Prognostic nomogram in patients with gastrointestinal stromal tumors: a SEER-based study.

Background: Gastrointestinal stromal tumor (GIST) is a common mesenchymal tumor of the gastrointestinal system. They originate from the interstitial cells of Cajal located within the muscle layer and are characterized by over-expression of the tyrosine kinase receptor KIT. Methods: Data from the Surveillance Epidemiology, and End Results (SEER) database of 1,213 patients diagnosed with GIST between 2010 and 2019 were dichotomized into a modeling set and a validation set at a 2:1 ratio. For the modeling set, both univariate and multivariate Cox regression analyses were used to identify independent prognostic factors. A nomogram was then constructed based on these determinants. Model efficacy was tested using receiver operating characteristic (ROC) curves, calibration curves, clinical decision curves, and risk stratification analysis in both subsets. Results: Identified prognostic determinants included age, sex, pathological differentiation level, tumor-node-metastasis (TNM) stage, surgical intervention, radiotherapy, and marital status. The constructed nomogram showed area under the ROC curve (AUC) values of 0.822, 0.793, and 0.779 for 1-, 3-, and 5-year overall survival (OS) in the modeling set, respectively, while in the validation set, the values were 0.796, 0.823, and 0.806, respectively. Calibration plots from both sets confirmed the concordance between predicted and observed survival. Decision curve analysis (DCA) indicated significant clinical utility for the nomogram. Risk stratification of the patient data revealed distinct survival differences between high-risk and low-risk cohorts in both sets (P<0.001). Conclusions: A novel and potent nomogram for the prognosis of GIST has been introduced. This model's precision offers crucial insights for clinical decisions, yet further external validation remains essential.

Moderate replacement of fish oil with palmitic acid-stimulated mitochondrial fusion promotes ß-oxidation by Mfn2 interacting with Cpt1α via its GTPase-domain.

The mitochondrial matrix serves as the principal locale for the process of fatty acids (FAs) ß-oxidation. Preserving the integrity and homeostasis of mitochondria, which is accomplished through ongoing fusion and fission events, is of paramount importance for the effective execution of FAs ß-oxidation. There has been no investigation to date into whether and how mitochondrial fusion directly enhances FAs ß-oxidation. The underlying mechanism of a balanced FAs ratio favoring hepatic lipid homeostasis remains largely unclear. To address such gaps, the present study was conducted to investigate the mechanism through which a balanced dietary FAs ratio enhances hepatic FAs ß-oxidation. The investigation specifically focused on the involvement of Mfn2-mediated mitochondrial fusion in the regulation of Cpt1α in this process. In the present study, the yellow catfish (Pelteobagrus fulvidraco), recognized as a model organism for lipid metabolism, were subjected to eight weeks of in vivo feeding with six distinct diets featuring varying FAs ratios. Additionally, in vitro experiments were conducted to inhibit Mfn2-mediated mitochondrial fusion in isolated hepatocytes, achieved through the transfection of hepatocytes with si-mfn2. Further, deletion mutants for both Mfn2 and Cpt1α were constructed to elucidate the critical regions responsible for the interactions between these two proteins within the system. The key findings were: (1) Substituting palmitic acid (PA) for fish oil (FO) proved to be enhanced in reducing hepatic lipid accumulation. This beneficial effect was primarily attributed to the activation of mitochondrial FAs ß-oxidation; (2) The balanced replacement of PA stimulated Mfn2-mediated mitochondrial fusion by diminishing Mfn2 ubiquitination, thereby enhancing its protein retention within the mitochondria; (3) Mfn2-mediated mitochondrial fusion promoted FAs ß-oxidation through direct interaction between Mfn2 and Cpt1α via its GTPase-domains, which is essential for the maintenance of Cpt1 activity. Notably, the present research results unveil a previously undisclosed mechanism wherein Mfn2-mediated mitochondrial fusion promotes FAs ß-oxidation by directly augmenting the capacity for FA transport into mitochondria (MT), in addition to expanding the mitochondrial matrix. This underscores the pivotal role of mitochondrial fusion in preserving hepatic lipid homeostasis. The present results further confirm that these mechanisms are evolutionarily conserved, extending their relevance from fish to mammals.

Treatment strategies and drug resistance mechanisms in adenocarcinoma of different organs.

Adenocarcinoma is a common type of malignant tumor, originating from glandular epithelial cells in various organs, such as pancreas, breast, lung, stomach, colon, rectus, and prostate. For patients who lose the opportunity for radical surgery, medication is available to provide potential clinical benefits. However, drug resistance is a big obstacle to obtain desired clinical prognosis. In this review, we provide a summary of treatment strategies and drug resistance mechanisms in adenocarcinoma of different organs, including pancreatic cancer, gastric adenocarcinoma, colorectal adenocarcinoma, lung adenocarcinoma, and prostate cancer. Although the underlying molecular mechanisms involved in drug resistance of adenocarcinoma vary from one organ to the other, there are several targets that are universal for drug resistance in adenocarcinoma, and targeting these molecules could potentially reverse drug resistance in the treatment of adenocarcinomas.

The Landscape of m6A Regulators in Multiple Brain Regions of Alzheimer's Disease.

Alzheimer's disease research has been conducted for many years, yet no effective cure methods have been found. N6-methyladenosine (m6A) RNA methylation, an essential post-transcriptional regulation mechanism, has been discovered to affect essential neurobiological processes, such as brain cell development and aging, which are closely related to neurodegenerative diseases such as Alzheimer's disease. The relationship between Alzheimer's disease and the m6A mechanism still needs further investigation. Our work evaluated the alteration profile of m6A regulators and their influences on Alzheimer's disease in 4 brain regions: the postcentral gyrus, superior frontal gyrus, hippocampus, and entorhinal cortex. We found that the expression levels of the m6A regulators FTO, ELAVL1, and YTHDF2 were altered in Alzheimer's disease and were related to pathological development and cognitive levels. We also assessed AD-related biological processes influenced by m6A regulators via GSEA and GSVA method. Biological Processes Gene Ontology terms including memory, cognition, and synapse-signaling were found to potentially be affected by m6A regulators in AD. We also found different m6A modification patterns in AD samples among different brain regions, mainly due to differences in m6A readers. Finally, we further evaluated the importance of AD-related regulators based on the WGCNA method, assessed their potential targets based on correlation relationships, and constructed diagnostic models in 3 of all 4 regions using hub regulators, including FTO, YTHDC1, YTHDC2, etc., and their potential targets. This work aims to provide a reference for the follow-up study of m6A and Alzheimer's disease.

Microglia-Mediated Neurovascular Unit Dysfunction in Alzheimer's Disease.

The neurovascular unit (NVU) is involved in the pathological changes in Alzheimer's disease (AD). The NVU is a structural and functional complex that maintains microenvironmental homeostasis and metabolic balance in the central nervous system. As one of the most important components of the NVU, microglia not only induce blood-brain barrier breakdown by promoting neuroinflammation, the infiltration of peripheral white blood cells and oxidative stress but also mediate neurovascular uncoupling by inducing mitochondrial dysfunction in neurons, abnormal contraction of cerebral vessels, and pericyte loss in AD. In addition, microglia-mediated dysfunction of cellular components in the NVU, such as astrocytes and pericytes, can destroy the integrity of the NVU and lead to NVU impairment. Therefore, we review the mechanisms of microglia-mediated NVU dysfunction in AD. Furthermore, existing therapeutic advancements aimed at restoring the function of microglia and the NVU in AD are discussed. Finally, we predict the role of pericytes in microglia-mediated NVU dysfunction in AD is the hotspot in the future.

The emerging roles of HDACs and their therapeutic implications in cancer.

Deregulation of protein post-translational modifications is intensively involved in the etiology of diseases, including degenerative diseases, inflammatory injuries, and cancers. Acetylation is one of the most common post-translational modifications of proteins, and the acetylation levels are controlled by two mutually antagonistic enzyme families, histone acetyl transferases (HATs) and histone deacetylases (HDACs). HATs loosen the chromatin structure by neutralizing the positive charge of lysine residues of histones; whereas HDACs deacetylate certain histones, thus inhibiting gene transcription. Compared with HATs, HDACs have been more intensively studied, particularly regarding their clinical significance. HDACs extensively participate in the regulation of proliferation, migration, angiogenesis, immune escape, and therapeutic resistance of cancer cells, thus emerging as critical targets for clinical cancer therapy. Compared to HATs, inhibitors of HDAC have been clinically used for cancer treatment. Here, we enumerate and integratethe mechanisms of HDAC family members in tumorigenesis and cancer progression, and address the new and exciting therapeutic implications of single or combined HDAC inhibitor (HDACi) treatment.

Blunt snout bream (Megalobrama amblycephala) MaCSF-1 contributes to proliferation, phagocytosis and immunoregulation of macrophages via MaCSF-1R.

CSF-1 and CSF-1R have been well demonstrated in humans, regulating the differentiation, proliferation and survival of the mononuclear phagocyte system. However, the functional study on MaCSF-1 and MaCSF-1R from blunt snout bream (Megalobrama amblycephala) is still unknown. In the present study, we cloned and functionally characterized MaCSF-1 and MaCSF-1R. Multiple sequence alignment and phylogenetic tree analysis showed that both MaCSF-1 and MaCSF-1R were mostly close to the grass carp counterparts. Tissue distribution analysis showed that both MaCSF-1 and MaCSF-1R were widely distributed in all examined tissues, dominantly distributed in spleen, blood and head kidney tissues. Furthermore, confocal microscopy assay and flow cytometry assay showed that MaCSF-1R was the marker on the surface of macrophages. Recombinant MaCSF-1 promoted macrophage proliferation, phagocytosis and the production of IL-10. Through the pull-down experiments and indirect immunofluorescence experiments, the interaction between MaCSF-1 and MaCSF-1R was confirmed. To explore the relationship between MaCSF-1 and its receptor, MaCSF-1R and MaCSF-1R antibody was prepared. Then the MaCSF-1R blockage assay indicated that the role of MaCSF-1 on the macrophages proliferation and phagocytosis was weakened, leading the reduction of IL-10 expression level. In conclusion, MaCSF-1R is the marker on the surface of macrophage membrane; and MaCSF-1 promotes macrophage proliferation, phagocytosis, and significantly increased the expression levels of IL-10 depended on the interacting with MaCSF-1R. This study provides basal data for the biological function of MaCSF-1 and MaCSF-1R, and is valuable for the exploration of MaCSF-1 and MaCSF-1R molecular interactions.

Systematic analysis of ferroptosis-related long non-coding RNA predicting prognosis in patients with lung squamous cell carcinoma.

Background: Ferroptosis is a novel iron-dependent cell death, and an increasing number of studies have shown that long non-coding RNA (lncRNAs) are involved in the ferroptosis process. However, studies on ferroptosis-related lncRNAs in lung squamous cell carcinoma (LUSC) are limited. In addition, the prognostic role of ferroptosis-related lncRNAs and their relationship with the immune microenvironment and methylation of LUSC is unclear. This study aimed to investigate the potential prognostic value of ferroptosis-related lncRNAs and their involved biological functions in LUSC. Methods: The Cancer Genome Atlas (TCGA) database and the FerrDb website were used to obtain ferroptosis-related genes for LUSC. The "limma" R package and Pearson analysis were used to find ferroptosis-related lncRNAs. The biological functions of the characterized lncRNAs were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). We evaluated the prognostic power of this model using Kaplan-Meier analysis, receiver operating characteristic (ROC), and decision curve analysis (DCA). Univariate and multifactor Cox (proportional-hazards) risk model and a nomogram were produced using risk models and clinicopathological parameters for further verification. In addition, the relationship between characterized lncRNAs and tumor immune infiltration and methylation was also discussed. Results: We identified 29 characterized lncRNAs to produce prognostic risk models. Kaplan-Meier analysis revealed the high-risk group was associated with poor prognosis in LUSC (P<0.001), and ROC (AUC =0.658) and DCA suggested that risk models could predict prognosis. Univariate and multifactorial Cox as well as nomogram further validated the prognostic model (P<0.001). Gene set enrichment analysis (GSEA) showed that the high-risk group was associated with pro-tumor pathways and high-frequency mutations in TP53 were present in both groups. Single sample gene set enrichment analysis (ssGSEA) showed significant differences in immune cell infiltration subtypes and corresponding functions between the two groups. Some immune checkpoint and methylation-related genes were significantly different between the two groups (P<0.05). Conclusions: We investigated the potential mechanisms of LUSC development from the perspective of ferroptosis-related lncRNAs, providing new insights into LUSC research, and identified 29 lncRNAs as biomarkers to predict the prognosis of LUSC patients.

Impact of microplastics on the treatment performance of constructed wetlands: Based on substrate characteristics and microbial activities.

Presence of microplastics (MPs) in wastewater has posed a huge ecosystem risk. Constructed wetlands (CWs) can effectively intercept MPs, while with MPs accumulation the response of CWs' performance is still unclear. In order to evaluate those effects, we conducted a 370-day experiment using CW microcosms fed with different levels (0, 10, 100, and 1000 µg/L) of polystyrene (PS) MPs (diameter: 50-100 µm). Results showed that nitrogen removal efficiency was increased (by 3.9%-24.7%) during the first 60 days and then decreased (by 7.1%-41.3%) with MPs accumulating, but no obvious change in COD and TP removal was observed. From further analysis, MPs accumulation changed the biofilm composition (TOC content increased from 41.4% to 52.7%), substrate porosity (electrical resistivity increased by 1.2-2.4 folds), and oxygen mass transfer (|KLa,O2| increased from 3.5% to 18.6%). Moreover, the microbial dynamics presented a higher abundance of nitrifiers (Nitrospira and Nitrosomonas) during the 60-day experiment and a lower abundance in the last days, while denitrifiers (Thauera, Thiobacillus, and Anaerolinea) had a high relative abundance throughout the experiment, being consistent with the variation of nitrification and denitrification rates. Finally, structural equation model analysis proved that due to the changes of substrate characteristics and microbial compositions and activities, the obvious decrease in nitrification efficiency was a direct reason for the decline of nitrogen removal during 370-day MPs accumulation. Overall, our study first prove that MPs accumulation can cause a series of changes in physicochemical and microbial characteristics of substrate, and ultimately affect the nitrogen-transforming process in CWs. Although our conclusions were based on the lab-scale CWs being different from the real wetlands, we hope that the conclusions can provide the effective regulatory strategies to guide the control of MPs in the actual wetlands.

The Programming of Antioxidant Capacity, Immunity, and Lipid Metabolism in Dojo Loach (Misgurnus anguillicaudatus) Larvae Linked to Sodium Chloride and Hydrogen Peroxide Pre-treatment During Egg Hatching.

Non-nutritional stress during early life period has been reported to promote the metabolic programming in fish induced by nutritional stimulus. Sodium chloride (NaCl) and hydrogen peroxide (H2O2) have been widely applied during fish egg hatching, but the influences on health and metabolism of fish in their later life remain unknown. In the present study, H2O2 treatment at 400mg/L but not 200mg/L significantly increased the loach hatchability and decreased the egg mortality, while NaCl treatment at 1,000 and 3,000mg/L showed no significant influences on the loach hatchability nor egg mortality. Further studies indicated that 400mg/L H2O2 pre-treatment significantly enhanced the antioxidant capacity and the mRNA expression of genes involved in immune response of loach larvae, accompanied by the increased expression of genes involved in fish early development. However, the expression of most genes involved in lipid metabolism, including catabolism and anabolism of loach larvae, was significantly upregulated after 200mg/L H2O2 pre-treatment. NaCl pre-treatment also increased the expression of antioxidant enzymes; however, only the expression of C1q within the detected immune-related genes was upregulated in loach larvae. One thousand milligram per liter NaCl pre-treatment significantly increased the expression of LPL and genes involved in fish early development. Thus, our results suggested the programming roles of 400mg/L H2O2 pre-treatment during egg hatching in enhancing antioxidant capacity and immune response of fish larvae via promoting fish early development.

Foul sewer model development using geotagged information and smart water meter data.

Hydraulic modeling of a foul sewer system (FSS) enables a better understanding of the behavior of the system and its effective management. However, there is generally a lack of sufficient field measurement data for FSS model development due to the low number of in-situ sensors for data collection. To this end, this study proposes a new method to develop FSS models based on geotagged information and water consumption data from smart water meters that are readily available. Within the proposed method, each sewer manhole is firstly associated with a particular population whose size is estimated from geotagged data. Subsequently, a two-stage optimization framework is developed to identify daily time-series inflows for each manhole based on physical connections between manholes and population as well as sewer sensor observations. Finally, a new uncertainty analysis method is developed by mapping the probability distributions of water consumption captured by smart meters to the stochastic variations of wastewater discharges. Two real-world FSSs are used to demonstrate the effectiveness of the proposed method. Results show that the proposed method can significantly outperform the traditional FSS model development approach in accurately simulating the values and uncertainty ranges of FSS hydraulic variables (manhole water depths and sewer flows). The proposed method is promising due to the easy availability of geotagged information as well as water consumption data from smart water meters in near future.

Adherence to the Standards for Reporting of Diagnostic Accuracy Studies (STARD): a survey of four journals in laboratory medicine.

BACKGROUND: The Standards for Reporting of Diagnostic Accuracy Studies (STARD) statement has been updated in 2015. Many diagnostic test accuracy (DTA) studies have been published in medical laboratory journals, but their adherence to the updated STARD statement remains unknown. METHODS: We searched the PubMed database to verify studies published in 4 laboratory journals, including Clinical Chemistry, Clinical Chemistry and Laboratory Medicine, Clinica Chimica Acta, and Clinical Biochemistry, in 2019. DTA studies were identified and their adherence to the STARD statement was assessed. RESULTS: A total of 45 studies were included in this analysis. Overall, 18 out of 34 STARD items were reported. The items (adherence rate) of sample size estimation (4%), adverse events (9%), protocol (9%), registration (16%), missing value (22%), indeterminate results (18%), and cross-tabulation (22%) were the most frequently unreported items. CONCLUSIONS: Adherence to the STARD statement in DTA articles published in laboratory medicine seems as yet unsatisfactory. Our study emphasizes the necessity to improve the reporting quality of DTA studies published in medical laboratory journals.

Water quality modeling in sewer networks: Review and future research directions.

Urban sewer networks (SNs) are increasingly facing water quality issues as a result of many challenges, such as population growth, urbanization and climate change. A promising way to addressing these issues is by developing and using water quality models. Many of these models have been developed in recent years to facilitate the management of SNs. Given the proliferation of different water quality models and the promise they have shown, it is timely to assess the state-of-the-art in this field, to identify potential challenges and suggest future research directions. In this review, model types, modeled quality parameters, modeling purpose, data availability, type of case studies and model performance evaluation are critically analyzed and discussed based on a review of 110 papers published between 2010 and 2019. The review identified that applications of empirical and kinetic models dominate those of data-driven models for addressing water quality issues. The majority of models are developed for prediction and process understanding using experimental or field sampled data. While many models have been applied to real problems, the corresponding prediction accuracies are overall moderate or, in some cases, low, especially when dealing with larger SNs. The review also identified the most common issues associated with water quality modeling of SNs and based on these proposed several future research directions. These include the identification of appropriate data resolutions for the development of different SN models, the need and opportunity to develop hybrid SN models and the improvement of SN model transferability.

Dietary Glutamine Inclusion Regulates Immune and Antioxidant System, as Well as Programmed Cell Death in Fish to Protect against Flavobacterium columnare Infection.

The susceptibility of animals to pathogenic infection is significantly affected by nutritional status. The present study took yellow catfish (Pelteobagrus fulvidraco) as a model to test the hypothesis that the protective roles of glutamine during bacterial infection are largely related to its regulation on the immune and antioxidant system, apoptosis and autophagy. Dietary glutamine supplementation significantly improved fish growth performance and feed utilization. After a challenge with Flavobacterium columnare, glutamine supplementation promoted il-8 and il-1ß expression via NF-κB signaling in the head kidney and spleen, but inhibited the over-inflammation in the gut and gills. Additionally, dietary glutamine inclusion also enhanced the systematic antioxidant capacity. Histological analysis showed the protective role of glutamine in gill structures. Further study indicated that glutamine alleviated apoptosis during bacterial infection, along with the reduced protein levels of caspase-3 and the reduced expression of apoptosis-related genes. Moreover, glutamine also showed an inhibitory role in autophagy which was due to the increased activation of the mTOR signaling pathway. Thus, our study for the first time illustrated the regulatory roles of glutamine in the fish immune and antioxidant system, and reported its inhibitory effects on fish apoptosis and autophagy during bacterial infection.

IFI30 as a prognostic biomarker and correlation with immune infiltrates in glioma.

BACKGROUND: Increased evidence indicates that the tumour microenvironment (TME) plays an essential role in the development, treatment and prognosis of glioma. High expression of interferon-gamma-inducible protein 30 (IFI30) is associated with the malignant phenotype, but the effect of IFI30 on the tumour immune microenvironment and its potential role in the carcinogenesis of glioma remain unknown. METHODS: The RNA sequencing (RNA-seq) data of 33 types of human cancer were obtained from The Cancer Genome Atlas (TCGA) Genomic Data Commons (GDC). R software was used to perform analyses, such as the expression of IFI30 in pan-cancer, evaluation of IFI30 as a prognostic biomarker in glioma, the relationship between IFI30 expression and clinical characteristics, and immune checkpoint. TIMER was used to analyse the correlation of IFI30 expression level with immune cell infiltration, and also to conduct survival analysis for immune cells and IFI30 in low grade glioma (LGG). DAVID was used for Gene Ontology (GO) functional annotations and Kyoto Encyclopedia of Genes and Genomes (KEGG) for pathway analysis of the genes similar to IFI30 in glioma. The differentially expressed genes (DEGs) between the high- and low-IFI30 expression groups were determined by DESeq2. Gene set enrichment analysis (GSEA) was then conducted to identify IFI30-related functional significance based on the hallmark gene set. RESULTS: Dysregulated expression of IFI30 was associated with human cancers. High IFI30 expression was associated with poor overall survival (OS), disease-specific survival (DSS) and progression-free interval (PFI). Univariate and multivariate analyses identified IFI30 as an independent predictor for glioma. Meanwhile, IFI30 overexpression significantly correlated with high-grade tumours, poor OS, and immune infiltration. In addition, IFI30-associated genes significantly enriched the hallmark tumour progression-related clusters and cancer pathways. CONCLUSIONS: IFI30 is a prognostic biomarker correlated with immune infiltrates and acts as an oncogene in glioma.

Real-time foul sewer hydraulic modelling driven by water consumption data from water distribution systems.

Real-time hydraulic modelling can be used to address a wide range of issues in a foul sewer system and hence can help improve its daily operation and maintenance. However, the current bottleneck within real-time FSS modelling is the lack of spatio-temporal inflow data. To address the problem, this paper proposes a new method to develop real-time FSS models driven by water consumption data from associated water distribution systems (WDSs) as they often have a proportionally larger number of sensors. Within the proposed method, the relationship between FSS manholes and WDS water consumption nodes are determined based on their underlying physical connections. An optimization approach is subsequently proposed to identify the transfer factor k between nodal water consumption and FSS manhole inflows based on historical observations. These identified k values combined with the acquired real-time nodal water consumption data drive the FSS real-time modelling. The proposed method is applied to two real FSSs. The results obtained show that it can produce simulated sewer flows and manhole water depths matching well with observations at the monitoring locations. The proposed method achieved high R2, NSE and KGE (Kling-Gupta efficiency) values of 0.99, 0.88 and 0.92 respectively. It is anticipated that real-time models developed by the proposed method can be used for improved FSS management and operation.

Changes in circulating follicular helper T cells in peripheral blood of patients with acute hepatitis C virus infection.

BACKGROUND: To investigate the changes in circulating follicular helper T cells (cTfh) in peripheral blood of patients with acute hepatitis C virus (HCV) infection and its correlation with symptom severity of the disease. METHODS: A total of 105 subjects were enrolled in this study, including 35 healthy people, 35 patients with acute HCV infection and 35 acute HCV patients with antiviral therapy. Flow cytometry was used to detect the expression of molecular markers related to the surface of cTfh cells, such as CD69, HLA-DR and CD57, and ELISA was used to detect the secretion of cytokines (IL-21, IL-4) in each group. The relationship between these markers and disease was analyzed statistically. RESULTS: Flow cytometry analysis demonstrated that the percentage of CD69 in peripheral blood of patients with acute hepatitis C infection was (18.90%±9.29%) significantly higher than that of normal control group (5.10%±4.21%) and antiviral treatment group (11.50%±5.38%). The difference was statistically significant (P<0.05). The results of HLA-DR and CD57 were consistent with CD69. The serum levels of IL-4 and IL-21 in the acute HCV infection group were significantly higher than those in the treatment and the control groups. After antiviral treatment, IL-4 and IL-21 levels significantly decreased but remained higher than those in the control group. This showed that antiviral treatment was effective, and the difference was statistically significant (P<0.05). The ratio of cTfh in infected group was negatively correlated with HCV RNA content (r=-0.6858, P=0.0028). CONCLUSIONS: Antiviral immune response in patients with acute hepatitis C infection may be related to the proportion of T helper cells in peripheral blood circulation follicles. Dynamic detection of the number of T helper cells in clinical practice is conducive to identifying more effective methods to treat acute hepatitis C infection, which has important theoretical and clinical significance.

Phenotype, Virulence and Immunogenicity of Edwardsiella piscicida Cyclic AMP Receptor Protein (Crp) Mutants in Catfish Host.

Edwardsiella piscicida, a facultative aerobic pathogen belonging to the Enterobacteriaceae family, is the etiological agent of edwardsiellosis that causes significant economic loses in the aquaculture industry. cAMP receptor protein (CRP) is one of the most important transcriptional regulators, which can regulate large quantities of operons in different bacteria. Here we characterize the crp gene and report the effect of a crp deletion in E. piscicida. The crp-deficient mutant lost the capacity to utilize maltose, and showed significantly reduced motility due to the lack of flagella synthesis. We further constructed a ΔPcrp mutant to support that the phenotype above was caused by the crp deletion. Evidence obtained in fish serum killing assay and competitive infection assay strongly indicated that the inactivation of crp impaired the ability of E. piscicida to evade host immune clearance. More importantly, the virulence of the crp mutant was attenuated in both zebrafish and channel catfish, with reductions in mortality rates. In the end, we found that crp mutant could confer immune protection against E. piscicida infection to zebrafish and channel catfish, indicating its potential as a live attenuated vaccine.

Assessing the global resilience of water quality sensor placement strategies within water distribution systems.

Water quality sensors are often spatially distributed in water distribution systems (WDSs) to detect contamination events and monitor quality parameters (e.g., chlorine residual levels), thereby ensuring safety of a WDS. The performance of a water quality sensor placement strategy (WQSPS) is not only affected by sensor spatial deployment that has been extensively analyzed in literature, but also by possible sensor failures that have been rarely explored so far. However, enumerating all possible sensor failure scenarios is computationally infeasible for a WQSPS with a large number of sensors. To this end, this paper proposes an evolutionary algorithm (EA) based method to systematically and efficiently investigate the WQSPS' global resilience considering all likely sensor failures. First, new metrics are developed in the proposed method to assess the global resilience of a WQSPS. This is followed by a proposal of an efficient optimization approach based on an EA to identify the values of global resilience metrics. Finally, the sensors within the WQSPS are ranked to identify their relative importance in maintaining the WQSPS's detection performance. Two real-world WDSs with four WQSPSs for each case study are used to demonstrate the utility of the proposed method. Results show that: (i) compared to the traditional global resilience analysis method, the proposed EA-based approach identifies improved values of global resilience metrics, (ii) the WQSPSs that deploy sensors close to large demand users are overall more resilient in handling sensor failures relative to other design solutions, thus offering important insight to facilitate the selection of WQSPSs, and (iii) sensor rankings based on the global resilience can identify those sensors whose failure would significantly reduce the WQSPS's performance thereby providing guidance to enable effective water quality sensor management and maintenance.

Variations of thermophysical properties and heat transfer performance of nanoparticle-enhanced ionic liquids.

The ionic liquid (IL) 1-ethyl-3-methylimidazolium acetate ([EMIm]Ac) was investigated as a promising absorbent for absorption refrigeration. To improve the thermal conductivity of pure [EMIm]Ac, IL-based nanofluids (ionanofluids, INFs) were prepared by adding graphene nanoplatelets (GNPs). The thermal stability of the IL and INFs was analysed. The variations of the thermal conductivity, viscosity and specific heat capacity resulting from the addition of the GNPs were then measured over a wide range of temperatures and mass fractions. The measured data were fitted with appropriate equations and compared with the corresponding classical models. The results revealed that the IL and INFs were thermally stable over the measurement range. The thermal conductivity greatly increased with increasing mass fraction, while only slightly changed with increasing temperature. A maximum enhancement in thermal conductivity of 43.2% was observed at a temperature of 373.15 K for the INF with a mass fraction of 5%. The numerical results revealed that the dispersion of the GNPs in the pure IL effectively improved the local heat transfer coefficient by up to 28.6%.