PE/PPE mutations in the transmission of Mycobacterium tuberculosis in China revealed by whole genome sequencing.

OBJECTIVE: This study aims to examine the impact of PE/PPE gene mutations on the transmission of Mycobacterium tuberculosis (M. tuberculosis) in China. METHODS: We collected the whole genome sequencing (WGS) data of 3202 M. tuberculosis isolates in China from 2007 to 2018 and investigated the clustering of strains from different lineages. To evaluate the potential role of PE/PPE gene mutations in the dissemination of the pathogen, we employed homoplastic analysis to detect homoplastic single nucleotide polymorphisms (SNPs) within these gene regions. Subsequently, logistic regression analysis was conducted to analyze the statistical association. RESULTS: Based on nationwide M. tuberculosis WGS data, it has been observed that the majority of the M. tuberculosis burden in China is caused by lineage 2 strains, followed by lineage 4. Lineage 2 exhibited a higher number of transmission clusters, totaling 446 clusters, of which 77 were cross-regional clusters. Conversely, there were only 52 transmission clusters in lineage 4, of which 9 were cross-regional clusters. In the analysis of lineage 2 isolates, regression results showed that 4 specific gene mutations, PE4 (position 190,394; c.46G > A), PE_PGRS10 (839,194; c.744 A > G), PE16 (1,607,005; c.620T > G) and PE_PGRS44 (2,921,883; c.333 C > A), were significantly associated with the transmission of M. tuberculosis. Mutations of PE_PGRS10 (839,334; c.884 A > G), PE_PGRS11 (847,613; c.1455G > C), PE_PGRS47 (3,054,724; c.811 A > G) and PPE66 (4,189,930; c.303G > C) exhibited significant associations with the cross-regional clusters. A total of 13 mutation positions showed a positive correlation with clustering size, indicating a positive association. For lineage 4 strains, no mutations were found to enhance transmission, but 2 mutation sites were identified as risk factors for cross-regional clusters. These included PE_PGRS4 (338,100; c.974 A > G) and PPE13 (976,897; c.1307 A > C). CONCLUSION: Our results indicate that some PE/PPE gene mutations can increase the risk of M. tuberculosis transmission, which might provide a basis for controlling the spread of tuberculosis.

[Pseudo-targeted metabolomics study of immune stress-mediated idiosyncratic liver injury induced by synergistic effects of bavachin and epimedin B].

Chinese patent medicine preparations containing Epimedii Folium and Psoraleae Fructus have been associated with the occurrence of idiosyncratic drug-induced liver injury(IDILI). However, the specific toxic biomarkers and mechanisms underlying these effects remain unclear. This study aimed to comprehensively assess the impact of bavachin and epimedin B, two principal consti-tuents found in Psoraleae Fructus and Epimedii Folium, on an IDILI model induced by tumor necrosis factor-α(TNF-α) treatment, both in vitro and in vivo. To evaluate the extent of liver injury, various parameters were assessed. Lactate dehydrogenase(LDH) release in the cell culture supernatant, as well as the levels of alanine aminotransferase(ALT) and aspartate transaminase(AST) in mouse plasma were measured. Additionally, histological analysis employing hematoxylin-eosin staining was performed to observe liver tissue changes indicative of the severity of liver injury. Furthermore, a pseudo-targeted metabolomics approach was employed, followed by multivariate analysis, to identify differential metabolites. These identified metabolites were subsequently subjected to Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis. The results showed that at the cellular level, after 2 hours of TNF-α stimulation, bavachin significantly increased the release of LDH in HepG2 cells compared to the normal group and the group treated alone; after the combination of bavachin and epimedin B, the release of LDH further significantly increased on the original basis. Similarly, although the individual or combination treatments of bavachin and epimedin B did not induce liver injury in normal mice, the combination of both drugs induced marked liver injury in TNF-α treated mice, leading to a significant elevation in plasma AST and ALT levels and substantial infiltration of inflammatory immune cells in the liver tissue. Pseudo-targeted metabolomics analysis identified seven common differential metabolites. Among these, D-glucosamine-6-phosphate, N1-methyl-2-pyridone-5-carboxamide, 17beta-nitro-5a-androstane, irisolidone-7-O-glucuronide, and N-(1-deoxy-1-fructosyl) valine emerged as potential biomarkers, with an area under the curve(AUC) exceeding 0.9. Furthermore, our results suggest that the metabolism of nicotinic acid and nicotinamide, as well as the linoleic acid metabolic pathway, may play pivotal roles in bavachin and epimedin B-induced IDILI. In conclusion, within an immune-stressed environment mediated by TNF-α, bavachin and epimedin B appear to induce IDILI through disruptions in metabolic processes.

Creeping and erupting dynamics in a pure-quartic soliton fiber laser.

Pure-quartic solitons (PQSs) are gradually becoming a hotspot in recent years due to their potential advantage to achieve high energy. Meanwhile, the fundamental research of PQSs is still in the fancy stage, and exploring soliton dynamics can promote the development of PQSs. Herein, we comprehensively and numerically investigate the impact of saturation power, small-signal gain, and output coupler on PQS dynamics in passively mode-locked fiber lasers. The result indicates that altering the above parameters makes PQSs exhibit pulsating or creeping dynamics similar to traditional solitons. Moreover, introducing an intra-cavity filter combined with intra-cavity large fourth-order dispersion makes PQSs go through stationary, pulsating to erupting. That is, the intra-cavity filter changes PQS dynamics. These findings provide new insights into PQS dynamics in fiber lasers.

Lysine demethylase LSD1 delivered via small extracellular vesicles promotes gastric cancer cell stemness.

Several studies have examined the functions of nucleic acids in small extracellular vesicles (sEVs). However, much less is known about the protein cargos of sEVs and their functions in recipient cells. This study demonstrates the presence of lysine-specific demethylase 1 (LSD1), which is the first identified histone demethylase, in the culture medium of gastric cancer cells. We show that sEVs derived from gastric cancer cells and the plasma of patients with gastric cancer harbor LSD1. The shuttling of LSD1-containing sEVs from donor cells to recipient gastric cancer cells promotes cancer cell stemness by positively regulating the expression of Nanog, OCT4, SOX2, and CD44. Additionally, sEV-delivered LSD1 suppresses oxaliplatin response of recipient cells in vitro and in vivo, whereas LSD1-depleted sEVs do not. Taken together, we demonstrate that LSD1-loaded sEVs can promote stemness and chemoresistance to oxaliplatin. These findings suggest that the LSD1 content of sEV could serve as a biomarker to predict oxaliplatin response in gastric cancer patients.

Histopathological features of glandular atrophy of the lamina propria of the gastric mucosa during its occurrence and development.

OBJECTIVE: To explore the histopathological features of glandular atrophy of the lamina propria of gastric mucosa during its occurrence and development. METHOD: We performed detailed histological observation and immunohistochemical examination on the endoscopic biopsy and ESD endoscopic resection specimens of 896 patients with glandular atrophy of the lamina propria of gastric mucosa. The EnVision two-step method was used for immunohistochemical staining, and the slices were incubated with primary antibody CK7, CK20, villin, CDX2, MUC5AC, MUC6, p53 and ki-67. Hematoxylin staining was performed and observed under the microscope and statistically analyzed. RESULTS: In the initial stage of glandular atrophy of the lamina propria, the proliferation area of the deep gastric pits, and the isthmus and neck of the gastric glands are characterized by roughly normal structure of the glandular structure, increased mesenchyme, and widened space between glands. Subsequently, the gland becomes smaller in volume and less in number, especially at the base, in the gastric glandular part of the gastric unit. The disease at this stage has higher incidence, and occurs more often in the elderly who account for 64.0% (573/896) of our study group. The disease in this stage may exhibit some lesions that are physiologic (age-related degeneration) while others are pathological. Therefore, this condition is called simple glandular atrophy of the lamina propria of the gastric mucosa. When the gastric mucosal epithelium is subjected to infection or repeated infections, chemical stimuli, immune factors, and genetic factors, it can lead to the proliferation and transformation of stem cells in the proliferation area of the deep gastric pits, and the isthmus and neck of the gastric glands, forming single ducts, multiple ducts, or a proliferation of patchy cells. Then, atypical hyperplasia (intraepithelial neoplasia) presents, finally leading to gastric adenocarcinoma. CONCLUSION: Understanding the histopathological characteristics of glandular atrophy of the lamina propria of gastric mucosa is of great significance in controlling the occurrence and development of gastric cancer.

Acetone Efficient Degradation under Simulated Humid Conditions by Mn-O-Pt Interaction Taming-Triggered Water Dissociation Intensification.

As a generally existing component in industrial streams, H2O usually inhibits the catalytic degradation efficiency of volatile organic compounds (VOCs) greatly. Here, we propose a novel strategy that accelerates the H2O dissociation and facilitates positive feedbacks during VOC oxidation by fabricating citric acid (CA)-assisted Pt(K)-Mn2O3/SiO2 (Pt-Mn/KS-xCA). Results reveal that the complexation of carboxyl groups of citric acid with Mn cations leads to the formation of small Mn2O3 (4.1 ± 0.2 nm) and further enhances the Mn-O-Pt interaction (strengthened by the Si-O-Mn interaction), which can transfer more electrons from Pt-Mn/KS-6CA to H2O, thus facilitating its breaking of covalent bonds. It subsequently produces abundant surface hydroxyl groups, improving the adsorption and activation abilities of acetone reactant and ethanol intermediate. Attributing to these, the acetone turnover frequency value of Pt-Mn/KS-6CA is 1.8 times higher than that of Pt-Mn/KS at 160 °C, and this multiple changes to 6.3 times in the presence of H2O. Remarkably, acetone conversion over Pt-Mn/KS-6CA increases by up to 14% in the presence of H2O; but it decreases by up to 26% for Pt-Mn/KS due to its weak dissociation ability and high adsorption capacity toward H2O. This work sheds new insights into the design of highly efficient catalytic materials for VOC degradation under humid conditions.

Single-plane versus real-time biplane approaches for ultrasound-guided central venous catheterization in critical care patients: a randomized controlled trial.

BACKGROUND: Critical care patients often require central venous cannulation (CVC). We hypothesized that real-time biplane ultrasound-guided CVC would improve first-puncture success rate and reduce mechanical complications. The purpose of this study was to compare the success rate and safety of single-plane and real-time biplane approaches for ultrasound-guided CVC. METHODS: From October 2022 to March 2023, 256 participants with critical illness requiring CVC were randomized to either the single-plane (n = 128) or biplane (n = 128) ultrasound-guided cannulation groups. The success rate, number of punctures, procedure duration, incidence of catheterization-related complications, and confidence score of operators were documented. RESULTS: The central vein was successfully cannulated in all 256 participants (163 [64%] man and 93 [36%] women; mean age 69 ± 19 [range 13-104 years]), including 182 and 74 who underwent internal jugular vein cannulation (IJVC) and femoral vein cannulation (FVC), respectively. The incidence of successful puncture on the first attempt was higher in the biplane group than that in the single-plane group (91.6% vs. 74.7%; relative risk (RR), 1.226; 95% confidence interval (CI), 1.069-1.405; P = 0.002 for the IJVC and 90.9% vs. 68.3%; RR, 1.331; 95% CI, 1.053-1.684; P = 0.019 for the FVC). The biplane group was also associated with a higher first-puncture single-pass catheterization success rate (87.4% vs. 69.0% and 90.9% vs. 68.3%), fewer undesired punctures (1[1-1(1-2)] vs. 1[1-2(1-4)] and 1[1-1(1-3)] vs. 1[1-2(1-4)]), shorter cannulation time (205 s [162-283 (66-1,526)] vs. 311 s [243-401 (136-1,223)] and 228 s [193-306 (66-1,669)] vs. 340 s [246-499 (130-944)]), and fewer immediate complications (10.5% vs. 28.7% and 9.1% vs. 34.1%) for both IJVC and FVC (all P < 0.05). CONCLUSION: Real-time biplane imaging of ultrasound-guided CVCs offers advantages over the single-plane approach for critically ill patients. TRIAL REGISTRATION: This prospective RCT was registered at Chinese Clinical Trial Registry (ChiCTR2200064843). Registered 19 October 2022.

A Rare Hemoglobin Variant Detected in a Pregnant Chinese Woman.

BACKGROUND: Hemoglobin Variant (HBB:c.155 C>A) is a rare mutation caused by ß-globin gene mutation called Hemoglobin North Manchester. So far, its existence has no adverse effect on human body, and it is a rare benign hemoglobin variant. METHODS: We reported a 32-year-old pregnant woman with discordant HbA1c and glucose measurements. In 75 g oral glucose tolerance test (OGTT), the pregnant woman got hyperglycemia at 1h-OGTT and 2h-OGTT. However, the pregnant woman had a low HbA1c of 3.9%. Subsequently, gene sequencing identified a rare mutation in the gene (HBB:c.155 C>A). RESULTS: We report for the first time that a case of North Manchester mutation in a Chinese female patient. In this case, it was found that the North Manchester variant could affect the examination of HbA1c when measured by ion-exchange high-performance liquid chromatography (HPLC), causing in falsely low HbA1c. CONCLUSIONS: Hemoglobin variants may lead to false HbA1c measurement. Clinicians should consider hemoglobin variants when HbA1c results are inconsistent with other laboratory tests.

Detection of Rickettsia spp. and Anaplasma ovis in Melophagus ovinus from southern Xinjiang, China.

Melophagus ovinus is a hematophagous insect that is distributed worldwide and plays a crucial role in transmitting disease-causing pathogens. From June 2021 to March 2022, a total of 370 M. ovinus were collected from 11 sampling points in southern Xinjiang, China. The specimens were identified using morphological and molecular analyses. Rickettsia spp. and Anaplasma ovis were detected from all the samples using seven Rickettsia-specific genetic markers and the msp-4 gene of A. ovis. Approximately 11% of the M. ovinus specimens were positive for Rickettsia spp., and Candidatus Rickettsia barbariae was the most predominant species (35/41; 85.4%), while R. massiliae was least prevalent (6/41; 14.6%). Approximately 10.5% (39/370) of the M. ovinus specimens were positive for A. ovis of genotype III, which was co-detected with Candidatus R. barbariae in M. ovinus (3/370; 0.8%). To the best of our knowledge, this is the first report of the detection of R. massiliae and Candidatus R. barbariae in M. ovinus globally. The detection and control of insect-borne diseases originating from M. ovinus should be strengthened in southern Xinjiang, an area important to animal husbandry and production.

Evaluation of housekeeping genes as references for quantitative real-time PCR analysis of European eel, Anguilla anguilla.

Eels are important aquaculture species for which an increasing number of reference genes are being identified and applied. In this study, five housekeeping genes [RPL7 (ribosomal protein L7), 18 S (18 S ribosomal RNA), EF1A (elongation factor 1α), ACTB (ß-actin) and GAPDH (glyceraldehyde-3-phosphate dehydrogenase)] were chosen to evaluate their reliability as reference genes for quantitative real-time PCR (qPCR) for the study of Anguilla anguilla. The expression of the selected genes in different eel tissues was determined using qPCR at different growth stages or upon challenge by Anguillid herpesvirus (AngHV), and the expression levels of these genes were then compared and evaluated using the geNorm and NormFinder algorithms. Then, RefFinder was used to comprehensively rank the examined housekeeping genes. Interestingly, the expression of the evaluated housekeeping genes exhibited tissue-dependent and treatment-dependent variations. In different growth periods A. anguilla tissues, the most stable genes were the following: ACTB in mucus; 18 S in skin and kidney; RPL7 in muscle, gill, intestine and brain; EF1A in heart and liver; and GAPDH in spleen. In contrast, in AngHV-challenged A. anguilla tissues, the most stable genes were the following: 18 S in mucus; RPL7 in skin, gill, heart, spleen, kidney and intestine; EF1A in muscle and liver; and ACTB in brain. Further comparison analysis indicated that the expression of RPL7 and EF1A was stable in multiple A. anguilla tissues in different growth periods and in eels challenged by AngHV. Nonetheless, the expression level of GAPDH in eel tissues was lower, and it was unstable in several tissues. These results indicated that the selection of reference genes for qPCR analysis in A. anguilla should be made in accordance with experimental parameters, and both RPL7 and EF1A could be used as reference genes for qPCR study of A. anguilla at different growth stages or upon challenge by AngHV. The reference genes identified in this study could improve the accuracy of qPCR data and facilitate further studies aimed at understanding the biology of eels.

Improved Hamiltonians for Quantum Simulations of Gauge Theories.

Quantum simulations of lattice gauge theories for the foreseeable future will be hampered by limited resources. The historical success of improved lattice actions in classical simulations strongly suggests that Hamiltonians with improved discretization errors will reduce quantum resources, i.e., require ≳2^{d} fewer qubits in quantum simulations for lattices with d-spatial dimensions. In this work, we consider O(a^{2})-improved Hamiltonians for pure gauge theories and design the corresponding quantum circuits for its real-time evolution in terms of primitive gates. An explicit demonstration for Z_{2} gauge theory is presented including exploratory tests using the ibm_perth device.

Elevation of spermine remodels immunosuppressive microenvironment through driving the modification of PD-L1 in hepatocellular carcinoma.

BACKGROUND: Spermine is frequently elevated in tumor tissues and body fluids of cancer patients and is critical for cancer cell proliferation, migration and invasion. However, the immune functions of spermine in hepatocellular carcinoma progression remains unknown. In the present study, we aimed to elucidate immunosuppressive role of spermine in hepatocellular carcinoma and to explore the underlying mechanism. METHODS: Whole-blood spermine concentration was measured using HPLC. Human primary HCC tissues were collected to examine the expression of CaSR, p-Akt, ß-catenin, STT3A, PD-L1, and CD8. Mouse model of tumorigenesis and lung metastasis were established to evaluate the effects of spermine on hepatocellular carcinoma. Western blotting, immunofluorescence, real time PCR, digital Ca2+ imaging, and chromatin immunoprecipitation assay were used to investigate the underlying mechanisms by which spermine regulates PD-L1 expression and glycosylation in hepatocellular carcinoma cells. RESULTS: Blood spermine concentration in the HCC patient group was significantly higher than that in the normal population group. Spermine could facilitate tumor progression through inducing PD-L1 expression and decreasing the CD8+ T cell infiltration in HCC. Mechanistically, spermine activates calcium-sensing receptor (CaSR) to trigger Ca2+ entry and thereby promote Akt-dependent ß-catenin stabilization and nuclear translocation. Nuclear ß-catenin induced by spermine then activates transcriptional expression of PD-L1 and N-glycosyltransferase STT3A, while STT3A in turn increases the stability of PD-L1 through inducing PD-L1 protein N-glycosylation in HCC cells. CONCLUSIONS: This study reveals the crucial function of spermine in establishing immune privilege by increasing the expression and N-glycosylation of PD-L1, providing a potential strategy for the treatment of hepatocellular carcinoma. Video Abstract.

Sodium Ferulate Inhibits Rat Cardiomyocyte Hypertrophy Induced by Angiotensin II Through Enhancement of Endothelial Nitric Oxide Synthase/Nitric Oxide/Cyclic Guanosine Monophosphate Signaling Pathway.

ABSTRACT: Sodium ferulate (SF) is the sodium salt of ferulic acid, which is one of the effective components of Angelica sinensis and Lignsticum chuanxiong , and plays an important role in protecting the cardiovascular system. In this study, myocardial hypertrophy was induced by angiotensin II 0.1 µmol/L in neonatal Sprague-Dawley rat ventricular myocytes. Nine groups were designed, that is, normal, normal administration, model, L-arginine (L-arg 1000 µmol/L), SF (50, 100, 200 µmol/L) group, and N G -nitro-L-arg-methyl ester 1500 µmol/L combined with SF 200 µmol/L or L-arg 1000 µmol/L group, respectively. Cardiomyocyte hypertrophy was confirmed by observing histological changes and measurements of cell diameter, protein content and atrial natriuretic factor, and ß-myosin heavy chain levels of the cells. Notably, SF could inhibit significantly myocardial hypertrophy of neonatal rat cardiomyocytes in a concentration-dependent manner without producing cytotoxicity, and the levels of nitric oxide, NO synthase (NOS), endothelial NOS, and cyclic guanosine monophosphate were increased, but the level of cyclic adenosine monophosphate was decreased in cardiomyocytes. Simultaneously, levels of protein kinase C beta, Raf-1, and extracellular regulated protein kinase 1/2 (ERK1/2) were downregulated, whereas levels of mitogen-activated protein kinase phosphatase-1 were significantly upregulated. All the beneficial effects of SF were blunted by N G -nitro-L-arg-methyl ester. Overall, these findings reveal that SF can inhibit angiotensin II-induced myocardial hypertrophy of neonatal rat cardiomyocytes, which is closely related to activation of endothelial NOS/NO/cyclic guanosine monophosphate, and inhibition of protein kinase C and mitogen-activated protein kinase signaling pathways.

Ultra-sensitive H2S sensor based on sunflower-like In-doped ZnO with enriched oxygen vacancies.

Metal oxide sensors face the challenge of high response and fast recovery at low operating temperatures for the detection of toxic and flammable hydrogen sulfide (H2S) gases. Herein, novel In-doped ZnO with a sunflower-like structure and tunable surface properties was rationally synthesized. The substitutional In atom in the ZnO crystal can dramatically enhance the concentration of oxygen vacancies (Ov), the In-ZnO sites are responsible for fast recovery, and the formation of sub-stable sulfide intermediates gives rise to the high response towards H2S. As a result, the response of the optimized 4In-ZnO sensor is 3538.36 to 50 ppm H2S at a low operating temperature of 110 °C, which is 106 times higher than that of pristine ZnO. Moreover, the response time and recovery time to 50 ppm H2S are 100 s and 27 s, respectively, with high selectivity and stability. First-principles calculations revealed that 4In-ZnO with rich Ov exhibited higher adsorption energy for the H2S molecule than pristine ZnO, resulting in effortless H2S detection. Our work lays the foundation for the rational design of highly sensitive gas sensors through precise doping of atoms in oxygen-rich vacancies in semiconductor materials.

Proteomic Profiling Skin Mucus of European Eel Anguilla anguilla Infected with Anguillid Herpesvirus.

Anguillid herpesvirus 1 (AngHV) is an important viral pathogen affecting eel. This study was designed to investigate the potential molecular mechanisms and immune response elicited at the protein levels in the skin mucus of AngHV-infected Anguilla anguilla. Tandem mass tag (TMT)-labelling proteomics with the liquid chromatography tandem mass spectrometry (LC-MS/MS) was used for performing quantitative identification of the proteins. In addition, the quantitative protein amount was detected by parallel reaction monitoring (PRM) analysis. A total of 3486 proteins were identified, of which 2935 were quantified. When a protein fold change was greater than 1.3 or less than 0.76, it indicated a differentially expressed protein (DEP). Overall, 187 up-regulated proteins and 126 down-regulated proteins were detected, and most of the DEPs were enriched in the CAMs pathway, intestinal immune pathway, herpes simplex virus 1 infection pathway, phagosome pathway and p53 signaling pathway. The results of the DEPs detected by PRM were highly consistent with the results of the TMT-labelled quantitative proteomic analysis. The findings of this study provide an important research basis for further understanding the pathogenesis of AngHV.

Level and determinants of willingness to donate organs among the general public: A cross-sectional survey in China.

This study aims to assess the level and determinants of the general public's willingness to organ donation. We conducted a population-based cross-sectional study of 4261 participants in China. The primary outcome was the willingness to donate organs. Logistic regression modelling was used to determine the factors that affect willingness to donate organs. Overall, the proportion of participants who showed a willingness to donate organs was 47.45% (95%CI: 0.46, 0.49) in this study. Logistic regression modelling showed participants from Western (OR = 1.33, 95%CI = 1.11-1.59) and Eastern China (OR = 1.40, 95%CI = 1.19-1.65) were more willing to donate organs compared with those from Central China. The odds of being willing to donate organs was higher in females than males (OR = 1.35, 95%CI = 1.17-1.55); and was higher in those participants with experience of organ donation (OR = 1.58, 95%CI = 1.13-2.21), experience of caring for organ transplant patients (OR = 1.45, 95%CI = 1.01-2.07), and those undertaking related voluntary activities (OR = 1.67, 95%CI = 1.45-1.94), than those without. The general public's level of willingness to organ donation was not high in this study. Geographical region, gender, experience of organ donation related activities, taking care of organ transplant patients and volunteering in related activities were independently associated with participants' willingness to donate organs.

[Retrograde Transurethral Contrast-enhanced Ultrasound in the Diagnosis of Bladder Rupture:Report of Two Cases].

Bladder rupture refers to a series of diseases caused by bladder wall laceration and urine flowing into the abdominal cavity.Two cases of bladder rupture diagnosed by retrograde transurethral contrast-enhanced ultrasound were reviewed in this report.We discussed the value of retrograde transurethral contrast-enhanced ultrasound in the diagnosis,classification,and prognosis evaluation of bladder rupture,aiming to provide evidence for clinical diagnosis and treatment.

Anguillid herpesvirus 1 (AngHV) ORF95 encodes a late, structural envelope protein.

Anguillid herpesvirus 1 (AngHV) is one of the vital pathogenic agents found in the wild and cultured eel populations, which has brought significant losses to eel culture industry in China. In this study, AngHV ORF95 was characterized. Bioinformatics analysis showed that ORF95 putatively encodes a structural protein that is homologous to hemagglutinin-esterase (HE) protein of infectious salmon anemia virus (ISAV). Temporal transcription and expression analysis indicated that ORF95 is a viral late gene. Subcellular localization analysis revealed that ORF95 was predominantly localized in the cytoplasm. Further, western blot analysis indicated that ORF95 is a structural protein of virion envelope. These results provide a novel basis to make further efforts to clarify the function of ORF95 in the process of AngHV infection and the possibility to use ORF95 as antigen to develop AngHV subunit vaccine.

Isolation of a novel adomavirus from cultured American eels, Anguilla rostrata, with haemorrhagic gill necrosis disease.

Recently, the culture of American eels (Anguilla rostrate) in China has been impacted by emergence of a disease with signs of haemorrhagic gill necrosis. The gills of diseased eels are covered with petecchia and they bleed when the operculum is pressed. In this study, a novel American eel adomavirus (AEAdoV) was isolated from the diseased eels using the eel ovary cell line (EO). The virus proliferated in the EO cells with a maximum TCID50 /ml of 106.29 ± 0.23 at 6 days post-infection. The virions were non-enveloped with a diameter of 75-85 nm and shown to be a DNA virus upon 5-iodo-2'-deoxyuridine (IDU) treatment. PCR assays showed that AEAdoV encodes a superfamily 3 helicases (S3H) replicase and shared high similarities with Anguilla marmorata adomavirus (MEAdoV). Although no clinical signs or mortality was observed among the eels injected with AEAdoV, the virus was reisolated from livers, kidneys and gills of injected eels at 35 days post-injection. Our results suggested that AEAdoV exhibited a latent infection in A. rostrata. The pathogenicity of the AEAdoV needs to be confirmed further.

Enhancing the Effect of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Signaling and Arginine Deprivation in Melanoma.

Melanoma as a very aggressive type of cancer is still in urgent need of improved treatment. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and arginine deiminase (ADI-PEG20) are two of many suggested drugs for treating melanoma. Both have shown anti-tumor activities without harming normal cells. However, resistance to both drugs has also been noted. Studies on the mechanism of action of and resistance to these drugs provide multiple targets that can be utilized to increase the efficacy and overcome the resistance. As a result, combination strategies have been proposed for these drug candidates with various other agents, and achieved enhanced or synergistic anti-tumor effect. The combination of TRAIL and ADI-PEG20 as one example can greatly enhance the cytotoxicity to melanoma cells including those resistant to the single component of this combination. It is found that combination treatment generally can alter the expression of the components of cell signaling in melanoma cells to favor cell death. In this paper, the signaling of TRAIL and ADI-PEG20-induced arginine deprivation including the main mechanism of resistance to these drugs and exemplary combination strategies is discussed. Finally, factors hampering the clinical application of both drugs, current and future development to overcome these hurdles are briefly discussed.