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Moisture variation and fissure formation of rice kernels during multi-stage intermittent drying (MSID) were simulated and analyzed based on the experimental data obtained in a laboratory-scale infr...

Osteosarcoma (OS) is the most common bone tumor in children and adolescents and is characterized by high metastatic and recurrence rates. In the past, it has been shown that microRNAs may play critical roles in hypoxia-related OS proliferation and invasion. However, the mechanisms by which OS cells acquire this malignant phenotype have remained largely unknown. In the present study, we report that let-7f-5p and TARBP2 were expressed in lower amounts in human OS cell lines when compared with the hFOB normal human osteoblastic cell line; however, both types of cells were repressed by hypoxia. let-7f-5p and TARBP2 significantly inhibited the proliferation and invasion of OS cells. Furthermore, TARBP2 as a downstream and functional target of let-7f-5p regulated the expression of let-7f-5p, and there was a regulatory feedback loop between let-7f-5p and TARBP2. This loop reduced the expression of let-7f-5p and TARBP2 in OS cells to a very low level, which was induced by hypoxia. Furthermore, the hypoxia-induced let-7f-5p/TARBP2 feedback loop contributed to activation of the Wnt signaling pathway. Taken together, our data clearly showed that the feedback loop between let-7f-5p and TARBP2 induced by the hypoxia-promoted OS cell malignant phenotype increased with activation of the Wnt signaling pathway.

Objective To describe delivery of recommended HIV care and work satisfaction among infectious disease (ID) physicians, non-ID physicians, nurse practitioners (NPs), and physician assistants (PAs). Data sources Medical Monitoring Project 2013-2014 HIV Provider Survey. Study design Population-based complex sample survey. Data collection/analysis methods We surveyed 2208 HIV care providers at 505 US HIV care facilities and computed weighted percentages of provider characteristics, stratified by provider type. Rao-Scott chi-square tests and logistic regression used to compare characteristics of ID physicians with each other provider type. Principal findings The adjusted provider response rate was 64 percent. Among US HIV care providers, 45 percent were ID physicians, 35 percent non-ID physicians, 15 percent NPs, and 5 percent PAs. Satisfaction with administrative burden was lowest among non-ID physicians (27 percent). Compared with ID physicians, satisfaction with remuneration was lower among non-ID physicians and higher among NPs (37, 28, and 51 percent, respectively). NPs were more likely than ID physicians to report performing four of six services that are key to providing comprehensive HIV care, but more NPs planned to leave clinical practice within 5 years (19 vs 7 percent). Conclusion Addressing physician dissatisfaction with remuneration and administrative burden could help prevent a provider shortage. Strengthening the role of NPs may help sustain a high-quality workforce.

Objective The activation of NLRP3 inflammasome is critical for rheumatoid arthritis (RA), however, the role of gasdermin D (GSDMD), a newly identified pyroptosis executioner downstream of NLRP3/ASC/Caspase-1, in RA has not been well defined. Methods Genetically susceptible mice (DBA/1J) are immunized with a type II bovine collagen emulsion in complete Freund's adjuvant (CFA). Peripheral blood neutrophils were isolated from healthy volunteers and RA patients; cells were treated with serum from RA patients. The activation of GSDMD was analyzed by confocal and western blot. Proinflammatory cytokines in joint of mice were detected by qPCR and ELISA. Results The expression of cleaved GSDMD-N terminal in peripheral blood neutrophils from RA patients and the expression of GSDMD-N was positively correlated with the level of IL-1β and IL-18 from RA patients. GSDMD was required for the pathogenesis of RA, and GSDMD inhibition disulfiram significantly suppressed proinflammatory cytokines production and joint damage, leading to reduced arthritis severity score and loss of cartilage in collagen-induced arthritis (CIA) mouse model. Mechanistically, the activation of GSDMD significantly promotes neutrophil extracellular traps (NETs), which are highly immunogenic and decorated with HMGB1 and MMPs. Furthermore, GSDMD-dependent NETs formation facilitated fibroblast-like synoviocytes (FLS) activation and proliferation, driving cartilage and bone destruction, and promoting disease activity in RA. Conclusions GSDMD-dependent NETs formation promotes FLS activation during RA pathogenesis.

As a subclass of noncoding RNAs, circular RNAs (circRNAs) have been demonstrated to play a critical role in regulating gene expression in eukaryotes. Recent studies have revealed the pivotal functions of circRNAs in cancer progression. Nevertheless, how circRNAs participate in osteosarcoma (OS) development and progression are not well understood. In the present study, we identified a circRNA circFAT1(e2) with an upregulated expression level in OS tissues. By functional experiments, we found that circFAT1(e2) depletion significantly suppressed the proliferation and reduced migration in OS. In terms of mechanism, we found that circFAT1(e2) inhibited miR-181b, while miR-181b targeted HK2. By releasing the inhibition of miR-181b on HK2 expression, leading to attenuated OS progression. Mechanistic investigations suggested that circFAT1(e2) served as a competing endogenous RNA (ceRNA) of miR-181b to enhance HK2 expression. On the whole, our study indicated that circFAT1(e2) exerted oncogenic roles in OS and suggested the circFAT1(e2)/miR-181b/HK2 axis might be a potential therapeutic target.

Osteosarcoma is a malignant tumor that seriously threatens human health. Numerous studies have pointed out the potential of long noncoding RNAs (lncRNAs) as new therapeutic targets for various human cancers. Therefore, we mainly investigate whether there is a new type of lncRNA pathway involved in regulating the development of osteosarcoma. The present study shows the higher expression levels of LINC00511 correlates to a shorter overall survival and disease-free survival time in patients with sarcoma. It is significantly higher in the clinical samples of osteosarcoma patients than in normal adjacent cancer tissues. We used U373 and SW1353 osteosarcoma cells to determine the effect of lncRNA on osteosarcoma proliferation and invasion by knocking down LINC00511 compared with controls. The results showed that the LINC00511 knockdown significantly suppressed osteosarcoma cell growth and metastasis. To explore the mechanisms of LINC00511 in osteosarcoma, we tested whether LINC00511 could competitively stimulate miR-185-3p and regulate E2F1 as a ceRNA. The results showed that LINC00511 knockdown induced the increased level of miR-185-3p levels; however, miR-185-3p overexpression suppressed LINC00511 levels. In addition, the results also demonstrated that LINC00511 knockdown or miR-185-3p overexpression could reduce E2F1 levels in osteosarcoma cells. The dual-luciferase reporter assay verified the direct interaction between miR-185-3p and LINC00511 or E2F1. These results may offer an explanation of how the lncRNA affects the progression of osteosarcoma, and our study shows that LINC00511 can be a novel biomarker in osteosarcoma.

Supplemental Digital Content is available in the text, Osteoporosis (OP) is a disease characterized by bone mass loss, bone microstructure damage, increased bone fragility, and easy fracture. The molecular mechanism underlying OP remains unclear. In this study, we identified 217 genes associated with OP, and formed a gene set [OP-related genes gene set (OPgset)]. The highly enriched GOs and pathways showed OPgset genes were significantly involved in multiple biological processes (skeletal system development, ossification, and osteoblast differentiation), and several OP-related pathways (Wnt signaling pathway, osteoclast differentiation, steroid hormone biosynthesis, and adipocytokine signaling pathway). Besides, pathway crosstalk analysis indicated three major modules, with first module consisted of pathways mainly involved in bone development-related signaling pathways, second module in Wnt-related signaling pathway and third module in metabolic pathways. Further, we calculated degree centrality of a node and selected ten key genes/proteins, including TGFB1, IL6, WNT3A, TNF, PTH, TP53, WNT1, IGF1, IL10, and SERPINE1. We analyze the K-core and construct three k-core sub-networks of OPgset genes. In summary, we for the first time explored the molecular mechanism underlying OP via network- and pathway-based methods, results from our study will improve our understanding of the pathogenesis of OP. In addition, these methods performed in this study can be used to explore pathogenesis and genes related to a specific disease.

// Shaohua Du 1, * , Jingxiong Li 2, * , Chonghua Du 3 , Zhongming Huang 4 , Guangnan Chen 1 , Weiqi Yan 1 1 Department of Orthopedic Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310008, China 2 Department of Obstetrics and Gynecology, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China 3 School of Economics, Dongbei University of Finance and Economics, Dalian, 116025, China 4 Department of Orthopaedic Surgery, Xiaoshan Chinese Medical Hospital, Hangzhou, 311201, China * These authors contributed equally to this work Correspondence to: Weiqi Yan, email: zeyanweiqi@163.com Keywords: superparamagnetic iron oxide particles, apoptosis, autophagy, osteosarcoma, spinning magnetic field Received: April 01, 2016 Accepted: December 12, 2016 Published: December 23, 2016 ABSTRACT The toxicity of superparamagnetic iron oxide nanoparticles (SPIONs) is still a vital topic of debate and the mechanisms remain unclear. In the present study, overdose SPIONs could induce osteosarcoma cell death and the effects were exaggerated when combined with spinning magnetic field (SMF). In the combination group, mitochondrial transmembrane potential decrease more obviously and reactive oxygen species (ROS) was found to generate much higher in line with that of the apoptosis ratio. Meantime, amount of autophagy was induced. Inhibiting the autophagy generation by 3-methyladenine (3-MA) increase cell viability but decrease the caspase 3/7 and caspase 8 activities in combination groups, and inhibiting apoptosis took the same effect. In the end, the SPIONs effects on xenograft mice was examed by intratumoral injection. The result showed that the combination group could greatly decrease the tumor volume and prolong the lifespan of mice. In sum, the result indicated that overdose SPIONs induced ROS generation, and excessive ROS induced by combination of SPIONs and SMF contribute to autophagy formation, which play a apoptosis-promoting role that formed as a platform to recruits initiate the caspase activities.

Osteoporosis (OP) is a systemic skeletal disorder with the characteristics of bone mass reduction and microarchitecture deterioration, resulting in bone fragility and increased fracture risk. A reduction in the osteoblast-differentiation of bone marrow mesenchymal stem cells (BMSCs) is considered as a basic pathogenesis of osteoporosis. miRNAs play a substantial role in the development and differentiation of BMSCs. In the present study, we found that miR-1-3p was significantly downregulated in the bones of Chinese osteoporotic patients (n = 29). Secreted frizzled-related protein 1 (SFRP1) was predicted as a target gene of miR-1-3p via the TargetScan and PicTar softwares and validated by dual-luciferase reporter assays. The findings revealed that the expression of SFRP1 was inversely correlated with miR-1-3p in osteoporotic patients. We induced mouse MSCs (mMSCs) to osteogenesis or adipogenesis and found that miR-1-3p was upregulated during osteogenesis but downregulated during adipogenesis. The overexpression of miR-1-3p stimulated osteogenesis and inhibited adipogenesis of mMSCs. In addition, ovariectomized (OVX) mice were tested and the function of miR-1-3p in vivo was explored. Immunohistochemistry and histomorphometric assays showed that in vivo inhibition of miR-1-3p increased the expression level of SFRP1 and reduced bone formation and bone mass. Furthermore, tartrate-resistant acid phosphatase (TRAP) staining indicated that the in vivo suppression of miR-1-3p promoted osteoclast activity, suggesting that miR-1-3p may influence bone mass by regulating bone resorption. It can be concluded that miR-1-3p plays a pivotal role in the pathogenesis of osteoporosis via targeting SFRP1 and may be a potential therapeutic target for osteoporosis.

The prevalence of diagnosed human immunodeficiency virus (HIV) infection among Hispanics/Latinos in the United States is approximately twice that of non-Hispanic whites (1). Barriers to, and experiences with, medical care have been found to vary by sex (2). Describing characteristics of Hispanics/Latinos in care by sex can help identify disparities and inform delivery of tailored services to this underserved population. Data from the 2013 and 2014 cycles of the Medical Monitoring Project (MMP) were analyzed to describe demographic, behavioral, and clinical characteristics among Hispanics/Latinos by sex. MMP is an annual cross-sectional, nationally representative surveillance system that, during 2013-2014, collected information about behaviors, medical care, and clinical outcomes among adults receiving outpatient HIV care. Hispanic/Latina women were significantly more likely than were men to live in poverty (78% versus 54%), report not speaking English well (38% versus 21%), and receive interpreter (27% versus 16%), transportation (35% versus 21%), and meal (44% versus 26%) services. There were no significant differences between Hispanic/Latino women and men in prescription of antiretroviral therapy (ART) (95% versus 96%) or sustained viral suppression (68% versus 73%). Although women faced greater socioeconomic and language-related challenges, the clinical outcomes among Hispanic/Latina women were similar to those among men, perhaps reflecting their higher use of ancillary services. Levels of viral suppression for Hispanics/Latinos are lower than those found among non-Hispanic whites (3) and lower than the national prevention goal of at least 80% of persons with diagnosed HIV infection. Providers should be cognizant of the challenges faced by Hispanics/Latinos with HIV infection in care and provide referrals to needed ancillary services.

Bone nonunion treatments pose a challenge in orthopedics. This study investigated the joint effects of using mesenchymal stem cell (MSC) sheets with local injection of stromal cell-derived factor-1 (SDF-1) on bone formation. In vitro, we found that migration of MSCs was mediated by SDF-1 in a dose-dependent manner. Moreover, stimulation with SDF-1 had no direct effect on the proliferation or osteogenic differentiation of MSCs. Furthermore, the results indicated elevated expression levels of bone morphogenetic protein 2, alkaline phosphatase, osteocalcin, and vascular endothelial growth factor in MSC sheets compared with MSCs cultured in medium. New bone formation in fractures was evaluated by X-ray, micro-computed tomography (micro-CT), hematoxylin and eosin (H&E) staining, Safranin-O staining, and immunohistochemistry in vivo. In the rat bone fracture model, the MSC sheets transplanted into the injured site along with injection of SDF-1 showed significantly more new bone formation within the gap. Moreover, at 8 weeks, complete bone union was obtained in this group. In contrast, the control group showed nonunion of the bone. Our study suggests a new strategy involving the use of MSC sheets with a local injection of SDF-1 for hard tissue reconstruction, such as the healing of nonunions and bone defects.

Reactive oxygen species (ROS)-induced chondrocytes apoptosis plays a key role in osteoarthritis (OA) pathogenesis. Uncoupling protein 4 (UCP4) can protect cells against oxidative stress via reducing ROS production and cell apoptosis. Here, silencing of UCP4 in primary chondrocytes significantly inhibited cell survival, but induced ROS production and cell apoptosis. UCP4 mRNA of cartilage tissues was decreased in osteoarthritis patients, which was negatively correlated with synovial fluid (SF) leptin concentration. Moreover, leptin treatment (5, 10 and 20 ng/ml) of primary cultured chondrocytes significantly decreased mRNA and protein levels of UCP4, but increased ROS production and cell apoptosis in a dose-dependent manner. The effects of leptin treatment (20 ng/ml) on chondrocytes was partially reversed by ectopic expression of UCP4. More importantly, intraarticularly injection of UCP4 adenovirus remarkably alleviate OA progression and cell apoptosis in a rat OA model induced by anterior cruciate ligament transection (ACLT). In conclusion, UCP4, whose expression was suppressed by leptin, may be involved in the ROS production and apoptosis of chondrocytes, thus contributing to the OA pathogenesis.

// Tingting Fang 1, * , Jiajia Lin 1, * , Yanru Wang 2 , Guangnan Chen 3 , Jing Huang 2 , Jie Chen 1 , Yan Zhao 1 , Ruixia Sun 1 , Chunmin Liang 2 , Binbin Liu 1 1 Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai, P. R. China 2 Laboratory of Tumor Immunology, Department of Anatomy, Histology, and Embryology, School of Basic Medical Sciences, Fudan University, Shanghai, P. R. China 3 The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, P.R. China * These authors have contributed equally to this work Correspondence to: Chunmin Liang, email: cmliang@fudan.edu.cn Binbin Liu, email: liu.binbin@zs-hospital.sh.cn Keywords: ADAM12, hepatocellular carcinoma, metastasis, TSPAN8 Received: October 06, 2015 Accepted: April 18, 2016 Published: June 01, 2016 ABSTRACT Recent evidence indicates that tetraspanin-8 (TSPAN8) promotes tumor progression and metastasis. In this study, we explored the effects of TSPAN8 and the molecular mechanisms underlying hepatocellular carcinoma (HCC) metastasis using various HCC cell lines, tissues from 149 HCC patients, and animal models of HCC progression. We showed that elevated expression of TSPAN8 promoted HCC invasion in vitro and metastasis in vivo , but did not influence HCC cell proliferation in vitro . Increased TSPAN8 expression in human HCC was predictive of poor survival, and multivariate analyses indicated TSPAN8 expression to be an independent predictor for both postoperative overall survival and relapse-free survival. Importantly, TSPAN8 enhanced HCC invasion and metastasis by increasing ADAM12m expression. We therefore conclude that TSPAN8 and ADAM12m may be useful therapeutic targets for the prevention of HCC progression and metastasis.

OBJECTIVE The aim of this study was to evaluate the effectiveness and accuracy of ultrasound-guided intraarticular and periarticular joint injections as compared with landmark-guided injections technique. METHODS A systematic literature search was performed in Medline, Web of Science, Embase, the Cochrane Central Register of Controlled Trials, reference lists of articles, and other sources. Only randomized controlled trials were included. Two reviewers independently selected and assessed each study for quality and extracted data. RESULTS Twelve randomized controlled trials were included in the meta-analysis. The results indicated that ultrasound-guided intraarticular and periarticular joint injections were more accurate than the landmark-guided injections (odds ratio, 0.36; 95% confidence interval, 0.22-0.60). Ultrasound-guided joint injections significantly decreased the visual analog scale scores at both 2 wks (mean difference, -9.57; 95% confidence interval, -13.14 to -5.99) (P < 0.00001) and 6 wks (mean difference, -14.21; 95% confidence interval, -18.20 to -10.21) (P < 0.00001) after injection. There was no statistically significant difference in visual analog scale score at 12 wks between ultrasound-guided and landmark-guided intraarticular and periarticular joint injections (mean difference, -4.42; 95% confidence interval, -11.71 to 2.87) (P = 0.23). CONCLUSIONS Intraarticular and periarticular injections using ultrasound guidance significantly improves the accuracy of joint injections, and there is a significant decrease in visual analog scale scores for up to 6 wks after injection. The effect of ultrasound guidance on the long-term outcome of joint injections is inconclusive. The improved accuracy of injections was associated with pain relief. The authors recommend routine ultrasound guidance for intraarticular and periarticular injections.

A critical issue for the plantation forest industry is the preservation and control of genetic material in order to facilitate the fertilisation process. This is best achieved by drying at low temperature and low humidity prior to extraction of seeds and pollen. For example, freshly picked green cones of Pinus radiata are best dried at 25°C, 20% relative humidity to avoid thermal damage and to prevent mould formation. Similar conditions are required for drying pollen catkins. These conditions can be met efficiently and reliably by the use of a dehumidifier dryer. This paper describes the design of such a drying system, including a review of the dehumidifier and the kiln design parameters necessary to achieve the required drying conditions. Performance data and commercial operating experience are also presented and analysed. The system is effective and reliable, and has increased both the speed of drying and the quality of the product.

Multiple sclerosis (MS) and osteoporosis (OP) affect a substantial proportion of the population. Accumulating evidence suggests that MS patients are at high risk for OP. We performed a meta-analysis to identify risk factors for lowered bone mineral density (BMD) in MS patients.We searched for articles within the Medline, Embase and Cochrane Library databases, published up to March 2014, pertaining to associations between MS and BMD. A total of 11 studies was included in the meta-analysis.The analysis indicated that MS patients have reduced lumbar spine, femur neck, and hip BMD compared with healthy controls (lumbar spine, standardized mean difference (SMD) = -0.76, 95% CI: -1.07, -0.45; femur neck, SMD = -0.56, 95% CI: -0.84, -0.29; and hip, SMD = -0.62, 95% CI: -0.96, -0.29). Further subgroup analysis revealed that a disease duration of7 years, total steroid dose during the disease of15 g, and an Expanded Disability Status Scale (EDSS) score of3, increased the risk of reduced BMD in the lumbar spine and femoral neck, but not in the hip. Meta-regression analysis did not explain the heterogeneity in the clinical characteristics or outcome definitions.Our meta-analysis suggests that MS patients have reduced overall BMD compared with healthy controls. Furthermore, disease duration (7 years), total steroid dose (15 g), and EDSS score (3) are risk factors for reduced BMD in MS patients.

Background: Previously, we reported that MEPE/OF45 interacting with CHK1 protects CHK1 from degradation and cells from DNA damage-induced killing (Nucleic Acids Res, 37: 7447-7454 2009; Brit J Cancer 102: 862-866, 2010). To further investigate the nature of the CHK1 stabilization and its effects on cell sensitivity to DNA damage inducers, we designed this study to identify the key domain of CHK1 interaction with MEPE/OF45 and the key ubiquitination site of CHK1. Methods: GST-MEPE/OF45 was expressed in E. coli BL 21. HA-wild type CHK1 and various CHK1 truncated mutations were expressed in 293FT. GST pull-down assay was used to identify the key domain of CHK1 interacting with MEPE/OF45. To identify the ubiquitination site of CHK1, GFP-CHK1 with different Lys mutations were co-transfected with Ub-expression vector to 293FT, and 48 hours later, whole cell lysate were prepared, Western blot was carried out using a GFP monoclonal antibody to detect ubiquitinaed CHK1. The CHK1 half-life was used to detect the stabilization of CHK1 and a clonogenic assay was used to detect the sensitivity of cells to DNA damage inducers. Results: The key domain of CHK1 interacting with MEPE/OF45 and the key site of CHK1 ubiquitination were identified. Most importantly, the mutation of CHK1 with the main domain or key site affected CHK1 stabilization and cell sensitivity to DNA damage inducers. Conclusion: The interaction of CHK1 with MEPE/OF45 plays an important role in preventing CHK1 ubiquitination and; therefore, stabilizes CHK1, which further affects cell sensitivity to DNA damage inducers. Because CHK1 is an essential DNA damage response protein, these results provide valuable information for understanding the role of CHK1 in genomic integrity, which could be used for improving cancer treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4059. doi:10.1158/1538-7445.AM2011-4059