Screening and identification of autophagy-related biomarkers for oral squamous cell carcinoma (OSCC) via integrated bioinformatics analysis.

Increasing evidences have showed that autophagy played a significant role in oral squamous cell carcinoma (OSCC). Purpose of our study was to explore the prognostic value of autophagy-related genes (ATGs) and screen autophagy-related biomarkers for OSCC. RNA-seq and clinical data were downloaded from The Cancer Genome Atlas (TCGA) database following extracting ATG expression profiles. Then, differentially expressed analysis was performed in R software and a risk score model according to ATGs was established. Moreover, comprehensive bioinformatics analyses were used to screen autophagy-related biomarkers which were later verified in OSCC tissues and cell lines. A total of 232 ATGs were extracted, and 37 genes were differentially expressed in OSCC. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis demonstrated that these genes were mainly located in autophagosome membrane and associated with autophagy. Furthermore, the risk score on basis of ATGs was identified as potential independent prognostic biomarker. Moreover, ATG12 and BID were identified as potential autophagy-related biomarkers of OSCC. This study successfully constructed a risk model, and the risk score could predict the prognosis of OSCC patients accurately. Moreover, ATG12 and BID were identified as two potential independent prognostic autophagy-related biomarkers and might provide new OSCC therapeutic targets.

Water use efficiency in a primary subtropical evergreen forest in Southwest China.

We calculated water use efficiency (WUE) using measures of gross primary production (GPP) and evapotranspiration (ET) from five years of continuous eddy covariance measurements (2009-2013) obtained over a primary subtropical evergreen broadleaved forest in southwestern China. Annual mean WUE exhibited a decreasing trend from 2009 to 2013, varying from ~2.28 to 2.68 g C kg H2O-1. The multiyear average WUE was 2.48 ± 0.17 (mean ± standard deviation) g C kg H2O-1. WUE increased greatly in the driest year (2009), due to a larger decline in ET than in GPP. At the diurnal scale, WUE in the wet season reached 5.1 g C kg H2O-1 in the early morning and 4.6 g C kg H2O-1 in the evening. WUE in the dry season reached 3.1 g C kg H2O-1 in the early morning and 2.7 g C kg H2O-1 in the evening. During the leaf emergence stage, the variation of WUE could be suitably explained by water-related variables (relative humidity (RH), soil water content at 100 cm (SWC_100)), solar radiation and the green index (Sgreen). These results revealed large variation in WUE at different time scales, highlighting the importance of individual site characteristics.

[Pectoralis major myocutaneous flap for repairing large tissue defects following oral cancer surgery].

OBJECTIVE: To investigate the method for reconstruction of large tissue defects following surgical resection of advanced oral cancer using pectoralis major myocutaneous flap. METHODS: From 2005 to 2009, 40 patients with advanced oral cancer received extensive surgical resection of oral cancer, and the intraoral defects were reconstructed using pectoralis major myocutaneous flaps. RESULTS: All the flaps survived except one flap with partial necrosis. CONCLUSION: Pectoralis major myocutaneous flap is effective for reconstruction of large tissue defects after resection of advanced oral cancer.

Early induction of interferon-responsive mRNAs in Creutzfeldt-Jakob disease.

Foreign infectious agents typically evoke a host immune response. In scrapie and Creutzfeldt-Jakob disease (CJD), no immune response has been detectable. However, many latent or persistent viruses evade immune recognition but still activate inflammatory pathways. Unique microglial responses in late CJD infection that could be part of a host defense mechanism were previously delineated, although changes secondary to neurodegeneration could not be excluded. Data here show these microglial transcriptional changes are detectable in CJD brain beginning at 30 days after innoculation. In addition, 10 other interferon-sensitive genes were similarly upregulated at very early stages of infection. These responses occurred well before abnormal prion protein (PrP) and clinical signs of CJD were detectable. Further analyses in very pure microglia from CJD brain suggested the CJD agent activated signaling pathways distinct from those induced by amyloidogenic proteins (including abnormal PrP). Although increases in interferon-alpha or -beta transcript levels were not seen in cultures or in whole brain, CJD microglia exhibited a potentiated interferon response when challenged with double-stranded RNA. The induction of interferon-sensitive genes without appreciable interferon synthesis was strikingly similar to that seen in some viral infections. These data suggest the CJD agent is recognized as a foreign virus-like entity. Moreover, the early reactive gene expression profiles described here may be useful in preclinical diagnosis.

New molecular markers of early and progressive CJD brain infection.

Transmissible spongiform encephalopathies (TSEs), including human Creutzfeldt-Jakob disease (CJD), are caused by a related group of infectious agents that can be transmitted to many mammalian species. Because the infectious component of TSE agents has not been identified, we examined myeloid cell linked inflammatory pathways to find if they were activated early in CJD infection. We here identify a specific set of transcripts in CJD infected mouse brains that define early and later stages of progressive disease. Serum amyloid A3 and L-selectin mRNAs were elevated as early as 20 days after intracerebral inoculation. Transcripts of myeloid cell recruitment factors such as MIP-1alpha, MIP-1beta, and MCP1, as well as IL1alpha and TNFalpha were upregulated > 10 fold between 30 and 40 days, well before prion protein (PrP) abnormalities that begin only after 80 days. At later stages of symptomatic neurodegenerative disease (100-110 days), a selected set of transcripts rose by as much as 100 fold. In contrast, normal brain inoculated controls showed no similar sequential changes. In sum, rapid and simple PCR tests defined progressive stages of CJD brain infection. These markers may also facilitate early diagnosis of CJD in accessible peripheral tissues such as spleen and blood. Because some TSE strains can differentially target particular cell types such as microglia, several of these molecular changes may also distinguish specific agent strains. The many host responses to the CJD agent challenge the assumption that the immune system does not recognize TSE infections because these agents are composed only of the host's own PrP.

Virus-like interference in the latency and prevention of Creutzfeldt-Jakob disease.

We previously showed that intracerebral (ic) inoculation of the attenuated SY strain of Creutzfeld-Jakob disease in mice could delay clinical signs and widespread neuropathology evoked by subsequent ic challenge with the more virulent FU strain. Using lower doses of SY and FU ic, we here demonstrate that mice can be protected well into old age without demonstrable neuropathology or pathologic prion protein (PrP-res). In contrast, parallel FU only controls became terminally diseased 1 year earlier. To determine whether factors elaborated in response to SY might be part of this effect, we evaluated brain and serum samples from additional parallel mice at 90 days after SY infection and just before FU challenge. The infectivity of FU preparations was significantly reduced by mixing with these fresh SY brain homogenates but not by mixing with SY serum samples, suggesting that brain cells were elaborating labile inhibitory factors that were part of the protective response. SY infectivity was too low to be detected in these brain homogenates. Although suppression could be overcome by higher FU doses ic, strong protection against maximal doses of FU was observed by using i.v. inoculations. Because myeloid microglia are infectious and also elaborate many factors in response to the foreign Creutzfeld-Jakob disease agent, it is likely that innate immunity underlies the profound protection shown here. In principle, it should be possible to artificially stimulate relevant myeloid pathways to better prevent and/or delay the clinical and pathological sequelae of these infections.