022

Evolutionary transitions occur when previously-independent replicating entities unite to form more complex individuals. Such transitions have profoundly shaped natural evolutionary history and occur in two forms: fraternal transitions involve lower-level entities that are kin (e.g., transitions to multicellularity or to eusocial colonies), while egalitarian transitions involve unrelated individuals (e.g., the origins of mitochondria). The necessary conditions and evolutionary mechanisms for these transitions to arise continue to be fruitful targets of scientific interest. Here, we examine a range of fraternal transitions in populations of open-ended self-replicating computer programs. These digital cells were allowed to form and replicate kin groups by selectively adjoining or expelling daughter cells. The capability to recognize kin-group membership enabled preferential communication and cooperation between cells. We repeatedly observed group-level traits that are characteristic of a fraternal transition. These included reproductive division of labor, resource sharing within kin groups, resource investment in offspring groups, asymmetrical behaviors mediated by messaging, morphological patterning, and adaptive apoptosis. We report eight case studies from replicates where transitions occurred and explore the diverse range of adaptive evolved multicellular strategies.
Heterogeneous Skeletal Muscle Cell and Nucleus Populations Identified by Single-Cell and Single-Nucleus Resolution Transcriptome Assays
Authors: Williams Katherine , Yokomori Kyoko , Mortazavi Ali
Published: May 2022

Single-cell RNA-seq (scRNA-seq) has revolutionized modern genomics, but the large size of myotubes and myofibers has restricted use of scRNA-seq in skeletal muscle. For the study of muscle, single-nucleus RNA-seq (snRNA-seq) has emerged not only as an alternative to scRNA-seq, but as a novel method providing valuable insights into multinucleated cells such as myofibers. Nuclei within myofibers specialize at junctions with other cell types such as motor neurons. Nuclear heterogeneity plays important roles in certain diseases such as muscular dystrophies. We survey current methods of high-throughput single cell and subcellular resolution transcriptomics, including single-cell and single-nucleus RNA-seq and spatial transcriptomics, applied to satellite cells, myoblasts, myotubes and myofibers. We summarize the major myonuclei subtypes identified in homeostatic and regenerating tissue including those specific to fiber type or at junctions with other cell types. Disease-specific nucleus populations were found in two muscular dystrophies, FSHD and Duchenne muscular dystrophy, demonstrating the importance of performing transcriptome studies at the single nucleus level in muscle.
Identification of Context-Specific Fitness Genes Associated With Metabolic Rearrangements for Prognosis and Potential Treatment Targets for Liver Cancer
Authors: Yu Shizhe , Wang Haoren , Gao Jie , Liu Long , Sun Xiaoyan , Wang Zhihui , Wen Peihao , Shi Xiaoyi , Shi Jihua , Guo Wenzhi , Zhang Shuijun
Published: May 2022

Liver cancer is the most frequent fatal malignancy. Furthermore, there is a lack of effective therapeutics for this cancer type. To construct a prognostic model for potential beneficiary screens and identify novel treatment targets, we used an adaptive daisy model (ADaM) to identify context-specific fitness genes from the CRISPR-Cas9 screens database, DepMap. Functional analysis and prognostic significance were assessed using data from TCGA and ICGC cohorts, while drug sensitivity analysis was performed using data from the Liver Cancer Model Repository (LIMORE). Finally, a 25-gene prognostic model was established. Patients were then divided into high- and low-risk groups; the high-risk group had a higher stemness index and shorter overall survival time than the low-risk group. The C-index, time-dependent ROC curves, and multivariate Cox regression analysis confirmed the excellent prognostic ability of this model. Functional enrichment analysis revealed the importance of metabolic rearrangements and serine/threonine kinase activity, which could be targeted by trametinib and is the key pathway in regulating liver cancer cell viability. In conclusion, the present study provides a prognostic model for patients with liver cancer and might help in the exploration of novel therapeutic targets to ultimately improve patient outcomes.
Down Syndrome Fetal Fibroblasts Display Alterations of Endosomal Trafficking Possibly due to SYNJ1 Overexpression
Authors: De Rosa Laura , Fasano Dominga , Zerillo Lucrezia , Valente Valeria , Izzo Antonella , Mollo Nunzia , Amodio Giuseppina , Polishchuk Elena , Polishchuk Roman , Melone Mariarosa Anna Beatrice , Criscuolo Chiara , Conti Anna , Nitsch Lucio , Remondelli Paolo , Pierantoni Giovanna Maria , Paladino Simona
Published: May 2022

Endosomal trafficking is essential for cellular homeostasis. At the crossroads of distinct intracellular pathways, the endolysosomal system is crucial to maintain critical functions and adapt to the environment. Alterations of endosomal compartments were observed in cells from adult individuals with Down syndrome (DS), suggesting that the dysfunction of the endosomal pathway may contribute to the pathogenesis of DS. However, the nature and the degree of impairment, as well as the timing of onset, remain elusive. Here, by applying imaging and biochemical approaches, we demonstrate that the structure and dynamics of early endosomes are altered in DS cells. Furthermore, we found that recycling trafficking is markedly compromised in these cells. Remarkably, our results in 18–20 week-old human fetal fibroblasts indicate that alterations in the endolysosomal pathway are already present early in development. In addition, we show that overexpression of the polyphosphoinositide phosphatase synaptojanin 1 (Synj1) recapitulates the alterations observed in DS cells, suggesting a role for this lipid phosphatase in the pathogenesis of DS, likely already early in disease development. Overall, these data strengthen the link between the endolysosomal pathway and DS, highlighting a dangerous liaison among Synj1, endosomal trafficking and DS.
An Aging and Senescence-Related Gene Signature for Prognosis Prediction in Clear Cell Renal Cell Carcinoma
Authors: Li Jiaying , Gui Chengpeng , Yao Haohua , Luo Chenggong , Song Hongde , Lin Haishan , Xu Quanhui , Chen Xu , Huang Yong , Luo Junhang , Chen Wei
Published: May 2022

Background: Clear cell renal cell carcinoma (ccRCC) is the most common solid lesion in the kidney. This study aims to establish an aging and senescence-related mRNA model for risk assessment and prognosis prediction in ccRCC patients.

Methods: ccRCC data were obtained from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) datasets. By applying univariate Cox regression, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression, a new prognostic model based on aging and senescence-related genes (ASRGs) was established. Depending on the prognostic model, high- and low-risk groups were identified for further study. The reliability of the prediction was evaluated in the validation cohort. Pan-cancer analysis was conducted to explore the role of GNRH1 in tumors.

Results: A novel prognostic model was established based on eight ASRGs. This model was an independent risk factor and significantly correlated with the prognosis and clinicopathological features of ccRCC patients. The high- and low-risk groups exhibited distinct modes in the principal component analysis and different patterns in immune infiltration. Moreover, the nomogram combining risk score and other clinical factors showed excellent predictive ability, with AUC values for predicting 1-, 3-, and 5-year overall survival in the TCGA cohort equal to 0.88, 0.82, and 0.81, respectively.

Conclusion: The model and nomogram based on the eight ASRGs had a significant value for survival prediction and risk assessment for ccRCC patients, providing new insights into the roles of aging and senescence in ccRCC.
TROY Modulates Cancer Stem-Like Cell Properties and Gefitinib Resistance Through EMT Signaling in Non–Small Cell Lung Cancer
Authors: Wu Linying , Yu Yuman , Xu Liming , Wang Xiaoling , Zhou Jianying , Wang Yuehong
Published: May 2022

Targeted therapy has made breakthrough progress in the treatment of advanced non–small cell lung cancer (NSCLC) in the last 20 years. Despite that, acquired resistance of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) is an urgent clinical problem. Our study established an acquired gefitinib-resistant cell line, which exhibited epithelial–mesenchymal transition (EMT) and stem cell–like properties. Transcriptional sequencing and bioinformatics analysis revealed that TROY was significantly increased in gefitinib-resistant cells. Gene set enrichment analysis (GSEA) showed EMT was the core enriched hallmark in the resistant cells. TROY siRNA interference could overcome the gefitinib resistance with the downregulated expression of EMT and CSC markers. In addition, immunohistochemistry indicated that TROY was overexpressed in tumor samples from patients who acquired resistance to first-generation EGFR-TKI without T790M mutation and the expression of TROY was associated with poor prognosis in LUAD. Here, we provided the potential role of TROY in the resistance of targeted therapy and a new strategy to overcome the acquired resistance to EGFR-TKI in NSCLC.
A New Risk Model Based on 7 Quercetin-Related Target Genes for Predicting the Prognosis of Patients With Lung Adenocarcinoma
Authors: Zhang Yun-Qiang , Li Kai , Guo Qiang , Li Dan
Published: May 2022

Background: Studies have reported that quercetin inhibits the growth and migration of lung adenocarcinoma (LUAD). This study aimed to explore the roles and mechanisms of quercetin target genes in the progression of LUAD.

Methods: The quercetin structure and potential target genes of quercetin were explored in the Traditional Chinese Medicine Systems Pharmacology and SwissTargetPrediction databases. The differentially expressed quercetin target genes were identified in The Cancer Genome Atlas (TCGA) database, and the clinical values of quercetin target genes were explored. Subsequently, a risk model was constructed via the Cox regression and survival analysis to evaluate the potential effects and possible mechanisms of quercetin target genes.

Results: The quercetin differential target genes involved in biological processes such as the oxidation-reduction process, cell proliferation, G2/M transition of the mitotic cell cycle, and were related to the lung cancer. NEK2, TOP2A, PLK1, CA4, CDK5R1, AURKB, and F2 were related to the prognosis, and were independent factors influencing the prognosis of LUAD patients. The risk model was related to the gender, clinical stage, T stage, lymph node metastasis, and survival status of LUAD patients, and was independent risk factor associated with poor prognosis. In the high-risk group, the risk model involved signaling pathways such as cell cycle, DNA replication, spliceosome, and homologous recombination.

Conclusion: The quercetin potential target genes NEK2, TOP2A, PLK1, CA4, CDK5R1, AURKB, and F2 were related to the diagnosis and prognosis of LUAD patients. A risk model based on 7 quercetin target genes could be used to assess the prognosis of patients with LUAD.
Recent Bioinformatic Progress to Identify Epigenetic Changes Associated to Transposable Elements
Authors: Lerat Emmanuelle
Published: May 2022

Transposable elements (TEs) are recognized for their great impact on the functioning and evolution of their host genomes. They are associated to various deleterious effects, which has led to the evolution of regulatory epigenetic mechanisms to control their activity. Despite these negative effects, TEs are also important actors in the evolution of genomes by promoting genetic diversity and new regulatory elements. Consequently, it is important to study the epigenetic modifications associated to TEs especially at a locus-specific level to determine their individual influence on gene functioning. To this aim, this short review presents the current bioinformatic tools to achieve this task.
Selection and Evaluation of Reference Genes for miRNA Expression Analysis in Bemisia tabaci Under Insecticide Tolerance
Authors: Zhang Qinghe , Gao Bingli , Qu Cheng , Luo Chen , Wang Jinda , Wang Ran
Published: May 2022

A growing number of studies have focused on the microRNA (miRNA) expression in Bemisia tabaci, one devastating agricultural insect pest of the tropical and subtropical areas for which the primary means of control are insecticides. In studying the genetic underpinnings of insecticide resistance, the choice of stable reference genes for normalizing data plays a key role to acquire unbiased expression profile results from quantitative real-time PCR (qPCR) analysis. Expression profiles of 11 selected reference genes were determined systematically in B. tabaci exposure to 11 insecticides. Furthermore, we assessed the stability of all the selected candidates in relation to other variables including sex, tissue type, and developmental stage. Candidate reference gene validation was conducted by analyzing the let-7-5p expression under various experimental treatments. Five programs BestKeeper, NormFinder, geNorm, △Ct, and RefFinder were applied to verify the accuracy of the selected candidates. Our results displayed that the best choices of the selected candidates for pymetrozine, sulfoxaflor, flonicamid, cyantraniliprole, afidopyropen, and deltamethrin treatment were miR-1-3p and miR-100-5p, U6 and miR-100-5p were best for chlorpyrifos and imidacloprid treatments, and U6 and miR-1-3p were best for flupyradifurone and β-cypermethrin treatments. The reference genes miR-624, miR-252, and miR-275 worked best in adult tissues, miR-100-5p and miR-1-3p worked best in either sex, and miR-624 and miR-11 were best to use across developmental stages. Not even one reference gene was found to be suitable for all experimental conditions. Our results contributed to the growing body of the literature on qPCR reference gene selection under various experimental conditions and facilitate further investigation on gene expression changes in B. tabaci, resulting from pesticide exposure.
Autoimmunity and Cancer—Two Sides of the Same Coin
Authors: Sakowska Justyna , Arcimowicz Łukasz , Jankowiak Martyna , Papak Ines , Markiewicz Aleksandra , Dziubek Katarzyna , Kurkowiak Małgorzata , Kote Sachin , Kaźmierczak-Siedlecka Karolina , Połom Karol , Marek-Trzonkowska Natalia , Trzonkowski Piotr
Published: May 2022

Autoimmune disease results from the immune response against self-antigens, while cancer develops when the immune system does not respond to malignant cells. Thus, for years, autoimmunity and cancer have been considered as two separate fields of research that do not have a lot in common. However, the discovery of immune checkpoints and the development of anti-cancer drugs targeting PD-1 (programmed cell death receptor 1) and CTLA-4 (cytotoxic T lymphocyte antigen 4) pathways proved that studying autoimmune diseases can be extremely helpful in the development of novel anti-cancer drugs. Therefore, autoimmunity and cancer seem to be just two sides of the same coin. In the current review, we broadly discuss how various regulatory cell populations, effector molecules, genetic predisposition, and environmental factors contribute to the loss of self-tolerance in autoimmunity or tolerance induction to cancer. With the current paper, we also aim to convince the readers that the pathways involved in cancer and autoimmune disease development consist of similar molecular players working in opposite directions. Therefore, a deep understanding of the two sides of immune tolerance is crucial for the proper designing of novel and selective immunotherapies.
Single Cell Transcriptome and Surface Epitope Analysis of Ankylosing Spondylitis Facilitates Disease Classification by Machine Learning
Authors: Alber Samuel , Kumar Sugandh , Liu Jared , Huang Zhi-Ming , Paez Diana , Hong Julie , Chang Hsin-Wen , Bhutani Tina , Gensler Lianne S. , Liao Wilson
Published: May 2022

Ankylosing spondylitis (AS) is an immune-mediated inflammatory disorder that primarily affects the axial skeleton, especially the sacroiliac joints and spine. This results in chronic back pain and, in extreme cases, ankylosis of the spine. Despite its debilitating effects, the pathogenesis of AS remains to be further elucidated. This study used single cell CITE-seq technology to analyze peripheral blood mononuclear cells (PBMCs) in AS and in healthy controls. We identified a number of molecular features associated with AS. CD52 was found to be overexpressed in both RNA and surface protein expression across several cell types in patients with AS. CD16+ monocytes overexpressed TNFSF10 and IL-18Rα in AS, while CD8+ TEM cells and natural killer cells overexpressed genes linked with cytotoxicity, including GZMH, GZMB, and NKG7. Tregs underexpressed CD39 in AS, suggesting reduced functionality. We identified an overrepresented NK cell subset in AS that overexpressed CD16, CD161, and CD38, as well as cytotoxic genes and pathways. Finally, we developed machine learning models derived from CITE-seq data for the classification of AS and achieved an Area Under the Receiver Operating Characteristic (AUROC) curve of > 0.95. In summary, CITE-seq identification of AS-associated genes and surface proteins in specific cell subsets informs our understanding of pathogenesis and potential new therapeutic targets, while providing new approaches for diagnosis via machine learning.
Helicobacter pylori and the Role of Lipopolysaccharide Variation in Innate Immune Evasion
Authors: Sijmons Daniel , Guy Andrew J. , Walduck Anna K. , Ramsland Paul A.
Published: May 2022

Helicobacter pylori is an important human pathogen that infects half the human population and can lead to significant clinical outcomes such as acute and chronic gastritis, duodenal ulcer, and gastric adenocarcinoma. To establish infection, H. pylori employs several mechanisms to overcome the innate and adaptive immune systems. H. pylori can modulate interleukin (IL) secretion and innate immune cell function by the action of several virulence factors such as VacA, CagA and the type IV secretion system. Additionally, H. pylori can modulate local dendritic cells (DC) negatively impacting the function of these cells, reducing the secretion of immune signaling molecules, and influencing the differentiation of CD4+ T helper cells causing a bias to Th1 type cells. Furthermore, the lipopolysaccharide (LPS) of H. pylori displays a high degree of phase variation and contains human blood group carbohydrate determinants such as the Lewis system antigens, which are proposed to be involved in molecular mimicry of the host. Lastly, the H. pylori group of outer membrane proteins such as BabA play an important role in attachment and interaction with host Lewis and other carbohydrate antigens. This review examines the various mechanisms that H. pylori utilises to evade the innate immune system as well as discussing how the structure of the H. pylori LPS plays a role in immune evasion.
Evaluation of the 10 Warning Signs in Primary and Secondary Immunodeficient Patients
Authors: Eldeniz Fadime Ceyda , Gul Yahya , Yorulmaz Alaaddin , Guner Sukru Nail , Keles Sevgi , Reisli Ismail
Published: May 2022

Objectives

Ten warning signs of primary immunodeficiency (PID) were suggested by the Jeffrey Modell Foundation (JMF), to increase physician awareness of PID. These warning signs have not yet been evaluated for patients with secondary immunodeficiency (SID). This study investigated whether the 10 warning signs used for the diagnosis of PID were also sufficient for the diagnosis of SID, and explored the possibility of additional signs.

Methods

This prospective study was conducted between June and December 2020. The mothers of 162 patients with PID and SID, and mothers of 200 healthy children, were asked to complete a questionnaire about family and personal history in addition to the warning signs of PID developed by the JMF. A JMF score was created by giving one point for each “Yes” answer for the 10 warning signs of PID. Medical records of the patients were evaluated for possible additional warning signs for PID and SID.

Results

The JMF scores of the PID (3.36 ± 1.65) and SID (3.72 ± 1.12) groups were significantly higher than the scores of the control group (0.34 ± 0.61) (p < 0.05). A sign for immunological evaluation in two patients without warning signs in the PID group was found to be chronic diarrhea. In addition to the 10 JMF warning signs, we found that consanguinity and a family history of tuberculosis were statistically significant in our PID group, compared with the SID and control groups.

Conclusions

The JMF warning signs are important for early diagnosis of PID. Our study showed that these signs may also be used for the early diagnosis of SID in patients and, according to our results, in addition to the 10 JMF signs for PID, parental consanguinity, chronic diarrhea, and a family history of tuberculosis may also be considered warning signs for the early diagnosis of PID.
Circulatory and Metabolic Physiology Disorder in Different Organs of the Subtropical Scallop Species Chlamys nobilis Under Thermal and Hypoxia Stress, Revealed by Doppler Ultrasonography Technique
Authors: Hao Yu , Sun Chunyang , Rong Yun , Wang Haiqing , Xu Qiang , Gao Fei , Wang Aimin
Published: May 2022

Extremely high temperature and hypoxia are mounting problems affecting the world’s coastal waters under the global warming environment, with severe consequences for marine life. Scallop is one of the most fragile species to hypoxia stress for their high respiration rate and lack of self-protection ability such as long-time shell closing. Circulatory physiology rhythm is sensitive to environmental stress and is an important means for shellfish to quickly respond to environmental stress. Therefore, monitoring the circulatory physiology indexes of Chlamys nobilis under hypoxia and high temperature stress is helpful to quickly diagnose its stress state and reveal the response process of circulatory system to the stress. In this study, using real-time Doppler ultrasonography technique, we continuously monitored the circulatory physiological indexes [heart rate (HR), blood flow volume (FV), blood velocity (PS and ED), resistance index (RI) and S/D ratio) of the scallop organs (gill, mantle and adductor muscle) under hypoxia (mild 4 mg/L DO, moderate 3 mg/L DO and severe 2 mg/L DO)] and fluctuating high temperature stress (29-31°C). Important metabolic function indexes [adenosine triphosphate (ATP), pyruvate kinase (PK) and cytochrome C oxidase (COX)] of various tissues were measured simultaneously. The results show that scallops are very sensitive to the changes of temperature and dissolved oxygen. Both high temperature and hypoxia will increase the HR, and severe hypoxia will bring greater load to the heart of the scallop. Hypoxia stress mainly caused the changes of PS, and the RI and S/D of the gill gradually increased. At 2mg/L DO level, the total blood flow of the mantle and adductor muscle decreased, but the blood flow supply in the gill was stable. The scallop is very sensitive to the change of high temperature and can make adjustments immediately. High temperature increased blood flow in various organs and preferentially supplied to the gill. The RI and S/D of branchial vessels under high temperature were lower than those under hypoxia. The ATP content of the mantle was continuous accumulated under high temperature and was significantly higher than that of the gill and adductor muscle, indicating the specificity of tissue metabolism. The overall circulatory physiological indexes of the gill showed a more positive response to the stress environment than the mantle and adductor muscle. All the results proved that the gill has the best resistance to the hypoxia and high temperature stress. Our study revealed the circulatory physiology regulation mechanism of the noble scallop C. nobilis under environmental stress, and provide effective data and technique supports for the timely diagnose of stress condition of the species, so as to formulate necessary handling strategies for the scallop farm.
Roughness Prediction and Performance Analysis of Data-Driven Superalloy Belt Grinding
Authors: Zhang Youdong , Xiao Guijian , Gao Hui , Zhu Bao , Huang Yun , Li Wei
Published: May 2022

Abrasive belt grinding has unique advantages in avoiding machining defects and improving surface integrity while grinding hard materials such as superalloys. However, the random distribution of abrasive particles on the abrasive belt surface is uncontrollable, and chatter and machining errors accompany the machining process, leading to unclear mapping relationship between process parameters and surface roughness, which brings great challenges to the prediction of surface roughness of superalloy. Traditional empirical equations are highly dependent on empirical knowledge and the development of scientific theories and can only solve problems with relatively simple and clear mechanisms, but cannot effectively solve complex and mutually coupled problems. The method based on data-driven patterns has a better idea for mining the implicit mapping relationship and eliminating the uncertainty of complex problems. This study presents a data-driven roughness prediction method for GH4169 superalloy. First, a superalloy grinding platform is built. According to the grinding empirical equation, the mapping relationship between process parameters and surface roughness is analyzed, and a prediction model is established based on the error back propagation (BP) algorithm. Second, genetic algorithm (GA) and particle swarm optimization (PSO) algorithm are used to optimize the weights and thresholds of the neural network, and the global optimal solution is obtained. Finally, the prediction performance of different algorithms is compared. The results show that the non-uniform absolute errors of the BP algorithm, GA-BP algorithm, and PSO-BP algorithm are 0.12, 0.085, and 0.078, respectively. The results show that the roughness prediction algorithm based on PSO-BP is more suitable for GH4169 superalloy.
A Network Pharmacology Study: Reveal the Mechanisms of Palovarotene Against Heterotopic Ossification
Authors: Huang Junchao , Liu Dachuan , Zhang Jingwei , Xiao Haijun
Published: May 2022

Heterotopic ossification (HO) occurs when bone forms within non-ossifying tissues, such as in muscle. Palovarotene, an activator of retinoic acid receptor γ (RAR-γ), has been shown to inhibit the formation of ectopic bone in HO model mice, but its specific mechanism of action remains unclear. This study will explore the target and molecular mechanism of Palovarotene's action on HO by network pharmacology study. We collected the relevant targets of Palovarotene and HO from the database, obtained the potential targets of Palovarotene acting on HO through Venn analysis, and constructed the protein-protein interaction (PPI) network. Then, Gene Ontology (GO) and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment Analysis and Module-based Network Analysis were performed for potential targets, and in addition, PPI Network Topology Analysis and Gene-Phenotype Correlation Analysis were performed. The results suggested that MAPK1, MDM2, and other targets as well as P53 signaling pathway and PI3K–Akt signaling pathway may be closely related to Palovarotene treatment of HO. We carried out verification experiments to confirm our finding, alkaline phosphatase and alizarin red staining in vitro and Micro-CT as well as hematoxylin-eosin staining in vivo were performed to verify treatment for HO of Palovarotene, reverse transcription polymerase chain reaction was also used to explore the transcription changes of MAPK1, MDM2, and osteogenic genes. This study systematically elucidated the possible mechanism of Palovarotene in the treatment of HO through network pharmacology study, revealing a new direction for the further application of Palovarotene in the treatment of HO.
Antimicrobial Susceptibility, and Molecular Characterization of Staphylococcus aureus Isolated From Different Raw Milk Samples in China
Authors: Liu Huimin , Dong Lei , Zhao Yankun , Meng Lu , Wang Jiaqi , Wang Cheng , Zheng Nan
Published: May 2022

Staphylococcus aureus (S. aureus) is one of the main pathogens in different raw milk and dairy products, which may lead to economic losses. Staphylococcus aureus is a significant and costly public health concern because it may enter the human food chain and contaminate milk causing foodborne illness. This study aimed to investigate the prevalence, antimicrobial susceptibility and virulence genes of S. aureus in raw milks. In total, 125 raw milk samples collected from goat (n = 50), buffalo (n = 25), camel (n = 25), and yak (n = 25) were collected from 5 provinces in China in 2016. Out of 125 samples, 36 (28.8%) S. aureus were isolated (16 from goat, 9 from buffalo, 6 from camel, and 5 from yak). Out of 36 S. aureus, 26 strains (26/36, 72.2%) showed antibiotics resistance, and 6 strains isolated from goats were identified as methicillin-resistant S. aureus (MRSA). The antimicrobial resistance against Penicillin G, tetracycline and gentamicin was 50% (18/36), 41.7% (15/36), and 36.1% (13/36), respectively. 19 S. aureus (52.8%) were considered as multidrug resistant. The highest prevalence of resistant S. aureus was observed in goat milk (13/36, 36.1%). Among the 36 strains, 16 isolates harbored three or more resistant genes. The resistance genes were detected in 25 S. aureus, including 13 strains in goat, 5 strains in buffalo, 4 strains in camel, and 3 strains in yak. Among the 26 resistant strains, 61.5% of isolates harbored three or more resistant genes. The resistance genes were detected in 25 S. aureus, including 13 strains in goat milk, 5 strains in buffalo milk, 4 strains in camel milk, and 3 strains in yak milk. The most predominant resistance genes were blaZ (18/26, 69.2%), aac6′-aph2″ (13/26, 50.0%), and tet(M) (10/26, 38.5%). The mecA, ant(6)-Ia and fexA gene were only detected in S. aureus from goat milk. The most predominant toxin gene were sec (8/26, 30.8%). The majority of S. aureus were multidrug resistant and carried multiple virulence genes, which may pose potential risk to public health. Our findings indicated that the prevalence and antimicrobial resistance of S. aureus was a serious concern in different raw milks in China, especially goat milks.
Dirammox Is Widely Distributed and Dependently Evolved in Alcaligenes and Is Important to Nitrogen Cycle
Authors: Hou Ting-Ting , Miao Li-Li , Peng Ji-Sen , Ma Lan , Huang Qiang , Liu Ying , Wu Meng-Ru , Ai Guo-Min , Liu Shuang-Jiang , Liu Zhi-Pei
Published: May 2022

Nitrogen cycle is an essential process for environmental health. Dirammox (direct ammonia oxidation), encoded by the dnfT1RT2ABCD cluster, was a novel pathway for microbial N2 production defined in Alcaligenes ammonioxydans HO-1. Here, a copy of the cluster dnfT1RT2ABCD as a whole was proved to have existed and very conserved in all Alcaligenes genomes. Phylogenetic analyses based on 16S rRNA gene sequences and amino acid sequences of DnfAs, together with G + C content data, revealed that dnf cluster was evolved associated with the members of the genus Alcaligenes. Under 20% O2 conditions, 14 of 16 Alcaligenes strains showed Dirammox activity, which seemed likely taxon-related. However, the in vitro activities of DnfAs catalyzing the direct oxidation of hydroxylamine to N2 were not taxon-related but depended on the contents of Fe and Mn ions. The results indicated that DnfA is necessary but not sufficient for Dirammox activity. The fact that members of the genus Alcaligenes are widely distributed in various environments, including soil, water bodies (both freshwater and seawater), sediments, activated sludge, and animal–plant-associated environments, strongly suggests that Dirammox is important to the nitrogen cycle. In addition, Alcaligenes species are also commonly found in wastewater treatment plants, suggesting that they might be valuable resources for wastewater treatment.
Changes in Microbiome Dominance Are Associated With Declining Lung Function and Fluctuating Inflammation in People With Cystic Fibrosis
Authors: Frey Dario L. , Bridson Calum , Dittrich Susanne , Graeber Simon Y. , Stahl Mirjam , Wege Sabine , Herth Felix , Sommerburg Olaf , Schultz Carsten , Dalpke Alexander , Mall Marcus A. , Boutin Sébastien
Published: May 2022

Airway inflammation and microbiome dysbiosis are hallmarks of cystic fibrosis (CF) lung disease. However, longitudinal studies are needed to decipher which factors contribute to the long-term evolution of these key features of CF. We therefore evaluated the relationship between fluctuation in microbiome and inflammatory parameters in a longitudinal study including a short- (1-year) and a long-term (3+ years) period. We collected 118 sputum samples from 26 CF adult patients and analyzed them by 16S rRNA gene sequencing. We measured the levels of inflammatory cytokines, neutrophil elastase, and anti-proteinases; lung function (FEV1% predicted); and BMI. The longitudinal evolution was analyzed based on (i) the rates of changes; (ii) the intra-patient stability of the variables; and (iii) the dependency of the rates of changes on the baseline values. We observed that the diversity of the microbiome was highly variable over a 1-year period, while the inflammatory markers showed a slower evolution, with significant changes only observed in the 3+ year cohort. Further, the degree of fluctuation of the biomass and the dominance of the microbiome were associated with changes in inflammatory markers, especially IL-1β and IL-8. This longitudinal study demonstrates for the first time that the long-term establishment and periodical variation of the abundance of a dominant pathogen is associated with a more severe increase in inflammation. This result indicates that a single time point or 1-year study might fail to reveal the correlation between microbial evolution and clinical degradation in cystic fibrosis.
Dysregulated Exosomes Result in Suppression of the Immune Response of Pregnant COVID-19 Convalescent Women
Authors: Cao Hang , Abd Aziz Nor Haslinda , Xavier Janet Raja , Shafiee Mohamad Nasir , Kalok Aida , Jee Babban , Salker Madhuri S. , Singh Yogesh
Published: May 2022

A successful pregnancy outcome is dependent on a delicate balance between inflammatory and anti-inflammatory processes throughout the different trimesters. Interruption in this balance can lead to an adverse outcome resulting in pregnancy loss. Since late 2019, the emergence of the new SARS-CoV-2 virus has affected lives worldwide, including pregnant women; therefore, there is an urgent need to address different approaches in relation to prevention, diagnostics, and therapeutics. Early pregnancy is affected by SARS-CoV-2 infection leading to fetal demise. Available evidence also suggests that 90% of pregnant women infected with the SARS-CoV-2 virus seem to be asymptomatic. Nonetheless, it is still unclear how COVID-19 affects exosome production in pregnant women recovered from COVID-19 and how these exosomes regulate the adaptive immune response. In this study, we found several exosomes including CD9, CD31, CD40, CD45, CD41b, CD42a, CD62P, CD69, CD81, CD105, and HLA-DRDPDQ in the plasma of COVID-19-recovered pregnant women were significantly less abundant than the control group. Furthermore, to understand how these exosomes affect the adaptive immune response, we co-cultured the peripheral blood mononuclear cells (PBMCs) from healthy control (HC) pregnant women with exosomes of either Preg-HC or Preg-recovered COVID-19 women. We identified that Preg-recovered COVID-19 women have reduced capacity for the inflammatory cytokine TNF-α from cytotoxic CD8+ T cells. In summary, our study highlights that pregnant recovered COVID-19 women have reduced production of several exosomes and possess fewer immunogenic properties. Our study implicates that exosomes can control inflammation and antigen presentation capacity of immune cells, thus limiting the infection in pregnant women.
Traditional Chinese Medicine and Sarcopenia: A Systematic Review
Authors: Guo Chao-yang , Ma Yun-jing , Liu Shu-ting , Zhu Ran-ran , Xu Xiao-ting , Li Zhen-rui , Fang Lei
Published: May 2022

Sarcopenia has become a key challenge for healthy aging in older adults. However, it remains unclear whether traditional Chinese medicine can effectively treat sarcopenia. This systematic review analyzes the current evidence for the effect of traditional Chinese medicine (TCM) on sarcopenia. We searched for articles regarding sarcopenia treated by TCM in Cochrane library, PubMed, SinoMed, Web of Science, Embase, and the China National Knowledge Infrastructure (from inception until 10 December 2021). Two researchers independently screened the literature in accordance with the inclusion and exclusion criteria designed by PICOS principles. The risk of bias was assessed by the Cochrane Risk of Bias (ROB) tool. The quality of evidence was assessed by the grading of recommendations, assessment, development, and evaluation (GRADE). Participants’ characteristics, interventions, and the relevant results of the included studies were extracted and synthesized in a narrative way. The total number of participants in the 21 included studies was 1,330. Most of the studies evaluated physical function (n = 20) and muscle strength (n = 18), and a small number of studies (n = 6) assessed muscle mass. Overall, it was found that TCM had a positive impact on muscle strength (grip strength, chair stand test) and physical function (6-m walking speed, timed up and go test, sit and reach) in patients with sarcopenia, inconsistent evidence of effects on muscle mass. However, the small sample size of the included studies led to imprecision in the results, and the presence of blinding of the studies, allocation concealment, and unreasonable problems with the control group design made the results low grade. Among these results, the quality of evidence for grip strength (n = 10) was of medium grade, and the quality of evidence related to the remaining indicators was of low grade. This systematic review showed that traditional Chinese Qigong exercises and Chinese herbal medicine have a positive and important effect on physical performance and muscle strength in older adults with sarcopenia. Future high-quality multicenter randomized controlled trials (RCTs) with large samples are needed to determinate whether acupuncture and other therapies are effective in treating sarcopenia.
Age-Related Changes in Topological Properties of Individual Brain Metabolic Networks in Rats
Authors: Xue Xin , Wu Jia-Jia , Huo Bei-Bei , Xing Xiang-Xin , Ma Jie , Li Yu-Lin , Wei Dong , Duan Yu-Jie , Shan Chun-Lei , Zheng Mou-Xiong , Hua Xu-Yun , Xu Jian-Guang
Published: May 2022

Normal aging causes profound changes of structural degeneration and glucose hypometabolism in the human brain, even in the absence of disease. In recent years, with the extensive exploration of the topological characteristics of the human brain, related studies in rats have begun to investigate. However, age-related alterations of topological properties in individual brain metabolic network of rats remain unknown. In this study, a total of 48 healthy female Sprague–Dawley (SD) rats were used, including 24 young rats and 24 aged rats. We used Jensen-Shannon Divergence Similarity Estimation (JSSE) method for constructing individual metabolic networks to explore age-related topological properties and rich-club organization changes. Compared with the young rats, the aged rats showed significantly decreased clustering coefficient (Cp) and local efficiency (Eloc) across the whole-brain metabolic network. In terms of changes in local network measures, degree (D) and nodal efficiency (Enod) of left posterior dorsal hippocampus, and Enod of left olfactory tubercle were higher in the aged rats than in the young rats. About the rich-club analysis, the existence of rich-club organization in individual brain metabolic networks of rats was demonstrated. In addition, our findings further confirmed that rich-club connections were susceptible to aging. Relative to the young rats, the overall strength of rich-club connections was significantly reduced in the aged rats, while the overall strength of feeder and local connections was significantly increased. These findings demonstrated the age-related reorganization principle of the brain structure and improved our understanding of brain alternations during aging.
Parkinson’s Disease Medication Adherence Scale: Conceptualization, Scale Development, and Clinimetric Testing Plan
Authors: Tosin Michelle H. S. , Goetz Christopher G. , Bispo Dharah P. C. F. , Ferraz Henrique B. , Leite Marco Antonio A. , Hall Deborah A. , Stebbins Glenn T. , Oliveira Beatriz Guitton R. B.
Published: May 2022

Background

Medication adherence is a crucial component in the management of patients with chronic diseases needing a long-term pharmacotherapy. Parkinson’s disease (PD) is a chronic, degenerative disease with complex drug treatment that poses challenging barriers to patient adherence. The adoption of best practices of scale development can contribute to generate solid concepts and, in the long run, a more stable knowledge base on the underlying constructs of medication adherence in PD measured by the items of the first scale to be created for this purpose.

Purpose

To present the development process and clinimetric testing plan of the Parkinson’s Disease Medication Adherence Scale (PD-MAS).

Method

We adopted a hybrid approach plan based on the United States Food and Drug Administration and Benson and Clark Guide that will create a patient-reported outcome instrument. We presented an overview of consecutive and interrelated steps, containing a concise description of each one. International research centers from Brazil and United States were initially involved in the planning and implementation of the methodological steps of this study.

Results

We developed a four-phase multimethod approach for the conceptualization and the clinimetric testing plan of the PD-MAS. First, we describe the development process of the conceptual framework of the PD-MAS underpinning the scale construct; second, we formalized the development process of the first version of the PD-MAS from the generation of item pools to the content validation and pre-testing; third, we established the steps for the first pilot testing and revision; fourth, we describe the steps plan for the first pilot testing and revision, to finally describe its clinimetric testing plan and validation.

Conclusion

The overview presentation of the development phases and the clinimetric testing plan of the PD-MAS demonstrate the feasibility of creating an instrument to measure the multidimensional and multifactorial components of the medication adherence process in people with PD.