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Background: Metabolic score for insulin resistance (METS-IR) is a surrogate index to estimate insulin sensitivity. The aim of this study was to examine the association between METS-IR and regression to normoglycemia in Chinese adults with prediabetes. Methods: A total of 15,415 Chinese adults with prediabetes defined by their fasting blood glucose were included in this retrospective study. The association between METS-IR and regression to normoglycemia from prediabetes was evaluated using the Cox proportional hazards regression model. A Cox proportional hazards regression with cubic spline function was performed to explore the nonlinear association between METS-IR and regression to normoglycemia. Kaplan-Meier curves was used to describe the probability of regression to normoglycemia from prediabetes. Results: In multivariate Cox proportional hazards regression analyses, the increase in METS-IR was independently associated with a reduced probability of regression to normoglycemia from prediabetes (all p < 0.01 in models 1–3). A nonlinear association between METS-IR and the probability of regression to normoglycemia was observed, with an inflection point of 49.3. The hazard ratio on the left side of the inflection point was 0.965 (95% CI 0.953–0.976). Subgroup analyses demonstrated the robustness of our findings. Conclusion: This study demonstrated a negative and nonlinear association between METS-IR and regression to normoglycemia in Chinese adults with prediabetes. When METS-IR is below 49.3, reducing METS-IR could significantly increase the probability of regression to normoglycemia from prediabetes. [ABSTRACT FROM AUTHOR]

Cardiac remodeling is the primary pathological feature of chronic heart failure (HF). Exploring the characteristics of cardiac remodeling in the very early stages of HF and identifying targets for intervention are essential for discovering novel mechanisms and therapeutic strategies. Silent mating type information regulation 2 homolog 3 (SIRT3), as a major mitochondrial nicotinamide adenine dinucleotide (NAD)-dependent deacetylase, is required for mitochondrial metabolism. However, whether SIRT3 plays a role in cardiac remodeling by regulating the biosynthesis of mitochondrial cardiolipin (CL) is unknown. In this study, we induced pressure overload in wild-type (WT) and SIRT3 knockout (SIRT3−/−) mice via transverse aortic constriction (TAC). Compared with WT mouse hearts, the hearts of SIRT3−/− mice exhibited more-pronounced cardiac remodeling and fibrosis, greater reactive oxygen species (ROS) production, decreased mitochondrial-membrane potential (ΔΨm), and abnormal mitochondrial morphology after TAC. Furthermore, SIRT3 deletion aggravated TAC-induced decrease in total CL content, which might be associated with the downregulation of the CL synthesis related enzymes cardiolipin synthase 1 (CRLS1) and phospholipid-lysophospholipid transacylase (TAFAZZIN). In our in vitro experiments, SIRT3 overexpression prevented angiotensin II (AngII)- induced aberrant mitochondrial function, CL biosynthesis disorder, and peroxisome proliferator-activated receptor gamma (PPARγ) downregulation in cardiomyocytes; meanwhile, SIRT3 knockdown exacerbated these effects. Moreover, the addition of GW9662, a PPARγ antagonist, partially counteracted the beneficial effects of SIRT3 overexpression. In conclusion, SIRT3 regulated PPARγ-mediated CL biosynthesis, maintained the structure and function of mitochondria, and thereby protected the myocardium against cardiac remodeling. [ABSTRACT FROM AUTHOR]

Background: Adherence to oral nutritional supplement therapy among postoperative patients with gastric cancer is low. There is little knowledge about patients' priorities and needs regarding oral nutritional supplement therapy. The discrete choice experiment is an innovative method used to elicit patients' preferences. Good practice guidelines emphasize that the development of attributes and levels is a fundamentally important process. Objective: To comprehensively describe the identification, refinement, and selection of attributes and levels for a discrete choice experiment. Methods: A mixed-methods approach, consisting of three consecutive steps: a literature review, in-depth interviews, and focus groups. First, the literature review allowed quick identification of attributes and levels. Then, 15 in-depth interviews were conducted to gather a rich description of the experience of patients taking oral nutritional supplements after gastrectomy and to verify and enrich the attributes and levels list. Finally, four focus group participants discussed the wording of the attributes and levels and reduced the number of attributes to manageable numbers through voting ranking methods. Results: Following the literature review and qualitative data collection, eight attributes were finally generated, each with two to three levels. The following attributes were included: 1) information provider; 2) health guidance approach; 3) adverse reactions; 4) flavor; 5) follow-up method; 6) follow-up frequency; 7) psychological support; 8) cost. These attributes covered the important attributes of nutritional preparations and health guidance included in ONS therapy that were relevant to patients. Conclusions: This study's mixed-methods approach has been found highly suitable to identify, refine and select attributes and levels for a discrete choice experiment. The three methods have pros and cons, and they complement each other, especially the analysis of qualitative data led to a deeper and broader understanding of attributes and levels. [ABSTRACT FROM AUTHOR]

Background: The safety of discontinuing oral anticoagulant (OAC) therapy after atrial fibrillation (AF) ablation remains controversial. A meta-analysis was performed to assess the safety and feasibility of discontinuing OAC therapy after successful AF ablation. Methods: PubMed and Embase were searched up to October 2020 for prospective cohort studies that reported the risk of thromboembolism (TE) after successful AF ablation in off-OAC and on-OAC groups. The primary outcome was the incidence of TE events. The Mantel-Haenszel method with random-effects modeling was used to calculate pooled odds ratios (ORs) and 95% confidence intervals (CIs). Results: A total of 11,148 patients (7,160 in the off-OAC group and 3,988 in the on-OAC group) from 10 studies were included to meta-analysis. No significant difference in TE between both groups was observed (OR, 0.73; 95%CI, 0.51–1.05; I2 = 0.0%). The risk of major bleeding in off-OAC group was significantly lower compared to the on-OAC group (OR, 0.18; 95%CI, 0.07–0.51; I2 = 51.7%). Conclusions: Our study suggests that it may be safe to discontinue OAC therapy in patients after successful AF ablation. Additionally, an increased risk of major bleeding was observed in patients on OAC. However, the results of this meta-analysis should be interpreted with caution because of the heterogeneity among the included study designs. Large-scale and adequately powered randomized controlled trials are warranted to confirm these findings. [ABSTRACT FROM AUTHOR]

Photoperiod is an important factor of mammalian seasonal rhythm. Here, we studied morphological differences in the Harderian gland (HG), a vital photosensitive organ, in male striped dwarf hamsters (Cricetulus barabensis) under different photoperiods (short photoperiod, SP; moderate photoperiod, MP; long photoperiod, LP), and investigated the underlying molecular mechanisms related to these morphological differences. Results showed that carcass weight and HG weight were lower under SP and LP conditions. There was an inverse correlation between blood melatonin levels and photoperiod in the order SP > MP > LP. Protein expression of hydroxyindole-O-methyltransferase (HIOMT), a MT synthesis-related enzyme, was highest in the SP group. Protein expression of bax/bcl2 showed no significant differences, indicating that the level of apoptosis remained stable. Protein expression of LC3II/LC3I was higher in the SP group than that in the MP group. Furthermore, comparison of changes in the HG ultrastructure demonstrated autolysosome formation in the LP, suggesting the lowest autophagy level in under MP. Furthermore, the protein expression levels of ATP synthase and mitochondrial fission factor were highest in the MP group, whereas citrate synthase, dynamin-related protein1, and fission1 remained unchanged in the three groups. The change trends of ATP synthase and citrate synthase activity were similar to that of protein expression among the three groups. In summary, the up-regulation of autophagy under SP and LP may be a primary factor leading to loss of HG weight and reduced mitochondrial energy supply capacity. [ABSTRACT FROM AUTHOR]

Objective: Pulmonary tuberculosis (TB) is a severe infectious respiratory disease, the burden of which remains high in China. To provide scientific evidence for developing more targeted prevention and control strategies, this study aimed to determine the incidence trends and explore the epidemiological characteristics of pulmonary TB in Anhui Province, Eastern China between 2013 and 2018. Methods: The retrospective study analyzed information regarding pulmonary TB cases reported by the National Infectious Disease Reporting System and census data collected from the Anhui Provincial Bureau of Statistics. Results: Overall, 211,892 cases of TB patients were reported in Anhui Province, China between 2013 and 2018, with an average annual reported incidence rate of 57.7 per 100,000 persons. A significant decrease in the incidence rate of pulmonary TB (p < 0.001) was observed during the study period. Men had a higher incidence rate of pulmonary TB than women (p < 0.001). The highest annual average reported incidence rate was 204.2 per 100,000 persons in those aged 70–74 years. The number of farmers with pulmonary TB, i.e., 155,415, accounted for 73.4% of all cases. Moreover, the peak period of reported cases was from January to March. Four cities along the Yangtze River—Anqing, Tongling, Chizhou, and Wuhu—reported significantly higher incidence rates of pulmonary TB than other cities (p < 0.001). Conclusions: From 2013 to 2018, there was a significant decline in the incidence rate of pulmonary TB in Anhui Province, with peaks occurring from January to March. Prevention and control strategies targeting men, people aged 70–74 years, farmers, and the four cities along the Yangtze River should be strengthened. [ABSTRACT FROM AUTHOR]

Fruit development in Lycium ruthenicum Murr. involves a succession of physiological and biochemical changes reflecting the transcriptional modulation of thousands of genes. Although recent studies have investigated the dynamic transcriptomic responses during fruit ripening in L. ruthenicum, most have been limited in scope, and thus systematic data representing the structural genes and transcription factors involved in anthocyanin biosynthesis are lacking. In this study, the transcriptomes of three ripening stages associated with anthocyanin accumulation, including S1 (green ripeness stage), S2 (skin color change) and S3 (complete ripeness stage) in L. ruthenicum were investigated using Illumina sequencing. Of a total of 43,573 assembled unigenes, 12,734 were differentially expressed during fruit ripening in L. ruthenicum. Twenty-five significantly differentially expressed structural genes (including PAL, C4H, 4CL, CHS, CHI, F3H, F3’H, F3’5’H, DFR, ANS and UFGT) were identified that might be associated with anthocyanin biosynthesis. Additionally, several transcription factors, including MYB, bHLH, WD40, NAC, WRKY, bZIP and MADS, were correlated with the structural genes, implying their important interaction with anthocyanin biosynthesis-related genes. Our findings provide insight into anthocyanin biosynthesis and regulation patterns in L. ruthenicum and offer a systematic basis for elucidating the molecular mechanisms governing anthocyanin biosynthesis in L. ruthenicum. [ABSTRACT FROM AUTHOR]

Background: T-type calcium channels (TTCCs) mediate calcium influx across the cell membrane. TTCCs regulate numerous physiological processes including cardiac pacemaking and neuronal activity. In addition, they have been implicated in the proliferation, migration and differentiation of tumour tissues. Although the signalling events downstream of TTCC-mediated calcium influx are not fully elucidated, it is clear that variations in the expression of TTCCs promote tumour formation and hinder response to treatment. Methods: We examined the expression of TTCC genes (all three subtypes; CACNA-1G, CACNA-1H and CACNA-1I) and their prognostic value in three major solid tumours (i.e. gastric, lung and ovarian cancers) via a publicly accessible database. Results: In gastric cancer, expression of all the CACNA genes was associated with overall survival (OS) among stage I-IV patients (all p<0.05). By combining the three potential biomarkers, a TTCC signature was developed, which retained a significant association with OS both in stage IV and stage I-III patients. In lung and ovarian cancer, association with OS was also significant when all tumour stages were considered, but was partly lost or inconclusive after splitting cases into localized and metastatic subsets. Conclusions: Alterations in CACNA gene expression are linked to tumour prognosis. Gastric cancer represents the most promising setting for further evaluation. [ABSTRACT FROM AUTHOR]

Pomegranate (Punica granatum L.) belongs to Punicaceae, and is valued for its social, ecological, economic, and aesthetic values, as well as more recently for its health benefits. The ‘Tunisia’ variety has softer seeds and big arils that are easily swallowed. It is a widely popular fruit; however, the molecular mechanisms of the formation of hard and soft seeds is not yet clear. We conducted a de novo assembly of the seed transcriptome in P. granatum L. and revealed differential gene expression between the soft-seed and hard-seed pomegranate varieties. A total of 35.1 Gb of data were acquired in this study, including 280,881,106 raw reads. Additionally, de novo transcriptome assembly generated 132,287 transcripts and 105,743 representative unigenes; approximately 13,805 unigenes (37.7%) were longer than 1,000 bp. Using bioinformatics annotation libraries, a total of 76,806 unigenes were annotated and, among the high-quality reads, 72.63% had at least one significant match to an existing gene model. Gene expression and differentially expressed genes were analyzed. The seed formation of the two pomegranate cultivars involves lignin biosynthesis and metabolism, including some genes encoding laccase and peroxidase, WRKY, MYB, and NAC transcription factors. In the hard-seed pomegranate, lignin-related genes and cellulose synthesis-related genes were highly expressed; in soft-seed pomegranates, expression of genes related to flavonoids and programmed cell death was slightly higher. We validated selection of the identified genes using qRT-PCR. This is the first transcriptome analysis of P. granatum L. This transcription sequencing greatly enriched the pomegranate molecular database, and the high-quality SSRs generated in this study will aid the gene cloning from pomegranate in the future. It provides important insights into the molecular mechanisms underlying the formation of soft seeds in pomegranate. [ABSTRACT FROM AUTHOR]

Paleogeological events and Pleistocene climatic fluctuations have had profound influences on the genetic patterns and phylogeographic structure of species in southern China. In this study, we investigated the population genetic structure and Phylogeography of the Odorrana schmackeri species complex, mountain stream-dwelling odorous frogs, endemic to southern China. We obtained mitochondrial sequences (1,151bp) of the complete ND2 gene and two flanking tRNAs of 511 individuals from 25 sites for phylogeographic analyses. Phylogenetic reconstruction revealed seven divergent evolutionary lineages, with mean pairwise (K2P) sequence distances from 7.8% to 21.1%, except for a closer ND2 distance (3.4%). The complex geological history of southern China drove matrilineal divergence in the O. schmackeri species complex into highly structured geographical units. The first divergence between lineage A+B and other lineages (C-G) had likely been influenced by the uplift of coastal mountains of Southeast China during the Mio-Pliocene period. The subsequent divergences between the lineages C-G may have followed the formation of the Three Gorges and the intensification of the East Asian summer monsoon during the late Pliocene and early Pleistocene. Demographic analyses indicated that major lineages A and C have been experienced recent population expansion (c. 0.045–0.245 Ma) from multiple refugia prior to the Last Glacial Maximum (LGM). Molecular analysis suggest that these seven lineages may represent seven different species, three described species and four cryptic species and should at least be separated into seven management units corresponding to these seven geographic lineages for conservation. [ABSTRACT FROM AUTHOR]

Acute and chronic lead (Pb) exposure might cause hypertension and cardiovascular diseases. The purpose of this study was to evaluate the effects of early acute exposure to Pb on the cellular morphology, apoptosis, and proliferation in rats and to elucidate the early mechanisms involved in the development of Pb-induced hypertension. Very young Sprague-Dawley rats were allowed to drink 1% Pb acetate for 12 and 40 days. Western blot analysis indicated that the expression of proliferating cell nuclear antigen (PCNA) decreased in the tissues of the abdominal and thoracic aortas and increased in the cardiac tissue after 12 and 40 days of Pb exposure, respectively. Bax was upregulated and Bcl-2 was downregulated in vascular and cardiac tissues after 40 days of Pb exposure. In addition, an increase in caspase-3 activity was observed after 40 days of exposure to Pb. In terms of morphology, we found that the internal elastic lamina (IEL) of aorta lost the original curve and the diameter of cardiac cell was enlarged after 40 days. Furthermore, the exposure led to a marked increase in acetylated histone H3 levels in the aortas and cardiac tissue after 12 and 40 days, than that in the control group. These findings indicate that Pb might increase the level of histone acetylation and induce apoptosis in vascular and cardiac tissues. However, the mechanism involved need to be further investigated. [ABSTRACT FROM AUTHOR]

Background: Interleukin-16 (IL-16), a pleiotropic cytokine, plays a fundamental role in inflammatory diseases. This study investigates the association between IL-16 polymorphisms and the risk of knee osteoarthritis (OA) in a Chinese population. Methods: The IL-16 rs11556218, rs4072111, and rs4778889 polymorphisms were determined in 150 knee OA cases and 147 healthy controls through polymerase chain reaction-restriction fragment length polymorphism. Results: The results suggested that the variants in IL-16 gene rs11556218 site were associated with a decreased knee OA risk after adjusting for age, sex, BMI, and smoking and drinking status (TG vs. TT: OR, 0.69; 95% CI, 0.53–0.89; P = 0.006; GG vs. TT: OR, 0.64; 95% CI, 0.45–0.90; P = 0.042; dominant model: OR, 0.68; 95% CI, 0.29–0.87; P = 0.002; G vs. T allele: OR, 0.77; 95% CI, 0.66–0.90; P = 0.003). Similarly, subjects bearing the rs4072111 variant genotypes and alleles also had a lower susceptibility to knee OA compared with those bearing the wild-type (CT vs. CC: OR, 0.66; 95% CI, 0.53–0.83; P = 0.002; TT vs. CC: OR, 0.57; 95% CI, 0.40–0.82; P = 0.027; dominant model: OR, 0.65; 95%, CI 0.52–0.80; P <0.001; T vs. C allele: OR, 0.69; 95% CI, 0.58–0.81; P <0.001). Further, the C allele and the combined genotype (CC+CT) of rs4778889 were associated with a slightly decreased risk of knee OA. In addition, we found two high-risk haplotypes: TTT (OR, 3.70) and GCC (OR, 6.22). Finally, serum IL-16 levels of knee OA patients were significantly higher than those of controls (P = 0.001). Conclusions: Despite the small sample size, this is the first study suggesting IL-16 gene polymorphisms to be associated with the risk of knee OA. [ABSTRACT FROM AUTHOR]

Dental caries continues to be the most prevalent bacteria-mediated non-contagious disease of humankind. Dental professionals assert the disease can be explained by poor oral hygiene and a diet rich in sugars but this does not account for caries free individuals exposed to the same risk factors. In order to test the hypothesis that amount of amelogenin during enamel development can influence caries susceptibility, we generated multiple strains of mice with varying levels of available amelogenin during dental development. Mechanical tests showed that dental enamel developed with less amelogenin is “weaker” while the dental enamel of animals over-expressing amelogenin appears to be more resistant to acid dissolution. [ABSTRACT FROM AUTHOR]

Integration of tissue-engineered bone grafts with the host bone is vital for the healing of critical-size bone defects. An important aspect of this process is bone resorption, which must be carried out by osteoclasts derived from the host. However, the mechanism underlying recruitment of host osteoclast precursors to graft sites remains unclear. Endothelial progenitor cells (EPCs) mobilize from the bone marrow into the circulation and home to sites of angiogenesis such as tissue remodeling. Since EPCs express SDF-1, and C/EBPβ is known to regulate SDF-1α expression, we hypothesized that EPCs may recruit CXCR4-expressing host osteoclast precursors to the repair area and that this recruitment may be mediated through C/EBPβ signaling. Using an inflammatory EPC model we showed that EPCs upregulate protein levels of both SDF-1α and C/EBPβ. A luciferase assay confirmed that C/EBPβ acts on the SDF-1α promoter in these cells, and that binding is increased under conditions of inflammation, while silencing of C/EBPβ reduces expression of SDF-1 α and C/EBPβ. Using RAW264.7 cells as a model of osteoclastic monocyte precursors, we investigated their responses to migratory factors in EPC conditioned medium. We showed that RAW264.7 cells migrate towards conditioned medium from EPCs treated with IL-1β, an effect which could be abolished by silencing C/EBPβ in EPCs, and was almost completely blocked by silencing CXCR4 in RAW264.7 cells. These findings show that EPCs respond to inflammatory stimuli by signaling to osteoclast precursors via SDF-1, and that C/EBPβ mediates this response. [ABSTRACT FROM AUTHOR]

The present study was designed to determine the underlying mechanism of low-intensity pulsed ultrasound (LIPUS) induced alveolar bone remodeling and the role of BMP-2 expression in a rat orthodontic tooth movement model. Orthodontic appliances were placed between the homonymy upper first molars and the upper central incisors in rats under general anesthesia, followed by daily 20-min LIPUS or sham LIPUS treatment beginning at day 0. Tooth movement distances and molecular changes were evaluated at each observation point. In vitro and in vivo studies were conducted to detect HGF (Hepatocyte growth factor)/Runx2/BMP-2 signaling pathways and receptor activator of NFκB ligand (RANKL) expression by quantitative real time PCR (qRT-PCR), Western blot and immunohistochemistry. At day 3, LIPUS had no effect on the rat orthodontic tooth movement distance and BMP-2-induced alveolar bone remodeling. However, beginning at day 5 and for the following time points, LIPUS significantly increased orthodontic tooth movement distance and BMP-2 signaling pathway and RANKL expression compared with the control group. The qRT-PCR and Western blot data in vitro and in vivo to study BMP-2 expression were consistent with the immunohistochemistry observations. The present study demonstrates that LIPUS promotes alveolar bone remodeling by stimulating the HGF/Runx2/BMP-2 signaling pathway and RANKL expression in a rat orthodontic tooth movement model, and LIPUS increased BMP-2 expression via Runx2 regulation. [ABSTRACT FROM AUTHOR]

Migratory insects adapt to and exploit the atmospheric environment to complete their migration and maintain their population. However, little is known about the mechanism of insect migration under the influence of extreme weather conditions such as typhoons. A case study was conducted to investigate the effect of typhoon Khanun, which made landfall in the eastern China in Sept. 2005, on the migration of brown planthopper, Nilaparvata lugens (Stål). The migration pathways of N. lugens were reconstructed for the period under the influence of the typhoon by calculating trajectories using the MM5, a mesoscale numerical weather prediction model, and migration events were examined in 7 counties of the Yangtze River Delta region with ancillary information. The light trap catches and field observations indicated that the migration peak of N. lugens coincided with the period when the typhoon made landfall in this region. The trajectory analyses revealed that most emigrations from this region during this period were hampered or ended in short distances. The sources of the light-trap catches were mainly located the nearby regions of each station (i.e. mostly less than 100 km away, with a few exceeding 200 km but all less than 300 km). This disrupted emigration was very different from the usual N. lugens migration which would bring them to Hunan, Jiangxi, and southern Anhui from this region at this time of year. This study revealed that the return migration of N. lugens was suppressed by the typhoon Khanun, leading to populations remaining high in the Yangtze River Delta and exacerbating later outbreaks. [ABSTRACT FROM AUTHOR]

This study aimed to study the effects of initial cell density and in vitro culture method on the construction of tissue-engineered bone grafts and osteogenic activities. Human mesenchymal stem cells (hMSCs) were seeded onto cubic scaffolds prepared from demineralized bone matrix (DBM) by three methods - static, hydrodynamic, or fibrin hydrogel-assisted seeding. The resulting cell-scaffold constructs were cultured in vitro by static flask culture or hydrodynamic culture. The initial cell density and the subsequent in vitro proliferation and alkaline phosphate activities of the constructs were analyzed. The constructs were also subcutaneously implanted in nude mice to examine their in vivo osteogenic activities. Hydrogel-assisted seeding gave the highest seeding efficiency, followed by hydrodynamic and conventional static seeding. During in vitro culture, hydrodynamic culture produced higher plateau cell densities, alkaline phosphatase (ALP) activities, and extracellular matrix production than static culture. After subcutaneous implantation in nude mice, the implants prepared by the combination of hydrogel-assisted seeding and hydrodynamic culture produced higher wet weight and bone mineral density than implants prepared by other methods. The results suggest that the hydrogel-assisted seeding can substantially increase the initial seed cell density in scaffolds. Subsequent hydrodynamic culture can promote the proliferation and osteoblastic differentiation of the seeded cells. Correspondingly, bone grafts produced by the combination of these two methods achieved the highest osteogenic activity among the three methods employed. [ABSTRACT FROM AUTHOR]

Clear cell ovarian cancer is an epithelial ovarian cancer histotype that is less responsive to chemotherapy and carries poorer prognosis than serous and endometrioid histotypes. Despite this, patients with these tumors are treated in a similar fashion as all other ovarian cancers. Previous genomic analysis has suggested that clear cell cancers represent a unique tumor subtype. Here we generated the first whole genomic expression profiling using epithelial component of clear cell ovarian cancers and normal ovarian surface specimens isolated by laser capture microdissection. All the arrays were analyzed using BRB Array Tools and Pathway Studio software to identify the signaling pathways. Identified pathways validated using serous, clear cell cancer cell lines and RNAi technology. In vivo validations carried out using an orthotopic mouse model and liposomal encapsulated siRNA. Patient-derived clear cell and serous ovarian tumors were grafted under the renal capsule of NOD-SCID mice to evaluate the therapeutic potential of the identified pathway. We identified major activated pathways in clear cells involving in hypoxic cell growth, angiogenesis, and glucose metabolism not seen in other histotypes. Knockdown of key genes in these pathways sensitized clear cell ovarian cancer cell lines to hypoxia/glucose deprivation. In vivo experiments using patient derived tumors demonstrate that clear cell tumors are exquisitely sensitive to antiangiogenesis therapy (i.e. sunitinib) compared with serous tumors. We generated a histotype specific, gene signature associated with clear cell ovarian cancer which identifies important activated pathways critical for their clinicopathologic characteristics. These results provide a rational basis for a radically different treatment for ovarian clear cell patients. [ABSTRACT FROM AUTHOR]

Fruit development in Lycium ruthenicum Murr. involves a succession of physiological and biochemical changes reflecting the transcriptional modulation of thousands of genes. Although recent studies have investigated the dynamic transcriptomic responses during fruit ripening in L. ruthenicum, most have been limited in scope, and thus systematic data representing the structural genes and transcription factors involved in anthocyanin biosynthesis are lacking. In this study, the transcriptomes of three ripening stages associated with anthocyanin accumulation, including S1 (green ripeness stage), S2 (skin color change) and S3 (complete ripeness stage) in L. ruthenicum were investigated using Illumina sequencing. Of a total of 43,573 assembled unigenes, 12,734 were differentially expressed during fruit ripening in L. ruthenicum. Twenty-five significantly differentially expressed structural genes (including PAL, C4H, 4CL, CHS, CHI, F3H, F3'H, F3'5'H, DFR, ANS and UFGT) were identified that might be associated with anthocyanin biosynthesis. Additionally, several transcription factors, including MYB, bHLH, WD40, NAC, WRKY, bZIP and MADS, were correlated with the structural genes, implying their important interaction with anthocyanin biosynthesis-related genes. Our findings provide insight into anthocyanin biosynthesis and regulation patterns in L. ruthenicum and offer a systematic basis for elucidating the molecular mechanisms governing anthocyanin biosynthesis in L. ruthenicum., Competing Interests: The authors have declared that no competing interests exist.

Migratory insects adapt to and exploit the atmospheric environment to complete their migration and maintain their population. However, little is known about the mechanism of insect migration under the influence of extreme weather conditions such as typhoons. A case study was conducted to investigate the effect of typhoon Khanun, which made landfall in the eastern China in Sept. 2005, on the migration of brown planthopper, Nilaparvata lugens (Stål). The migration pathways of N. lugens were reconstructed for the period under the influence of the typhoon by calculating trajectories using the MM5, a mesoscale numerical weather prediction model, and migration events were examined in 7 counties of the Yangtze River Delta region with ancillary information. The light trap catches and field observations indicated that the migration peak of N. lugens coincided with the period when the typhoon made landfall in this region. The trajectory analyses revealed that most emigrations from this region during this period were hampered or ended in short distances. The sources of the light-trap catches were mainly located the nearby regions of each station (i.e. mostly less than 100 km away, with a few exceeding 200 km but all less than 300 km). This disrupted emigration was very different from the usual N. lugens migration which would bring them to Hunan, Jiangxi, and southern Anhui from this region at this time of year. This study revealed that the return migration of N. lugens was suppressed by the typhoon Khanun, leading to populations remaining high in the Yangtze River Delta and exacerbating later outbreaks.

This study aimed to study the effects of initial cell density and in vitro culture method on the construction of tissue-engineered bone grafts and osteogenic activities. Human mesenchymal stem cells (hMSCs) were seeded onto cubic scaffolds prepared from demineralized bone matrix (DBM) by three methods - static, hydrodynamic, or fibrin hydrogel-assisted seeding. The resulting cell-scaffold constructs were cultured in vitro by static flask culture or hydrodynamic culture. The initial cell density and the subsequent in vitro proliferation and alkaline phosphate activities of the constructs were analyzed. The constructs were also subcutaneously implanted in nude mice to examine their in vivo osteogenic activities. Hydrogel-assisted seeding gave the highest seeding efficiency, followed by hydrodynamic and conventional static seeding. During in vitro culture, hydrodynamic culture produced higher plateau cell densities, alkaline phosphatase (ALP) activities, and extracellular matrix production than static culture. After subcutaneous implantation in nude mice, the implants prepared by the combination of hydrogel-assisted seeding and hydrodynamic culture produced higher wet weight and bone mineral density than implants prepared by other methods. The results suggest that the hydrogel-assisted seeding can substantially increase the initial seed cell density in scaffolds. Subsequent hydrodynamic culture can promote the proliferation and osteoblastic differentiation of the seeded cells. Correspondingly, bone grafts produced by the combination of these two methods achieved the highest osteogenic activity among the three methods employed.

Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV) associated malignancy with high prevalence in Southern Chinese. In order to assess whether defects of EBV-specific immunity may contribute to the tumor, the phenotype and function of circulating T-cells and tumor infiltrating lymphocytes (TILs) were investigated in untreated NPC patients. Circulating naïve CD3+CD45RA+ and CD4+CD25- cells were decreased, while activated CD4+CD25+ T-cells and CD3-CD16+ NK-cells were increased in patients compared to healthy donors. The frequency of T-cells recognizing seven HLA-A2 restricted epitopes in LMP1 and LMP2 was lower in the patients and remained low after stimulation with autologous EBV-carrying cells. TILs expanded in low doses of IL-2 exhibited an increase of CD3+CD4+, CD3+CD45RO+ and CD4+CD25+ cells and 2 to 5 fold higher frequency of LMP1 and LMP2 tetramer positive cells compared to peripheral blood. EBV-specific cytotoxicity could be reactivated from the blood of most patients, whereas the TILs lacked cytotoxic activity and failed to produce IFNgamma upon specific stimulation. Thus, EBV-specific rejection responses appear to be functionally inactivated at the tumor site in NPC.

Here we report the unexpected finding that specific human ANK2 variants represent a new example of balanced human variants. The prevalence of certain ANK2 (encodes ankyrin-B) variants range from 2 percent of European individuals to 8 percent in individuals from West Africa. Ankyrin-B variants associated with severe human arrhythmia phenotypes (eg E1425G, V1516D, R1788W) were rare in the general population. Variants associated with less severe clinical and in vitro phenotypes were unexpectedly common. Studies with the ankyrin-B(+/-) mouse reveal both benefits of enhanced cardiac contractility, as well as costs in earlier senescence and reduced lifespan. Together these findings suggest a constellation of traits that we term "ankyrin-B syndrome", which may contribute to both aging-related disorders and enhanced cardiac function.