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TianWei Guo,1,* Wei Wang,2,* YueXia Ji,1 Min Zhang,3 GuoYing Xu,4 Sen Lin5 1Department of Pathology, Changshu Hospital Affiliated to Nanjing University of Chinese Medicine, Changshu, Jiangsu, People’s Republic of China; 2Department of Pathology, The Affiliated Obstetrics and Gynecology Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, Jiangsu, People’s Republic of China; 3Department of Pathology, Children’s Hospital Affiliated to Soochow University, Suzhou, Jiangsu, People’s Republic of China; 4School of Medical Technology, Jiangsu College of Nursing, Huai’an, Jiangsu, People’s Republic of China; 5The Affiliated Huai’an Hospital of Xuzhou Medical University and the Second People’s Hospital of Huai’an, Huai’an, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Sen LinThe Affiliated Huai’an Hospital of Xuzhou Medical University and the Second People’s Hospital of Huai’an, Huai’an, Jiangsu, People’s Republic of ChinaEmail linsen378@163.comGuoYing XuSchool of Medical Technology, Jiangsu College of Nursing, Huai’an, Jiangsu, People’s Republic of ChinaEmail xuguoying3@163.comIntroduction: Growing evidences imply that multiple long non-coding RNAs (lncRNAs) play a significant role in the treatment of cancer. Therefore, it is of great significance to discover new biomarkers or therapeutic targets of gastric cancer (GC). However, the potential molecular mechanism of lncPROX1-AS1 in GC remains unknown. The objective of current study is to investigate the effect of PROX1-AS1 in GC.Methods: Thus, we detect that PROX1-AS1 is over-expressed in tissues and cell lines of GC using qRT-PCR analysis. CCK-8, colony formation, flow cytometry, wounding healing and transwell analyses were performed to explore the effect of PROX1-AS1 on GC malignant behaviors.Results: It is further disclosed that silencing of PROX1-AS1 represses cell proliferation, migration, and invasion, whereas promotes cell apoptosis in GC. Bioinformatics analysis suggests that miR-877-5p is negatively regulated by PROX1-AS1 and ectopic of miR-877-5p alleviates the malignant behaviors of GC. Subsequently, miR-877-5p suppresses the activity of PD-L1-3ʹ UTR. At last, rescue assays demonstrated that the GC progression is suppressed by sh-PROX1-AS1 and facilitated on account of miR-877-5p inhibitors and then is retrieved by sh-PD-L1.Discussion: Our findings reveal that PROX1-AS1 exerts its role via miR-877-5p/PD-L1 axis in the GC progression, suggesting that PROX1-AS1 may represent a new therapeutic target for the diagnosis and treatment of GC patients.Keywords: PROX1-AS1, miR-877-5p, PD-L1, proliferation, apoptosis, gastric cancer

Objectives: A subset of laryngeal squamous cell carcinoma (LSCC) patients undergoing larynx preserving treatment ultimately require total laryngectomy (TL) for oncologic or functional reasons. This study aims to identify TL risk factors in these patients., Methods: Retrospective cohort study using Veterans Affairs (VA) database. T1-T4 LSCC cases treated with primary radiotherapy (XRT) or chemoradiotherapy (CRT) were assessed for TL and recurrence. Binary logistic and Cox regression and Kaplan-Meier analyses were implemented., Results: Of 5390 cases, 863 (16.0%) underwent TL. On multivariable analysis, age (adjusted odds ratio: 0.97 [0.96-0.98]; p  < .001) and N3 disease (0.42 [0.18-1.00]; p  = .050) were associated with reduced risk of TL, whereas current alcohol use (1.22 [1.04-1.43]; p  = .015) and >T1 disease (T2, 1.76 [1.44-2.17]; p  < .001; T3, 2.06 [1.58-2.68]; p  < .001; T4, 1.79 [1.26-2.53]; p  = .001) were associated with increased risk of TL. However, N2 (adjusted hazard ratio: 1.30 [1.10-1.55]; p  = .003) and N3 (2.02 [1.25-3.26]; p  = .004) disease were associated with an increased risk for local recurrence. Compared to XRT, treatment with CRT was associated with reduced risk for local recurrence after adjusting for other factors (0.84 [0.70-0.99]; p  = .044). Those who do not receive TL following local recurrence have poorer disease-specific survival (log-rank, p  < .001). In patients without local recurrence, N2 disease was associated with a fourfold increase in risk of TL (4.24 [1.83-9.82]; p  < .001)., Conclusion: Advanced nodal stage was associated with reduced rates of salvage TL in the setting of local recurrence, and subsequent worse prognosis after recurrence. Conversely, advanced nodal stage may increase the risk for functional salvage TL in patients without recurrence., Level of Evidence: Level 3., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s). Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.)

Objectives: The goal of this case report is to detail experiences and challenges experienced in the training of Primary Care residents in secondary analysis using All of Us Researcher Workbench. At our large, urban safety net hospital, Primary Care/Internal Medicine residents in their third year undergo a research intensive block, the Research Practicum, where they work as a team to conduct secondary data analysis on a dataset with faculty facilitation. In 2023, this research block focused on use of the All of Us Researcher Workbench for secondary data analysis., Materials and Methods: Two groups of 5 residents underwent training to access the All of Us Researcher Workbench, and each group explored available data with a faculty facilitator and generated original research questions. Two blocks of residents successfully completed their research blocks and created original presentations on "social isolation and A1C" levels and "medical discrimination and diabetes management.", Results: Departmental faculty were satisfied with the depth of learning and data exploration. In focus groups, some residents noted that for those without interest in performing research, the activity felt extraneous to their career goals, while others were glad for the opportunity to publish. In both blocks, residents highlighted dissatisfaction with the degree to which the All of Us Researcher Workbench was representative of patients they encounter in a large safety net hospital., Discussion: Using the All of Us Researcher Workbench provided residents with an opportunity to explore novel questions in a massive data source. Many residents however noted that because the population described in the All of Us Researcher Workbench appeared to be more highly educated and less racially diverse than patients they encounter in their practice, research may be hard to generalize in a community health context. Additionally, given that the data required knowledge of 1 of 2 code-based data analysis languages (R or Python) and work within an idiosyncratic coding environment, residents were heavily reliant on a faculty facilitator to assist with analysis., Conclusion: Using the All of Us Researcher Workbench for research training allowed residents to explore novel questions and gain first-hand exposure to opportunities and challenges in secondary data analysis., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

In order to investigate the effects of ammonium sulfate, an industrial by-product, on soil nutrients and microbial community when applied in different proportions instead of using urea as nitrogen fertilizer, a pot corn experiment was conducted. A completely randomized block experimental design was used, with a total of five treatments:CK (no fertilization), U 10 S 0 (100 % urea), U 8 S 2 (80 % urea + 20 % ammonium sulfate), U 6 S 4 (60 % urea + 40 % ammonium sulfate), and U 0 S 10 (100 % ammonium sulfate). The basic physical and chemical properties of soil and the dry weight of maize plants were determined by conventional methods, and microbial sequencing was performed using the Illumina NovaSeq platform. The experiment results showed that:① In each growth stage of maize, the pH of soil treated with fertilization (7.85-8.15) was decreased compared with that of CK (8.1-8.21), and the pH showed a decreasing trend with the increase in ammonium sulfate content. ② The soil available nitrogen content increased gradually with the increase in the ammonium sulfate ratio at each growth stage of maize. Compared with that in the CK and U 10 S 0 treatments, the ratio in the U 0 S 10 treatment increased 30.56 % to 63.68 % and 13.22 % to 38.43 %, respectively. The variation trend of organic carbon content was opposite to that of available nitrogen (U 8 S 2 &gt; U 6 S 4 &gt; U 0 S 10 ), and the addition of ammonium sulfate was still higher than that of U 10 S 0 at other growth stages except for the seedling stage. ③ The protease activity of all fertilization treatments was higher than that of the control, and the protease activity was gradually enhanced with the continuous growth of corn and the increase in the ammonium sulfate ratio. The protease activity of the U 0 S 10 treatment was higher than that of the U 10 S 0 treatment at each growth stage of corn, which increased by 10.54 %-100 %. Soil sucrase activity ranged from 0.04 to 0.24 mg·(g·24 h) -1 , and those in the U 0 S 10 treatments were significantly higher than those in the U 10 S 0 and CK treatments at all growth stages, increasing by 20.32 % to 99.16 % and 24.31 % to 79.33 %, respectively. ④ The species abundance of bacteria and fungi in maize rhizosphere under all fertilization treatments were lower than those under the CK treatment, followed by those under the U 10 S 0 treatment. The species diversity trend of the bacterial community in the three treatments with ammonium sulfate replacing urea were U 8 S 2 &gt; U 0 S 10 &gt; U 6 S 4 , and that of fungi were U 6 S 4 &gt; U 8 S 2 &gt; U 0 S 10 . ⑤ The maize dry weight of the U 10 S 0 treatment and U 0 S 10 treatment was the highest, which was 39.47 % and 36.16 % higher than that of the CK treatment, respectively, but the difference was not significant. The Pearson model showed that the species abundance and diversity of soil rhizosphere fungi and bacteria were affected by relevant environmental variables, among which pH value and soil available nitrogen content were the most important factors affecting microbial diversity. In conclusion, when corn planting in calcareous brown soil, replacing urea with a certain proportion of ammonium sulfate can improve soil nutrients more than urea alone, which affects the growth and rhizosphere microbial community of corn to a certain extent and has a greater yield.

Objective: To identify socioeconomic factors influencing the presentation and outcomes of cutaneous head and neck squamous cell carcinoma (cHNSCC)., Study Design: Retrospective cohort study., Setting: Tertiary academic medical center with comprehensive cancer center., Methods: Patients treated for cHNSCC at a single institution between 2008 and 2022 were included. Demographic, socioeconomic data and disease characteristics were obtained from medical record abstraction. Outcome measures included tumor stage, number of distinct primaries, recurrence, and disease-related death. χ 2 and Mann-Whitney tests were implemented to evaluate clinicopathologic distributions across disease stages. Survival analyses were performed using Cox regression and Kaplan-Meier analysis., Results: A total of 346 patients met the inclusion criteria. The median age at presentation and length of follow-up was 70.8 and 3.1 years, respectively. The majority of the cohort was white, male, and English-speaking. 13.3% of patients were underinsured and 27.5% were immunosuppressed. Patients who presented with advanced disease were more likely to be underinsured (21.7% vs 9.6%, P = .006) and have a history of homelessness (8.5% vs 2.1%, P = .014). Immunosuppressed patients were more likely to be underinsured (P = .009). Insurance status (1.97 [1.06-3.66], P = .032) and immune status (2.35 [1.30-4.26], P = .005) were independently associated with worse recurrence-free survival., Conclusion: Socioeconomic factors that influence access to care, such as insurance status, are associated with cHNSCC disease stage and disease recurrence. These factors may impose barriers that delay diagnosis and treatment. This may result in worse disease-related outcomes and greater treatment-associated morbidity for certain patients., (© 2023 American Academy of Otolaryngology-Head and Neck Surgery Foundation.)

A common surgical disease, intervertebral disc degeneration (IVDD), is increasing at an alarming rate in younger individuals. Repairing damaged intervertebral discs (IVDs) and promoting IVD tissue regeneration at the molecular level are important research goals.Exosomes are extracellular vesicles (EVs) secreted by cells and can be derived from most body fluids. Mesenchymal stem cell-derived exosomes (MSC-exos) have characteristics similar to those of the parental MSCs. These EVs can shuttle various macromolecular substances, such as proteins, messenger RNAs (mRNAs), and microRNAs (miRNAs) and regulate the activity of recipient cells through intercellular communication. Reducing inflammation and apoptosis can significantly promote IVD regeneration to facilitate the repair of the IVD. Compared with MSCs, exosomes are more convenient to store and transport, and the use of exosomes can prevent the risk of rejection with cell transplantation. Furthermore, MSC-exo-mediated treatment may be safer and more effective than MSC transplantation. In this review, we summarize the use of bone marrow mesenchymal stem cells (BMSCs), adipose-derived mesenchymal stem cells (AMSCs), nucleus pulposus mesenchymal stem cells (NPMSCs), and stem cells from other sources for tissue engineering and use in IVDD. Here, we aim to describe the role of exosomes in inhibiting IVDD, their potential therapeutic effects, the results of the most recent research, and their clinical application prospects to provide an overview for researchers seeking to explore new treatment strategies and improve the efficacy of IVDD treatment., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Sentinel lymph node biopsy (SLNB) has been used across oncological specialties for prognostication, staging, and identification of occult nodal metastasis. Recent studies demonstrated the potential clinical utility of SLNB in oral cavity squamous cell carcinoma (OCSCC). Elective neck dissection is the current standard of care in early management of OCSCC with depth of invasion greater than 2-4 mm; however, majority of patients ultimately do not have nodal disease on final pathology. SLNB is an alternative procedure widely adopted in early cancer management in many oncological subspecialities. Several considerations such as depth of invasion, nodal mapping, histopathology methods, operator variability, postoperative complications, and advancement in preoperative and intraoperative imaging technology can guide the appropriate application to SLNB in OCSCC. The aim of this review is to discuss the current evidence for SLNB in the treatment of early stage OCSCC, imaging technologies that support SLNB procedures, and studies that are currently underway., (© 2022 Wiley Periodicals LLC.)

Background: Although osteosarcoma (OS) is the most common malignant bone tumor, the biological mechanism underlying its incidence and improvement remains unclear. This study investigated early diagnosis and treatment objectives using bioinformatics strategies and performed experimental verification., Methods and Results: The top 10 OS hub genes-CCNA2, CCNB1, AURKA, TRIP13, RFC4, DLGAP5, NDC80, CDC20, CDK1, and KIF20A-were screened using bioinformatics methods. TRIP13 was chosen for validation after reviewing literature. TRIP13 was shown to be substantially expressed in OS tissues and cells, according to Western blotting (WB) and quantitative real-time polymerase chain reaction data. Subsequently, TRIP13 knockdown enhanced apoptosis and decreased proliferation, migration, and invasion in U2OS cells, as validated by the cell counting kit-8 test, Hoechst 33,258 staining, wound healing assay, and WB. In addition, the levels of p-PI3K/PI3K and p-AKT/AKT in U2OS cells markedly decreased after TRIP13 knockdown. Culturing U2OS cells, in which TRIP13 expression was downregulated, in a medium supplemented with a PI3K/AKT inhibitor further reduced their proliferation, migration, and invasion and increased their apoptosis., Conclusions: TRIP13 knockdown reduced U2OS cell proliferation, migration, and invasion via a possible mechanism involving the PI3K/AKT signaling pathway., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Induction chemotherapy (IC) has been associated with a decreased risk of distant metastasis in locally advanced head and neck squamous cell carcinoma. However, its role in the treatment of oropharyngeal squamous cell carcinoma (OPSCC) is not well established., Methods: The outcomes of patients with OPSCC treated with IC followed by concurrent chemoradiation (CRT) were compared with the outcomes of those treated with CRT alone. The primary outcome was overall survival (OS), and the secondary end points were the times to locoregional and distant recurrence., Results: In an existing database, 585 patients met the inclusion criteria: 137 received IC plus CRT, and 448 received CRT. Most patients were positive for human papillomavirus (HPV; 90.9%). Patients receiving IC were more likely to present with a higher T stage, a higher N stage, and low neck disease. The 3-year OS rate was significantly lower in patients receiving IC (75.7%) versus CRT alone (92.9%). In a multicovariate analysis, receipt of IC (adjusted hazard ratio [aHR], 3.4; P < .001), HPV tumor status (aHR, 0.36; P = .002), and receipt of concurrent cetuximab (aHR, 2.7; P = .002) were independently associated with OS. The risk of distant metastasis was also significantly higher in IC patients (aHR, 2.8; P = .001), whereas an HPV-positive tumor status (aHR, 0.44; P = .032) and completion of therapy (aHR, 0.51; P = .034) were associated with a lower risk of distant metastasis. In HPV-positive patients, IC remained associated with distant metastatic progression (aHR, 2.6; P = .004) but not OS., Conclusions: In contrast to prior studies, IC was independently associated with worse OS and a higher risk of distant metastasis in patients with OPSCC. Future studies are needed to validate these findings., (© 2021 American Cancer Society.)

Ethnopharmacological Relevance: Simiao Wan (SMW) is a classical traditional Chinese medicine (TCM) prescription to empirically treat gouty arthritis (GA) in TCM clinical practice. However, the potential mechanisms of SMW on GA are not fully evaluated., Aim of Study: The aim of this study is to investigate the role of macrophage polarization in the anti-GA activity of SMW., Materials and Methods: Rats were intragastricly treated with SMW for consecutive 7 days. On day 6, monosodium urate (MSU) crystal-induced arthritis (MIA) in the ankle joint was prepared. Paw volume, gait score and histological score were measured. Levels of interleukin (IL)-1β and IL-10 in serum were detected by enzyme-linked immunosorbent assay. Expressions of inducible nitric oxide synthase (iNOS), arginase (Arg)-1, phosphorylated (p)-p65, inhibitor of nuclear factor (NF)-κB (IκB)α, p-signal transducer and transcription activator (STAT)3 and p-Janus kinase (JAK)2 in synovial tissues were determined by Western blot., Results: The elevated paw volume, gait score and histological score in MIA rats were significantly decreased by SMW treatment. Meanwhile, SMW significantly decreased the IL-1β level and increased the IL-10 level in serum of MIA rats. Furthermore, SMW reduced the expressions of iNOS, p-p65 and enhanced the expressions of Arg-1, IκBα, p-STAT3 and p-JAK2 in synovial tissues of MIA rats., Conclusions: The results suggest that SMW attenuates the inflammation in MIA rats through promoting macrophage M2 polarization., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Tocilizumab, an interleukin-6 receptor blocker, has been used in the inflammatory phase of COVID-19, but its impact independent of corticosteroids remains unclear in patients with severe disease., Methods: In this retrospective analysis of patients with COVID-19 admitted between March 2 and April 14, 2020 to a large academic medical center in New York City, we describe outcomes associated with tocilizumab 400 mg (without methylprednisolone) compared to a propensity-matched control. The primary endpoints were change in a 7-point ordinal scale of oxygenation and ventilator free survival, both at days 14 and 28. Secondary endpoints include incidence of bacterial superinfections and gastrointestinal perforation. Primary outcomes were evaluated using t-test., Results: We identified 33 patients who received tocilizumab and matched 74 controls based on demographics and health measures upon admission. After adjusting for illness severity and baseline ordinal scale, we failed to find evidence of an improvement in hypoxemia based on an ordinal scale at hospital day 14 in the tocilizumab group (OR 2.2; 95% CI, 0.7-6.5; p = 0.157) or day 28 (OR 1.1; 95% CI, 0.4-3.6; p = 0.82). There also was no evidence of an improvement in ventilator-free survival at day 14 (OR 0.8; 95% CI, 0.18-3.5; p = 0.75) or day 28 (OR 1.1; 95% CI, 0.1-1.8; p = 0.23). There was no increase in secondary bacterial infection rates in the tocilizumab group compared to controls (OR 0.37; 95% CI, 0.09-1.53; p = 0.168)., Conclusions: There was no evidence to support an improvement in hypoxemia or ventilator-free survival with use of tocilizumab 400 mg in the absence of corticosteroids. No increase in secondary bacterial infections was observed in the group receiving tocilizumab., Competing Interests: There are no conflict of interests to declare authors, except Anne-Catrin Uhlemann, MD, PhD has previously received NIH grant support rom Allergan, GSK and Merck unrelated to this project. Joan Bathon, MD has participated in, and been reimbursed for, a grant review panel for Gilead Sciences, unrelated to this project. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development or marketed products associated with this research to declare.

Several comprehensive studies have demonstrated that the NOTCH pathway is altered in a bimodal manner in head and neck squamous cell carcinoma (HNSCC). In a previous study, it was found that the NOTCH4/HEY1 pathway was specifically upregulated in HNSCC and promoted epithelial‑mesenchymal transition (EMT), and that HEY1 activation supported SOX2 expression. However, the interactions in this pathway have not yet been fully elucidated. The present study investigated the NOTCH4/HEY1/SOX2 axis in HNSCC using in vitro models and the Cancer Genome Atlas (TCGA) database. To explore the association, reporter and ChIP RT‑qPCR assays using SOX2‑overexpressing (SOX2‑OE) cells were performed. The association between NOTCH4 and HEY1 was examined in the same manner using HEY1‑overexpressing (HEY1‑OE) cells. The results of the in vitro experiments indicated that HEY1 promoted EMT in the HNSCC cells. Furthermore, the overexpression of HEY1 also promoted sphere formation and increased murine xenograft tumorigenicity. Reporter assays and ChIP RT‑qPCR experiments indicated that SOX2 regulated HEY1 expression via direct binding of the HEY1 promoter. HEY1 expression significantly correlated with SOX2 expression in primary lung SCC and other SCCs using the TCGA database. HEY1 also regulated NOTCH4 expression to create a positive reciprocal feedback loop. On the whole, the present study demonstrates that HEY1 expression in HNSCC is regulated via the promotion of SOX2 and promotes EMT. The NOTCH4/HEY1 pathway is specifically upregulated via a positive reciprocal feedback loop mediated by the HEY1‑medaited regulation of NOTCH4 transcription, and SOX2 correlates with HEY1 expression in SCC from other primary sites.

Background: The clinical impact of coronavirus disease 2019 (COVID-19) among people with HIV (PWH) remains unclear. In this retrospective cohort study of COVID-19, we compared clinical outcomes and laboratory parameters among PWH and controls., Methods: Sixty-eight PWH diagnosed with COVID-19 were matched 1:4 to patients without known HIV diagnosis, drawn from a study population of all patients who were diagnosed with COVID-19 at an academic urban hospital. The primary outcome was death/discharge to hospice within 30 days of hospital presentation., Results: PWH were more likely to be admitted from the emergency department than patients without HIV (91% vs 71%; P  = .001). We observed no statistically significant difference between admitted PWH and patients without HIV in terms of 30-day mortality rate (19% vs 13%, respectively) or mechanical ventilation rate (18% vs 20%, respectively). PWH had higher erythrocyte sedimentation rates than controls on admission but did not differ in other inflammatory marker levels or nasopharyngeal/oropharyngeal severe acute respiratory syndrome coronavirus 2 viral load estimated by reverse transcriptase polymerase chain reaction cycle thresholds., Conclusions: HIV infection status was associated with a higher admission rate; however, among hospitalized patients, PWH did not differ from HIV-uninfected controls by rate of mechanical ventilation or death/discharge to hospice., (© The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Alternative mRNA splicing increases protein diversity, and alternative splicing events (ASEs) drive oncogenesis in multiple tumor types. However, the driving alterations that underlie the broad dysregulation of ASEs are incompletely defined. Using head and neck squamous cell carcinoma (HNSCC) as a model, we hypothesized that the genomic alteration of genes associated with the spliceosome may broadly induce ASEs across a broad range of target genes, driving an oncogenic phenotype. We identified 319 spliceosome genes and employed a discovery pipeline to identify 13 candidate spliceosome genes altered in HNSCC using The Cancer Genome Atlas (TCGA) HNSCC data. Phenotypic screens identified amplified and overexpressed CPSF1 as a target gene alteration that was validated in proliferation, colony formation, and apoptosis assays in cell line and xenograft systems as well as in primary HNSCC. We employed knockdown and overexpression assays followed by identification of ASEs regulated by CPSF1 overexpression to identify changes in ASEs, and the expression of these ASEs was validated using RNA from cell line models. Alterations in expression of spliceosome genes, including CPSF1, may contribute to HNSCC by mediating aberrant ASE expression., Competing Interests: The authors have declared that no competing interests exist.

Background: Human papillomavirus (HPV)-associated oropharyngeal cancer is a disease clinically and biologically distinct from smoking-related head and neck squamous cell carcinoma (HNSCC). Despite its rapidly increasing incidence, the mutational landscape of HPV+ oropharyngeal squamous cell carcinoma (OPSCC) remains understudied., Methods: This article presents the first mutational analysis of the 46 HPV+ OPSCC tumors within the newly expanded cohort of 530 HNSCC tumors from The Cancer Genome Atlas. A separate exome sequencing analysis was also performed for 46 HPV+ OPSCCs matched to their normal lymphocyte controls from the Johns Hopkins University cohort., Results: There was a strikingly high 33% frequency of mutations within genes associated with chromatin regulation, including mutations in lysine methyltransferase 2C (KMT2C), lysine methyltransferase 2D (KMT2D), nuclear receptor binding SET domain protein 1 (NSD1), CREB binding protein (CREBBP), E1A-associated protein p300 (EP300), and CCCTC-binding factor (CTCF). In addition, the commonly altered genes phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α (PIK3CA) and fibroblast growth factor receptor 3 (FGFR3) showed distinct domain-specific hotspot mutations in comparison with their HPV- counterparts. PIK3CA showed a uniquely high rate of mutations within the helicase domain, and FGFR3 contained a predominance of hotspot S249C alterations that were not found in HPV- HNSCC., Conclusions: This analysis represents one of the largest studies to date of HPV+ OPSCC and lends novel insight into the genetic landscape of this biologically distinct disease, including a high rate of mutations in histone- and chromatin-modifying genes, which may offer novel therapeutic targets., (© 2019 American Cancer Society.)

Biomechanical methods may provide a novel way to understand blood accumulation in intracerebral hemorrhage (ICH). The current study presents the results of a biomechanical analysis of blood accumulation in ICH using a finite element analysis, with an emphasis on the pressure exerted by the mass effect of blood in early ICH. A two-dimensional finite model of the human brain parenchyma and the human ventricular system was developed and analyzed under two preloading conditions. The material properties of the human parenchyma were derived from previous reports. Ogden's theory was applied to describe the stress-strain association in soft tissue. The results of the present study indicated that maximal stress was located at the two ends of the hemorrhage cavity, with the majority of stresses distributed on the zone surrounding the bleed. The two load environments demonstrated similar stress distributions. The loads put on the detached edges were not less than the intracranial pressure (ICP) when the stress threshold was reached. The results of the present study suggest that the direction of blood accumulation can be determined by the shape of the initial blood mass. Mechanical factors (blood pressure and ICP) did not serve a definitive role in preventing blood from accumulating in the early stages of ICH. The present study may aid in understanding the effects of mechanical factors in blood accumulation and hemostasis in patients with early ICH.

Purpose: To explore the methods and characteristics of removable denture restoration in children with congenital missing teeth., Methods: From 1998 to 2018, 61 children aging 3 to 12 years old with congenital dental deficiency were treated with removable dentures. There were 59 males and 2 females. Removable denture prostheses were designed according to the characteristics of the children and the residual teeth in the mouth. There were 42 complete dentures in 21 cases, 40 single jaw complete dentures and maxillary removable partial dentures in 20 cases and 40 removable partial dentures in upper and lower jaw, totally 61 cases and 122 dentures., Results: After wearing the removable denture, the appearance, chewing and pronunciation of the children were improved significantly., Conclusions: Although the etiology of congenital tooth defect is not completely clear, children can have early denture restoration. It solves the difficulty of eating, improves appearance and pronunciation, and promotes growth and physical and mental health of children.

Intracerebral hemorrhage (ICH) may lead to physical and pathological damage and has been a focus of research for decades. Evaluating tensile damage caused by deformation in ICH is an important component of damage assessment for correct diagnosis and treatment. Traditional research on ICH paid little attention to quantified brain tissue damage resulting from mechanical factors, and only a few reported the mechanical properties of damaged brain tissue. The aim of the present study was to present an effective method that is able to evaluate the tissue damage degree in ICH, based on strain energy function. Two finite element analysis (FEA) models were analyzed: A three-dimensional (3D) model for tissue's tension experiment and a two-dimensional (2D) model for brain tissue's deformation in ICH. The polynomial fitting function of stress vs. stretch curve, which was derived from previous reports, was used in the FEA as the constitutive function of brain tissue. The present study demonstrated that white matter could be regarded as hyperelastic material when stretch was <1.343, and with stretch increasing, tissue injury exacerbated when stretch was >1.343. The strain energy loss was not linear in this process, and Neo-Hookean and Ogden model's results demonstrated a similar change in trend, but a difference in quantity. The results from 2D and 3D simulation, respectively, demonstrated the degree of damage according to the above dividing criteria and the possible distribution of tissue damage after ICH ictus. An analytical model from a biomechanical perspective for white matter injury in ICH may facilitate to improve clinical diagnosis and treatment.

Atmospheric temperature increases along with increasing atmospheric CO2 concentration. This is a major concern for agroecosystems. Although the impact of an elevated temperature or increased CO2 has been widely reported, there are few studies investigating the combined effect of these two environmental factors on plant-insect interactions. In this study, plant responses (phenological traits, defensive enzyme activity, secondary compounds, defense-related gene expression and phytohormone) of Cnaphalocrocis medinalis (Guenée) (Lepidoptera: Pyralidae) -susceptible and resistant rice under various conditions (environment, soil type, variety, C. medinalis infestation) were used to examine the rice-C. medinalis interaction. The results showed that leaf chlorophyll content and trichome density in rice were variety-dependent. Plant defensive enzyme activities were affected environment, variety, or C. medinalis infestation. In addition, total phenolic content of rice leaves was decreased by elevated CO2 and temperature and C. medinalis infestation. Defense-related gene expression patterns were affected by environment, soil type, or C. medinalis infestation. Abscisic acid and salicylic acid content were decreased by C. medinalis infestation. However, jasmonic acid content was increased by C. medinalis infestation. Furthermore, under elevated CO2 and temperature, rice plants had higher abscisic acid content than plants under ambient conditions. The adult morphological traits of C. medinalis also were affected by environment. Under elevated CO2 and temperature, C. medinalis adults had greater body length in the second and third generations. Taken together these results indicated that elevated CO2 and temperature not only affects plants but also the specialized insects that feed on them.

The Salmonella typhimurium trans-membrane FliF MS ring templates assembly of the rotary bacterial flagellar motor, which also contains a cytoplasmic C-ring. A full-frame fusion of FliF with the rotor protein FliG assembles rings in non-motile expression hosts. 3D electron microscopy reconstructions of these FliFFliG rings show three high electron-density sub-volumes. 3D-classification revealed heterogeneity of the assigned cytoplasmic volume consistent with FliG lability. We used residue coevolution to construct homodimer building blocks for ring assembly, with X-ray crystal structures from other species and injectisome analogs. The coevolution signal validates folds and, importantly, indicates strong homodimer contacts for three ring building motifs (RBMs), initially identified in injectisome structures. It also indicates that the cofolded domains of the FliG N-terminal domain (FliG&#95;N) with embedded α-helical FliF carboxy-terminal tail homo-oligomerize. The FliG middle and C-terminal domains (FliG&#95;MC) have a weak signal for homo-dimerization but have coevolved to conserve their stacking contact. The homodimers and their ring models fit well into the 3D reconstruction. We hypothesize that a stable FliF periplasmic hub provides a platform for FliG ring self-assembly, but the FliG&#95;MC ring has only limited stability without the C-ring. We also present a mechanical model for torque transmission in the FliFFliG ring.

Purpose: Recently, several comprehensive genomic analyses demonstrated NOTCH1 and NOTCH3 mutations in head and neck squamous cell carcinoma (HNSCC) in approximately 20% of cases. Similar to other types of cancers, these studies also indicate that the NOTCH pathway is closely related to HNSCC progression. However, the role of NOTCH4 in HNSCC is less well understood. Experimental Design: We analyzed NOTCH4 pathway and downstream gene expression in the TCGA data set. To explore the functional role of NOTCH4 , we performed in vitro proliferation, cisplatin viability, apoptosis, and cell-cycle assays. We also compared the relationships among NOTCH4, HEY1 , and epithelial-mesenchymal transition (EMT)-related genes using the TCGA data set and in vitro assays. Results: HEY1 is specifically upregulated in HNSCC compared with normal tissues in the TCGA data set. NOTCH4 is more significantly related to HEY1 activation in HNSCC in comparison with other NOTCH receptors. NOTCH4 promotes cell proliferation, cisplatin resistance, inhibition of apoptosis, and cell-cycle dysregulation. Furthermore, NOTCH4 and HEY1 upregulation resulted in decreased E-cadherin expression and increased Vimentin, Fibronectin, TWIST1 , and SOX2 expression. NOTCH4 and HEY1 expression was associated with an EMT phenotype as well as increased invasion and cell migration. Conclusions: In HNSCC, the NOTCH4-HEY1 pathway is specifically upregulated, induces proliferation and cisplatin resistance, and promotes EMT. Clin Cancer Res; 24(3); 619-33. ©2017 AACR ., (©2017 American Association for Cancer Research.)

Prokaryotic cells possess CRISPR-mediated adaptive immune systems that protect them from foreign genetic elements, such as invading viruses. A central element of this immune system is an RNA-guided surveillance complex capable of targeting non-self DNA or RNA for degradation in a sequence- and site-specific manner analogous to RNA interference. Although the complexes display considerable diversity in their composition and architecture, many basic mechanisms underlying target recognition and cleavage are highly conserved. Using cryoelectron microscopy (cryo-EM), we show that the binding of target double-stranded DNA (dsDNA) to a type I-F CRISPR system yersinia (Csy) surveillance complex leads to large quaternary and tertiary structural changes in the complex that are likely necessary in the pathway leading to target dsDNA degradation by a trans-acting helicase-nuclease. Comparison of the structure of the surveillance complex before and after dsDNA binding, or in complex with three virally encoded anti-CRISPR suppressors that inhibit dsDNA binding, reveals mechanistic details underlying target recognition and inhibition., (Published by Elsevier Inc.)

The specific mechanisms for epigenetic regulation of gene transcription remain to be elucidated. We previously demonstrated that hyperacetylation of histone H3K9 in promoter II of glioma cells promotes high transcription of the glial cell line-derived neurotrophic factor (GDNF) gene. This hyperacetylation significantly enhanced Egr-1 binding and increased the recruitment of RNA polymerase II (RNA POL II) to that region (P < 0.05). Egr-1 expression was abnormally increased in C6 glioma cells. Further overexpression of Egr-1 significantly increased Egr-1 binding to GDNF promoter II, while increasing RNA POL II recruitment, thus increasing GDNF transcription (P < 0.01). When the acetylation of H3K9 in the Egr-1 binding site was significantly reduced by the histone acetyltransferase (HAT) inhibitor curcumin, binding of Egr-1 to GDNF promoter II, RNA POL II recruitment, and GDNF mRNA expression were significantly downregulated (P < 0.01). Moreover, curcumin attenuated the effects of Egr-1 overexpression on Egr-1 binding, RNA POL II recruitment, and GDNF transcription (P < 0.01). Egr-1 and RNA POL II co-existed in the nucleus of C6 glioma cells, with overlapping regions, but they were not bound to each other. In conclusion, highly expressed Egr-1 may be involved in the recruitment of RNA POL II in GDNF promoter II in a non-binding manner, and thereby involved in regulating GDNF transcription in high-grade glioma cells. This regulation is dependent on histone hyperacetylation in GDNF promoter II.

Purpose: To evaluate the physical and mechanical properties of pure titanium castings cast by self- made FUS-invest dental investment, and evaluate casting accuracy., Methods: Seven pure titanium castings were cast by self-made FUS-invest zirconium investment and analyzed using servo hydraulic dynamic experiment system (JJG139-83 standard), scanning electron microscope and energy spectrum analysis. Thirty-eight crowns of pure titanium were cast by two different methods. One cast by FUS-invest zirconium embedding material was used for experiment and the other cast by phosphate embedding material was used as control. Casting accuracy was assessed through measuring the difference value d at the marginal marker points and distance between casting pieces of wall and working modes of casting were examined under microscope. Scanning electron microscope with energy-dispersive spectrum (EDS) was used to analyze the status of composition of the casting surface. SPSS 17.0 software package was used to investigate the difference of two groups., Results: ①Qualitative analysis of servo hydraulic dynamic experiment system showed various mechanical properties: elastic modulus (123.5±14.2) GPa, yield strength (569.3±16.5) MPa, tensile strength (668.4±16.1) MPa, elongation (4.5±0.2)%. EDS analysis of the fracture was observed at different depth (13, 25, 50, 350 μm) under the surface of pollution layer, a little Si and Fe with different atomic percentage was found but no Zr. ②No significant difference (P>0.05) was found between each group of four markers on the marginal fit, and internal fit, whereas significant difference (P<0.01) was found at different marker point., Conclusions: The mechanical properties of commercially pure titanium casting by self-made FUS-invest zirconium-based investment can meet the qualification of dental metal materials, although elongation was a little lower. Both the marginal adaptation and internal fit between the two groups had no significant difference. The mean marginal difference was 46 μm, the mean internal difference at axial angle was 56 μm and approximately 0 at axial wall.

Background/aims: Glial cell line-derived neurotrophic factor (GDNF) is an important factor promoting invasive glioma growth. This study was performed to reveal a unique mechanism of glioma cell proliferation and migration., Methods: Human U251 glioma cells were used to screen the optimal GDNF concentration and treatment time to stimulate proliferation and migration. MicroRNA (MiRNA) expression profiles were detected by microarray and confirmed by real-time polymerase chain reaction (PCR). The target genes of differentially expressed miRNAs were predicted by miRWalk, and those targeted by multiple miRNAs were screened with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. A regulatory miRNA network was constructed using ingenuity pathway analysis (IPA). Target gene expression of differentially expressed miRNAs was examined by real-time PCR or mRNA microarray., Results: The results show that 50 ng/mL GDNF for 24 h significantly promotes U251 glioma cell proliferation and migration (P < 0.05). Seven miRNAs (hsa-miR-194-5p, hsa-miR-152-3p, hsa-miR-205-5p, hsa-miR-629-5p, hsa-miR-3609, hsa-miR-183-5p, and hsa-miR-487b-3p) were significantly up-regulated after GDNF treatment (P < 0.05). These miRNAs are primarily involved in signal transduction, cell adhesion and cell cycle through mitogen-activated protein kinase (MAPK) signaling, focal adhesion and glioma signal pathways. Five of these miRNAs (hsa-miR-194-5p, hsa-miR-152-3p, hsa-miR-205-5p, hsa-miR-183-5p, and hsa-miR-487b-3p) co-regulate TP53 and Akt. mRNA expression levels of four genes co-targeted by two or more up-regulated miRNAs were significantly decreased after GDNF treatment (P < 0.05)., Conclusion: GDNF treatment of U251 glioma cells significantly increased the expression of seven miRNAs involved in cell adhesion and the cell cycle., (© 2017 The Author(s). Published by S. Karger AG, Basel.)

Enzymatic glycosylation of sterols/steroids with glycosyltransferase HP0421 shows protein plasticity on generation of configurationally rare steryl-α-glucosides. Investigation of trans-androsteronyl-α-glucoside on tamoxifen-treated MCF-7 breast cancer cells shows dose-dependent depression of cell viability and enhanced drug effectiveness, illustrating a new avenue for the production of novel steryl-α-glucosides with useful biological activities., (© 2016 John Wiley & Sons A/S.)

Subthreshold depression (StD) is a highly prevalent condition associated with increased service utilization and social morbidity. Nevertheless, due to limitations in current diagnostic systems that set the boundary for major depressive disorder (MDD), very few brain imaging studies on the neurobiology of StD have been carried out, and its underlying neurobiological mechanism remains unclear. In recent years, accumulating evidence suggests that the disruption of the default mode network (DMN), a network involved in self-referential processing, affective cognition, and emotion regulation, is involved in major depressive disorder. Using independent component analysis, we investigated resting-state default mode network (DMN) functional connectivity (FC) changes in two cohorts of StD patients with different age ranges (young and middle-aged, n = 57) as well as matched controls (n = 79). We found significant FC increase between the DMN and ventral striatum (key region in the reward network), in both cohorts of StD patients in comparison with controls. In addition, we also found the FC between the DMN and ventral striatum was positively and significantly associated with scores on the Center for Epidemiologic Studies Depression Scale (CES-D), a measurement of depressive symptomatology. We speculate that this enhanced FC between the DMN and the ventral striatum may reflect a self-compensation to ameliorate the lowered reward function., (Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.)

During virus assembly, HIV-1 Gag-Pol is packaged into virions via interaction with Pr55gag. Studies suggest that Gag-Pol by itself is incapable of virus particle assembly or cell release, perhaps due to the lack of a budding domain in the form of p6gag, which is truncated within Gag-Pol because of a ribosomal frameshift during Gag translation. Additionally (or alternatively), large molecular size may not support Gag-Pol assembly into virus-like particles (VLPs) or release from cells. To test these hypotheses, we constructed Gag-Pol expression vectors retaining and lacking p6gag, and then reduced Gag-Pol molecular size by removing various lengths of the Pol sequence. Results indicate that Gag-Pol constructs retaining p6gag were capable of forming VLPs with a WT HIV-1 particle density. Gag-Pol molecular size reduction via partial removal of the Pol sequence mitigated the Gag-Pol assembly defect to a moderate degree. Our results suggest that the Gag-Pol assembly and budding defects are largely due to a lack of p6gag, but also in part due to size limitation.

The clinical effect of electroacupuncture on depression is widely recognized. However, the signal transduction pathways and target proteins involved remain unclear. In the present study, rat models of chronic restraint stress were used to explore the mechanism by which electroacupuncture alleviates depression. Rats were randomly divided into control, model, and electroacupuncture groups. Chronic restraint stress was induced in the model and electroacupuncture groups by restraining rats for 28 days. In the electroacupuncture group, electroacupuncture pretreatment at Baihui (GV20) and Yintang (GV29) acupoints was performed daily (1 mA, 2 Hz, discontinuous wave, 20 minutes) prior to restraint for 28 days. Open field tests and body weight measurements were carried out to evaluate the depressive symptoms at specific time points. On day 28, the crossing number, rearing number, and body weights of the model group were significantly lower than those in the control group. Behavior test results indicated that rat models of depressive-like symptoms were successfully established by chronic restraint stress combined with solitary raising. On day 28, an isobaric tag for a relative and absolute quantitation-based quantitative proteomic approach was performed to identify differentially expressed proteins in hippocampal samples obtained from the model and electroacupuncture groups. The potential function of these differential proteins was predicted through the use of the Cluster of Orthologous Groups of proteins (COG) database. Twenty-seven differential proteins (uncharacteristic proteins expected) were selected from the model and electroacupuncture groups. In addition to unknown protein functions, COG are mainly concentrated in general prediction function, mechanism of signal transduction, amino acid transport and metabolism groups. This suggests that electroacupuncture improved depressive-like symptoms by regulating differential proteins, and most of these related proteins exist in nerve cells.

Grapevine red blotch-associated virus is a recently discovered plant monopartite gemini-like virus found in North American grapevines. Leaf discoloration and a decrease in fruit quality are associated with its infection. Two of its six open reading frames (ORFs), V2 and V3, are of unknown function and share no obvious homology with plant or viral genes. Transient expression of these ORFs in fusion with the green fluorescent protein demonstrated that the V2 protein localizes in the nucleoplasm, Cajal bodies, and cytoplasm; and the V3 protein localizes in various unidentified subnuclear bodies. Additionally, the V2 protein is redirected to the nucleolus upon co-expression with the nucleolus and Cajal body-associated protein Fib2.

This work demonstrates that a full laboratory-quality immunoassay can be run on a smartphone accessory. This low-cost dongle replicates all mechanical, optical, and electronic functions of a laboratory-based enzyme-linked immunosorbent assay (ELISA) without requiring any stored energy; all necessary power is drawn from a smartphone. Rwandan health care workers used the dongle to test whole blood obtained via fingerprick from 96 patients enrolling into care at prevention of mother-to-child transmission clinics or voluntary counseling and testing centers. The dongle performed a triplexed immunoassay not currently available in a single test format: HIV antibody, treponemal-specific antibody for syphilis, and nontreponemal antibody for active syphilis infection. In a blinded experiment, health care workers obtained diagnostic results in 15 min from our triplex test that rivaled the gold standard of laboratory-based HIV ELISA and rapid plasma reagin (a screening test for syphilis), with sensitivity of 92 to 100% and specificity of 79 to 100%, consistent with needs of current clinical algorithms. Patient preference for the dongle was 97% compared to laboratory-based tests, with most pointing to the convenience of obtaining quick results with a single fingerprick. This work suggests that coupling microfluidics with recent advances in consumer electronics can make certain laboratory-based diagnostics accessible to almost any population with access to smartphones., (Copyright © 2015, American Association for the Advancement of Science.)

Here we describe a low-cost mobile device that combines cell-phone and satellite communication technologies with fluid miniaturization techniques for performing all essential functions of enzyme-linked immunosorbent assay (ELISA). Disease-specific antigens are immobilized on the microfluidic surface, and disease specific antibodies are captured on the surface and visualized with silver-gold amplification. The diagnostic result is automatically determined by the device by measuring the absorbance through the silver-gold amplification in the microchannel. The results are displayed for the user and are synchronized to a remote patient record. The overall system aims to be portable, robust, low-power, and fully utilize the ability of mobile devices for bringing better health care to resource poor areas.

As an editor of dental journals, the author found that some inappropriate writing and mistakes existed in many articles, which reduced the quality of the published papers. The problems can be divided into three categories: irregular terminology; not concise, inaccurate description; improper use of punctuation and title code. They were illustrated respectively in this article for readers to avoid these mistakes in the future.

Based on the 7-year field experiment on the dryland of east Gansu of Northwest China in 2005-2011, this paper analyzed the variations of soil moisture content, bulk density, and nutrients content at harvest time of winter wheat and of the grain yield under no-tillage and conventional tillage and five fertilization modes, and approached the effects of different tillage and fertilization modes on the soil water storage and conservation, soil fertility, and grain yield under winter wheat/ spring corn rotation. In 2011, the soil moisture content in 0-200 cm layer and the soil bulk density and soil organic matter and available nitrogen and phosphorus contents in 0-20 cm and 20-40 cm layers under different fertilization modes were higher under no-tillage than under conventional tillage. Under the same tillage modes, the contents of soil organic matter and available nitrogen and available phosphorus were higher under the combined application of organic and inorganic fertilizers, as compared with other fertilization modes. The soil available potassium content under different tillage and fertilization modes decreased with years. The grain yield under conventional tillage was higher than that under no-tillage. Under the same tillage modes, the grain yield was the highest under the combined application of organic and inorganic fertilizers, and the lowest under no fertilization. In sum, no-tillage had the superiority than conventional tillage in improving the soil water storage and conservation and soil fertility, and the combined application of organic and inorganic fertilizers under conventional tillage could obtain the best grain yield.

High-risk human papillomavirus (HPV) is an established cause of head and neck carcinomas arising in the oropharynx. The presence of HPV has also been reported in some carcinomas arising in the sinonasal tract, but little is known about their overall incidence or their clinicopathologic profile. The surgical pathology archives of The Johns Hopkins Hospital were searched for all carcinomas arising in the sinonasal tract from 1995 to 2011, and tissue microarrays were constructed. p16 immunohistochemical analysis and DNA in situ hybridization for high-risk types of HPV were performed. Demographic and clinical outcome data were extracted from patient medical records. Of 161 sinonasal carcinomas, 34 (21%) were positive for high-risk HPV DNA, including type 16 (82%), type 31/33 (12%), and type 18 (6%). HPV-positive carcinomas consisted of 28 squamous cell carcinomas and variants (15 nonkeratinizing or partially keratinizing, 4 papillary, 5 adenosquamous, 4 basaloid), 1 small cell carcinoma, 1 sinonasal undifferentiated carcinoma, and 4 carcinomas that were difficult to classify but exhibited adenoid cystic carcinoma-like features. Immunohistochemistry for p16 was positive in 59/161 (37%) cases, and p16 expression strongly correlated with the presence of HPV DNA: 33 of 34 (97%) HPV-positive tumors exhibited high p16 expression, whereas only 26 of 127 (20%) HPV-negative tumors were p16 positive (P<0.0001). The HPV-related carcinomas occurred in 19 men and 15 women ranging in age from 33 to 87 years (mean, 54 y). A trend toward improved survival was observed in the HPV-positive group (hazard ratio=0.58, 95% confidence interval [0.26, 1.28]). The presence of high-risk HPV in 21% of sinonasal carcinomas confirms HPV as an important oncologic agent of carcinomas arising in the sinonasal tract. Although nonkeratinizing squamous cell carcinoma is the most common histologic type, there is a wide morphologic spectrum of HPV-related disease that includes a variant that resembles adenoid cystic carcinoma. The distinctiveness of these HPV-related carcinomas of the sinonasal tract with respect to risk factors, clinical behavior, and response to therapy remains to be clarified.

Recent accumulating evidence has indicated that ZNF804A (zinc finger protein 804A) may be one of the most robustly implicated genes in schizophrenia. In this report, we examined ZNF804A single nucleotide polymorphisms (SNPs) encompassing exon 4 by performing an association study that used a Han Chinese sample comprised of 492 schizophrenia patients and 516 healthy control subjects. A meta-analysis based on previous studies was also performed. For markers rs4667000 and rs1366842, significant differences in allele frequencies were found between cases and controls (Mantel-Haenszel corrected P=0.014 and P=0.025, respectively). Analysis of haplotype rs61739290-rs1366842 showed significant association with schizophrenia (global P=0.0018). Moreover, several other two-, three-, and four-SNP tests of haplotype association were also significant. A meta-analysis comprised of studies that utilized sample sets of either European and/or Han Chinese origin revealed statistically significant associations for two SNPs (rs1366842, P=0.002; and rs3731834, P=0.03) and schizophrenia. In addition, we observed a significant association between marker rsl344706 and schizophrenia (P<1.0×10(-5)) in combined populations. When we separately analyzed the studies by population, consistent and significant differences were found between cases and controls both in the European samples (P<1.0×10(-4)) and in the Chinese samples (P=0.03). In summary, we have added new evidence supporting the association between ZNF804A and schizophrenia in our Han Chinese sample. Further functional exploration of ZNF804A will greatly help us to elucidate the pathogenesis of schizophrenia and find promising new approaches for the treatment of this disorder., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Objective: To study the corrosion resistance of casted titanium by plasma nitriding and TiN-coated compound treatments in the artificial saliva with different fluoride concentrations and to investigate whether compound treatments can increase the corrosion resistance of casted titanium., Methods: Potentiodynamic polarization technique was used to depict polarization curve and to measured the current density of corrosion (Icorr) and the electric potential of corrosion (Ecorr) of casted titanium (Group A) and casted titanium by compound treatments (Group B) in the artificial saliva with different fluoride concentrations. After electrochemical experiment, the microstructure was observed by scanning electron microscope (SEM)., Results: The Icorrs of Group A and B in the artificial saliva of different fluoride concentrations were (1530.23 ± 340.12), (2290.36 ± 320.10), (4130.52 ± 230.17) nA and (2.62 ± 0.64), (7.37 ± 3.59), (10.76 ± 6.05) nA, respectively. The Ecorrs were (-0.93 ± 0.10), (-0.89 ± 0.21), (-0.57 ± 0.09) V and (-0.21 ± 0.04), (-0.17 ± 0.03), (-0.22 ± 0.03) V, respectively.The Icorrs of Group B were significantly lower (P < 0.01)than that of Group A. The Icorrs increased significantly with the increasing of fluoride concentrations (P < 0.01). The Ecorrs of Group B were significantly higher than that of Group A (P < 0.01). The SEM confirmed the microstructure in the casted titanium was much severely than that in Group B, the microstructure in Group A and B corroded more and more heavily with increasing of fluoride concentrations., Conclusions: The increase of fluoride concentrations influence the corrosion resistance of both treated and untreated casted titanium negatively, but plasma nitriding and TiN-coated compound treatments can significantly increase the corrosion resistance of casted titanium.

Purpose: To study the bonding strength between the FCVA (filtered cathode vacuum arc) film and the titanium substrate., Methods: According to the Engineer Manual of Germany (VDI3198), the indentation test was applied to evaluate the bonding strength between the FCVA film and the titanium substrate. The structure of the FCVA film and the interface between the film and the substrate were observed by means of scanning electron microscope(SEM)., Results: The fracture pattern of the film was classified as HF3 at the load of 400N, the bonding strength was enough between the FCVA film and the titanium substrate. SEM photograph showed the thickness of the FCVA film was about 1.2μm equably and the film bonded to the substrate well. CONCLSION: The bonding strength between the FCVA film and the titanium substrate was enough to meet clinical demand.

Objective: To determine the optimal composition of a self-developing investment material by measuring physical and mechanical properties of mould., Methods: L(9) (3(4)) orthogonal design was adopted. One hundred and fifty specimens with the size of 80 mm × 20 mm × 20 mm were prepared to measure the atmospheric temperature bending strength, high temperature bending strength and residual bending strength. Nine specimens with the size of 5 mm diameter 25 mm heigh were prepared to survey the thermal expansion curve from ambient temperature to 1150°C., Results: Strengths were greatly affected by fine powder proportion in refractory and water/powder ratio. When the content of fine powder was 35% and water/powder ratio was 1:7.5, adequate atmospheric temperature strength and high temperature strength could be achieved. Moreover, the residual strength was moderate. The thermal extension curves of specimens in experiment group were almost similar. And the average linear expansion coefficient was (4 ∼ 5) × 10(-6)/°C., Conclusions: The three kinds of bending strength of self-developing investment material are compared with commercialized investment material for titanium casting when water/powder ratio and the content of fine powder are carefully controlled.

Recently, evidence of linkage of schizophrenia to chromosome 13q22-q34 has been demonstrated in multiple studies. Based on structure and function, EFNB2 may be considered as a compelling candidate gene for schizophrenia on chromosome 13q33. We genotyped three single-nucleotide polymorphisms (SNPs: rs9520087, rs11069646, and rs8000078) in this region in 846 Han Chinese subjects (477 cases and 369 controls). Significant association between an allele of marker rs9520087 and schizophrenia was found. Furthermore, since no LD was observed in the three SNPs linkage disequilibrium estimation, all three SNPs were used in multiple SNPs haplotype analysis, and a strongly significant difference was found for the common haplotype TTC. Overall our findings indicate that EFNB2 gene may be a candidate susceptibility gene for schizophrenia in the Han Chinese population, and also provide further support for the potential importance of the NMDA receptor pathway in the etiology of schizophrenia., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

In this paper, the effects of nitrogen (N) fertilization on the wheat leaf photosynthesis under long-term elevated atmospheric CO2 concentration (760 micromol x mol(-1)) was studied, based on the measurements of photosynthetic gas exchange parameters and light intensity-photosynthetic rate response curves at jointing stage. Under the long-term elevated atmospheric CO2 concentration, applying sufficient N could increase the wheat leaf photosynthetic rate (Pn), transpiration rate (Tr), and instantaneous water use efficiency (WUEi). Comparing with those under ambient atmospheric CO2 concentration, the Po and WUEi under the elevated atmospheric CO2 concentration increased, while the stomatal conductance (Gs) and intercellular CO2 concentration (Ci) decreased. With the increase of light flux intensity, the Pn and WUEi under the elevated atmospheric CO2 concentration were higher those under ambient atmospheric CO2 concentration, Gs was in adverse, while Ci and Tr had less change. At high fertilization rate of N, the Gs was linearly positively correlated with Pn, Tr, and WUEi, and the Gs and Ci had no correlation with each other under the elevated atmospheric CO2 concentration but negatively correlated under ambient atmospheric CO2 concentration. At low fertilization rate of N, the Gs had no correlations with Pn and WUEi but linearly positively correlated with Ci and Tr. It was suggested that under the elevated atmospheric CO2 concentration, the wheat leaf Pn at low N fertilization rate was limited by non-stomatal factor.

Obstructive sleep apnea and hypopnea syndrome (OSAHS) is characterized by obstruction of upper airway and respiratory disturbance, excessive daytime sleepiness and tiredness.The possible causes are obesity, hypertension, and upper airway malformations,etc. The location and degree of upper airway structure narrowing in patients have been investigated in many ways, such as X-ray, multi-slices spiral computed tomography, etc. With multi-planar reconstruction technique,3-dimensional construction of upper airway can be established which shows the delicate changes of the upper airway structure. Mandibular advancement device is known as an effective treatment on mild and moderate OSAHS. By advancing the mandible forward, it can increase the space of upper airway, especially the oropharyngeal space. This paper reviewed the methods of investigating on OSAHS and the change of upper airway structure in OSAHS patients treated with mandibular advancement device. Supported by Combined Research Fund of Bureau of Health, Yunan Province and Kunming Medical College(Grant No.2009CD205).

Recently, the DAOA gene locus on chromosome 13q32-q34 has been implicated in the etiology of schizophrenia. We genotyped three single-nucleotide polymorphisms (SNPs: rs778294, rs779293 and rs3918342) in this region in 126 Chinese family trios. In this study, we have identified statistically significant transmission disequilibrium in two markers rs778293 (P=0.01) and rs3918342 (P=0.02), and a highly significant under-transmission between haplotype CAT (P=0.0005) and schizophrenia. The results provide further evidence to support that DAOA gene locus is involved in conferring susceptibility to schizophrenia.

Partially sintered 3 mol % yttria-stabilized tetragonal zirconium dioxide (ZrO(2), zirconia) polycrystal (3Y-TZP) ceramics are used in dental posterior restorations with computer-aided design-computer-aided manufacturing (CAD/CAM) techniques. High strength is acquired after sintering, but shape distortion of preshaped compacts during their sintering is inevitable. The aim of this study is to fabricate new machinable ceramic composites with strong mechanical properties that are fit for all-ceramic dental restorations. Aluminum oxide (Al(2)O(3))-coated 3Y-TZP powders were first prepared by the heterogeneous precipitation method starting with 3Y-TZP, Al(NO(3))(3) . 9H(2)O, and ammonia, then amorphous boron nitride (BN) was produced and the as-received composite powders were coated via in situ reaction with boric acid and urea. Transmission electron microscopy (TEM) and X-ray diffraction (XRD) were used to analyze the status of Al(2)O(3)-BN on the surface of the 3Y-TZP particles. TEM micrographs show an abundance of Al(2)O(3) particles and amorphous BN appearing uniformly on the surface of the 3Y-TZP particles after the coating process. The size of the Al(2)O(3) particles is about 20 nm. The XRD pattern shows clearly the peak of amorphous BN among the peaks of ZrO(2).

Objective: To investigate the effect of self-developing investment (FUS-invest) on the reactive layer of titanium castings., Methods: Three 10 mm x 10 mm x 1 mm pure titanium castings were founded using FUS-invest. Metallographical structure of reactive layer was observed. X-ray diffraction (XRD) and scanning electron microscope with energy-dispersive spectrum (EDS) were used to analyze the status of composition of the casting surface. Micro-Vickers hardness was measured., Results: The metallograph indicated that the reactive layer was composed of coarse flake-shaped alpha phase of grains. The value of micro-Vickers hardness with the range 243 to 314 MPa had not significantly difference under the depth of 105 microm beneath the surface. The XRD pattern clearly showed the peaks of ZrO2, SiO2, Mg2TiO4 and TiO2. EDS analysis demonstrated that the main elements were Al, Si, Zr and Cl., Conclusion: FUS-invest is suited for pure titanium casting because of the thin reactive layer and less change to metallographical structure.

Epidermal growth factor (EGF) receptor-mediated cell migration plays a vital role in invasion of many tumor types. EGF receptor ligands increase invasiveness in vivo, but it remains unclear how consequent effects on intrinsic cell motility behavior versus effects on extrinsic matrix properties integrate to result in net increase of translational speed and/or directional persistence of migration in a 3D environment. Understanding this convolution is important for therapeutic targeting of tumor invasion, as key regulatory pathways for intrinsic versus extrinsic effects may not be coincident. Accordingly, we have undertaken a quantitative single-cell imaging study of glioblastoma cell movement in 3D matrices and on 2D substrata across a range of collagen densities with systematic variation of protease-mediated matrix degradation. In 3D, EGF induced a mild increase in cell speed and a strong increase in directional persistence, the latter depending heavily on matrix density and EGF-stimulated protease activity. In contrast, in 2D, EGF induced a similarly mild increase in speed but conversely a decrease in directional persistence (both independent of protease activity). Thus, the EGF-enhanced 3D tumor cell migration results only partially from cell-intrinsic effects, with override of cell-intrinsic persistence decrease by protease-mediated cell-extrinsic reduction of matrix steric hindrance.