bluuebunny/crossref_metadata_2025 huggingface dataset:
Natural Fractures in Low-Permeability Sandstone Reservoirs in the LD-A HPHT Gas Field, Yinggehai Basin: Implications for Hydrocarbon Exploration and Development
Authors: Li Hui , Fan Caiwei , Jiang Zhenxue , Li Jun , Li Chao , Xu Xuhui , Li Fang , Hu Gaowei
Published: July 2022

Research on the characteristics and distribution of natural fractures is of great importance for the exploration and development of low-permeability sandstone gas reservoirs. In this study, fracture identification and characterization were carried out using cores and imaging logging. Then, comprehensive fracture development indicators were constructed to predict the distribution of fractures in wells by conventional logging. The main factors that affect the development of natural fractures and the implications of fractures on hydrocarbon exploration and development were discussed. The results showed that the natural fractures were mainly low-angle tectonic fractures in sandstone reservoirs. Most of fractures are unfilled, but the distribution of the fractures in the thin sections has a discrete fracture structure, indicating that the connectivity of the fracture system is poor. The development of natural fractures is mainly influenced by rock strength, petrographic composition, and petrology, and the fractures are more developed in sandstones with a higher content of brittle minerals. The fracture densities are mainly distributed below 0.05 m/m and up to 0.1 m/m. In the present in situ stress state, all of the natural fractures in the LD-A gas field are invalid fractures. The critical pressure of the natural fracture is approximately 16.5–25.4 MP/km; when the pore pressure exceeds this value, the fractures become effective fractures. These results provide new geological knowledge and guidance for the exploration and development of LD-A gas fields and other low-permeability tight sandstone reservoirs.
Learning barriers at the workplace: Development and validation of a measurement instrument
Authors: Anselmann Sebastian
Published: July 2022

While facilitating factors to learning at the workplace have been well investigated, throughout the past decade less has emerged about the barriers that occur when approaching a learning activity at the workplace. Barriers to learning at the workplace are factors that hinder the initiation of successful learning, interrupt learning possibilities, delay proceedings or end learning activities much earlier than intended. The aim of this study is to develop and validate an instrument that measures barriers to informal and formal learning at the workplace. An interview pre-study asked 26 consultants about their learning barriers based on existing instruments. Using this data as groundwork, a novel measuring instrument of barriers to informal and formal learning was developed. The instrument is comprised of five factors with items on individual barriers, organizational/structural barriers, technical barriers, change and uncertainty. To validate the scales, a cross-sectional questionnaire with 112 consultancy employees and freelancers was conducted. The validation included exploratory factor analysis, internal consistency assessment, confirmatory factor analysis (CFA) and convergent validity assessment. The results generated a three-factor scale barrier measurement for formal learning and a two-factor scale barrier measurement for informal learning. All scales featured Cronbach’s alpha values ranging between 0.80 and 0.86. With this developed and validated scales it is intended to help offer insights into factors that hinder individuals from learning at the workplace, and show organizations their potential for change.
Systemic and Ocular Anti-Inflammatory Mechanisms of Green Tea Extract on Endotoxin-Induced Ocular Inflammation
Authors: Chu Kai On , Chan Kwok Ping , Yip Yolanda Wong Ying , Chu Wai Kit , Wang Chi Chiu , Pang Chi Pui
Published: July 2022

Introduction

Green tea extract (GTE) alleviated ocular inflammations in endotoxin-induced uveitis (EIU) rat model induced by lipopolysaccharide (LPS) but the underlying mechanism is unclear.

Objectives

To investigate the systematic and local mechanisms of the alleviation by untargeted metabolomics using liquid chromatography-tandem mass spectrometry

Methods

Sprague-Dawley rats were divided into control group, LPS treatment group, and LPS treatment group treated with GTE two hours after LPS injection. The eyes were monitored by slip lamp and electroretinography examination after 24 hours. The plasma and retina were collected for metabolomics analysis

Results

In LPS treated rats, the iris showed hyperemia. Plasma prostaglandins, arachidonic acids, corticosteroid metabolites, and bile acid metabolites increased. In the retina, histamine antagonists, corticosteroids, membrane phospholipids, free antioxidants, and sugars also increased but fatty acid metabolites, N-acetylglucosamine-6-sulphate, pyrocatechol, and adipic acid decreased. After GTE treatment, the a- and b- waves of electroretinography increased by 13%. Plasma phosphorylcholine lipids increased but plasma prostaglandin E1, cholanic metabolites, and glutarylglycine decreased. In the retina, tetranor-PGAM, pantothenic derivatives, 2-ethylacylcarinitine, and kynuramine levels decreased but anti-oxidative seleno-peptide level increased. Only phospholipids, fatty acids, and arachidonic acid metabolites in plasma and in the retina had significant correlation (p < 0.05, r > 0.4 or r < -0.4).

Conclusions

The results showed GTE indirectly induced systemic phosphorylcholine lipids to suppress inflammatory responses, hepatic damage, and respiratory mitochondrial stress in EIU rats induced by LPS. Phospholipids may be a therapeutic target of GTE for anterior chamber inflammation
Ghrelin and the Control of Energy Balance in Females
Authors: Smith Andrea , Woodside Barbara , Abizaid Alfonso
Published: July 2022

Ghrelin is considered one of the most potent orexigenic peptide hormones and one that promotes homeostatic and hedonic food intake. Research on ghrelin, however, has been conducted predominantly in males and particularly in male rodents. In female mammals the control of energy metabolism is complex and it involves the interaction between ovarian hormones like estrogen and progesterone, and metabolic hormones. In females, the role that ghrelin plays in promoting feeding and how this is impacted by ovarian hormones is not well understood. Basal ghrelin levels are higher in females than in males, and ghrelin sensitivity changes across the estrus cycle. Yet, responses to ghrelin are lower in female and seem dependent on circulating levels of ovarian hormones. In this review we discuss the role that ghrelin plays in regulating homeostatic and hedonic food intake in females, and how the effects of ghrelin interact with those of ovarian hormones to regulate feeding and energy balance.
Ankylosing Spondylitis and the Risk of Lung Cancer: A Meta-Analysis and Mendelian Randomization
Authors: Ao Yiyuan , Wen Yaokai , Li Yutian , Peng Haoxin , Wu Xiangrong , Wang Zhufeng , Jiang Yu , Lin Yuechun , Li Shuben
Published: July 2022

Background: It remains uncertain whether ankylosing spondylitis is associated with an increased risk of lung cancer.

Methods: We conducted a meta-analysis to comprehensively evaluate the correlation between ankylosing spondylitis and lung cancer based on existing literature. Eligible studies were identified by searching the PubMed, Web of Science, Embase, and Cochrane Library before 26 March 2021. Subgroup analyses based on regions were also carried out. To further explore their causality, a two-sample Mendelian randomization analysis was performed, with 25 ankylosing spondylitis-related single nucleotide polymorphisms derived from the largest sample genome-wide association study of ankylosing spondylitis (ebi-a-GCST005529, 22,647 individuals). The inverse variance-weighted method was applied to estimate the causality, and the pleiotropy was assessed utilizing the Mendelian randomization-Egger regression approach.

Results: The meta-analysis including seven studies, with a total of 39,186 individuals, suggested no significant association between ankylosing spondylitis and lung cancer (relative risk, 1.10; 95% confidence interval, 0.89–1.36; I2, 61.8%). After excluding one study leading to high heterogeneity, we found that ankylosing spondylitis was associated with a 19% increased risk of lung cancer (relative risk, 1.19; 95% confidence interval, 1.01–1.40; I2, 0.0%). Subgroup analyses suggested that ankylosing spondylitis was not associated with increased risks of lung cancer in neither European (relative risk, 1.05; 95% confidence interval, 0.80–1.39; I2, 0.0%) nor non-European (relative risk, 1.14; 95% confidence interval, 0.84–1.55; I2, 79.6%) patients. Nevertheless, the Mendelian randomization results indicated that genetically determined ankylosing spondylitis was causally correlated with a remarkably increased risk of lung cancer among European populations (odds ratio, 1.26; 95% confidence interval, 1.07–1.48). Subgroup analyses further elucidated that genetically determined ankylosing spondylitis was causally associated with a notably higher risk of only squamous cell lung cancer (odds ratio, 1.39; 95% confidence interval, 1.05–1.83), rather than lung adenocarcinoma (odds ratio, 1.18; 95% confidence interval, 0.91–1.54). In addition, the results indicated the absence of pleiotropy.

Conclusion: The results of both modified meta-analysis and Mendelian randomization analysis suggested that ankylosing spondylitis was likely to be correlated with the development of lung cancer. Further research is warranted to clarify the specific mechanism regarding the causality between the two diseases.
A Diagnostic Model Using Exosomal Genes for Colorectal Cancer
Authors: Lei Tianxiang , Zhang Yongxin , Wang Xiaofeng , Liu Wenwei , Feng Wei , Song Wu
Published: July 2022

Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide. Exosomes have great potential as liquid biopsy specimens due to their presence and stability in body fluids. However, the function and diagnostic values of exosomal genes in CRC are poorly understood. In the present study, exosomal data of CRC and healthy samples from the exoRBase 2.0 and Gene Expression Omnibus (GEO) databases were used, and 38 common exosomal genes were identified. Through the least absolute shrinkage and selection operator (Lasso) analysis, support vector machine recursive feature elimination (SVM-RFE) analysis, and logistic regression analysis, a diagnostic model of the training set was constructed based on 6 exosomal genes. The diagnostic model was internally validated in the test and exoRBase 2.0 database and externally validated in the GEO database. In addition, the co-expression analysis was used to cluster co-expression modules, and the enrichment analysis was performed on module genes. Then a protein–protein interaction and competing endogenous RNA network were constructed and 10 hub genes were identified using module genes. In conclusion, the results provided a comprehensive understanding of the functions of exosomal genes in CRC as well as a diagnostic model related to exosomal genes.
BNEMDI: A Novel MicroRNA–Drug Interaction Prediction Model Based on Multi-Source Information With a Large-Scale Biological Network
Authors: Guan Yong-Jian , Yu Chang-Qing , Li Li-Ping , You Zhu-Hong , Ren Zhong-Hao , Pan Jie , Li Yue-Chao
Published: July 2022

As a novel target in pharmacy, microRNA (miRNA) can regulate gene expression under specific disease conditions to produce specific proteins. To date, many researchers leveraged miRNA to reveal drug efficacy and pathogenesis at the molecular level. As we all know that conventional wet experiments suffer from many problems, including time-consuming, labor-intensity, and high cost. Thus, there is an urgent need to develop a novel computational model to facilitate the identification of miRNA–drug interactions (MDIs). In this work, we propose a novel bipartite network embedding-based method called BNEMDI to predict MDIs. First, the Bipartite Network Embedding (BiNE) algorithm is employed to learn the topological features from the network. Then, the inherent attributes of drugs and miRNAs are expressed as attribute features by MACCS fingerprints and k-mers. Finally, we feed these features into deep neural network (DNN) for training the prediction model. To validate the prediction ability of the BNEMDI model, we apply it to five different benchmark datasets under five-fold cross-validation, and the proposed model obtained excellent AUC values of 0.9568, 0.9420, 0.8489, 0.8774, and 0.9005 in ncDR, RNAInter, SM2miR1, SM2miR2, and SM2miR MDI datasets, respectively. To further verify the prediction performance of the BNEMDI model, we compare it with some existing powerful methods. We also compare the BiNE algorithm with several different network embedding methods. Furthermore, we carry out a case study on a common drug named 5-fluorouracil. Among the top 50 miRNAs predicted by the proposed model, there were 38 verified by the experimental literature. The comprehensive experiment results demonstrated that our method is effective and robust for predicting MDIs. In the future work, we hope that the BNEMDI model can be a reliable supplement method for the development of pharmacology and miRNA therapeutics.
High-Density Genomic Characterization of Native Croatian Sheep Breeds
Authors: Drzaic Ivana , Curik Ino , Lukic Boris , Shihabi Mario , Li Meng-Hua , Kantanen Juha , Mastrangelo Salvatore , Ciani Elena , Lenstra Johannes A. , Cubric-Curik Vlatka
Published: July 2022

A recent comprehensive genomic analysis based on 50K SNP profiles has shown that the regional Balkan sheep populations have considerable genetic overlap but are distinctly different from surrounding breeds. All eight Croatian sheep breeds were represented by a small number of individuals per breed. Here, we genotyped 220 individuals representing the native Croatian sheep breeds (Istrian Sheep, Krk Island Sheep, Cres Island Sheep, Rab Island Sheep, Lika Pramenka, Pag Island Sheep, Dalmatian Pramenka, Dubrovnik Sheep) and mouflon using the Ovine Infinium® HD SNP BeadChip (606,006 SNPs). In addition, we included publicly available Balkan Pramenka and other Mediterranean sheep breeds. Our analyses revealed the complex population structure of Croatian sheep breeds and their origin and geographic barriers (island versus mainland). Migration patterns confirmed the historical establishment of breeds and the pathways of gene flow. Inbreeding coefficients (FROH>2 Mb) between sheep populations ranged from 0.025 to 0.070, with lower inbreeding coefficients observed in Dalmatian Pramenka and Pag Island Sheep and higher inbreeding in Dubrovnik sheep. The estimated effective population size ranged from 61 to 1039 for Krk Island Sheep and Dalmatian Pramenka, respectively. Higher inbreeding levels and lower effective population size indicate the need for improved conservation management to maintain genetic diversity in some breeds. Our results will contribute to breeding and conservation strategies of native Croatian sheep breeds.
Detection of Genomic Imprinting for Carcass Traits in Cattle Using Imputed High-Density Genotype Data
Authors: Kenny David , Sleator Roy D. , Murphy Craig P. , Evans Ross D. , Berry Donagh P.
Published: July 2022

Genomic imprinting is an epigenetic phenomenon defined as the silencing of an allele, at least partially, at a given locus based on the sex of the transmitting parent. The objective of the present study was to detect the presence of SNP-phenotype imprinting associations for carcass weight (CW), carcass conformation (CC) and carcass fat (CF) in cattle. The data used comprised carcass data, along with imputed, high-density genotype data on 618,837 single nucleotide polymorphisms (SNPs) from 23,687 cattle; all animal genotypes were phased with respect to parent of origin. Based on the phased genotypes and a series of single-locus linear models, 24, 339, and 316 SNPs demonstrated imprinting associations with CW, CC, and CF, respectively. Regardless of the trait in question, no known imprinted gene was located within 0.5 Mb of the SNPs demonstrating imprinting associations in the present study. Since all imprinting associations detected herein were at novel loci, further investigation of these regions may be warranted. Nonetheless, knowledge of these associations might be useful for improving the accuracy of genomic evaluations for these traits, as well as mate allocations systems to exploit the effects of genomic imprinting.
KIR- Ligand Interactions in Hypertensive Disorders in Pregnancy
Authors: Stefańska Katarzyna , Tomaszewicz Martyna , Dębska-Zielkowska Joanna , Zamkowska Dorota , Piekarska Karolina , Sakowska Justyna , Studziński Maciej , Tymoniuk Bogusław , Adamski Przemysław , Jassem-Bobowicz Joanna , Wydra Piotr , Leszczyńska Katarzyna , Świątkowska-Stodulska Renata , Kwiatkowski Sebastian , Preis Krzysztof , Trzonkowski Piotr , Marek-Trzonkowska Natalia , Zieliński Maciej
Published: July 2022

Hypothesis

The activity of natural killer (NK) cells is considered an important factor for the tolerance of the fetus during pregnancy. The complications of pregnancy, such as hypertensive disorders (HDP), may be therefore associated with this immune compartment.

Methods

The current study included 41 pregnant women diagnosed with HDPs (Gestational Hypertension; GH or Preeclampsia; PE) and 21 healthy women. All the patients were under continuous obstetric care during the pregnancy and labour. The number of mother-child mismatches within killer immunoglobulin-like receptors (KIRs), their ligands [MM], and missing KIR ligands [MSLs] was assessed. KIRs and their ligands were assessed with Next Generation Sequencing (NGS) and Polymerase Chain Reaction Sequence-Specific Oligonucleotide (PCR-SSO) typing. The subsets of NK cells were assessed with multicolor flow cytometry and correlated to the number of MSLs.

Results

The number of MSLs was significantly higher in HDP patients when compared to healthy non-complicated pregnancy patients. Some MSLs, such as those with 2DS2 activating KIR, were present only in HDP patients. The percentage of CD56+CD16-CD94+ NK cells and CD56+CD16-CD279+ NK cells correlated with the number of MSLs with inhibiting KIRs only in healthy patients. In HDP patients, there was a correlation between the percentage of CD56-CD16+CD69+ NK cells and the number of MSLs with inhibiting and activating KIRs. As compared to the healthy group, the percentage of CD56+CD16-CD279+ NK cells and CD56-CD16+CD279+ NK cells were lower in HDP patients. HDP patients were also characterized by a higher percentage of CD56+CD16+perforin+ NK cells than their healthy counterparts.

Conclusions

Patients with HDP were characterized by a higher number of MSLs within the KIRs receptors. It seemed that the number of MSLs in the healthy group was balanced by various receptors, such as CD94 or inhibitory CD279, expressed on NK cells. Conversely, in HDP patients the number of MSLs was associated with the activation detected as the increased level of CD69+ NK cells.
Fine Analysis of Lymphocyte Subpopulations in SARS-CoV-2 Infected Patients: Differential Profiling of Patients With Severe Outcome
Authors: Clavarino Giovanna , Leroy Corentin , Epaulard Olivier , Raskovalova Tatiana , Vilotitch Antoine , Pernollet Martine , Dumestre-Pérard Chantal , Defendi Federica , Le Maréchal Marion , Le Gouellec Audrey , Audoin Pierre , Bosson Jean-Luc , Poignard Pascal , Roustit Matthieu , Jacob Marie-Christine , Cesbron Jean-Yves
Published: July 2022

COVID-19 is caused by the human pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has resulted in widespread morbidity and mortality. CD4+ T cells, CD8+ T cells and neutralizing antibodies all contribute to control SARS-CoV-2 infection. However, heterogeneity is a major factor in disease severity and in immune innate and adaptive responses to SARS-CoV-2. We performed a deep analysis by flow cytometry of lymphocyte populations of 125 hospitalized SARS-CoV-2 infected patients on the day of hospital admission. Five clusters of patients were identified using hierarchical classification on the basis of their immunophenotypic profile, with different mortality outcomes. Some characteristics were observed in all the clusters of patients, such as lymphopenia and an elevated level of effector CD8+CCR7- T cells. However, low levels of T cell activation are associated to a better disease outcome; on the other hand, profound CD8+ T-cell lymphopenia, a high level of CD4+ and CD8+ T-cell activation and a high level of CD8+ T-cell senescence are associated with a higher mortality outcome. Furthermore, a cluster of patient was characterized by high B-cell responses with an extremely high level of plasmablasts. Our study points out the prognostic value of lymphocyte parameters such as T-cell activation and senescence and strengthen the interest in treating the patients early in course of the disease with targeted immunomodulatory therapies based on the type of adaptive response of each patient.
Imaging Mass Cytometry Analysis of immune Checkpoint Inhibitor-Related Pneumonitis: A Case Report
Authors: Cheng Yuan , Wang Xiao-Ming , Hu Qin , Sun Kunyan , Zhao Xiang , Zhang Meng , Wang Guangfa , Wang He , Xiong Yan
Published: July 2022

Immune checkpoint inhibitor-related pneumonitis (CIP) is a rare but well-recognized immune-related adverse event (irAE), causes 35% of irAE related deaths. However, the mechanism of CIP remains unclear and no evidence-based treatment except for glucocorticoids is available. Herein, we report the case of a patient with metastatic bladder cancer who received tislelizumab and was diagnosed with CIP. The patient underwent transbronchial cryobiopsy. The patient was treated with glucocorticoid, but CIP recurred when the glucocorticoid tapering. The paraffine-embedded lung tissue was sectioned, stained with 31 heavy-metal tagged antibodies, and analyzed using imaging mass cytometry (IMC) technology. We identified multiple immune cell subsets in the lung tissue and observed the infiltration of memory T cells and the CD4+ DC subset. The data indicated the great potential of IMC technology in the identification and characterization of irAEs. Further investigation is warranted to identify the mechanism of action of CIP.
An evidence review of the association of immune and inflammatory markers with obesity-related eating behaviors
Authors: Meng Ying , Kautz Amber
Published: July 2022

Background

Eating behaviors contribute to disproportionate energy intake and are linked to the development of obesity. Animal studies support the role of inflammatory cytokines and chemokines in the regulation of obesity-related eating behaviors and offer a potential target to combat obesity through the modulation of inflammation. However, more complex eating behaviors are present in humans, and their relationships with immune/inflammation markers are unclear. The present study reviewed current literature to synthesize the evidence on the association of immune/inflammation markers with obesity-related eating behaviors in humans.

Methods

A systematic search of three electronic databases yielded 811 articles, of which 11 met the inclusion criteria.

Results

The majority of the included studies (91%) were either case-control or cross-sectional studies. A variety of immune/inflammation markers and obesity-related eating behaviors have been assessed in the chosen studies. Three out of four studies identified a positive relationship between C-reactive protein (CRP)/high-sensitivity CRP and loss of control eating. Other inflammatory markers that potentially have a positive relationship with obesity-related eating behaviors include fractalkine and fibrinogen. Additionally, immune molecules, including interferon gamma (INF-γ), interleukin (IL)-7, IL-10, and α-melanocyte-stimulating hormone-reactive immunoglobulin G (α-MSH/IgG) immune complex, may have negative associations with obesity-related eating behaviors. However, most findings were identified by single studies.

Conclusion

Limited studies have been conducted in humans. Current evidence indicates a potential bi-directional relationship between inflammatory/immune markers and obesity-related eating behaviors. Additional studies with sophisticated research design and comprehensive theoretical models are warranted to further delineate the relationship between immune/inflammation markers and obesity-related eating behaviors.
Mining of Marburg Virus Proteome for Designing an Epitope-Based Vaccine
Authors: Soltan Mohamed A. , Abdulsahib Waleed K. , Amer Mahmoud , Refaat Ahmed M. , Bagalagel Alaa A. , Diri Reem M. , Albogami Sarah , Fayad Eman , Eid Refaat A. , Sharaf Sherin M. A. , Elhady Sameh S. , Darwish Khaled M. , Eldeen Muhammad Alaa
Published: July 2022

Marburg virus (MARV) is one of the most harmful zoonotic viruses with deadly effects on both humans and nonhuman primates. Because of its severe outbreaks with a high rate of fatality, the world health organization put it as a risk group 4 pathogen and focused on the urgent need for the development of effective solutions against that virus. However, up to date, there is no effective vaccine against MARV in the market. In the current study, the complete proteome of MARV (seven proteins) was analyzed for the antigenicity score and the virulence or physiological role of each protein where we nominated envelope glycoprotein (Gp), Transcriptional activator (VP30), and membrane-associated protein (VP24) as the candidates for epitope prediction. Following that, a vaccine construct was designed based on CTL, HTL, and BCL epitopes of the selected protein candidates and to finalize the vaccine construct, several amino acid linkers, β-defensin adjuvant, and PADRE peptides were incorporated. The generated potential vaccine was assessed computationally for several properties such as antigenicity, allergenicity, stability, and other structural features where the outcomes of these assessments nominated this potential vaccine to be validated for its binding affinity with two molecular targets TLR-8 and TLR-4. The binding score and the stability of the vaccine-receptor complex, which was deeply studied through molecular docking-coupled dynamics simulation, supported the selection of our designed vaccine as a putative solution for MARV that should be validated through future wet-lab experiments. Here, we describe the computational approach for designing and analysis of this potential vaccine.
Field Application of Automated Spectrophotometric Analyzer for High-Resolution In Situ Monitoring of pH in Dynamic Estuarine and Coastal Waters
Authors: Nehir Münevver , Esposito Mario , Loucaides Socratis , Achterberg Eric P.
Published: July 2022

High quality pH measurements are required in estuarine and coastal waters to assess the impacts of anthropogenic atmospheric CO2 emissions on the marine carbonate system, including the resulting decrease in pH. In addition, pH measurements are needed to determine impacts on carbonate chemistry of phytoplankton blooms and their breakdown, following enhanced anthropogenic nutrient inputs. The spectrophotometric pH technique provides high quality pH data in seawater, and is advantageous for long-term deployments as it is not prone to drift and does not require in situ calibration. In this study, a field application of a fully automated submersible spectrophotometric analyzer for high-resolution in situ pH measurements in dynamic estuarine and coastal waters is presented. A Lab-on-Chip (LOC) pH sensor was deployed from a pontoon in the inner Kiel Fjord, southwestern Baltic Sea, for a total period of 6 weeks. We present a time-series of in situ pHT (total pH scale) and ancillary data, with sensor validation using discretely collected samples for pHT and laboratory analysis. The difference between the sensor and laboratory analyses of discrete samples was within ±0.015 pHT unit, with a mean difference of 0.001 (n=65), demonstrating that the LOC sensor can provide stable and accurate pHT measurements over several weeks.
Static Behavior of Circular Section CFRP Concrete-Filled Steel Tubes Under Compressive–Torsional Load
Authors: Wang Qing-li , Zhao Jie , Peng Kuan
Published: July 2022

In order to study the compressive torsional behavior of concrete-filled CFRP steel tubes (CF-CFRP-STs), the static test of eight circular section CF-CFRP-ST compression torsional specimens was carried out. The characteristics of the torque–angle (T–θ) curve and shear stress shear–strain (τ–γ) curve, failure mode, cooperative work between steel tubes and CFRP, and cross-section assumption were studied. The T–θ curve, τ–γ curve, and failure mode of the specimen are simulated by ABAQUS. Based on the above research, the stress distribution of each component material is analyzed. The effects of transverse CFRP layers, material strength, steel ratio, and axial compression ratio on the static performance of members are discussed. Based on the performance analysis, the bearing capacity equation of CF-CFRP-ST compression-torsional members is proposed.
Silicocarnotite: Novel Silicate Bioceramic With Osteogenic Property for Repairing Rat Cranial Critical-Sized Bone Defects
Authors: Shao Yongke , Deng Fanyan , Chang Yongyun , Shi Songqing , Li Huiwu , Yuan Yao
Published: July 2022

Critical-sized bone defects are an intractable orthopedic disease which often fails to regenerate spontaneously and requires additional intervention. Current therapies, including autografts and allografts, are not always satisfactory. Herein, the novel calcium phosphate bioceramic-containing silicon (CPS) with a carnotite structure was synthesized. In the present study, CPS was prepared for investigating the biocompatibility and bioactivity in vitro and in vivo in comparison to hydroxyapatite (HA). Our results showed that CPS bioceramics had favorable biocompatibility and rBMSCs could adhere on the surface well in vitro. Moreover, CPS could promote osteogenic differentiation of rBMSCs and the expression of osteogenic differentiation marker genes, including ALP, Runx-2, BSP, OCN, and OPN. In vivo, the results of micro-CT, histomorphometry, and histology analyses showed that CPS significantly enhanced critical-sized calvarial defects healing compared with HA. Overall, the present study demonstrated that CPS bioceramics had satisfactory bioactivities and osteogenic capacities, which could be a potential option for reconstructing critical-sized bone defects.
On Modeling of Spray G ECN Using ROI-Based Eulerian-Lagrangian Simulation
Authors: Ailaboina Akhil , Saha Kaushik
Published: July 2022

A numerical study has been carried out to understand the effects of Unsteady Reynolds Averaged Navier-Stokes (standard k ― ε and RNG k ― ε model) and large eddy simulations (LES) on a multi-hole gasoline direct injection (GDI) system. The fuel injector considered in this study is the Spray G nozzle from the Engine Combustion Network (ECN). A blob injection model, based on empirical rate of injection (ROI) profile, is considered in this study. The latest data on spray penetrations from Engine Combustion Network is used for model validation along with experimental findings on suction velocity and local droplet diameter. The spray breakup is simulated by using the KH-RT breakup length model. The turbulence model constant Cε1, is tuned to match with the experimental data of liquid and vapor penetrations in simulations while using the standard k-ε turbulence model. On the other hand, the Kelvin-Helmholtz breakup model time constant (B1) and Rayleigh Taylor breakup length constant (Cbl) are tuned for the RNG k ― ε turbulence model. From this work it is observed that by increasing the breakup length model constants (Cbl), the radial dispersion of the spray increases, and the extent of breakup is lowered. The set of optimized model parameters used with RNG k - ε is also used for LES modeling studies with different sub-grid models. The spray penetrations with standard k ― ε turbulence (Cε1=1.44) model are reported underpredicting, and the RNG k ― ε and LES sub-grid models predicted well with the latest and recommended data from ECN. In terms of gas axial velocity comparison, the standard k-ε(Cε1=1.44) simulation setup does not perform as well as the simulation setups using RNG k-ε and LES turbulence models (with breakup parameters: Cbl = 16 and B1 = 32). However, the standard k-ε(Cε1=1.44) simulation setup perform better than the simulation setups using RNG k-ε and LES turbulence models (with breakup parameters: Cbl = 16 and B1 = 32) when it comes to predicting local droplet diameter at 15 mm downstream of the injector tip. A parametric study is also performed considering the geometry of the stepped holes in the computational domain. The rate of injection based simulation is initiated at the end of the smaller hole. The case including the stepped holes led to over-prediction compared to the case with the usual computational domain (i.e., without the stepped holes), in terms of spray penetrations, but exhibited higher levels of fluctuations in the spray morphology. Finally, parametric studies were carried out to understand the relative importance of the individual spray sub-models (breakup, evaporation and collision) and the results are conclusive that for a spray simulation the breakup models are the dominant factors.
Multidisciplinary approach to treatment with immune checkpoint inhibitors in patients with HIV, tuberculosis, or underlying autoimmune diseases
Authors: Aguilar-Company Juan , Lopez-Olivo Maria A. , Ruiz-Camps Isabel
Published: July 2022

We reviewed the available information on the use of immune checkpoint inhibitors (ICIs) in populations with special conditions, namely, patients with HIV, tuberculosis, or underlying autoimmune disease. Available data show that treatment with ICIs is safe in patients with HIV; it is advisable, however, that these patients receive adequate antiretroviral therapy and have an undetectable viral load before ICIs are initiated. Tuberculosis reactivation has been reported with the use of ICIs, possibly due to immune dysregulation. Tuberculosis has also been associated with the use of immunosuppressors to treat immune-related adverse events (irAEs). Active tuberculosis must be ruled out in patients with symptoms or signs, and selected patients may benefit from screening for latent tuberculosis infection, although more data are required. Limited data exist regarding the safety of ICIs in patients with cancer and autoimmune disease. Data from observational studies suggest that up to 29% of patients with a preexisting autoimmune disease treated with an ICI present with an autoimmune disease flare, and 30% present with a de novo irAE of any type. The frequency of flares appears to differ according to the type of ICI received, with higher rates associated with PD-1/PD-L1 inhibitors. The most common autoimmune diseases for which patients reported flares with ICI therapy are rheumatoid arthritis, other inflammatory arthritis, and psoriasis. Most studies have reported flares or de novo irAEs associated with ICIs that were mild to moderate, with low rates of discontinuation and no deaths due to flares. Therefore, the use of ICIs in these patients is possible, but careful monitoring is required.
Metabolome and Microbiome Signatures in the Leaves of Wild Tea Plant Resources Resistant to Pestalotiopsis theae
Authors: Zhang Yuqian , Zhang Jie , Yan Changyu , Fang Meishan , Wang Lijie , Huang Yahui , Wang Feiyan
Published: July 2022

Tea (Camellia sinensis) is an important crop that is mainly used in the food industry. This study using the metabolome and microbiome investigates the resistance factors of wild tea plant resources against tea gray blight disease, which is caused by Pestalotiopsis theae (Sawada) Steyaert. According to the interaction analysis of tea leaves and pathogenic fungus, the resistance of wild tea plant resource “R1” (Resistance 1) to tea gray blight disease was significantly higher than that of wild tea plant resource “S1” (Susceptibility 1). The difference between “R1” and “S1” in the metabolome was obvious. There were 145 metabolites that significantly changed. The phenolic acids and flavonoids were the major increased categories in “R1,” and it included 4-O-glucosyl-sinapate and petunidin-3-o-(6”-o-p-coumaroyl) rutinoside. Six metabolic pathways were significantly enriched, including aminoacyl-tRNA biosynthesis, flavone, and flavonol biosynthesis. In terms of bacteria, there was no significant difference between “S1” and “R1” in the principal component analysis (PCA). Pseudomonas was the major bacterial genus in “S1” and “R1.” In addition, each of the two resources had its own predominant genus: Cellvibirio was a predominant bacterial genus in “S1” and Candidatus_competibacter was a predominant bacterial genus in “R1.” In terms of fungi, the fungal diversity and the abundance of the two tea plant resource samples could be distinguished clearly. The fungal component of “S1” was more abundant than that of “R1” at the genus level. Toxicocladosporium was the predominant fungal genus of “S1,” and Filobasidium was the predominant fungal genus of “R1.” The relative abundance of unclassified-norank-norank-Chloroplast and Penicillium were significantly different between “S1” and “R1.” Penicillium was identified as a potential biomarker. They correlated with some metabolites enriched in “S1” or “R1,” such as L-arginine and quercetin-3-o-(2”-o-rhamnosyl) rutinoside-7-o-glucoside. Overall, phenolic acids, flavonoids, and Penicillium could be functional metabolites or microorganisms that contributed to improving the resistance of wild tea plant resources to tea gray blight disease.
PDL1Binder: Identifying programmed cell death ligand 1 binding peptides by incorporating next-generation phage display data and different peptide descriptors
Authors: He Bifang , Li Bowen , Chen Xue , Zhang Qianyue , Lu Chunying , Yang Shanshan , Long Jinjin , Ning Lin , Chen Heng , Huang Jian
Published: July 2022

Monoclonal antibody drugs targeting the PD-1/PD-L1 pathway have showed efficacy in the treatment of cancer patients, however, they have many intrinsic limitations and inevitable drawbacks. Peptide inhibitors as alternatives might compensate for the drawbacks of current PD-1/PD-L1 interaction blockers. Identifying PD-L1 binding peptides by random peptide library screening is a time-consuming and labor-intensive process. Machine learning-based computational models enable rapid discovery of peptide candidates targeting the PD-1/PD-L1 pathway. In this study, we first employed next-generation phage display (NGPD) biopanning to isolate PD-L1 binding peptides. Different peptide descriptors and feature selection methods as well as diverse machine learning methods were then incorporated to implement predictive models of PD-L1 binding. Finally, we proposed PDL1Binder, an ensemble computational model for efficiently obtaining PD-L1 binding peptides. Our results suggest that predictive models of PD-L1 binding can be learned from deep sequencing data and provide a new path to discover PD-L1 binding peptides. A web server was implemented for PDL1Binder, which is freely available at http://i.uestc.edu.cn/pdl1binder/cgi-bin/PDL1Binder.pl.
Effect of Saccharomyces cerevisiae culture mitigates heat stress-related dame in dairy cows by multi-omics
Authors: Du Dewei , Jiang Wenbo , Feng Lei , Zhang Yu , Chen Peng , Wang Chengqiang , Hu Zhiyong
Published: July 2022

The effect of heat stress on ruminants is an important issue. In recent years, the growth of the Chinese dairy industry has rapidly increased, generating RMB 468,738 million revenue in 2021. A decreased milk yield is the most recognized impact of heat stress on dairy cows and results in significant economic loss to dairy producers. Heat stress also lowers immunity and antioxidant capacity and changes the bacterial composition and metabolites of the rumen. The purpose of this study was to investigate the effect of additionSaccharomyces cerevisiaeculture on heat-stressed cows. The impact ofS. cerevisiaeculture on microbiota composition, functional profiles, and metabolomics was assessed in heat-stressed cows. A total of 45 Holstein cows in mid-lactation were selected and randomly divided into three groups (15 cows per group). Groups D-C, D-A, and D-B were fed with the basal diet, the basal diet + firstS. cerevisiaeculture 100 g/day, and the basal diet + secondS. cerevisiaeculture 30 g/day, respectively. The trial lasted 60 days. There was an increased abundance of the Phylum Firmicutes in the rumen of heat-stressed dairy cows fed withS. cerevisiae, of which four genera had significantly higher abundance,Ruminococcus_gauvreauii_group, Butyrivibrio_2, Moryella, andRuminiclostridium_6.At the functional level, ten pathways differed significantly between the three groups (P< 0.05), with an increase in fatty acid biosynthesis, fatty acid metabolism, PPAR signaling pathway, ferroptosis, and biotin metabolism in the treatment groups. More differential metabolites were found in the D-C and D-A groups than in the D-C and D-B groups. These results indicate thatS. cerevisiaecultures can influence the health status of heat-stressed cows by modulating rumen microbial composition, function, and metabolites, thereby improving rumen cellulolytic capacity. This study can provide or offer suggestions or recommendations for the development and utilization of feed additives.
Replacement of the Dominant ST191 Clone by ST369 Among Carbapenem-Resistant Acinetobacter baumannii Bloodstream Isolates at a Tertiary Care Hospital in South Korea
Authors: Kim Seong Eun , Choi Su-Mi , Yu Yohan , Shin Sung Un , Oh Tae Hoon , Kang Seung-Ji , Park Kyung-Hwa , Shin Jong Hee , Kim Uh Jin , Jung Sook In
Published: July 2022

The clonal dissemination of carbapenem-resistant Acinetobacter baumannii (CRAB) bacteremia is a serious clinical problem worldwide. However, the factors related to the emergence and replacement of predominant CRAB clones in nosocomial settings are unclear. By multilocus sequence typing (MLST), we evaluated the genetic relatedness of CRAB bloodstream isolates at a tertiary care hospital over a 3.5-year period and investigated the clinical and microbiologic characteristics of the predominant sequence types (STs). One hundred and seventy-nine CRAB bloodstream isolates were collected from June 2016 to December 2019, and their MLSTs according to Oxford scheme and clinical data were obtained. The predominant STs were assessed for in vitro growth, competitive growth, and virulence in a mouse model of intraperitoneal infection. Two dominant clones—ST369 (n = 98) and ST191 (n = 48)—belonging to international clone 2 (IC2) were recovered from patients admitted to intensive care units (ICUs) or wards. ST191 predominated (61%, 27/43) from June 2016 to July 2017, whereas ST369 (72%, 98/136), which was first isolated from a patient admitted to the emergency room, replaced ST191 (15%, 21/136) after August 2017. In a multivariate analysis, leukopenia (OR = 3.62, 95% CI 1.04–12.6, p = 0.04) and ST191 or 369 (OR = 5.32, 95% CI 1.25–22.65, p = 0.02) were independent risk factors for 7-day mortality. Compared with non-ST369, ST369 was associated with a shorter time to bacteremia from ICU admission (7 vs. 11 days, p = 0.01), pneumonia as an origin of bacteremia (67 vs. 52%, p = 0.04), leukopenia (28 vs. 11%, p < 0.01), and a lower 7-day survival rate (41 vs. 70%, p < 0.01). In vitro, ST 369 isolates had significantly higher growth rates and enhanced competitive growth compared to ST191. Finally, ST369 had greater virulence and a higher mortality rate than other STs in a mouse infection model. We report almost-complete replacement of the predominant ST191 clone by ST369 within an 8-month period at our hospital. ST369 had a high incidence density rate of CRAB bacteremia, a short time to bacteremia after ICU admission, and a high early mortality rate, which may be in part explained by its faster competitive growth rate and higher virulence than ST191.
Diverse Effects of Amino Acids on Monascus Pigments Biosynthesis in Monascus purpureus
Authors: Yin Sheng , Zhu Yiying , Zhang Bin , Huang Baozhu , Jia Ru
Published: July 2022

Amino acids could act as nitrogen sources, amido group donors, or bioactive molecules in fungi fermentation, and consequently, play important roles in Monascus pigments (MPs) biosynthesis. But the understanding of the effects of various amino acids on MPs biosynthesis is still incomprehensive. In this work, 20 free amino acids were added to the fermentation medium to evaluate their effects on MPs biosynthesis in Monascus purpureus RP2. Six amino acids, namely, histidine (HIS), lysine (LYS), tyrosine (TYR), phenylalanine (PHE), methionine (MET), and cysteine (CYS), were selected as the valuable ones as they exerted significant effects on the production yield and even on the biosynthesis metabolic curves of MPs. Moreover, the dose-dependent and synergistic effects of valuable amino acids on MPs biosynthesis were observed by tests of serial concentrations and different combinations. In addition, it revealed that HIS and MET were the prominent amino acids with dominant and universal influences on MPs biosynthesis. The analog compounds of HIS (amitrole) and MET [calcium 2-hydroxy-4-(methylthio)] were added to the fermentation medium, and the results further confirmed the extraordinary effects of HIS and MET and their analogs on MPs biosynthesis. Furthermore, the gene transcription profile indicated that a differential expression pattern was observed in the polyketide synthase (PKS) cluster responsible for MPs biosynthesis in response to HIS and MET, revealing that they could oppositely regulate MPs biosynthesis in different ways. These findings would benefit the understanding of MPs biosynthesis regulation mechanism in M. purpureus and contribute to the industrial production of MPs by fermentation.
Huangqin Decoction Exerts Beneficial Effects on Rotenone-Induced Rat Model of Parkinson's Disease by Improving Mitochondrial Dysfunction and Alleviating Metabolic Abnormality of Mitochondria
Authors: Gao Li , Cao Min , Du Guan-hua , Qin Xue-mei
Published: July 2022

Parkinson's disease (PD) is a common neurodegenerative disease, and the pathogenesis of PD is closely related to mitochondrial dysfunction. Previous studies have indicated that traditional Chinese medicine composition of Huangqin Decoction (HQD), including Scutellariae Radix, licorice, and Paeoniae Radix Alba, has therapeutic effects on PD, but whether HQD has a therapeutic effect on PD has not been reported. In this study, the protective effects of HQD on rotenone-induced PD rats were evaluated by behavioral assays (open field, rotating rod, suspension, gait, inclined plate, and grid) and immunohistochemistry. The mechanisms of HQD on attenuation of mitochondrial dysfunction were detected by biochemical assays and mitochondrial metabolomics. The results showed that HQD (20 g/kg) can protect rats with PD by improving motor coordination and muscle strength, increasing the number of tyrosine hydroxylase (TH)-positive neurons in rats with PD. Besides, HQD can improve mitochondrial dysfunction by increasing the content of adenosine triphosphate (ATP) and mitochondrial complex I. Mitochondrial metabolomics analysis revealed that the ketone body of acetoacetic acid (AcAc) in the rotenone group was significantly higher than that of the control group. Ketone bodies have been known to be used as an alternative energy source to provide energy to the brain when glucose was deficient. Further studies demonstrated that HQD could increase the expression of glucose transporter GLUT1, the content of tricarboxylic acid cycle rate-limiting enzyme citrate synthase (CS), and the level of hexokinase (HK) in rats with PD but could decrease the content of ketone bodies [AcAc and β-hydroxybutyric acid (β-HB)] and the expression of their transporters (MCT1). Our study revealed that the decrease of glucose metabolism in the rotenone group was parallel to the increase of substitute substrates (ketone bodies) and related transporters, and HQD could improve PD symptoms by activating the aerobic glycolysis pathway.