Dopamine ß-hydroxylase shapes intestinal inflammation through modulating T cell activation.

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic and relapsing disease characterized by immune-mediated dysfunction of intestinal homeostasis. Alteration of the enteric nervous system and the subsequent neuro-immune interaction are thought to contribute to the initiation and progression of IBD. However, the role of dopamine beta-hydroxylase (DBH), an enzyme converting dopamine into norepinephrine, in modulating intestinal inflammation is not well defined. METHODS: CD4+CD45RBhighT cell adoptive transfer, and 2,4-dinitrobenzene sulfonic acid (DNBS) or dextran sodium sulfate (DSS)-induced colitis were collectively conducted to uncover the effects of DBH inhibition by nepicastat, a DBH inhibitor, in mucosal ulceration, disease severity, and T cell function. RESULTS: Inhibition of DBH by nepicastat triggered therapeutic effects on T cell adoptive transfer induced chronic mouse colitis model, which was consistent with the gene expression of DBH in multiple cell populations including T cells. Furthermore, DBH inhibition dramatically ameliorated the disease activity and colon shortening in chemically induced acute and chronic IBD models, as evidenced by morphological and histological examinations. The reshaped systemic inflammatory status was largely associated with decreased pro-inflammatory mediators, such as TNF-α, IL-6 and IFN-γ in plasma and re-balanced Th1, Th17 and Tregs in mesenteric lymph nodes (MLNs) upon colitis progression. Additionally, the conversion from dopamine (DA) to norepinephrine (NE) was inhibited resulting in increase in DA level and decrease in NE level and DA/NE showed immune-modulatory effects on the activation of immune cells. CONCLUSION: Modulation of neurotransmitter levels via inhibition of DBH exerted protective effects on progression of murine colitis by modulating the neuro-immune axis. These findings suggested a promising new therapeutic strategy for attenuating intestinal inflammation.

Identification of mitochondrial respiratory chain signature for predicting prognosis and immunotherapy response in stomach adenocarcinoma.

Stomach adenocarcinoma (STAD) is the third leading cause of cancer-related deaths and the fifth most prevalent malignancy worldwide. Mitochondrial respiratory chain complexes play a crucial role in STAD pathogenesis. However, how mitochondrial respiratory chain complex genes (MRCCGs) affect the prognosis and tumor microenvironment in STAD remains unclear. In this study, we systematically analyzed genetic alterations and copy number variations of different expression densities of MRCCGs, based on 806 samples from two independent STAD cohorts. Then we employed the unsupervised clustering method to classify the samples into three expression patterns based on the prognostic MRCCG expressions, and found that they were involved in different biological pathways and correlated with the clinicopathological characteristics, immune cell infiltration, and prognosis of STAD. Subsequently, we conducted a univariate Cox regression analysis to identify the prognostic value of 1175 subtype-related differentially expressed genes (DEGs) and screened out 555 prognostic-related genes. Principal component analysis was performed and developed the MG score system to quantify MRCCG patterns of STAD. The prognostic significance of MG Score was validated in three cohorts. The low MG score group, characterized by increased microsatellite instability-high (MSI-H), tumor mutation burden (TMB), PD-L1 expression, had a better prognosis. Interestingly, we demonstrated MRCCG patterns score could predict the sensitivity to ferroptosis inducing therapy. Our comprehensive analysis of MRCCGs in STAD demonstrated their potential roles in the tumor-immune-stromal microenvironment, clinicopathological features, and prognosis. Our findings highlight that MRCCGs may provide a new understanding of immunotherapy strategies for gastric cancer and provide a new perspective on the development of personalized immune therapeutic strategies for patients with STAD.

Cloning and expression of the mitochondrial cytochrome c oxidase subunit II gene in Sitophilus zeamais and interaction mechanism with allyl isothiocyanate.

In the United States, allyl isothiocyanate (AITC) has been registered as an insecticide, bactericide, and nematicide. And it has been confirmed that AITC has significant insecticidal activities against four stored product pests including Sitophilus zeamais Mostchulky (Coleoptera: Curculionidae). This study aimed to verify the mechanism of action of AITC on cytochrome c oxidase core subunits II in S. zeamais. Enzyme - catalyzed reactions and Fourier transform infrared spectrometer (FTIR) analysis revealed that the expressed COX II proteins could competitively bind and inhibit the activity of COX II. Furthermore, molecular docking results showed that a sulfur atom of AITC could form a 2.9 Å hydrogen bond with Ile-30, having a binding energy of -2.46 kcal/mol.

The Inhibitory Effect of (-)-Epigallocatechin-3-Gallate on Breast Cancer Progression via Reducing SCUBE2 Methylation and DNMT Activity.

Epigenetic modifications are important mechanisms responsible for cancer progression. Accumulating data suggest that (-)-epigallocatechin-3-gallate (EGCG), the most abundant catechin of green tea, may hamper carcinogenesis by targeting epigenetic alterations. We found that signal peptide-CUB (complement protein C1r/C1s, Uegf, and Bmp1)-EGF (epidermal growth factor) domain-containing protein 2 (SCUBE2), a tumor suppressor gene, was hypermethylated in breast tumors. However, it is unknown whether EGCG regulates SCUBE2 methylation, and the mechanisms remain undefined. This study was designed to investigate the effect of EGCG on SCUBE2 methylation in breast cancer cells. We reveal that EGCG possesses a significantly inhibitory effect on cell viability in a dose- and time-dependent manner and presents more effects than other catechins. EGCG treatment resulted in enhancement of the SCUBE2 gene, along with elevated E-cadherin and decreased vimentin expression, leading to significant suppression of cell migration and invasion. The inhibitory effect of EGCG on SCUBE2 knock-down cells was remarkably alleviated. Further study demonstrated that EGCG significantly decreased the SCUBE2 methylation status by reducing DNA methyltransferase (DNMT) expression and activity. In summary, this study reported for the first time that SCUBE2 methylation can be reversed by EGCG treatment, finally resulting in the inhibition of breast cancer progression. These results suggest the epigenetic role of EGCG and its potential implication in breast cancer therapy.

Divergent patterns of genic copy number variation in KCNIP1 gene reveal risk locus of type 2 diabetes in Chinese population.

Copy number variation (CNV) has emerged as another important genetic marker in addition to SNP for understanding etiology of complex disease. Kv channel interacting protein 1 (KCNIP1) is a Ca2+-dependent transcriptional modulator that contributes to the regulation of insulin secretion. Previous genome-wide CNV assay identified the KCNIP1 gene encompassing a CNV region, however, its further effect and risk rate on type 2 diabetes (T2D) have rarely been addressed, especially in Chinese population. The current study aims to detect and excavate genetic distribution profile of KCNIP1 CNV in Chinese T2D and control populations, and further to investigate the associations with clinical characteristics. Divergent patterns of the KCNIP1 CNV were identified (p < 0.01), in which the copy number gain was predominant in T2D, while the copy number normal accounted for the most in control group. Consistently, the individuals with copy number gain showed significant risk on T2D (OR = 4.550, p < 0.01). The KCNIP1 copy numbers presented significantly positive correlations with fasting plasma glucose and glycated hemoglobin in T2D. For OGTT test, the T2D patients with copy number gain had remarkably elevated glucose contents (60, 120, 180-min, p < 0.05 or p < 0.01) and diminished insulin levels (60, 120-min, p < 0.05) than those with copy number loss and normal, which suggested that the KCNIP1 CNV was correlated with the glucose and insulin action. This is the first CNV association study of the KCNIP1 gene in Chinese population, and these data indicated that KCNIP1 might function as a T2D-susceptibility gene whose dysregulation alters insulin production.

Establishing a health risk assessment for metal speciation in soil-A case study in an industrial area in China.

An improved method was proposed which integrates the distribution of metal speciation simulated by chemical equilibrium model, different exposure models and average daily intake dose modified by analytic hierarchy process for human health risk assessment of metal species (MS). With the rapid development of economic and urbanization, the metals pollution had become more serious in industrial areas. Adverse effects of soil contaminants on human health in typical industrial area should be assessed to evaluate the risks of soils in these areas. The method was applied to study nickel (Ni) species health risks in soil of industrial areas. The pH possessed significant impact to determine distribution/existence and solubility of Ni species, followed by DOC. The non-carcinogenic risk (HQ) of Ni species were less than 1 in each sampling points, except Ni2+. In addition, the carcinogenic risk (CR) of different Ni species were less than 10-6, except for FANi and Ni2+.

Expressions of MUC1 and vascular endothelial growth factor mRNA in blood are biomarkers for predicting efficacy of gefitinib treatment in non-small cell lung cancer.

BACKGROUND: Gefitinib, an EGFR-tyrosine kinase inhibitor, significantly improve prognosis in patients with advanced non-small cell lung cancer (NSCLC). The aim of this study was to evaluate the usefulness of MUC1 and vascular endothelial growth factor (VEGF) mRNA expression in peripheral blood as means of predicting benefit from gefitinib therapy in NSCLC patients. METHODS: MUC1 and VEGF mRNA expressions were detected in peripheral blood of 66 patients with advanced NSCLC before (B0) and 4 weeks after treatment (B4w) with gefitinib, using real-time quantitative-PCR assay. Correlations between blood MUC1 and VEGF mRNA expression at B0 and B4w and the response to gefitinib treatment and survival were analyzed. RESULTS: Blood levels of MUC1 and VEGF mRNA at B0 and at B4w were significantly higher in patients with progressive disease than in those with partial response and stable disease. Furthermore, blood MUC1 and VEGF mRNA positivity at two time points were strongly associated with shorter progression-free survival (PFS) and overall survival (OS) (P = 0.005 and P = 0.008 at B0, and P < 0.001 and P = 0.001 at B4w, respectively, for MUC1; P = 0.004 and P = 0.009 at B0, and P = 0.001 and P < 0.001 at B4w, respectively, for VEGF). Multivariate analyses demonstrated that blood MUC1 and VEGF mRNA positivity at B0 and B4w were independent factors for predicting worse PFS and OS. CONCLUSIONS: MUC1 and VEGF mRNA positivity in blood seem to be indicators of unfavorable response and poor PFS and OS in patients with advanced NSCLC treated with gefitinib and may be promising noninvasive and repeatable markers for predicting efficacy of gefitinib treatment.

Investigation of porcine circovirus type 2 and porcine circovirus type 3 infections based on dual TaqMan fluorescent quantitative PCR method and genetic evolutionary analysis of these two viruses.

Introduction: Porcine circovirus type 2 (PCV2) is the pathogen of Porcine Circovirus Associated Diseases. Porcine circovirus type 3 (PCV3) is a novel porcine circovirus associated with porcine dermatitis and nephropathy syndrome (PDNS) and reproductive failure. PCV2 is clearly pathogenic, while the pathogenicity of PCV3 remains controversial, so it is crucial to monitor the prevalence of PCV2 and PCV3 in healthy and diseased pigs to investigate the effects of PCV3 and PCV2 on the health status of pigs. Methods: Here, we developed a PCV2 and PCV3 dual TaqMan quantitative PCR (qPCR) method to test samples from healthy and diseased pigs, to clarify the differences in the positive rates and viral copy numbers of PCV2 and PCV3, and to analyze the genetic evolution and molecular characterization of the viral genomes obtained with sequence alignment and phylogenetic analysis, homology and structural analysis of Cap proteins, and selection pressure analysis. Results: We successfully established a dual TaqMan qPCR method for PCV2 and PCV3 with good repeatability, specificity and sensitivity. In total, 1,385 samples from 15 Chinese provinces were tested with the established qPCR. The total positive rates were 37.47% for PCV3 and 57.95% for PCV2, and the coinfection rate for was 25.49%. The positive rates of PCV3 and PCV2 in 372 healthy pigs were 15.05 and 69.89%, respectively, and the coinfection rate was 12.90%. The positive rates of PCV3 and PCV2 in 246 diseased pigs were 55.69 and 83.33%, respectively, and the coinfection rate was 47.97%. Eighteen PCV3 genomes and 64 PCV2 genomes were identified, including nine each of the PCV3a-1 and PCV3b genotypes, eight of PCV2a, 16 of PCV2b, and 40 of PCV2d. The amino acid identity within the PCV3 Cap proteins was 94.00-100.0%, whereas the PCV2 Cap proteins showed an identity of 81.30-100.0%. PCV3 Cap was most variable at amino acid sites 24, 27, 77, 104 and 150, whereas PCV2 Cap had 10-13 unique sites of variation between genotypes. Discussion: These results clarify the prevalence and variations of PCV2 and PCV3 in healthy and diseased pigs, which will provide a basis for the prevention and control of the two viral infections.

Efficient adsorption of Cu2+ and Cd2+ from groundwater by MgO-modified sludge biochar in single and binary systems.

In this study, MgO-modified sludge biochar (1MBC) prepared from sewage sludge was successfully used as an efficient adsorbent to remove heavy metals from groundwater. The adsorption performance and mechanism of 1MBC on Cu2+ and Cd2+ were investigated in single and binary systems, and the contribution of different mechanisms was quantified. Adsorption kinetics and isotherms analysis revealed that the adsorption processes of Cu2+ and Cd2+ by 1MBC followed the pseudo-second-order kinetic and Langmuir isotherm model in both systems, indicating that Cu2+ and Cd2+ were mainly controlled by chemisorption, and their theoretical maximum adsorption capacities were 240.36 and 219.06 mg·g-1, respectively. The results of the binary system showed that due to the competitive adsorption, the adsorption capacity of 1MBC for both heavy metals was lower than that of the single system, and the selective adsorption of Cu2+ was higher. The influencing variable experiments revealed that the adsorption of Cu2+ and Cd2+ by 1MBC had a wide pH adaption range and strong anti-interference ability to coexisting organics and ions. The adsorption mechanisms involved ion exchange (Cu: 47.39%, Cd: 53.17%), mineral precipitation (Cu: 35.31%, Cd: 24.18%), functional group complexation (Cu: 10.44%, Cd: 14.53%), and other possible mechanisms (Cu: 6.87%, Cd: 8.12%). Furthermore, 1MBC demonstrated excellent regeneration potential after five cycle times. Overall, the results have significant reference value for the practical application of removing heavy metals.

Pseudomonas aeruginosa improved the phytoremediation efficiency of ryegrass on nonylphenol-cadmium co-contaminated soil.

The effect of Pseudomonas aeruginosa (P. aeruginosa) on the phytoremediation efficiency of ryegrass on soil contaminated with nonylphenol (NP) and cadmium (Cd) was investigated by pot experiments. Pseudomonas aeruginosa application stimulated the adsorption of Cd by ryegrass and facilitated the biodegradation of NP in the soil. Exogenous P. aeruginosa inoculation increased the activities of urease, dehydrogenase, and polyphenol oxidase in the soil of the T4 treatment by 38.5%, 50.0%, and 56.5% compared to that of the T2 treatment, respectively. There was a significant positive correlation between the activities of dehydrogenase and polyphenol oxidase and the NP removal rate (P < 0.001). The relative abundances of beneficial microorganisms (such as Sphingomonas, Lysobacter, Streptomyces, Chloroflexia, Deltaproteobacteria, and Alphaproteobacteria) were increased as a result of P. aeruginosa inoculation. These microorganisms play important roles in nutrient cycling, Cd adsorption, and NP degradation. Additionally, P. aeruginosa was not the dominate bacterial species at the end of the experiment. According to this study, P. aeruginosa application improved the phytoremediation efficiency of ryegrass on soil contaminated with NP and Cd, with a minimal risk of alien microbial invasion.

Eukaryotic Expression of the Cytochrome c Oxidase Subunit I of Sitophilus zeamais and Its Interaction with Allyl Isothiocyanate.

Sitophilus zeamais Motschulsky (Coleoptera: Curculionidae) is a destructive pest of stored grains around the world. Allyl isothiocyanate (AITC) was shown to have good bioactivity in the control of S. zeamais. In this study, the interaction of AITC on cytochrome c oxidase core subunits I (COX I) and their binding mechanism were determined using spectroscopic, isothermal titration calorimetry and molecular docking techniques. The results indicate the binding constant (Ka) of AITC and COX I was 6.742 × 103 L/mol. Analysis of spectroscopic revealed that the binding of COX I to reduced Cyt c induced conformational changes of reduced Cyt c, while AITC could competitively bind and inhibit the activity of the COX I protein. Moreover, molecular docking results suggested a sulfur atom in the AITC structure could form a hydrogen bond having a length of 3.3 Å with the Gly- 27 of COX I.

Dietary cadmium health risk assessment for the Chinese population.

Cadmium (Cd) has high rates of soil-to-plant transference, coupled with its non-biodegradability and persistence; long-term management of Cd in agriculture is thus required to ensure better soil and food security and safety. Identifications of regions with high soil Cd concentration or high dietary Cd intakes are critical public health priorities. Human health risk assessment for dietary Cd intake was thus undertaken by employing three approaches: FCA (food chain approach), TDA (total diet approach), and FQA (food quality approach). The correlation between green/total vegetable consumption rates and dietary Cd intake from vegetables was statistically significant. For consumption, the hazard quotients (HQs) calculated by FCA and TDA were all less than 1 except for Hunan and Sichuan province. For rice consumption, the HQs derived by FCA or TDA approach for eight provinces exceeded 1. Residents in Hubei, Guangxi, Jilin, Zhejiang, Liaoning, Shanghai, Sichuan, and Guangxi were more vulnerable due to their notable higher consumption rates.Weighted rankings of the health risk levels were determined to derive the comparative risk management priority. For Cd intake from vegetables, four provinces/cities have high relative priority; for Cd intake from grains, three provinces have high relative priority. The comparative risk management priority for Hunan and Sichuan was high for dietary intake from vegetables or rice. Weighted average HQs were derived to determine the integrated dietary Cd intake health risk levels for dietary intake from vegetables or grains. The risk levels for Hunan, Guangxi, Sichuan, and Zhejiang are high, so effective measures should be taken to reduce Cd dietary intakes to ensure health protection.It is envisaged that the methodology employed in this study could provide useful insights into how various approaches can be integrated to determine human health risk levels for Cd intake, so more effective and targeted measures can be taken accordingly for the relevant regions.

[Exogenous Spermidine Regulates Ryegrass Root System Response to Cd Stress and Its Transcriptome Analysis].

The application of exogenous growth-regulating substances is an effective technique to enhance plant stress tolerance. Here, a hydroponic experiment was conducted to investigate the effects of exogenous basal application of 0.1 mmol·L-1 spermidine (Spd) on both the physiology and molecular biology of ryegrass root systems under varying degrees (0, 5, and 10 mg·L-1) of cadmium (Cd) stress using ryegrass as the test plants. The results of physiological studies revealed that Cd stress significantly reduced the physiological functions of the ryegrass root system, whereas the addition of Spd effectively alleviated the negative effects caused by Cd. The most significant effect was on the root soluble protein content, which increased by 90.91% and 158.35% compared with 5 mg·L-1and 10 mg·L-1 Cd alone. Spd also inhibited the accumulation of oxidative stress products malondialdehyde (MDA) and hydrogen peroxide (H2O2) by increasing the ascorbic acid (ASA) and glutathione (GSH) content and peroxidase (POD) activity, whereas the effects on root activity and superoxide dismutase (SOD) activity were not significant. The results of molecular biology studies demonstrated that 10 mg·L-1 Cd stress caused differential expression of a large number of genes in ryegrass roots, and the number of differentially expressed genes, differential significance, and differential multiplicity were significantly reduced after the application of exogenous Spd. The most significant part of the GO enrichment analysis shifted from responding to organic cyclic compounds and aldehyde/ketone group transferase activity to responding to trivalent iron ions and 2'-deoxymugineic-acid 2'-dioxygenase activity. Single gene expression heat map analysis revealed that exogenous Spd upregulated the expression of genes encoding zinc-iron transporter protein and 2'-deoxymugineic-acid 2'-dioxygenase, which improved the uptake and utilization of iron by the root system. In conclusion, the application of certain concentrations of Spd could effectively regulate the response of ryegrass roots to Cd stress, enhance its tolerance physiology, and mitigate the toxic effects of Cd.

[Sludge Biochar Modified by B-doped and Its Adsorption Behavior and Mechanism of 1,2-DCA in Water].

Sludge biochar (BC600) and B-doped sludge biochar (BBC600) were prepared with the boric acid doping modified co-pyrolysis method using municipal sludge as precursors, and the materials were structurally characterized by SEM, BET, FTIR, and Zeta potential and static contact angle to investigate the adsorption behavior, mechanism of BC600 and BBC600 on 1,2-DCA in water, and the influencing factors. The results of structural characterization showed that the B element content, specific surface area, and pore volume of biochar increased by 76%, 48%, and 30%, respectively, after the B doping modification; the effect of B doping modification on the surface charge and hydrophobicity of biochar was not significant. The results of adsorption experiments showed that the adsorption of 1,2-DCA by BBC600 was better than that by BC600 due to the larger specific surface area and higher strength of oxygen-containing functional groups of BBC600; the pseudo-first-order kinetic equation could better describe the adsorption of 1,2-DCA by BC600, and the pseudo-second-order kinetic equation could better fit the adsorption of 1,2-DCA by BBC600. The intraparticle diffusion was not the only rate-limiting step affecting the adsorption rate; the biochar material was more dispersed and stable under alkaline conditions, and its oxygen-containing functional groups were deprotonated and had enhanced electron-donating ability, which was beneficial to the adsorption of 1,2-DCA. Humic acid (HA) showed a low concentration-promoting and high concentration-inhibiting effect on the adsorption of 1,2-DCA by BC600, whereas both low and high concentrations of HA showed an inhibitory effect on the adsorption of 1,2-DCA by BBC600. The adsorption of 1,2-DCA by BC600 was inhibited by both low and high concentrations of HA, and HA competed with 1,2-DCA for adsorption; Cl-, SO42-, and NO3- all inhibited the adsorption of 1,2-DCA by biochar, and the degree of inhibition ordered from small to large was Cl-

Systematic comparison of cervical and extra-cervical surgical approaches for endoscopic thyroidectomy.

OBJECTIVE: To evaluate the clinical application of different surgical approaches for endoscopic thyroidectomy and provide more rational treatment criteria. METHODS: Collect all randomized controlled trials, multi-center studies, clinical controlled trials, clinical trials and other comparative studies of endoscopic thyroidectomy with a large sample size in different databases through an established search strategy, make a systematic analysis of all the included literature. RESULTS: This study selected 12 publications for analysis from more than 800 articles: these included six publications describing cervical thyroidectomy (A) and six publications describing extra-cervical thyroidectomy (B). Conversion to open surgery occurred in 29 patients in group A and only 4 in group B (p < 0.001). The patients in group A experienced shorter hospital stays than patients in group B (1.90 ± 0.80 vs. 4.03 ± 0.99 days, p < 0.001), and there was shorter operating time in group A (p < 0.001). Hemorrhage occurred in 3 cases in group A and 8 cases in group B (p = 0.04), Seroma occurred in 25 cases in group B but in no cases in group A (p < 0.001). Postoperative cosmetic results evaluated by verbal response scales (VRS) registered showed: group A (3.35 ± 0.60) and group B (3.74 ± 0.50; p < 0.001). Other complications such as recurrent laryngeal nerve injury and hypocalcemia showed no significant differences. CONCLUSIONS: Evaluation of the different surgical approaches for endoscopic thyroidectomy shows that the incidence of hemorrhage and seroma are higher in the extra-cervical group, but the rate of conversion to conventional open surgery is significantly higher in the cervical group. Furthermore, patients who undergo extra-cervical endoscopic thyroidectomy are associated with longer operating time and hospital stays; however, these studies suggest that the extra-cervical surgical approach for endoscopic thyroidectomy is preferable for dealing with more kinds of thyroid tumor and leaving no scars on neck.

[Impact of liver steatosis on antiviral effects of pegylated interferon-alpha in patients with chronic hepatitis B].

OBJECTIVE: To investigate the impact of hepatic steatosis on virologic response in chronic hepatitis B (CHB) patients treated with pegylated interferon-alpha (PEG-IFNa). METHODS: Ninety-six naive patients positive for hepatitis B e antigen (HBeAg) and with biopsy-proven CHB were administered PEG-IFNa-2a or PEG-IFNa-2b for 48 weeks. Virologic response (HBeAg clearance and hepatitis B virus (HBV) DNA less than 5 log10 copies/ml) and biochemical response (alanine transaminase (ALT) normalization) were compared between patients with (n=34) and without (n=62) steatosis. RESULTS: The HBV DNA titer in the steatosis group was significantly lower than that of the non-steatosis group (6.961.27 vs. 7.541.28 log10 copies/ml; t=2.161, P=0.033). After 48 weeks of PEG-IFNa treatments, there was no significant difference in HBeAg seroconversion or the percentage of undetectable HBV DNA (less than 3 log10 copies/ml) between steatosis and non-steatosis patients. However, the steatosis patients presented with a significantly lower complete response rate (virologic response plus biochemical response) compared to non-steatosis patients (26.5% vs. 48.4%; x² =4.373, P=0.037). Of the 45 CHB patients with undetectable HBV DNA after 48 weeks of treatment, seven did not achieve ALT normalization. The rate of patients with non-biochemical response was significantly higher in the steatosis group than in the non-steatosis group (33.3% vs. 6.67%; P=0.032). CONCLUSION: Hepatic steatosis does not affect the virologic response, but does affect the biochemical response in CHB patients treated with PEG-IFNa for 48 weeks.

A total infectome approach to understand the etiology of infectious disease in pigs.

BACKGROUND: The global pork industry is continuously affected by infectious diseases that can result in large-scale mortality, trade restrictions, and major reductions in production. Nevertheless, the cause of many infectious diseases in pigs remains unclear, largely because commonly used diagnostic tools fail to capture the full diversity of potential pathogens and because pathogen co-infection is common. RESULTS: We used a meta-transcriptomic approach to systematically characterize the pathogens in 136 clinical cases representing different disease syndromes in pigs, as well as in 12 non-diseased controls. This enabled us to simultaneously determine the diversity, abundance, genomic information, and detailed epidemiological history of a wide range of potential pathogens. We identified 34 species of RNA viruses, nine species of DNA viruses, seven species of bacteria, and three species of fungi, including two novel divergent members of the genus Pneumocystis. While most of these pathogens were only apparent in diseased animals or were at higher abundance in diseased animals than in healthy animals, others were present in healthy controls, suggesting opportunistic infections. Importantly, most of the cases examined here were characterized by co-infection with more than two species of viral, bacterial, or fungal pathogens, some with highly correlated occurrence and abundance levels. Examination of clinical signs and necropsy results in the context of relevant pathogens revealed that a multiple-pathogen model was better associated with the data than a single-pathogen model was. CONCLUSIONS: Our data demonstrate that most of the pig diseases examined were better explained by the presence of multiple rather than single pathogens and that infection with one pathogen can facilitate infection or increase the prevalence/abundance of another. Consequently, it is generally preferable to consider the cause of a disease based on a panel of co-infecting pathogens rather than on individual infectious agents. Video abstract.

Vaccination with different M2e epitope densities confers partial protection against H5N1 influenza A virus challenge in chickens.

OBJECTIVE: Currently, research is focused on universal influenza vaccines based on various ectodomains of the influenza matrix protein 2 (M2e). Such vaccines are tested mostly using mouse-adapted influenza viruses and in mouse or ferret models. The aim of this study was to investigate in a chicken model the protective efficacy of vaccines based on avian-type M2e at different epitope densities. METHODS: On the basis of the optimized avian-type M2e gene, recombinant plasmids that contained tandem copies of different M2e were constructed and expressed in Escherichia coli. The expression and immunogenicity of the proteins were confirmed by SDS-PAGE and Western blot, as well as immunofluorescence assay and enzyme-linked immunosorbent assay. Animals were immunized with fusion proteins emulsified with an appropriate adjuvant and then infected with highly pathogenic influenza virus of A/chicken/Guangdong/04 (H5N1). Antibody levels, survival rate and weight loss were investigated. RESULTS: Multiple copies of M2e were highly expressed; higher epitope density engendered better protection but there was not a linear increase. Among the fusion proteins, the MBP-3·M2e fusion protein showed the best protective efficacy. CONCLUSIONS: This study has provided evidence that the immune response to avian-type M2e-based subunit vaccines was greater in chickens than that in mice. In addition, higher M2e epitope density can yield better protection, but not in a linear fashion.

[Investigating Adsorption of Naphthalene to Organo-Modified Montmorillonites and Influencing Factors].

There are many sites contaminated by polycyclic aromatic hydrocarbons (PAHs) or combined PAHs-heavy metal in China, which pose serious health-risks to local people and environments. Dissipative quartz crystal microbalance (QCM-D) was applied to investigate the adsorption of naphthalene to two organic-modified smectite clays (cetyltrimethyl ammonium bromide modified montmorillonite, CTAB-SMF, and 3-mercapto propyl trimethoxy silane modified montmorillonite, TMSP-SMF) and original SMF, together with batch adsorption experiments. The results, based on in-situ online QCM-D experiments, showed that the adsorption sites of CTAB-SMF on naphthalene were mainly CTAB grouped between the interlayers of clay particles, while TMSP-SMF's were TMSP grouped on the surfaces of clay particles. The isotherms of naphthalene adsorption to CTAB-SMF fitted well (R2>0.92) with the Freundlich model, while the adsorption isotherms to TMSP-SMF and SMF fitted well with the Langmuir model (R2>0.96). The parameters of CTAB-SMF (n>1) indicated that the adsorption sites of naphthalene to CTAB-SMF were heterogeneous and the adsorption increases at higher equilibrium concentration. The adsorption capacity qmax of TMSP-SMF is significantly greater than that of SMF (P<0.05). Based on the calculation, the value of ΔHobs for these three clays (CTAB-SMF, TMSP-SMF, and SMF) were within the range of -30 to -10 kJ·mol-1, which indicated that it was a spontaneous exothermic physical process. The solution ionic strength could decrease the adsorption of naphthalene to SMF, but had limited effects on naphthalene adsorption to the two organo-modified clay particles. The existence of Cu2+ in the solution could enhance naphthalene adsorption to the three particles, and naphthalene could improve Cu2+ adsorption to these two modified clays. The results of this study show that QCM-D is a useful technique to indicate the changes of clay film during the process of adsorption, and the two organo-modified clay particles have the potential to be remediation materials to remediate PAHs or PAHs-heavy metal-contaminated sites.

[Mechanism and Influencing Factors of Increasing Soil Temperature by in-situ Electrical Resistance Heating].

The mechanism and influencing factors of an in-situ thermal remediation using electrical resistance heating were investigated. The effects of electrical current, heating method, rehydration, and negative pressure on soil heating and energy consumption were studied using in-situ electrical resistance heating equipment. The results showed that there were two main mechanisms for soil heating. Firstly, electric energy was converted into heat energy, whereby direct heating of the soil by electricity increased the soil temperature. This mechanism mainly existed in the soil between two electrodes. The second was heat conduction, whereby the soil temperature between the electrodes was the highest, and the heat gradually transferred from the high-temperature soil to the low-temperature soil, such that the temperature of the soil far away from the electrode connection gradually increased. The heating current affected the rate of increase of the soil temperature. The higher the current was, the faster the soil temperature rate of increase was and the lower the unit energy consumption was. Compared with continuous heating, intermittent heating had a slower heating rate and required a longer time to reach the same temperature. However, the energy consumption per unit was low and only 45.2% of that of continuous heating. During the heating process, water should be continuously added to the soil around the electrode to maintain a high current and continuous heating. The negative pressure of extraction was large, the soil heat loss was large, and the unit energy consumption was high. In actual projects, appropriate technological conditions should be selected according to time, cost, and the removal rate as a means of improving the efficiency of the in-situ resistance thermal desorption remediation of contaminated soil, reducing energy consumption, and shortening the time limit.