SHFL inhibits enterovirus A71 infection by triggering degradation of viral 3Dpol protein via the ubiquitin-proteasome pathway.

Enterovirus A71 (EV-A71) is a highly contagious virus that poses a major threat to global health, representing the primary etiological agent for hand-foot and mouth disease (HFMD) and neurological complications. It has been established that interferon signaling is critical to establishing a robust antiviral state in host cells, mainly mediated through the antiviral effects of numerous interferon-stimulated genes (ISGs). The host restriction factor SHFL is a novel ISG with broad antiviral activity against various viruses through diverse underlying molecular mechanisms. Although SHFL is widely acknowledged for its broad-spectrum antiviral activity, it remains elusive whether SHFL inhibits EV-A71. In this work, we validated that EV-A71 triggers the upregulation of SHFL both in cell lines and in a mouse model. Knockdown and overexpression of SHFL in EVA71-infected cells suggested that this factor could markedly suppress EV-A71 replication. Our findings further revealed an intriguing mechanism of SHFL that it could interact with the nonstructural proteins 3Dpol of EV-A71 and promoted the degradation of 3Dpol through the ubiquitin-proteasome pathway. Furthermore, the zinc-finger domain and the 36 amino acids (164-199) of SHFL were crucial to the interaction between SHFL and EV-A71 3Dpol . Overall, these findings broadened our understanding of the pivotal roles of SHFL in the interaction between the host and EV-A71.

Sea cucumber extract TBL-12 inhibits the proliferation, migration, and invasion of human prostate cancer cells through the p38 mitogen-activated protein kinase and intrinsic caspase apoptosis pathway.

BACKGROUND: Sea cucumber is a kind of nutritious echinoderm that has multiple biological activities, including antioxidant, antibacterial, and antitumor activities. However, there is no extensive study on the antitumor effect of sea cucumber extract on prostate cancer (PCa). TBL-12 is a new sea cucumber extract. In this study, we investigated the in vivo anti-PCa effect of TBL-12 and its in vitro effects on the proliferation, apoptosis, migration, and invasion of the human PCa cell lines LNCaP, 22RV1, PC-3, and DU145, and evaluated its possible mechanisms. METHODS: Cell proliferation was analyzed by cell counting kit-8 and colony formation assays. Scratch migration assay and transwell invasiveness assay were used to observe TBL-12 effect on the migration and invasion of PCa cells. Matrix metalloproteinase 2 (MMP-2) and MMP-9 expression and enzymatic activity was determined by Western blot analysis, quantitative reverse-transcription polymerase chain reaction, and gelatin zymography. Apoptosis level was detected by flow cytometry analysis. Western blot analysis was used to analyze p38 mitogen-activated protein kinase (MAPK) and apoptosis pathways. Angiogenic array analysis was used to explore autocrine and paracrine growth factors in PCa cell lines. Xenograft tumor model was built to observe the in vivo anticancer effect. RESULTS: TBL-12 could significantly inhibit tumor growth in xenograft PCa mice in vivo, and dramatically inhibit the proliferation, colony formation, migration, and invasiveness of PCa cells in vitro (P < 0.05 and P < 0.001). The expression and enzyme activity of MMP-2 and MMP-9 were significantly suppressed by TBL-12 ( P < 0.01), and decreased phosphorylation level of p38 in PCa cells was detected ( P < 0.001). Furthermore, TBL-12 could reinforce the MMP-2/MMP-9 inhibitory effect of SB203580, a specific inhibitor of the p38 MAPK pathway ( P < 0.05). Besides, TBL-12 could induce the apoptosis of PCa cells by activating caspase-9, caspase-7, and poly(ADP-ribose) polymerase and suppressing survivin, and inhibit the secretion of angiogenin, angiopoietin-2, and vascular endothelial growth factor in PCa cells. CONCLUSIONS: Sea cucumber extract TBL-12 could suppress the proliferation and metastasis of human PCa cells by inhibiting MMP-2 and MMP-9 via blocking the p38 MAPK pathway, inducing apoptosis through intrinsic caspase apoptosis pathway and inhibiting the secretion of angiogenic factors. Our findings may be of importance and significance for the research and clinical applications of sea cucumber extract in PCa treatment.

First report of novel genetic array aacA4-blaIMP-25-oxa30-catB3 and identification of novel metallo-ß-lactamase gene blaIMP25: A Retrospective Study of antibiotic resistance surveillance on Psuedomonas aeruginosa in Guangzhou of South China, 2003-2007.

Carbapenem, imipenem and meropenem have been broadly prescribed contributing to the global occurrence and prevalence of carbapenem resistance in Psuedomonas aeruginosa, and the associated resistance genotypes remains clinically significant. A retrospective surveillance had been conducted on 499 P. aeruginosa isolates in South China during 2003-2007, including antimicrobial resistance and characterization of MBLs on carbapenem-resistant strains. One hundred and sixty-four out of 499 strains were carbapenem-resistant, with 11, 4 and 5 strains positive for blaIMP-9, blaIMP-25 and blaVIM-2, respectively. Sixteen out of 20 isolates were positive for intI1 and contained identical flanking regions (as indicated in KM384735), and all tested isolates containing the qacE△1-sul1 of the typical 3'-conserved region. A novel blaIMP-25 metallo-ß-lactamase and a genetic array of aacA4-blaIMP-25-oxa30-catB3 have been discovered from this retrospective surveillance on antimicrobial resistance of P. aeruginosa.

Vasculogenic mimicry plays an important role in adrenocortical carcinoma.

OBJECTIVES: To determine the prognostic role of vasculogenic mimicry in adrenocortical carcinoma, and to explore its relationship with vascular endothelial growth factor receptor 2 expression. METHODS: A total of 46 samples of adrenocortical carcinoma were collected and reviewed. Vasculogenic mimicry and vascular endothelial growth factor receptor 2 were detected by immunohistochemistry and double staining. Survival analysis was carried out to access pronostic significance. Three-dimensional culture method was applied to test the ability of vasculogenic mimicry formation by adrenocortical carcinoma cell lines SW-13 and H295R. Quantitative polymerase chain reaction and western blotting were used to monitor the expression of vascular endothelial growth factor receptor 2 in SW-13 and H295R. After being treated with specific inhibitor or small interfering ribonucleic acid to downregulate expression of vascular endothelial growth factor receptor 2, vasculogenic mimicry formation and cell prolifration of SW-13 cells were evaluated by 3-D culture and Cell Counting Kit-8 methods. RESULTS: Vasculogenic mimicry was observed in 19 of the 46 (41.30%) adrenocortical carcinoma samples. Both vasculogenic mimicry and vascular endothelial growth factor receptor 2 expressions showed a positive association with Weiss score and TNM stage, whereas vascular endothelial growth factor receptor 2 was also associated with tumor size (all P < 0.05). Vasculogenic mimicry was closely correlated with vascular endothelial growth factor receptor 2 expressions (r = 0.470, P < 0.01). The median overall survival of patients with vasculogenicmimicry-positive or vascular endothelial growth factor receptor 2-positive was shorter than that of patients with vasculogenic mimicry-negative or vascular endothelial growth factor receptor 2-negative (P = 0.001 and 0.028, respectively). The vasculogenic mimicry-forming SW-13 cells expressed higher levels of vascular endothelial growth factor receptor 2 than that of H295R, which was unable to form vasculogenic mimicry on Matrigel. However, downregulation of vascular endothelial growth factor receptor 2 only decreased cell proliferation, but not vasculogenic mimicry formation by SW-13 cells. CONCLUSIONS: Vasculogenic mimicry and overexpression of vascular endothelial growth factor receptor 2 seem to correlate with poor prognostic outcomes in adrenocortical carcinoma. Anti-angiogenesis treatments targeting vascular endothelial growth factor receptor 2 should be combined with therapies targeting vasculogenic mimicry in adrenocortical carcinoma.

Tim-3-expressing CD4+ and CD8+ T cells in human tuberculosis (TB) exhibit polarized effector memory phenotypes and stronger anti-TB effector functions.

T-cell immune responses modulated by T-cell immunoglobulin and mucin domain-containing molecule 3 (Tim-3) during Mycobacterium tuberculosis (Mtb) infection in humans remain poorly understood. Here, we found that active TB patients exhibited increases in numbers of Tim-3-expressing CD4(+) and CD8(+) T cells, which preferentially displayed polarized effector memory phenotypes. Consistent with effector phenotypes, Tim-3(+)CD4(+) and Tim-3(+)CD8(+) T-cell subsets showed greater effector functions for producing Th1/Th22 cytokines and CTL effector molecules than Tim-3(-) counterparts, and Tim-3-expressing T cells more apparently limited intracellular Mtb replication in macrophages. The increased effector functions for Tim-3-expressing T cells consisted with cellular activation signaling as Tim-3(+)CD4(+) and Tim-3(+)CD8(+) T-cell subsets expressed much higher levels of phosphorylated signaling molecules p38, stat3, stat5, and Erk1/2 than Tim-3- controls. Mechanistic experiments showed that siRNA silencing of Tim-3 or soluble Tim-3 treatment interfering with membrane Tim-3-ligand interaction reduced de novo production of IFN-γ and TNF-α by Tim-3-expressing T cells. Furthermore, stimulation of Tim-3 signaling pathways by antibody cross-linking of membrane Tim-3 augmented effector function of IFN-γ production by CD4(+) and CD8(+) T cells, suggesting that Tim-3 signaling helped to drive stronger effector functions in active TB patients. This study therefore uncovered a previously unknown mechanism for T-cell immune responses regulated by Tim-3, and findings may have implications for potential immune intervention in TB.

Aperiodic dynamical quantum phase transition in multi-band Bloch Hamiltonian and its origin.

We investigate the dynamical quantum phase transition (DQPT) in the multi-band Bloch Hamiltonian of the one-dimensional periodic Kitaev model, focusing on quenches from a Bloch band. By analyzing the dynamical free energy and Pancharatnam geometric phase (PGP), we show that the critical times of DQPTs deviate from periodic spacing due to the multi-band effect, contrasting with results from two-band models. We propose a geometric interpretation to explain this non-uniform spacing. Additionally, we clarify the conditions needed for DQPT occurrence in the multi-band Bloch Hamiltonian, highlighting that a DQPT only arises when the quench from the Bloch states collapses the band gap at the critical point. Moreover, we establish that the dynamical topological order parameter, defined by the winding number of the PGP, is not quantized but still exhibits discontinuous jumps at DQPT critical times due to periodic modulation. Additionally, we extend our analysis to mixed-state DQPT and find its absence at non-zero temperatures.

Elevated expression of LCN13 through FXR activation ameliorates hepatocellular lipid accumulation and inflammation.

BACKGROUND: Lipocalin 13 (LCN13) is a member of the lipocalin family that consists of numerous secretory proteins. LCN13 high-expression has been reported to possess anti-obesity and anti-diabetic effects. Although metabolic dysfunction-associated steatotic liver diseases (MASLD) including metabolic dysfunction-associated steatohepatitis (MASH) are frequently associated with obesity and insulin resistance, the functional role of endogenous LCN13 and the therapeutic effect of LCN13 in MASH and related metabolic deterioration have not been evaluated. METHODS: We employed a methionine-choline deficient diet model and MASH cell models to investigate the role of LCN13 in MASH development. We sought to explore the effects of LCN13 on lipid metabolism and inflammation in hepatocytes under PA/OA exposure using Western blotting, real-time RT-PCR, enzyme-linked immunosorbent assay, hematoxylin and eosin staining, oil red O staining. Using RNA sequencing, chromatin immunoprecipitation assay, and luciferase reporter assays to elucidate whether farnesoid X receptor (FXR) regulates human LCN13 transcription as a transcription factor. RESULTS: Our study found that LCN13 was down-regulated in MASH patients, MASH mouse and cell models. LCN13 overexpression in hepatocyte cells significantly inhibited lipid accumulation and inflammation in vitro. Conversely, LCN13 downregulation significantly exacerbated lipid accumulation and inflammatory responses in vivo and in vitro. Mechanistically, we provided the first evidence that LCN13 was transcriptionally activated by FXR, representing a novel direct target gene of FXR. And the key promoter region of LCN13 binds to FXR was also elucidated. We further revealed that LCN13 overexpression via FXR activation ameliorates hepatocellular lipid accumulation and inflammation in vivo and in vitro. Furthermore, LCN13-down-regulated mice exhibited aggravated MASH phenotypes, including increased hepatic lipid accumulation and inflammation. CONCLUSION: Our findings provide new insight regarding the protective role of LCN13 in MASH development and suggest an innovative therapeutic strategy for treating MASH or related metabolic disorders.

Properties of Pacific white shrimp (Litopenaeus vannamei) collagen and its degradation by endogenous proteinases during cold storage.

Many factors are responsible for the diminished quality of shrimp during cold storage, while the role of collagen has rarely been studied. This study therefore investigated the relationship between collagen degradation and changes of textural properties of Pacific white shrimp, and its hydrolysis by endogenous proteinases. The textural properties of shrimp decreased gradually along with disruption of shrimp muscle tissues, and the chewiness property of shrimp muscle showed a linear relationship with collagen contents in muscle during 6-day-storage at 4 °C. Pepsin-solubilized collagen in shrimp muscle consisted of one α1 chain and two α2 chains, revealing a typical tripeptide sequence (i.e., Gly-X-Y) in their molecules. In addition, collagen could be hydrolyzed by crude endogenous proteinases extracted from shrimp hepatopancreas, and serine proteinase plays a critical role in the process. These findings strongly suggested that the quality reduction of shrimp during cold storage is closely associated with collagen degradation.

Tumor antigen-pulsed CD8α(+) dendritic cells induce T cell-mediated graft-versus-tumor effect in vitro.

The graft-versus-tumor (GVT) effect of T cells induced by tumor antigen-pulsed CD8α(+) dendritic cells (DCs) in vitro was investigated in this study. Immature CD8α(+) DCs were prepared from C57BL/6 (H-2(b)) bone marrow cells by using a cytokine cocktail. On the 3rd day of culture, CD8α(+) DCs were pulsed by allogeneic (Balb/c, H-2(d)) EL9611 leukemia antigen, or RM-1 syngeneic prostate cancer antigen, with the concentration series of 0, 2.5, 5.0, 10.0, 20.0 µg/mL, respectively, then antigen-loaded immature CD8α(+) DCs were co-cultured with syngeneic T cells according to the DC/T ratio of 1:1, 2:1 and 4:1. T cell proliferation was measured by MTT assay. Cytokines including interferon gamma (IFN-γ) and interleukin-10 (IL-10) in CD8α(+) DCs and T co-culture supernatant were detected by using ELISA. Cytotoxic effect of antigen-specific T cells was tested by LDH release assay. Conventional mature DCs (mDCs) induced from C57BL/6 (H-2(b)) bone marrow cells by using granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin-4 (IL-4) served as a control. The results showed that the proliferative activity of T cells stimulated by CD8α(+) DCs loaded with allogeneic or syngeneic tumor antigen was augmented with the CD8α(+) DC/T ratio increased (P<0.05). When antigen concentration ≤ 5 µg/mL and CD8α(+) DC/T ratio ≤ 2:1, the ability of CD8α(+) DCs to stimulate T cell proliferation was higher than mDC control in allogeneic tumor antigen-pulsed groups (P<0.05), but not in syngeneic tumor antigen-pulsed groups (P>0.05). The level of IFN-γ and IL-10 in CD8α(+) DCs and T cell co-culture supernatant were increased in both allogeneic and syngeneic antigen-pulsed groups (P<0.05), and the cytokine level was higher in allogeneic antigen-pulsed groups than in syngeneic antigen groups when the CD8α(+) DC/T was 1:1 or 2:1 (P<0.05). There existed a negative correlation between the level of IL-10 and T cell proliferation. T cell cytotoxicity assay showed that when CD8α(+) DCs were pulsed with allogeneic tumor antigen, the maximal T cell killing efficiency could reach (100±7.7)%, whereas syngeneic tumor antigen-pulsed group had only (65.0±3.4)%. It was concluded that syngeneic and allogeneic tumor antigen-pulsed immature CD8α(+) DCs could stimulate T cells to exert the GVT effect in vitro, and the GVT effect was more obvious with allogeneic tumor antigen than with syngeneic tumor antigen. The optimal condition was low allogeneic tumor antigen pulsation (≤ 5 µg/mL) and low CD8α(+) DC/T ratio (1:1 and 2:1).

Amino acid sequence analysis and identification of mutations under positive selection in hemagglutinin of 2009 influenza A (H1N1) isolates.

The 2009 flu pandemic is caused by a new strain of influenza A (H1N1) virus, A/H1N1/09. With its high transmissibility, this novel virus has caused a pandemic and infected over 600,000 people globally. By comparing the hemagglutinin (HA) gene and protein sequences among over 700 A/H1N1/09 isolates, mutations in the receptor-binding sites and antigenic epitope regions were identified. Among these mutations, T220 and E/G239 were found to be strongly positively selected over the course of spreading of the A/H1N1/09 virus worldwide. Interestingly, both sites are located in the highly variable epitope regions of HA1, and residue 239 also plays an important role in the receptor-binding process. Further analyses demonstrated that the percentage of T220 mutants among all isolates increased rapidly during the evolution, and that an E/G239 mutation could decrease the binding affinity of the virus with its cellular receptor. Thus, due to a potential functional importance of residues 220 and 239, mutations at these sites, as well as the significant of positive selection on these sites deserves more attention, while new vaccines and therapeutic drugs are developed against this novel virus.

In situ generation of silver nanoparticles and nanocomposite films based on electrodeposition of carboxylated chitosan.

Herein, for the first time the electrodeposition of carboxylated chitosan is studied and utilized for the synthesis of silver nanoparticles (AgNPs) and generation of AgNPs/carboxylated chitosan nanocomposite films. Particularly, AgNPs are in situ synthesized on electrodes or substrates during the electrodeposition. Carboxylated chitosan not only acts as the green reducing agent and stabilizing agent for preparing AgNPs, but also serves as the main component in the electrodeposited nanocomposite film. The experimental results indicate that a smooth and homogeneous film is formed on the silver plate after electrodeposition, and the electrodeposited film can be detached from the silver plate as an independent film. The TEM observation and spectroscopic analysis results confirm the existence of AgNPs (the average size of 10 nm) in the nanocomposite film. The nanocomposite films with various shapes can be fabricated by the spatial selectivity of electrodeposition. In addition, the nanocomposite film containing AgNPs shows favorable antibacterial properties.

Epidemiological characteristics of respiratory viruses in patients with acute respiratory infections during 2009-2018 in southern China.

BACKGROUND: Acute respiratory infections (ARIs) remain a significant public threat with high morbidity and mortality worldwide; viruses are significant pathogens that cause ARIs. This study was conducted to better understand the epidemiological characteristics of respiratory viruses circulating in southern China. METHODS: We collected 22,680 respiratory samples from ARI patients in 18 hospitals in southern China during 2009-2018; seven common respiratory viruses including Flu, RSV, PIV, hMPV, ADV, HCoV, and HBoV were screened using in-house real-time PCR. RESULTS: Of all samples, 9760 ARI cases (9760/22680, 43.03%) tested positive for the seven common respiratory viruses. The most detected virus was Flu (14.15%), followed by RSV (10.33%) and PIV (5.43%); Flu-A, PIV3, and HCoV-OC43 were the predominant subtypes. Although most of the viruses were detected in male inpatients, Flu was more likely detected in female outpatients. Flu infection was more likely to cause URTI (upper respiratory tract infection), whereas RSV infection was more likely to cause pneumonia and bronchitis. The prevalence of Flu was particularly high in 2009. The epidemic level was found notably high in 2014-2018 for RSV, in 2016-2018 for PIV, in the summer of 2018 for ADV, in the summer of 2016 and winter of 2018 for HCoV, and in the summer of 2011 and autumn of 2018 for HBoV. The co-detection rate of the seven viruses was 4.70%; RSV, PIV, and Flu were the most commonly co-detected viruses. CONCLUSIONS: This work demonstrates the epidemiological characteristics of seven common respiratory viruses in ARI patients in southern China.

Epidemiological characteristics and phylogenic analysis of human respiratory syncytial virus in patients with respiratory infections during 2011-2016 in southern China.

BACKGROUND: Human respiratory syncytial virus (RSV) is one of the most important pathogens that cause acute respiratory infections in children and immunocompromised adults. This work was conducted to understand the epidemiological and phylogenetic features of RSV in southern China during 2011-2016. METHODS: A total of 16 024 nasopharyngeal swabs were collected from patients with respiratory infections in 14 hospitals, and screened for RSV and seven other respiratory viruses using real-time PCR. Six hundred and twenty-three RSV-positive samples from 13 hospitals were further analyzed for subtypes. G gene sequencing and phylogenetic analysis were performed based on 46 RSV-A and 15 RSV-B strains. RESULTS: RSV was detected in 9.5% of the 16 024 specimens, the highest among the eight respiratory viruses screened. Most of these specimens came from inpatients and children under 3 years of age. The incidence of RSV-A (9.4%) was higher than that of RSV-B (4.4%) in children (<15 years), but not in adults (0.64% vs. 0.58%). A 2-year RSV-A dominance followed by a 1-year RSV-B dominance pattern was found. The co-detection rate of RSV was 25.1%. The main prevalent genotypes were NA1, ON1, and BA9. The prevalent RSV-A genotype in 2011-2012 was NA1, close to Chongqing and Brazil, but a new Hong Kong ON1 genotype was introduced and became the prevalent genotype in Guangzhou in 2014-2015. Deduced amino acid sequence analysis confirmed the ongoing evolution and a high selection pressure of RSV-A and B strains, especially in RSV-A ON1 and NA1 genotypes. CONCLUSIONS: This study demonstrated the molecular epidemiological characteristics of RSV in patients with respiratory infections in southern China.

Identification of a Novel Betacoronavirus (Merbecovirus) in Amur Hedgehogs from China.

While dromedaries are the immediate animal source of Middle East Respiratory Syndrome (MERS) epidemic, viruses related to MERS coronavirus (MERS-CoV) have also been found in bats as well as hedgehogs. To elucidate the evolution of MERS-CoV-related viruses and their interspecies transmission pathway, samples were collected from different mammals in China. A novel coronavirus related to MERS-CoV, Erinaceus amurensis hedgehog coronavirus HKU31 (Ea-HedCoV HKU31), was identified from two Amur hedgehogs. Genome analysis supported that Ea-HedCoV HKU31 represents a novel species under Merbecovirus, being most closely related to Erinaceus CoV from European hedgehogs in Germany, with 79.6% genome sequence identity. Compared to other members of Merbecovirus, Ea-HedCoV HKU31 possessed unique non-structural proteins and putative cleavage sites at ORF1ab. Phylogenetic analysis showed that Ea-HedCoV HKU31 and BetaCoV Erinaceus/VMC/DEU/2012 were closely related to NeoCoV and BatCoV PREDICT from African bats in the spike region, suggesting that the latter bat viruses have arisen from recombination between CoVs from hedgehogs and bats. The predicted HKU31 receptor-binding domain (RBD) possessed only one out of 12 critical amino acid residues for binding to human dipeptidyl peptidase 4 (hDPP4), the MERS-CoV receptor. The structural modeling of the HKU31-RBD-hDPP4 binding interphase compared to that of MERS-CoV and Tylonycteris bat CoV HKU4 (Ty-BatCoV HKU4) suggested that HKU31-RBD is unlikely to bind to hDPP4. Our findings support that hedgehogs are an important reservoir of Merbecovirus, with evidence of recombination with viruses from bats. Further investigations in bats, hedgehogs and related animals are warranted to understand the evolution of MERS-CoV-related viruses.

Vasculogenic mimicry in bladder cancer and its association with the aberrant expression of ZEB1.

The aim of the present study was to investigate the associations between vasculogenic mimicry (VM) and zinc finger E-box binding homeobox 1 (ZEB1) in bladder cancer. VM structure and ZEB1 expression were analyzed by cluster of differentiation 34/periodic acid Schiff (PAS) double staining and immunohistochemical staining in 135 specimens from patients with bladder cancer, and a further 12 specimens from normal bladder tissues. Three-dimensional (3-D) culture was used to detect VM formation in the bladder transitional cancer cell lines UM-UC-3 and J82, and the immortalized human bladder epithelium cell line SV-HUC-1 in vitro. ZEB1 expression in these cell lines was compared by reverse transcription-quantitative polymerase chain reaction and western blot assays. In addition, small interfering RNA was used to inhibit ZEB1 in UM-UC-3 and J82 cells, followed by 3-D culturing of treated cell lines. As a result, VM was observed in 31.1% of specimens from bladder cancer tissues, and cases with high ZEB1 expression accounted for 60.0% of patients with bladder cancer. In addition, ZEB1 expression was closely associated with VM (r=0.189; P<0.05), and also increased as the grade and stage of the tumor developed. In an in vitro assay, UM-UC-3 and J82 cells exhibited VM formation, however, SV-HUC-1 did not. Furthermore, VM-forming cancer cell lines UM-UC-3 and J82 exhibited higher ZEB1 expression. Notably, VM formation was inhibited following knockdown of ZEB1. In conclusion, ZEB1 may be associated with VM in bladder cancer and serve an important role in the process of VM formation. However, its detailed mechanism requires further study.

Epidemiology characteristics of human coronaviruses in patients with respiratory infection symptoms and phylogenetic analysis of HCoV-OC43 during 2010-2015 in Guangzhou.

Human coronavirus (HCoV) is one of the most common causes of respiratory tract infection throughout the world. To investigate the epidemiological and genetic variation of HCoV in Guangzhou, south China, we collected totally 13048 throat and nasal swab specimens from adults and children with fever and acute upper respiratory infection symptoms in Gunazhou, south China between July 2010 and June 2015, and the epidemiological features of HCoV and its species were studied. Specimens were screened for HCoV by real-time RT-PCR, and 7 other common respiratory viruses were tested simultaneously by PCR or real-time PCR. HCoV was detected in 294 cases (2.25%) of the 13048 samples, with most of them inpatients (251 cases, 85.4% of HCoV positive cases) and young children not in nursery (53.06%, 156 out of 294 HCoV positive cases). Four HCoVs, as OC43, 229E, NL63 and HKU1 were detected prevalent during 2010-2015 in Guangzhou, and among the HCoV positive cases, 60.20% were OC43, 16.67% were 229E, 14.97% were NL63 and 7.82% were HKU1. The month distribution showed that totally HCoV was prevalent in winter, but differences existed in different species. The 5 year distribution of HCoV showed a peak-valley distribution trend, with the detection rate higher in 2011 and 2013 whereas lower in 2010, 2012 and 2014. The age distribution revealed that children (especially those <3 years old) and old people (>50 years) were both high risk groups to be infected by HCoV. Of the 294 HCoV positive patients, 34.69% (101 cases) were co-infected by other common respiratory viruses, and influenza virus was the most common co-infecting virus (30/101, 29.70%). Fifteen HCoV-OC43 positive samples of 2013-2014 were selected for S gene sequencing and phylogenetic analysis, and the results showed that the 15 strains could be divided into 2 clusters in the phylogenetic tree, 12 strains of which formed a separate cluster that was closer to genotype G found in Malaysia. It was revealed for the first time that genotype B and genotype G of HCoV-OC43 co-circulated and the newly defined genotype G was epidemic as a dominant genotype during 2013-2014 in Guanzhou, south China.

Reconfigurable all-dielectric metasurface based on tunable chemical systems in aqueous solution.

Dynamic control transmission and polarization properties of electromagnetic (EM) wave propagation is investigated using chemical reconfigurable all-dielectric metasurface. The metasurface is composed of cross-shaped periodical teflon tubes and inner filled chemical systems (i.e., mixtures and chemical reaction) in aqueous solution. By tuning the complex permittivity of chemical systems, the reconfigurable metasurface can be easily achieved. The transmission properties of different incident polarized waves (i.e., linear and circular polarization) were simulated and experimentally measured for static ethanol solution as volume ratio changed. Both results indicated this metasurface can serve as either tunable FSS (Frequency Selective Surface) or tunable linear-to-circular/cross Polarization Converter at required frequency range. Based on the reconfigurable laws obtained from static solutions, we developed a dynamic dielectric system and researched a typical chemical reaction with time-varying permittivity filled in the tubes experimentally. It provides new ways for realizing automatic reconfiguration of metasurface by chemical reaction system with given variation laws of permittivity.

Bax-interacting factor-1 inhibits cell proliferation and promotes apoptosis in prostate cancer cells.

Prostate cancer (PCa) is one of the most common malignant tumors and the second leading cause of cancer-related death among males. Bax-interacting factor-1 (Bif-1) is a member of Endophilin family, which binds to and activates the BAX protein in response to the apoptosis signaling pathway. Loss of Bif-1 may suppress the intrinsic pathway of apoptosis and promote tumorigenesis, but there is also converse evidence that Bif-1 could in part be responsible for the tumorigenesis and the role of Bif-1 in PCa development is not clear. In the present study, we aimed to understand the relationships between Bif-1 expression and PCa development. The mRNA and protein expression levels of Bif-1 in PCa cell lines, benign prostatic hyperplasia (BPH) (n=100) and PCa tissues (n=100, including low Gleason-scored PCa n=43 and high Gleason-scored PCa n=57) were detected and the effects of Bif-1 overexpression on the apoptosis, proliferation and migration in LNCaP cells were explored. Bif-1 mRNA levels of PCa cell lines were analyzed by real-time PCR and the protein levels were detected by western blotting. Bif-1 expression in BPH and PCa samples was detected by immunohistochemistry. To build Bif-1 overexpression PCa cells, Bif-1 gene was transfected into LNCaP cells by pcDNA3.1(+)­Bif-1 vector. Cell apoptosis was detected by flow cytometric analysis, cell proliferation measured by 3­(4,5­dimethylthiazol­2­yl)­2,5­diphenyltetrazolium bromide (MTT) assay and cell migration was analyzed by wound­healing assay. The results proved that Bif-1 is downregulated in both PCa cell lines (P<0.01) and clinical samples (P<0.05), and Bif-1 expression is suppressed with the cancer progression (BPH vs. PCa P<0.01, and low Gleason-scored PCa vs. high Gleason-scored PCa P<0.05). Overexpression of Bif-1 could significantly inhibit cell proliferation (P<0.05) and enhancing PCa cell apoptosis (P<0.05), but it did not affect the migration ability (P>0.05). Our findings give strong evidence that Bif-1 is involved in PCa tumorigenesis and acts as a suppressor in PCa progression, and may have significance in understanding the process of PCa development.

[The effect of cell killing and apoptosis by human herpes simplex virus- thymidine kinase/ganciclovir system combined with allitride in BIU87 cells].

OBJECTIVE: To study the killing effect of human herpes simplex virus-thymidine kinase/ganciclovir (HSV-TK/GCV) system combined with allitride and the possible apoptosis mechanism in BIU87 cells. METHODS: The cytotoxicity after combination were estimated by theamine blue tetrazolium bromide (MTT). The morphological changes were observed with inverted microscope and in-situ cell apoptosis detection kit. Changes of apoptosis rate and cell cycle were assessed by flow cytometry. B-cell lymphoma-2 (bcl-2), bax, caspase-3 (cysteine aspartate specific proteinase) mRNA changes were detected by reverse transcriptase polymerase chain reaction, and caspase-3 activity was estimated with colorimetry. RESULTS: For combination group, the cell killing rate was raised to 72.50% to compare with 35.00% of GCV and 37.00% of allitride separately and there was a synergistic effect between these two drugs. The cell apoptosis was induced in all three groups and for the combination group the time of S-phase and G(2)-phase arrest were earlier than other two groups. Both drugs could inhibit the expression of bcl-2 and promote the expression and activity of caspase-3. CONCLUSIONS: The combination of HSV-TK/GCV system with allitride can inhibit the proliferation of BIU87 cells congenerously through apoptosis, which may be correlated with S- and G(2)-phase arrest, down-regulation of bcl-2 and increased caspase-3 expression and its activity.