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Supplementary Figure 2 from The Antitumor Activity of Homoharringtonine against Human Mast Cells Harboring the KIT D816V Mutation

Supplementary Figure Legends 1-2 from The Antitumor Activity of Homoharringtonine against Human Mast Cells Harboring the KIT D816V Mutation

Supplementary Figure 1 from The Antitumor Activity of Homoharringtonine against Human Mast Cells Harboring the KIT D816V Mutation

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.

Quantum dots (QDs) have drawn great attention for their attractive applications ranging from light-emitting diodes to fluorescence bioimaging. In this study, for the first time, ZnS QDs/gelatin nan...

Highlights • For respiratory syncytial virus (RSV), an annual distribution pattern of 2-year RSV-A dominance followed by a 1-year RSV-B dominance was found in Guangzhou. • In 2011–2016 in south China, prevalent RSV-A genotypes were NA1 and ON1 and the prevalent RSV-B genotype was BA9. • The prevalent RSV-A genotype changed from Chongqing NA1 in 2011 to Hong Kong ON1 in 2014. • The highest RSV epidemic peak occurred in 2015, indicating a possible biennial peak. • The ongoing evolution of RSV-A ON1 and NA1 genotypes indicated high selection pressure., 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 (

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

The dynamical quantum phase transitions (DQPTs) after a sudden quench in periodic quantum Ising chains (QICs) are studied. We obtain the formulas of the Loschmidt echo and the Fisher zeros of the Loschmidt amplitude in the periodic QIC. It is found that for the quench across the quantum phase transitions (QPTs), the periodic QICs have richer DQPTs than that in the homogeneous QIC, and the number of critical times of the DQPTs are dependent on the specifical parameter of the pre- and post-quench Hamiltonian. For instance, in the period-two QIC, there is one critical time for the quench from the FM phase to the PM phase, and three critical times for the quench from the PM phase to the FM phase. In the period-three QIC, there may have three or four critical times for the quench from FM phase to the PM phase, but may have two or three critical times for the quench from PM to the FM phase. The reason is that the periodic QICs have multiple quasiparticle excitation spectra, and the Fisher zeros of the periodic systems consist of several separated branches, which is different from that in the homogeneous QIC. For different quenches across the QPTs, different branches will intersect with the imaginary axis, which correspond to different critical times. Our conclusion also provides insight in the property of the DQPT in the inhomogeneous systems.

We study the dynamical quantum phase transitions (DQPTs) in the XY chains with the Dzyaloshinskii–Moriya interaction and the XZY–YZX type of three-site interaction after a sudden quench. Both the models can be mapped to the spinless free fermion models by the Jordan–Wigner and Bogoliubov transformations with the form H = ∑ k ε k ( η k † η k − 1 2 ) , where the quasiparticle excitation spectra εk may be smaller than 0 for some k and are asymmetrical (εk ≠ ε –k ). It is found that the factors of Loschmidt echo equal 1 for some k corresponding to the quasiparticle excitation spectra of the pre-quench Hamiltonian satisfying εk ⋅ ε –k < 0, when the quench is from the gapless phase. By considering the quench from different ground states, we obtain the conditions for the occurrence of DQPTs for the general XY chains with gapless phase, and find that the DQPTs may not occur in the quench across the quantum phase transitions regardless of whether the quench is from the gapless phase to gapped phase or from the gapped phase to gapless phase. This is different from the DQPTs in the case of quench from the gapped phase to gapped phase, in which the DQPTs will always appear. Moreover, we analyze the different reasons for the absence of DQPTs in the quench from the gapless phase and the gapped phase. The conclusion can also be extended to the general quantum spin chains.

We study the influence of disorder on the dynamical quantum phase transitions (DQPTs) in the transverse-field anisotropic XY chain after a sudden quench. The formulas to calculate the Loschmidt echo and Fisher zeros of the inhomogeneous XY chain are derived in real space. It is found that new DQPTs appear in the presence of weak disorder for the quenches across the Ising transition and two quantum phase transitions (Ising and anisotropic transitions). As the disorder strength increases, it's demonstrated that the Fisher zeros coalesce to regions on the imaginary axis in the thermodynamic limit. The DQPTs occur at the critical times corresponding to the boundaries of the Fisher zeros regions on the imaginary axis. However, for the quench across the anisotropic transition, the Fisher zeros regions appear even for the very weak disorder. Finally, for the quench within the same phase, the weak disorder is found having no effect on the DQPTs, but the DQPTs will be washed out in the presence of strong disorder.

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.

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‑(4,5‑dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide (MTT) assay and cell migration was analyzed by wound‑healing assay. The results proved that Bif-1 is downregulated in both PCa cell lines (P0.01) and clinical samples (P0.05), and Bif-1 expression is suppressed with the cancer progression (BPH vs. PCa P0.01, and low Gleason-scored PCa vs. high Gleason-scored PCa P0.05). Overexpression of Bif-1 could significantly inhibit cell proliferation (P0.05) and enhancing PCa cell apoptosis (P0.05), but it did not affect the migration ability (P0.05). 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.

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-β-lactamase and a genetic array of aacA4-blaIMP-25-oxa30-catB3 have been discovered from this retrospective surveillance on antimicrobial resistance of P. aeruginosa.

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.

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.

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

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-β-lactamase and a genetic array of aacA4-blaIMP-25-oxa30-catB3 have been discovered from this retrospective surveillance on antimicrobial resistance of P. aeruginosa.

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 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.

Graft-vs.-host disease (GVHD) remains the major limitation of allogeneic bone marrow transplantation (BMT) and stem cell transplantation, and leukemia recurrence is another important complication in leukemia treatment. Immature CD8alpha+ dendritic cells (DC) have good potential in GVHD treatment and immunological tolerance studies. To find a new way to prevent GVHD, not increasing the risk of leukemia recurrence, in this study, predominant CD8alpha+ immature DC were induced from murine bone marrow (BM) cells by 5 ng/mL granulocyte-macrophage colony stimulating factor (GM-CSF) plus 20-ng/mL interleukin (IL)-4, 100-ng/mL stem cell factor (SCF) and 25-ng/mL Flt3L, and 97.09 of prepared DC were CD8alpha+ on day 3. These DC were identified as morphologically and phenotypically immature CD8alpha+ DC. The suppressive function was observed in vitro, and then in vivo on allo-BMT leukemia model. The prepared predominant immature CD8alpha+ DC were weak syngeneic lymphocyte stimulators and could suppress mixed leukocyte reaction in vitro. In vivo, they prevented the pathological changes of GVHD and prolonged the surviving time of allo-BMT leukemia mice. The effect showed a dose-effect relationship. 86.7% of allo-BMT plus 1 million predominant CD8alpha+ DC leukemia mice reached long-term survival. Although predominant immature CD8alpha+ DC had the function of GVHD suppression, they did not increase leukemia recurrence. The method and findings may have important potency for GVHD treatment in clinical application.

Background Expression of the non-receptor tyrosine kinase ETK/BMX has been reported in several solid tumors, but the underlying molecular mechanisms and its clinical significance in renal cell carcinoma (RCC) remain to be elucidated. Methods ETK expression in 90 human RCC and 30 human normal renal tissue samples was examined by immunohistochemistry and compared with several clinicopathologic parameters. To further demonstrate the biological function of ETK in RCC, Western blot was used to test the expression level of ETK protein in RCC cell lines. Subsequent to the downregulation of ETK by small interfering RNA, the effects of ETK on RCC cell growth, apoptosis, migration and invasion were assessed by methyl thiazol tetrazolium assay, flow cytometry and transwell assay. And the varying expression of VEGF, STAT3 and phosphorylated STAT3 (p-STAT3) in RCC were evaluated by Western blot. Results Immunohistochemistry analysis showed that ETK expression was highly increased in RCC and was positively correlated with clinical stage, grade and metastasis. Simultaneously, the overall survival time in patients with higher ETK expression was obviously shorter than that in patients with lower ETK expression. ETK was also detected in RCC cell lines. Moreover, the down-regulating ETK significantly inhibited RCC cell growth, migration, invasion and promoted apoptosis. The expression of VEGF and p-STAT3 were also decreased. Conclusions Our study suggests that the overexpression of ETK is associated with the malignancy and disease progression of RCC. Since ETK is also involved in RCC cell biological function and VEGF-ETK-STAT3 loop, ETK may be used as a potential therapeutic target for RCC.

Human bocavirus (HBoV) is a novel parvovirus associated with respiratory tract diseases and gastrointestinal illness in adult and pediatric patients throughout the world. To investigate the epidemiological and genetic variation of HBoV in Guangzhou, South China, we screened 3460 throat swab samples from 1686 children and 1774 adults with acute respiratory infection symptoms for HBoV between March 2010 and February 2011, and analyzed the complete genome sequence of 2 HBoV strains. Specimens were screened for HBoV by real-time PCR and other 6 common respiratory viruses by RT-PCR or PCR. HBoV was detected in 58 (1.68%) out of 3460 samples, mostly from pediatric patients (52/58) and inpatient children (47/58). Six adult patients were detected as HBoV positive and 5 were emergency cases. Of these HBoV positive cases, 19 (32.76%) had co-pathogens including influenza virus (n = 5), RSV (n = 5), parainfluenza (n = 4), adenovirus (n = 1), coronavirus (n = 7). The complete genome sequences of 2 HBoVs strains (Genbank no. JN794565 and JN794566) were analyzed. Phylogenetic analysis showed that the 2 HBoV strains were HBoV1, and were most genetically close to ST2 (GenBank accession number DQ0000496). Recombination analysis confirmed that HBoV strain GZ9081 was an intra-genotype recombinant strain among HBoV1 variants., published_or_final_version

PSM-E is a newly discovered alternatively spliced variant of prostate-specific membrane antigen (PSMA). In the current study, its role on the proliferation, invasiveness and migration in prostate cancer cell lines was analyzed. PSM-E and PSMA (as a comparison) eukaryotic expression vectors pcDNA3.0/PSM-E and pcDNA3.0/PSMA were constructed, validated by RT-PCR and Western blotting, and PSMA/PSM-E overexpression PC-3 cell models were built. Gene interference was used to block PSMA and the expression of its splice variants in LNCap cells. Three shRNA fragments were synthesized against PSMA, cloned into the vector pSilencer 2.1-U6-neo, their interference effect was evaluated by RT-PCR and Western blotting, and pSilencer 2.1-U6-neo‑shRNA3 (named p‑shRNA3) was chosen in further analyses. Growth curves were drawn to observe the proliferation change, which showed that PSM-E had the potential to suppress proliferation (P0.05), but no significant change was observed in PSMA/PC-3 cells and in PSMA/PSM-E interfering LNCap cells (P0.05). Cross-river test showed that the migration speeds of PSM-E/PC-3 and PSMA/PC-3 were both significantly slower than the vector negative control, and faster in p-shRNA3 interfering LNCap cells compared with its vector negative control (P0.05), and no significant difference existed between PSM-E/PC-3 and PSMA/PC-3 (P0.05). Transwell assay showed that the invasive cells of both PSMA/PC-3 and PSM-E/PC-3 were fewer compared to the vector negative control (P0.05), and the invasive suppression effect of PSM-E was weaker than PSMA (P0.05), and accordingly, invasiveness of interfering LNCaP cells was enhanced compared with the vector negative control (P0.05). These results showed that PSM-E could suppress proliferation, migration and invasiveness of prostate cancer cells. Its suppression effect on cell proliferation is stronger compared to PSMA and the suppression effect on invasiveness is weaker than that of PSMA.

Protein kinase C epsilon (PKCε), an oncogene overexpressed in several human cancers, is involved in cell proliferation, migration, invasion, and survival. However, its roles in clear cell renal cell carcinoma (RCC) are unclear. This study aimed to investigate the functions of PKCε in RCC, especially in clear cell RCC, to determine the possibility of using it as a therapeutic target. By immunohistochemistry, we found that the expression of PKCε was up-regulated in RCCs and was associated with tumor Fuhrman grade and T stage in clear cell RCCs. Clone formation, wound healing, and Borden assays showed that down-regulating PKCε by RNA interference resulted in inhibition of the growth, migration, and invasion of clear cell RCC cell line 769P and, more importantly, sensitized cells to chemotherapeutic drugs as indicated by enhanced activity of caspase-3 in PKCε siRNA-transfected cells. These results indicate that the overexpression of PKCε is associated with an aggressive phenotype of clear cell RCC and may be a potential therapeutic target for this disease.

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.

BACKGROUND Prostate-specific membrane antigen (PSMA) overexpressed in prostate cancer (PCa) has been targeted for therapy and diagnosis of PCa. In the current study, PSMA cDNA was cloned from PCa tissue by RT-PCR. After sequencing, a new spliced variant of PSMA (PSM-E) was discovered and its specificity in PCa was evaluated. METHODS PSM-E and PSMA mRNA were measured in LNCaP, PC-3 and prostate or nonprostatic malignancies. Following transfection of PC-3 with PSM-E cDNA in the pcDNA3.0 vector, PSM-E expression was measured by immunofluorescence and Western-blot. PSM-E and PSMA mRNA levels were quantified by a real-time PCR assay in normal prostate (n = 7), benign prostatic hyperplasia (BPH) (n = 22) and PCa (n = 41). The correlation between their levels and tumor grade was analyzed. RESULTS PSM-E cDNA is identical to PSMA except for a 97-nucleotide region and a 93-nucleotide region. PSM-E and PSMA mRNA were detected in PCa and LNCaP, not in PC-3; PSMA could be detected in some nonprostatic tumors whereas PSM-E not. The expression of PSM-E protein was detected in transfected cells. Significant difference of PSM-E mRNA levels was observed among normal prostate, BPH and PCa (P

In this two-years surveillance of 2009 pandemic influenza A (H1N1) (pH1N1) in Guangzhou, China, we reported here that the scale and duration of pH1N1 outbreaks, severe disease and fatality rates of pH1N1 patients were significantly lower or shorter in the second epidemic year (May 2010-April 2011) than those in the first epidemic year (May 2009-April 2010) (P0.05). Similar to seasonal influenza, pre-existing chronic pulmonary diseases was a risk factor associated with fatal cases of pH1N1 influenza. Different from seasonal influenza, which occurred in spring/summer seasons annually, pH1N1 influenza mainly occurred in autumn/winter seasons in the first epidemic year, but prolonged to winter/spring season in the second epidemic year. The information suggests a tendency that the epidemics of pH1N1 influenza may probably further shift to spring/summer seasons and become a predominant subtype of seasonal influenza in coming years in Guangzhou, China., published_or_final_version

Summary Background The World Health Organization (WHO) ranks respiratory tract infection (RTI) as the second leading cause of death worldwide for children under 5 years of age. The aim of this work was to evaluate the epidemiology characteristics of respiratory viruses found in children and adults with RTI from July 2009 to June 2012 in southern China. Methods In this work, a total of 14 237 nasopharyngeal swabs (14 237 patients from 25 hospitals) were analyzed, and seven respiratory viruses (influenza virus, respiratory syncytial virus, parainfluenza virus, adenovirus, human metapneumovirus, human coronavirus, human bocavirus) were detected using PCR/RT-PCR from nasopharyngeal swabs. Results The demographic characteristics, viral prevalence, age distribution, seasonal distribution, and pathogen spectrum of the patients with RTIs were analyzed. Co-infection was observed in 483 specimens, but it was more common in male patients, inpatients, children, and young adults. It varied by season, being more prevalent in the spring and summer and less so in the winter. Human coronavirus and human bocavirus were the most common pathogens, tending to occur in co-infection with other respiratory viruses. Conclusions This work adds to our knowledge of the epidemiology characteristics of these seven common respiratory viruses among patients with RTI in southern China. The detection of the specific viral causes of infection provides a useful starting point for an understanding of illness attributable to respiratory infection, and might also provide data relevant to the development of prevention strategies.