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Platelets are small anucleated blood cells primarily known for their vital hemostatic role. Allogeneic platelet concentrates (PCs) collected from healthy donors are an essential cellular product transfused by hospitals to control or prevent bleeding in patients affected by thrombocytopenia or platelet dysfunctions. Platelets fulfill additional essential functions in innate and adaptive immunity and inflammation, as well as in wound-healing and tissue-repair mechanisms. Platelets contain mitochondria, lysosomes, dense granules, and alpha-granules, which collectively are a remarkable reservoir of multiple trophic factors, enzymes, and signaling molecules. In addition, platelets are prone to release in the blood circulation a unique set of extracellular vesicles (p-EVs), which carry a rich biomolecular cargo influential in cell–cell communications. The exceptional functional roles played by platelets and p-EVs explain the recent interest in exploring the use of allogeneic PCs as source material to develop new biotherapies that could address needs in cell therapy, regenerative medicine, and targeted drug delivery. Pooled human platelet lysates (HPLs) can be produced from allogeneic PCs that have reached their expiration date and are no longer suitable for transfusion but remain valuable source materials for other applications. These HPLs can substitute for fetal bovine serum as a clinical grade xeno-free supplement of growth media used in the in vitro expansion of human cells for transplantation purposes. The use of expired allogeneic platelet concentrates has opened the way for small-pool or large-pool allogeneic HPLs and HPL-derived p-EVs as biotherapy for ocular surface disorders, wound care and, potentially, neurodegenerative diseases, osteoarthritis, and others. Additionally, allogeneic platelets are now seen as a readily available source of cells and EVs that can be exploited for targeted drug delivery vehicles. This article aims to offer an in-depth update on emerging translational applications of allogeneic platelet biotherapies while also highlighting their advantages and limitations as a clinical modality in regenerative medicine and cell therapies. [ABSTRACT FROM AUTHOR]

Background: The remarkable abilities of the human brain are distinctive features that set us apart from other animals. However, our understanding of how the brain has changed in the human lineage remains incomplete, but is essential for understanding cognition, behavior, and brain disorders in humans. Here, we compared the expression trajectory in brain development between humans and rhesus macaques (Macaca mulatta) to explore their divergent transcriptome profiles. Results: Results showed that brain development could be divided into two stages, with a demarcation date in a range between 25 and 26 postconception weeks (PCW) for humans and 17-23PCWfor rhesus macaques, rather than birth time that have been widely used as a uniform demarcation time of neurodevelopment across species. Dynamic network biomarker (DNB) analysis revealed that the two demarcation dates were transition phases during brain development, after which the brain transcriptome profiles underwent critical transitions characterized by highly fluctuating DNB molecules. We also found that changes between early and later brain developmental stages (as defined by the demarcation points) were substantially greater in the human brain than in the macaque brain. To explore the molecular mechanism underlying prolonged timing during early human brain development, we carried out expression heterochrony tests. Results demonstrated that compared to macaques, more heterochronic genes exhibited neoteny during early human brain development, consistent with the delayed demarcation time in the human lineage, and proving that neoteny in human brain development could be traced to the prenatal period. We further constructed transcriptional networks to explore the profile of early human brain development and identified the hub gene RBFOX1 as playing an important role in regulating early brain development. We also found RBFOX1 evolved rapidly in its non-coding regions, indicating that this gene played an important role in human brain evolution. Our findings provide evidence that RBFOX1 is a likely key hub gene in early human brain development and evolution. Conclusions: By comparing gene expression profiles between humans and macaques, we found divergent expression trajectories between the two species, which deepens our understanding of the evolution of the human brain. [ABSTRACT FROM AUTHOR]

Background: The underlying pathophysiology of BA distribution is unclear and intriguing. Using high-resolution magnetic resonance imaging (HR-MRI), we sought to explore the plaque distribution of low-grade basilar artery (BA) atherosclerosis and its clinical relevance.Methods: We retrospectively analyzed the imaging and clinical data of 61 patients with low-grade atherosclerotic BA stenosis (<50%). On HR-MRI, the plaques were categorized based on the involvement of the ventral, dorsal, or lateral sides of BA wall. A culprit plaque was defined if it was on the same slice or neighboring slices of symptomatic pontine infarcts and played a probable causal role (dorsal plaques with median pontine infarcts or lateral plaques with ipsilateral pontine infarcts). The relationships between plaque distribution and clinical presentations were analyzed.Results: Twenty-five symptomatic and thirty-six asymptomatic BAs with 752 HR-MRI image slices were studied. The average length of BA atherosclerosis plaques was 12.16 ± 5.61mm (10.30 ± 6.44mm in symptomatic and 13.46 ± 7.03mm in asymptomatic patients, p = 0.079). The plaque distribution was similar at ventral (29.0%), dorsal (37.6%) and lateral walls (33.1%). The BA plaques in symptomatic patients were more frequently located at the dorsal (42.5%) and lateral (41.2%) walls than at the ventral walls (16.1%; P < 0.05). Compared with symptomatic patients, asymptomatic patients more likely had their plaques distributed at the ventral walls (P = 0.022). Culprit plaques were observed in 85.0% (17/20) pontine infarcts in symptomatic patients and only 14.3% (2/14) silent pontine infarcts in asymptomatic patients (p < 0.001).Conclusions: Low-grade BA atherosclerosis has a long distribution and evenly involves ventral, dorsal and lateral walls. The plaques at dorsal and lateral walls are associated with symptomatic pontine infarcts but not with silent infarcts. [ABSTRACT FROM AUTHOR]

Background: A lot of time and money was needed during the diagnosis and treatment process of leprosy, the delayed leprosy would also impair the labor capability of patients as well, and these put a heavy burden for the leprosy patients. The migrant leprosy patient is a special group and need more concern. Our goal was to assess the economic burden of leprosy on migrant and resident patient populations in Guangdong province, China.Methods: We conducted a population-based cross-sectional survey from February to July of 2016. A self-designed questionnaire was administered to leprosy patients who: (1) had registered in Leprosy Management Information System in China (LEPMIS) by the end of February 2016, (2) had received multiple drug treatment (MDT) drugs at a local leprosy control institution for three consecutive months or had had at least one physical check in the past half year, and (3) were willing to take part in the investigation and give informed written consent. Demographic characteristics, Financial and disease information, and costs before and after leprosy diagnosis were collected and compared using t-test and χ2 test.Results: A total of 254 participants completed the questionnaires, including 168 males and 86 females. Migrants and residents accounted for 33.9% and 66.1% of patients, respectively. Among migrant patients, the median cost before diagnosis was $131.6 (39.2-450.9), the median yearly cost of leprosy treatment after diagnosis was $300.6 (158.4-868.5), and the median yearly cost of leprosy complications was $69.5 (11-178.4). In comparison, among residents the median yearly costs were $152.4 (30.7-770.9) pre-diagnosis, $309.7 (103.2-1016.7) after diagnosis, and $91.9 (32.6-303.1) for leprosy complications. Base on this, we determined that the median yearly total expense after diagnosis amounted to 15% of migrant and 38% of resident patients' annual income.Conclusion: Leprosy places a heavy economic burden on both migrant and resident leprosy patients and governmental policies and programs could substantially alleviate this. Measures to implement more active surveillance and early diagnosis would benefit both populations, while labor protection and medical insurance are urgently needed for migrant patients and easier access to medical services and social aids could substantially decrease the burden of leprosy for resident patients. [ABSTRACT FROM AUTHOR]

Background: Our study aimed to design a tool of evaluating intersectional collaboration on Non-communicable Chronic Disease (NCD) prevention and control, and further to understand the current status of intersectional collaboration in community health service institutions of China.Methods: We surveyed 444 main officials of community health service institutions in Beijing, Tianjin, Hubei and Ningxia regions of China in 2014 by using a questionnaire. A model of collaboration measurement, including four relational dimensions of governance, shared goals and vision, formalization and internalization, was used to compare the scores of evaluation scale in NCD management procedures across community healthcare institutions and other ones. Reliability and validity of the evaluation tool on inter-organizational collaboration on NCD prevention and control were verified.Results: The test on tool evaluating inter-organizational collaboration in community NCD management revealed a good reliability and validity (Cronbach's Alpha = 0.89,split-half reliability = 0.84, the variance contribution rate of an extracted principal component = 49.70%). The results of inter-organizational collaboration of different departments and management segments showed there were statistically significant differences in formalization dimension for physical examination (p = 0.01).There was statistically significant difference in governance dimension, formalization dimension and total score of the collaboration scale for health record sector (p = 0.01,0.00,0.00). Statistical differences were found in the formalization dimension for exercise and nutrition health education segment (p = 0.01). There were no statistically significant difference in formalization dimension of medication guidance for psychological consultation, medical referral service and rehabilitation guidance (all p > 0.05).Conclusion: The multi-department collaboration mechanism of NCD prevention and control has been rudimentarily established. Community management institutions and general hospitals are more active in participating in community NCD management with better collaboration score, whereas the CDC shows relatively poor collaboration in China. Xing-ming Li and Alon Rasooly have the same contribution to the paper. Xing-ming Li and Alon Rasooly listed as the same first author. [ABSTRACT FROM AUTHOR]

Background: Sugarcane (Saccharum officinarum L.) is an economically important crop, mainly due to the production of sugar and biofuel (Azevedo RA, Carvalho RF, Cia MC, & Gratão PL, Trop Plant Biol 4:42-51, 2011). Grown mainly in tropical and subtropical countries, sugarcane is a highly polyploid plant with up to ten copies of each chromosome, which increases the difficulties of genome assembly and genetic, physiologic and biochemical analyses. The increasing demands of sugar and the increasing cost of sugarcane harvest require sugarcane varieties which can shed their leaves during the maturity time, so it is important to study the mechanism of leaf abscission in sugarcane. Results: To improve the understanding of miRNA roles in sugarcane leaf abscission, we reported the genome-wide characterization of miRNAs and their putative targets in sugarcane using deep sequencing for six small RNA libraries. In total, 93 conserved miRNAs and 454 novel miRNAs were identified in sugarcane using previously reported transcriptome as reference. Among them, 25 up-regulated and 13 down-regulated miRNAs were identified in leaf abscission sugarcane plants (LASP) compared to leaf packaging sugarcane plants (LPSP). Target prediction revealed several miRNA-mRNA modules including miR156-SPL, miR319-TPR2, miR396-GRF and miR408-LAC3 might be involved in the sugarcane leaf abscission. KEGG pathway enrichment analysis showed differentially expressed miRNAs may regulate pathways like "plant hormone signal transduction" and "plant-pathogen interaction", which is consistent with previous transcriptome study. In addition, we identified 96 variant miRNAs with 135 single nucleotide polymorphisms (SNPs). The expression of sugarcane miRNAs and variant miRNAs were confirmed by qRT-PCR. We identified a possible poaceae specific miRNA called miR5384 for the first time in sugarcane. Conclusions: We not only reported miR5384, a possible poaceae specific miRNA, for the first time in sugarcane but also presented some miRNA-mRNA modules including miR156-SPL, miR319-TPR2, miR396-GRF and miR408-LAC in sugarcane. These modules might be involved in the regulation of sugarcane leaf abscission during the maturity time. All of these findings may lay ground work for future application of sugarcane breeding program and benefit research studies of sugarcane miRNAs. [ABSTRACT FROM AUTHOR]

Background: Cerebral amyloid angiopathy (CAA) is characterized by the deposition of ß-amyloid peptides (Aß) in and surrounding the wall of microvasculature in the central nervous system, together with parenchymal amyloid plaques collectively referred to as cerebral amyloidosis, which occurs in the brain commonly among the elderly and more frequently in patients with Alzheimer's disease (AD). CAA is associated with vascular injury and may cause devastating neurological outcomes. No therapeutic approach is available for this lesion to date.Main Body: ß-Secretase 1 (BACE1) is the enzyme initiating Aß production. Brain permeable BACE1 inhibitors targeting primarily at the parenchymal plaque pathology are currently evaluated in clinical trials. This article presents findings in support of a role of BACE1 elevation in the development of CAA, in addition to plaque pathogenesis. The rationale, feasibility, benefit and strategic issues for developing BACE1 inhibitors against CAA are discussed. Brain impermeable compounds are considered preferable as they might exhibit sufficient anti-CAA efficacy without causing significant neuronal/synaptic side effects.Conclusion: Early pharmacological intervention to the pathogenesis of CAA is expected to provide significant protection for cerebral vascular health and hence brain health. Brain impermeable BACE1 inhibitors should be optimized and tested as potential anti-CAA therapeutics. [ABSTRACT FROM AUTHOR]

Background: Autophagy is a conserved catabolic process to degrade cellular organelles. The role of autophagy in cancer development is complex. Amplification of fibroblast growth factor receptor 1 (FGFR1) is one of the most frequent targets in lung squamous cell carcinoma (SQCC). Whether fibroblast growth factor 2 (FGF2)/FGFR1 contributes to the regulation of autophagy remains elusive. Methods: Autophagic activity was evaluated by immunoblotting for microtubule-associated protein 1 light chain 3 (LC3), formation of GFP-LC3 puncta, and monodansylcadaverine (MDC) staining. The effect of autophagy inhibition on cell survival was assessed by cell viability and apoptosis assays. Results: We elucidated that FGFR1 activation suppressed autophagy. Pharmacological or genetic inhibition of FGFR1 by AZD4547 or FGFR1 short hairpin RNA (shRNA) induced autophagy in FGFR1-amplified non-small cell lung cancer (NSCLC) cells, H1581 and H520 cells. Mechanistic study revealed that the induction of autophagy by FGFR1 inhibition was mediated through inhibiting the ERK/MAPK pathway not by AKT pathway, accompanied by upregulation of beclin-1. Furthermore, activation of ERK/MAPK by transfection with a constitutively active MEK1 (caMEK1) construct or knockdown of beclin-1 by RNAi could attenuate autophagy induced by FGFR1 inhibition. Beclin-1 expression was inversely correlated with MEK1 phosphorylation. Inhibition of autophagy by beclin-1 silencing could enhance apoptosis after AZD4547 treatment in H1581 and H520 cells. High levels of LC3B mRNA was a marker of poor prognosis in NSCLC patients. Conclusions: Simultaneously inhibiting FGFR1 and autophagy could enhance cell death which should be further explored in vivo. [ABSTRACT FROM AUTHOR]

Background: Probiotic bacteria are known to modulate host immune responses against various pathogens. Recently, extracellular vesicles (EVs) have emerged as potentially important mediators of host-pathogen interactions. In this study, we explored the role of L. plantarum derived EVs in modulating host responses to vancomycin-resistant Enterococcus faecium (VRE) using both Caenorhabditis elegans and human cells. Results: Our previous work has shown that probiotic conditioning C. elegans with L. acidophilus NCFM prolongs the survival of nematodes exposed to VRE. Similarly, L. plantarum WCFS1 derived extracellular vesicles (LDEVs) also significantly protected the worms against VRE infection. To dissect the molecular mechanisms of this EV-induced protection, we found that treatment of C. elegans with LDEVs significantly increased the transcription of host defense genes, cpr-1 and clec-60. Both cpr-1 and clec-60 have been previously reported to have protective roles against bacterial infections. Incubating human colon-derived Caco-2 cells with fluorescent dye-labeled LDEVs confirmed that LDEVs could be transported into the mammalian cells. Furthermore, LDEV uptake was associated with significant upregulation of CTSB, a human homologous gene of cpr-1, and REG3G, a human gene that has similar functions to clec-60. Conclusions: We have found that EVs produced from L. plantarum WCFS1 up-regulate the expression of host defense genes and provide protective effects on hosts. Using probiotic-derived EVs instead of probiotic bacteria themselves, this study provides a new direction to treat antimicrobial resistant pathogens, such as VRE. [ABSTRACT FROM AUTHOR]

Background: Non-small cell lung cancer (NSCLC) is the most commonly diagnosed type of lung cancer that is associated with poor prognosis. In this study we explored the potential role of p53-induced gene 3 (PIG3) in the progression of NSCLC. Methods: Immunohistochemistry was used to determine the expression levels of PIG3 in 201 NSCLC patients. We performed in vitro studies and silenced endogenous PIG3 by using specific siRNAs that specific target PIG3. Immunofluorescent staining was performed to determine the effect of PIG3 on mitotic progression in NSCLC cells. The growth rates of microtubules were determined by microtubule nucleation analysis. Cell proliferation and chemosensitivity were analyzed by CCK8 assays. Annexin V staining and β-galactosidase activity analysis were used to evaluate PIG3 deficiency-related apoptosis and senescence, respectively. Results: PIG3 expression levels negatively correlated with overall survival and disease-free survival of NSCLC patients. Knock down of PIG3 resulted in repressed proliferation of NSCLC cells and increased aberrant mitosis, which included misaligning and lagging chromosomes, and bi-or multi-nucleated giant cells. In addition, PIG3 contributed to mitotic spindle assembly by promoting microtubule growth. Furthermore, loss of PIG3 sensitized NSCLC cells to docetaxel by enhancing docetaxel-induced apoptosis and senescence. Conclusions: Our results indicate that PIG3 promotes NSCLC progression and therefore suggest that PIG3 may be a potential prognostic biomarker and novel therapeutic target for the treatment of NSCLC. [ABSTRACT FROM AUTHOR]

Background& Aims: Early oral nutrition (EON) has been shown to improve recovery of gastrointestinal function, length of stay and mortality after abdominal surgery; however, early oral nutrition often fails during the first week after surgery. Here, a multi-modal early oral nutrition program is introduced to promote recovery of gastrointestinal function and tolerance of oral nutrition.Methods: Consecutive patients scheduled for abdominal surgery were randomized to the multimodal EON group or a group receiving conventional care. The primary endpoint was the time of first defecation. The secondary endpoints were outcomes and the cost-effectiveness ratio in treating infectious complications. The rate of infectious-free patients was regarded as the index of effectiveness.Results: One hundred seven patients were randomly assigned to groups. Baseline characteristics were similar for both groups. In intention-to-treat analysis, the success rate of oral nutrition during the first week after surgery in the multimodal EON group was 44 (83.0%) versus 31 (57.4%) in the conventional care group (P = 0.004). Time to first defecation, time to flatus, recovery time of bowel sounds, and prolonged postoperative ileus were all less in the multimodal EON group (P < 0.05). The median postoperative length of stay in the multimodal EON group was 8 days (6, 12) versus 10 days (7, 18) in the conventional care group (P < 0.001). The total cost of treatment and nutritional support were also less in the multi-modal early oral nutrition group (P < 0.001). The effectiveness was 84.9 and 79.9% in the multimodal EON and conventional care group, respectively (P = 0.475). However, the cost-effectiveness ratio was USD 537.6 (506.1, 589.3) and USD 637.8 (593.9, 710.3), respectively (P < 0.001).Conclusion: The multi-modal early oral nutrition program was an effective way to improve tolerance of oral nutrition during the first week after surgery, decrease the length of stay and improve cost-effectiveness after abdominal surgery.Trial Registration: Registration number: ChiCTR-TRC-14004395 . Registered 15 March 2014. [ABSTRACT FROM AUTHOR]

Background: The study aimed to investigate the utility of dynamic contrast enhanced MRI (DCE-MRI) in the differentiation of malignant, borderline, and benign complex ovarian tumors. Methods: DCE-MRI data of 102 consecutive complex ovarian tumors (benign 15, borderline 16, and malignant 71), confirmed by surgery and histopathology, were analyzed retrospectively. The patterns (I, II, and III) of time-signal intensity curve (TIC) and three semi-quantitative parameters, including enhancement amplitude (EA), maximal slope (MS), and time of half rising (THR), were evaluated and compared among benign, borderline, and malignant ovarian tumors. The types of TIC were compared by Pearson Chi-square X² between malignant and benign, borderline tumors. The mean values of EA, MS, and THR were compared using one-way ANOVA or nonparametric Kruskal-Wallis test. Results: Fifty-nine of 71 (83%) malignant tumors showed a type-III TIC; 9 of 16 (56%) borderline tumors showed a type-II TIC, and 10 of 15 (67%) benign tumors showed a type-II TIC, with a statistically significant difference between malignant and benign tumors (P < 0.001) and between malignant and borderline tumors (P < 0.001). MS was significantly higher in malignant tumors than in benign tumors and in borderline than in benign tumors (P < 0.001, P = 0.013, respectively). THR was significantly lower in malignant tumors than in benign tumors and in borderline than in benign tumors (P < 0.001, P = 0.007, respectively). There was no statistically significant difference between malignant and borderline tumors in MS and THR (P = 0.19, 0.153) or among malignant, borderline, and benign tumors in EA (all P > 0.05). Conclusions: DCE-MRI is helpful for characterizing complex ovarian tumors; however, semi-quantitative parameters perform poorly when distinguishing malignant from borderline tumors. [ABSTRACT FROM AUTHOR]

Background: Building highly qualified General Practitioners (GPs) is key to the development of primary health care. It's therefore urgent to ensure the GPs' quality service under the background of the new round of health care system reforms in China. A new model of GP qualification examination was originally implemented in Pudong New Area of Shanghai, China, which aimed to empirically evaluate the GPs' capability in terms of clinical performance and social recognition. In the current study, an analysis was made of the first two years (2014-2015) of such theoretical and practical examinations on the GPs there with a view to getting a deep insight into the GP community so as to identify the barriers to such a form of GP qualification examination. Methods: The agency survey method was applied to the two-year database of the GP examinees, the formative research conducted to explore the key elements for developing the examination model. The data analysis was performed with SPSS for Windows (Version 19.0) to describe the GPs' overall characteristics, and to make comparisons between different groups. Results: In 2015, the total number of GPs was 1264 in the area, in different districts of which, statistically significant differences were found in sex, age, professional title and employment span (P < 0.05). Such results were found to be similar to those in 2014. The examinees' theoretical scores were statistically different (F = 7.76; P < 0.05), showing a sloping trend from the urban district to the suburban, to the rural and then to the farther rural, as indicated by LSD-t test (P < 0.05). From the theoretical examinations the scores were higher on the western medicine than on the traditional Chinese medicine (F = 22.11; P < 0.05). Conclusions: As suggested by the current study on the GPs' qualification examination, which was pioneered in Pudong New Area of Shanghai, the construction of GP community was far from sufficient. It was a preliminary study and further studies are merited along the construction and development in terms of continuing medical education, performance appraisal and incentive mechanism. [ABSTRACT FROM AUTHOR]

Background: Biohythane production via two-stage fermentation is a promising direction for sustainable energy recovery from lignocellulosic biomass. However, the utilization of lignocellulosic biomass suffers from specific natural recalcitrance. Hydrothermal liquefaction (HTL) is an emerging technology for the liquefaction of biomass, but there are still several challenges for the coupling of HTL and two-stage fermentation. One particular challenge is the limited efficiency of fermentation reactors at a high solid content of the treated feedstock. Another is the conversion of potential inhibitors during fermentation. Here, we report a novel strategy for the continuous production of biohythane from cornstalk through the integration of HTL and two-stage fermentation. Cornstalk was converted to solid and liquid via HTL, and the resulting liquid could be subsequently fed into the two-stage fermentation systems. The systems consisted of two typical high-rate reactors: an upflow anaerobic sludge blanket (UASB) and a packed bed reactor (PBR). The liquid could be efficiently converted into biohythane via the UASB and PBR with a high density of microbes at a high organic loading rate. Results: Biohydrogen production decreased from 2.34 L/L/day in UASB (1.01 L/L/day in PBR) to 0 L/L/day as the organic loading rate (OLR) of the HTL liquid products increased to 16 g/L/day. The methane production rate achieved a value of 2.53 (UASB) and 2.54 L/L/day (PBR), respectively. The energy and carbon recovery of the integrated HTL and biohythane fermentation system reached up to 79.0 and 67.7%, respectively. The fermentation inhibitors, i.e., 5-hydroxymethyl furfural (41.4-41.9% of the initial quantity detected) and furfural (74.7-85.0% of the initial quantity detected), were degraded during hydrogen fermentation. Compared with single-stage fermentation, the methane process during two-stage fermentation had a more efficient methane production rate, acetogenesis, and COD removal. The microbial distribution via Illumina MiSeq sequencing clarified that the biohydrogen process in the two-stage systems functioned not only for biohydrogen production, but also for the degradation of potential inhibitors. The higher distribution of the detoxification family Clostridiaceae, Bacillaceae, and Pseudomonadaceae was found in the biohydrogen process. In addition, a higher distribution of acetate-oxidizing bacteria (Spirochaetaceae) was observed in the biomethane process of the two-stage systems, revealing improved acetogenesis accompanied with an efficient conversion of acetate. Conclusions: Biohythane production could be a promising process for the recovery of energy and degradation of organic compounds from hydrothermal liquefied biomass. The two-stage process not only contributed to the improved quality of the gas fuels but also strengthened the biotransformation process, which resulted from the function of detoxification during biohydrogen production and enhanced acetogenesis during biomethane production. [ABSTRACT FROM AUTHOR]

Objective: To investigate the impact of nutritional support on clinical outcomes in patients at nutritional risk who receive nutritional support that meets guideline standards and those who do not.Methods: This prospective cohort study enrolled hospitalized patients from the Second Affiliated Hospital of Kunming Medical University from February 2010 to June 2012. The research protocols were approved by the university's ethics committee, and the patients signed informed consent forms. The clinical data were collected based on nutritional risk screening, administration of enteral and parenteral nutrition, surgical information, complications, and length of hospital stay.Results: During the study period, 525 patients at nutritional risk were enrolled in the cohorts. Among patients who received nutritional support that met the guideline standards (Cohort 1), the incidence of infectious complications was lower than that in patients who did not meet guideline standards (Cohort 2) (17.1 % vs. 26.9 %, P = 0.01). Subgroup analysis showed that individuals who received a combination of parenteral nutrition (PN) and enteral nutrition (EN) for 7 or more days had a significantly lower incidence of infectious complications (P = 0.001) than those who received only PN for 7 or more days or those who received nutritional support for less than 7 days or at less than 10 kcal/kg/d. Binary logistic regression analysis showed that, after adjusting for confounding factors, nutritional support that met guideline standards for patients with nutritional risk was a protective factor for complications (OR: 0.870, P < 0.002).Conclusions: In patients at nutritional risk after abdominal surgery, nutritional support that meets recommended nutrient guidelines (especially regimens involving PN + EN ≥ 7 days) might decrease the incidence of infectious complications and is worth recommending; however, well-designed trials are needed to confirm our findings. Nutritional support that does not meet the guideline standards is considered clinically undesirable. [ABSTRACT FROM AUTHOR]

Background: The PIK3CA (H1047R) mutation is considered to be a potential predictive biomarker for EGFR-targeted therapies. In this study, we developed a novel PCR-PFLP approach to detect the PIK3CA (H1047R) mutation in high effectiveness.Methods: A 126-bp fragment of PIK3CA exon-20 was amplified by PCR, digested with FspI restriction endonuclease and separated by 3 % agarose gel electrophoresis for the PCR-RFLP analysis. The mutant sequence of the PIK3CA (H1047R) was spiked into the corresponding wild-type sequence in decreasing ratios for sensitivity analysis. Eight-six cases of formalin-fixed paraffin-embedded colorectal cancer (CRC) specimens were subjected to PCR-RFLP to evaluate the applicability of the method.Results: The PCR-RFLP method had a capability to detect as litter as 0.4 % of mutation, and revealed 16.3 % of the PIK3CA (H1047R) mutation in 86 CRC tissues, which was significantly higher than that discovered by DNA sequencing (9.3 %). A positive association between the PIK3CA (H1047R) mutation and the patients' age was first found, except for the negative relationship with the degree of tumor differentiation. In addition, the highly sensitive detection of a combinatorial mutation of PIK3CA, KRAS and BRAF was achieved using individual PCR-RFLP methods.Conclusions: We developed a sensitive, simple and rapid approach to detect the low-abundance PIK3CA (H1047R) mutation in real CRC specimens, providing an effective tool for guiding cancer targeted therapy. [ABSTRACT FROM AUTHOR]

Background: Sugarcane (Saccharum officinarum L.) is an important sugar crop which belongs to the grass family and can be used for fuel ethanol production. The growing demands for sugar and biofuel is asking for breeding a sugarcane variety that can shed their leaves during the maturity time due to the increasing cost on sugarcane harvest. Results: To determine leaf abscission related genes in sugarcane, we generated 524,328,950 paired reads with RNA-Seq and profiled the transcriptome of new born leaves of leaf abscission sugarcane varieties (Q1 and T) and leaf packaging sugarcane varieties (Q2 and B). Initially, 275,018 transcripts were assembled with N50 of 1,177 bp. Next, the transcriptome was annotated by mapping them to NR, UniProtKB/Swiss-Prot, Gene Ontology and KEGG pathway databases. Further, we used TransDecoder and Trinotate to obtain the likely proteins and annotate them in terms of known proteins, protein domains, signal peptides, transmembrane regions and rRNA transcripts. Different expression analysis showed 1,202 transcripts were up regulated in leaf abscission sugarcane varieties, relatively to the leaf packaging sugarcane varieties. Functional analysis told us 62, 38 and 10 upregulated transcripts were involved in plant-pathogen interaction, response to stress and abscisic acid associated pathways, respectively. The upregulation of transcripts encoding 4 disease resistance proteins (RPM1, RPP13, RGA2, and RGA4), 6 ABC transporter G family members and 16 transcription factors including WRK33 and heat stress transcription factors indicate they may be used as candidate genes for sugarcane breeding. The expression levels of transcripts were validated by qRT-PCR. In addition, we characterized 3,722 SNPs between leaf abscission and leaf packaging sugarcane plants. Conclusion: Our results showed leaf abscission associated genes in sugarcane during the maturity period. The output of this study provides a valuable resource for future genetic and genomic studies in sugarcane. [ABSTRACT FROM AUTHOR]

Background: Since chemosensory genes play key roles in insect behaviour, they can potentially be used as new targets for pest control. The cabbage beetle, Colaphellus bowringi, is a serious insect pest of cruciferous vegetables in China and other Asian countries. However, a systematic identification of the chemosensory genes expressed in the antennae has not been reported. Results: We assembled the antennal transcriptome of C. bowringi by using Illumina sequencing technology and identified 104 candidate chemosensory genes by analyzing transcriptomic data, which included transcripts encoding 26 odorant-binding proteins (OBPs), 12 chemosensory proteins (CSPs), four sensory neuron membrane proteins (SNMPs), 43 odorant receptors (ORs), nine ionotropic receptors (IRs), and ten gustatory receptors (GRs). The data obtained are similar to those found in other coleopteran species, suggesting that our approach successfully identified the chemosensory genes of C. bowringi. The expression patterns of 43 OR genes, some of which were predominately found in the antenna or associated with sex-biased expression, were analyzed using quantitative real time RT-PCR (qPCR). Conclusions: Our study revealed that a large number of chemosensory genes are expressed in C. bowringi. These candidate chemosensory genes and their expression profiles in various tissues provide further information on understanding their function in C. bowringi as well as other insects, and identifying potential targets to disrupt the odorant system in C. bowringi so that new methods for pest management can be developed. [ABSTRACT FROM AUTHOR]

Background: Childhood lead poisoning is a public health problem gained widely attention for the health damage caused by lead exposure. Pediatrics defines lead poisoning as BLL of or higher than 10 μg/dL, which leads to harmful effects in nervous system, hematological system and urinary system. This study investigates the percentage of 0-18 year old Chinese population with blood lead level (BLL) ≥10 μg/dL during 1990-2012 by searching epidemiologic studies from electronic database focused on BLL in mainland China. Methods: Epidemiologic studies about BLL in China mainland between January 1990 and October 2012 were searched from electronic databases including CNKI, CBM disc, Wanfang Data, Pubmed and Medline. Data extraction, data analysis and risk of bias assessments were performed. Results: Fifty-five articles were included in analysis containing 200,002 subjects, covering 19 provinces, autonomous regions and municipalities. The corrected pooled rate by trim and fill method under random effect model was 9 % (95 CI: 6 %, 12 %). The corrected pooled lead poisoning rate by trim and fill method was 28.1 % (95 % CI: 21.6 %, 34.6 %) from data published during 1990-2000, much higher than the rate during 2001-2005 (10.5 %, 95 % CI: 6.4 %, 14.5 %) and the rate during 2006-2012 (5.3 %, 95 % CI: 3.7 %, 7 %). The corrected pooled lead poisoning percentage in eastern zone (4.3 %, 95 % CI: 2 %, 6.6 %) was slightly lower than that in western zone (5.8 %, 95 % CI: 3.2 %, 8.5 %) and much lower than in central zone (8.5 %, 95 % CI: 4.9 %, 12.1 %). The corrected pooled rate of population living around mining area (70 %, 95 % CI: 62.7 %, 77.3 %) was much higher than that of population in urban area (9.6 %, 95 % CI: 7.1 %, 12.1 %), suburban area (23.6 %, 95 % CI: 17 %, 30.3 %), rural area (23.8 %, 95 % CI: 6.7 %, 40.9 %) and industrial area (57.5 %, 95 % CI: 28 %, 86.9 %). In male population, the corrected pooled rate (10 %, 95 % CI: 7 %, 13 %) was slightly higher than that in female population (7.7 %, 95 % CI: 5 %, 10.4 %). Considering different age groups, the lead poisoning prevalence gradually rose with the increase of age and reached peak level at preschool age, then declined slightly with age. Conclusion: This meta-analysis revealed lead exposure situation of Chinese population in recent decades which provide robust evidence for policy making. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a multifactorial chronic disease primarily characterized by the degeneration of articular cartilage. Currently, there is a lack of effective treatments for OA other than surgery. The exploration of the mechanisms of occurrence is important in exploring other new and effective treatments for OA. The current evidence shows that the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway plays a vital role in cytogenesis and is involved in OA progression. The terms "JAK2", "STAT3", and "Osteoarthritis"were used in a comprehensive literature search in PubMed to further investigate the relationship between the JAK2/STAT3 signaling pathway and OA. This review focuses on the role and mechanism of JAK2/STAT3 signaling in cartilage degradation, subchondral bone dysfunction, and synovial inflammation. In addition, this review summarizes recent evidence of therapeutic approaches to treat OA by targeting the JAK2/STAT3 pathway to accelerate the translation of evidence into the progression of strategies for OA treatment. Aq2kuF8RhmhLRVBTwsgJsc Video abstract [ABSTRACT FROM AUTHOR]

Background: Childhood lead poisoning is a public health problem gained widely attention for the health damage caused by lead exposure. Pediatrics defines lead poisoning as BLL of or higher than 10 μg/dL, which leads to harmful effects in nervous system, hematological system and urinary system. This study investigates the percentage of 0–18 year old Chinese population with blood lead level (BLL) ≥10 μg/dL during 1990–2012 by searching epidemiologic studies from electronic database focused on BLL in mainland China. Methods: Epidemiologic studies about BLL in China mainland between January 1990 and October 2012 were searched from electronic databases including CNKI, CBM disc, Wanfang Data, Pubmed and Medline. Data extraction, data analysis and risk of bias assessments were performed. Results: Fifty-five articles were included in analysis containing 200,002 subjects, covering 19 provinces, autonomous regions and municipalities. The corrected pooled rate by trim and fill method under random effect model was 9 % (95 CI: 6 %, 12 %). The corrected pooled lead poisoning rate by trim and fill method was 28.1 % (95 % CI: 21.6 %, 34.6 %) from data published during 1990–2000, much higher than the rate during 2001–2005 (10.5 %, 95 % CI: 6.4 %, 14.5 %) and the rate during 2006–2012 (5.3 %, 95 % CI: 3.7 %, 7 %). The corrected pooled lead poisoning percentage in eastern zone (4.3 %, 95 % CI: 2 %, 6.6 %) was slightly lower than that in western zone (5.8 %, 95 % CI: 3.2 %, 8.5 %) and much lower than in central zone (8.5 %, 95 % CI: 4.9 %, 12.1 %). The corrected pooled rate of population living around mining area (70 %, 95 % CI: 62.7 %, 77.3 %) was much higher than that of population in urban area (9.6 %, 95 % CI: 7.1 %, 12.1 %), suburban area (23.6 %, 95 % CI: 17 %, 30.3 %), rural area (23.8 %, 95 % CI: 6.7 %, 40.9 %) and industrial area (57.5 %, 95 % CI: 28 %, 86.9 %). In male population, the corrected pooled rate (10 %, 95 % CI: 7 %, 13 %) was slightly higher than that in female population (7.7 %, 95 % CI: 5 %, 10.4 %). Considering different age groups, the lead poisoning prevalence gradually rose with the increase of age and reached peak level at preschool age, then declined slightly with age. Conclusion: This meta-analysis revealed lead exposure situation of Chinese population in recent decades which provide robust evidence for policy making. [ABSTRACT FROM AUTHOR]

Purpose: To investigate magnetic resonance imaging (MRI) features for differentiating ovarian endometrioid adenocarcinoma (OEC) from high-grade serous adenocarcinoma (HGSC). Materials and methods: Twenty-three patients with 25 OECs and 93 patients with 139 HGSCs confirmed by surgery and pathology underwent conventional MRI and diffusion-weighted imaging (DWI). The MRI features of the tumors, including laterality, size, shape, configuration, signal intensity, ADC value of solid component, enhancement, ascites, synchronous primary cancer (SPC) of the ovary and endometrium, and clinical stage, were evaluated and compared between two groups. Results: The following characteristics were significantly more common for OECs than HGSCs: unilateral (91.3% vs 50.5%, P < 0.001), larger mass (80.0% vs 48.2%, P = 0.005), round or oval shape (64.0% vs 17.3%, P < 0.001), mainly cystic with mural nodules or papillary projections (72.0% vs 18.7%, P < 0.001), cystic component with homogeneous iso- or hyperintensity on T1WI (82.6% vs 4.3%, P < 0.001), moderate enhancement (52.0% vs 26.6%, P = 0.011), no or mild ascites (91.3% vs 57.0%, P = 0.002), and SPC (43.5% vs 4.3%, P < 0.001). The ADC value of the solid component was higher in OECs (0.979 ± 0.197 × 10-3 mm2/s) than in HGSCs (0.820 ± 0.112 × 10-3 mm2/s) (P = 0.002). When a mainly cystic mass with mural nodules or papillary projections was associated with any one of homogeneously iso- or hyperintense cystic component on TIWI, a relatively higher ADC value and SPC, the sensitivity, specificity, accuracy, and positive and negative predictive values for characterizing OEC were 87.0%, 93.5%, 92.2%, 76.9%, and 96.7%, respectively. Conclusions: Conventional MRI combining DWI is helpful for differentiating OECs from HGSCs. [ABSTRACT FROM AUTHOR]

Background: Indigenous women in remote North Queensland have a high prevalence of unhealthy lifestyle behaviors and associated health conditions such as sexual transmitted infections (STI). The association of severe pelvic inflammatory disease (PID) with these factors has not been studied. The purpose of this study is to associate the factors with severe PID, as indicated by hospitalization in a high risk population in North Queensland Indigenous communities. Methods: A cross-sectional association of 1445 Indigenous women using linked hospital separation and survey data during 1998-2005. Results: The mean age of participating women was 37.4 years, 60% were of Aboriginal and 40% were Torres Strait Island (TSI) people. More than half of them (52.5%) were smokers, 9.3% had chlamydia and 2.6% had gonorrhoea with the overall prevalence of STI among those less than 25 years of age being 23.9%. Among the 47 participants diagnosed with PID in the study period, 42.5% were under 25 years and 95.7% (45 cases) were under 55 years (OR 2.5, 95% CI 1.2-4.1 among women younger than 25 compared to those 25 years and over). PID was strongly associated with smoking (OR 3.1, 95% CI 1.4-9.2) independent of age, ethnicity, STI and folate status. Low red cell folate increased PID hospitalization by 4 times (95% CI 1.5-13.2 of lowest quartile compared to the highest quartile) regardless of age. Having a STI significantly increased the likelihood of severe PID by 2.2 times (95% CI: 1.03-4.5) in Indigenous women younger than 45 years, independent of smoking and folate level. The risk of PID hospitalization was higher for gonorrheal infections (OR 3.2, 955 CI 1.1-9.6) compared to chlamydial infections (OR 1.5 95% CI 0.7-3.5). Conclusions: Young Indigenous women in North Queensland communities are at very high risk for STI and PID. Smoking, low folate, and STI are clustered, and are associated with PID hospitalizations. Much of this can be prevented with improved nutrition and access to preventive services, especially tobacco control, regular STI screening and treatment, as well as more investment in sexual health education and awareness. [ABSTRACT FROM AUTHOR]

Background: DNA in herbal decoctions is usually fragmented by extensive boiling and is usually regarded as unsuitable for molecular authentication. This study aims to evaluate the feasibility for molecular authentication methods by multiplex polymerase chain reaction (PCR) and DNA sequencing for decoctions. Methods: The DNA extraction procedure, sample pulverization and boiling time were examined in (1) single herb decoction with Panax ginseng ("ginseng") or P. quinquefolius ("American ginseng"), (2) decoctions of two classical ginseng prescriptions of five herbal materials (Aconitum carmichaeli, Atractylodes macrocephala, P. ginseng, Glycyrrhiza uralensis and Zingiber officinale) and (3) a commercial ready-to-serve ginseng soup. Primers were designed from 26S-18S, ITS2 and trnH-psbA region, with DNA sequences obtained from GenBank. Multiplex PCR was also employed in ginseng or American ginseng decoctions to differentiate between these two herbs. Results: All six herbal species tested in this study could be identified in decoctions. We had four main observations: (1) sample pulverization before boiling improved PCR detection; (2) prolonged boiling increased the DNA concentration but decreased the intactness of DNA fragments; (3) ginseng could be differentiated from American ginseng by multiplex PCR; (4) identification of individual herbs in multi-herb decoctions with prolonged boiling time of 180 min could be achieved. Conclusions: DNA could be amplified from extensively boiled ginseng decoctions, multi-herb decoctions and commercial soup although DNA degradation was critical to successful PCR. [ABSTRACT FROM AUTHOR]

Background DNA in herbal decoctions is usually fragmented by extensive boiling and is usually regarded as unsuitable for molecular authentication. This study aims to evaluate the feasibility for molecular authentication methods by multiplex polymerase chain reaction (PCR) and DNA sequencing for decoctions. Methods The DNA extraction procedure, sample pulverization and boiling time were examined in (1) single herb decoction with Panax ginseng ("ginseng") or P. quinquefolius ("American ginseng"), (2) decoctions of two classical ginseng prescriptions of five herbal materials (Aconitum carmichaeli, Atractylodes macrocephala, P. ginseng, Glycyrrhiza uralensis and Zingiber officinale) and (3) a commercial ready-to-serve ginseng soup. Primers were designed from 26S-18S, ITS2 and trnH-psbA region, with DNA sequences obtained from GenBank. Multiplex PCR was also employed in ginseng or American ginseng decoctions to differentiate between these two herbs. Results All six herbal species tested in this study could be identified in decoctions. We had four main observations: (1) sample pulverization before boiling improved PCR detection; (2) prolonged boiling increased the DNA concentration but decreased the intactness of DNA fragments; (3) ginseng could be differentiated from American ginseng by multiplex PCR; (4) identification of individual herbs in multi-herb decoctions with prolonged boiling time of 180 min could be achieved. Conclusions DNA could be amplified from extensively boiled ginseng decoctions, multi-herb decoctions and commercial soup although DNA degradation was critical to successful PCR. [ABSTRACT FROM AUTHOR]

Background: Peanut is one of the major source for human consumption worldwide and its seed contain approximately 50% oil. Improvement of oil content and quality traits (high oleic and low linoleic acid) in peanut could be accelerated by exploiting linked markers through molecular breeding. The objective of this study was to identify QTLs associated with oil content, and estimate relative contribution of FAD2 genes (ahFAD2A and ahFAD2B) to oil quality traits in two recombinant inbred line (RIL) populations. Results: Improved genetic linkage maps were developed for S-population (SunOleic 97R x NC94022) with 206 (1780.6 cM) and T-population (Tifrunner x GT-C20) with 378 (2487.4 cM) marker loci. A total of 6 and 9 QTLs controlling oil content were identified in the S- and Tpopulation, respectively. The contribution of each QTL towards oil content variation ranged from 3.07 to 10.23% in the S-population and from 3.93 to 14.07% in the T-population. The mapping positions for ahFAD2A (A sub-genome) and ahFAD2B (B sub-genome) genes were assigned on a09 and b09 linkage groups. The ahFAD2B gene (26.54%, 25.59% and 41.02% PVE) had higher phenotypic effect on oleic acid (C18:1), linoleic acid (C18:2), and oleic/linoleic acid ratio (O/L ratio) than ahFAD2A gene (8.08%, 6.86% and 3.78% PVE). The FAD2 genes had no effect on oil content. This study identified a total of 78 main-effect QTLs (M-QTLs) with up to 42.33% phenotypic variation (PVE) and 10 epistatic QTLs (E-QTLs) up to 3.31% PVE for oil content and quality traits. Conclusions: A total of 78 main-effect QTLs (M-QTLs) and 10 E-QTLs have been detected for oil content and oil quality traits. One major QTL (more than 10% PVE) was identified in both the populations for oil content with source alleles from NC94022 and GT-C20 parental genotypes. FAD2 genes showed high effect for oleic acid (C18:1), linoleic acid (C18:2), and O/L ratio while no effect on total oil content. The information on phenotypic effect of FAD2 genes for oleic acid, linoleic acid and O/L ratio, and oil content will be applied in breeding selection. [ABSTRACT FROM AUTHOR]

Background: Recent studies have revealed an inverse epidemiological correlation between Alzheimer’s disease (AD) and cancer − patients with AD show a reduced risk of cancer, while cancer survivors are less likely to develop AD. These late discoveries in human subjects call for explorative studies to unlock the underlying biological mechanism, but also may shed new light on conceptual interrogation of the principal pathogenic players in AD etiology. Discussion: Here we hypothesize that this negative correlation reflects a rebalance of biosynthetic propensity between body systems under the two disease statuses. In normal condition the body cellular systems are maintained homeostatically under a balanced cell degenerative vs. surviving/regenerative propensities, determined by biosynthetic resources for anabolic processing. AD pathogenesis involves neurodegeneration but also aberrant regenerative, or reactive anabolic, burden, while cancer development is driving by uncontrolled proliferation inherent with excessive anabolic activity. The aberrant neural regenerative propensity in AD pathogenesis and the uncontrolled cellular proliferative propensity in cancer pathogeneses can manifest as competitive processes, which could result in the inverse epidemiological correlation seen among the elderly. Summary: The reduced prevalence of AD in cancer survivors may implicate a strong impact of aberrant neural regenerative burden in neurodegeneration. Further explorative studies into the inverse correlation between AD and cancer should include examinations of the proliferative propensity of tumor cells in AD models, and the development of AD-like neuropathology in cancer models as well as following anti-proliferative drug treatment. [ABSTRACT FROM AUTHOR]

We first reported the role of 5-hydroxymethyl-2-furfural (5-HMF) against hypoxia. Here, we studied the mechanism by using oxygen-dependent degradation domain (ODD)-Luc mice, which are a useful model to probe the stabilization of hypoxiainducible factor 1α (HIF-1α). Compared with three other compounds that have been reported to have a role in stabilizing HIF-1α, 5-HMF caused stronger bioluminescence, which is indicative of HIF-1α stability in the brain and kidney of ODD-Luc mice. We further demonstrated that the HIF-1α protein accumulated in response to 5-HMF in the brains and kidneys of these mice, as well as in PC12 cells. Additionally, 5-HMF promoted the nuclear translocation of HIF-1α and the transcriptional activity of HIF-1, which was evaluated by detecting vascular endothelial growth factor (VEGF ) mRNA expression. These results suggest that 5-HMF stabilized HIF-1α and increased its activity. Considering the role of proline hydroxylases (PHDs) in negatively regulating HIF-1α stability, we explored whether 5-HMF interacts with the substrates and cofactors of PHDs, such as 2-oxoglutarate (2-OG), Fe2+ and vitamin C (VC), which affects the activity of PHDs. The result revealed that 5-HMF did not interact with Fe2+ or 2-OG but interacted with VC. This interaction was confirmed by subsequent experiments, in which 5-HMF entered into cells and reduced the VC content. The enhanced stability of HIF-1α by 5-HMF was reversed by VC supplementation, and the improved survival of mice caused by 5-HMF under hypoxia was abrogated by VC supplementation. Thus, we demonstrated for the first time that 5-HMF increases HIF-1α stability by reducing the VC content, which mediates the protection against hypoxia. [ABSTRACT FROM AUTHOR]

Background Cox-regression-based methods have been commonly used for the analyses of survival outcomes, such as age-at-disease-onset. These methods generally assume the hazard functions are proportional among various risk groups. However, such an assumption may not be valid in genetic association studies, especially when complex interactions are involved. In addition, genetic association studies commonly adopt case-control designs. Direct use of Cox regression to case-control data may yield biased estimators and incorrect statistical inference. Results We propose a non-parametric approach, the weighted Nelson-Aalen (WNA) approach, for detecting genetic variants that are associated with age-dependent outcomes. The proposed approach can be directly applied to prospective cohort studies, and can be easily extended for population-based case-control studies. Moreover, it does not rely on any assumptions of the disease inheritance models, and is able to capture high-order gene-gene interactions. Through simulations, we show the proposed approach outperforms Cox-regression-based methods in various scenarios. We also conduct an empirical study of progression of nicotine dependence by applying the WNA approach to three independent datasets from the Study of Addiction: Genetics and Environment. In the initial dataset, two SNPs, rs6570989 and rs2930357, located in genes GRIK2 and CSMD1, are found to be significantly associated with the progression of nicotine dependence (ND). The joint association is further replicated in two independent datasets. Further analysis suggests that these two genes may interact and be associated with the progression of ND. Conclusions As demonstrated by the simulation studies and real data analysis, the proposed approach provides an efficient tool for detecting genetic interactions associated with age-at-onset outcomes. [ABSTRACT FROM AUTHOR]

We first reported the role of 5-hydroxymethyl-2-furfural (5-HMF) against hypoxia. Here, we studied the mechanism by using oxygen-dependent degradation domain (ODD)-Luc mice, which are a useful model to probe the stabilization of hypoxiainducible factor 1α (HIF-1α). Compared with three other compounds that have been reported to have a role in stabilizing HIF-1α, 5-HMF caused stronger bioluminescence, which is indicative of HIF-1α stability in the brain and kidney of ODD-Luc mice. We further demonstrated that the HIF-1α protein accumulated in response to 5-HMF in the brains and kidneys of these mice, as well as in PC12 cells. Additionally, 5-HMF promoted the nuclear translocation of HIF-1α and the transcriptional activity of HIF-1, which was evaluated by detecting vascular endothelial growth factor (VEGF ) mRNA expression. These results suggest that 5-HMF stabilized HIF-1α and increased its activity. Considering the role of proline hydroxylases (PHDs) in negatively regulating HIF-1α stability, we explored whether 5-HMF interacts with the substrates and cofactors of PHDs, such as 2-oxoglutarate (2-OG), Fe2+ and vitamin C (VC), which affects the activity of PHDs. The result revealed that 5-HMF did not interact with Fe2+ or 2-OG but interacted with VC. This interaction was confirmed by subsequent experiments, in which 5-HMF entered into cells and reduced the VC content. The enhanced stability of HIF-1α by 5-HMF was reversed by VC supplementation, and the improved survival of mice caused by 5-HMF under hypoxia was abrogated by VC supplementation. Thus, we demonstrated for the first time that 5-HMF increases HIF-1α stability by reducing the VC content, which mediates the protection against hypoxia. [ABSTRACT FROM AUTHOR]

Objective The aim of this study is to assess the association between the degree of insulin resistance and the different components of the metabolic syndrome among Chinese children and adolescents. Moreover, to determine the cut-off values for homeostasis model assessment of insulin resistance (HOMA-IR) at MS risk. Methods 3203 Chinese children aged 6 to 18 years were recruited. Anthropometric and biochemical parameters were measured. Metabolic syndrome (MS) was identified by a modified Adult Treatment Panel III (ATP III) definition. HOMA-IR index was calculated and the normal reference ranges were defined from the healthy participants. Receiver operating characteristic (ROC) analysis was used to find the optimal cutoff of HOMA-IR for diagnosis of MS. Results With the increase of insulin resistance (quintile of HOMA-IR value), the ORs of suffering MS or its related components were significantly increased. Participants in the highest quintile of HOMA-IR were about 60 times more likely to be classified with metabolic syndrome than those in the lowest quintile group. Similarly, the mean values of insulin and HOMA-IR increased with the number of MS components. The present HOMA-IR cutoff point corresponding to the 95th percentile of our healthy reference children was 3.0 for whole participants, 2.6 for children in prepubertal stage and 3.2 in pubertal period, respectively. The optimal point for diagnosis of MS was 2.3 in total participants, 1.7 in prepubertal children and 2.6 in pubertal adolescents, respectively, by ROC curve, which yielded high sensitivity and moderate specificity for a screening test. According to HOMA-IR > 3.0, the prevalence of insulin resistance in obese or MS children were 44.3% and 61.6% respectively. Conclusions Our data indicates insulin resistance is common among Chinese obese children and adolescents, and is strongly related to MS risk, therefore requiring consideration early in life. As a reliable measure of insulin resistance and assessment of MS risk, the optimal HOMA-IR cut-off points in this cohort were developed with variation regarding puberty. HOMA-IR may be useful for early evaluating insulin resistance in children and teenagers and could have a long-term benefit of preventive and diagnostic therapeutic intervention. [ABSTRACT FROM AUTHOR]

Background Studies suggest that not only is insecticide resistance conferred via multiple gene upregulation, but it is mediated through the interaction of regulatory factors. However, no regulatory factors in insecticide resistance have yet been identified, and there has been no examination of the regulatory interaction of resistance genes. Our current study generated the first reference transcriptome from the adult house fly and conducted a whole transcriptome analysis for the multiple insecticide resistant strain ALHF (wild-type) and two insecticide susceptible strains: aabys (with morphological recessive markers) and CS (wild type) to gain valuable insights into the gene interaction and complex regulation in insecticide resistance of house flies, Musca domestica. Results Over 56 million reads were used to assemble the adult female M. domestica transcriptome reference and 14488 contigs were generated from the de novo transcriptome assembly. A total of 6159 (43%) of the contigs contained coding regions, among which 1316 genes were identified as being co-up-regulated in ALHF in comparison to both aabys and CS. The majority of these up-regulated genes fell within the SCOP categories of metabolism, general, intra-cellular processes, and regulation, and covered three key detailed function categories: redox detailed function category in metabolism, signal transduction and kinases/phosphatases in regulation, and proteases in intra-cellular processes. The redox group contained detoxification gene superfamilies, including cytochrome P450s, glutathione S-transferases, and esterases. The signal transduction and kinases/phosphatases groups contained gene families of rhodopsin-like GPCRs, adenylate and guanylate cyclases, protein kinases and phosphatases. The proteases group contained genes with digestive, catalytic, and proteinase activities. Genetic linkage analysis with house fly lines comparing different autosomal combinations from ALHF revealed that the up-regulation of gene expression in the three key SCOP detailed function categories occurred mainly through the co-regulation of factors among multiple autosomes, especially between autosomes 2 and 5, suggesting that signaling transduction cascades controlled by GPCRs, protein kinase/phosphates and proteases may be involved in the regulation of resistance P450 gene regulation. Conclusion Taken together, our findings suggested that not only is insecticide resistance conferred via multi-resistance mechanisms or up-regulated genes, but it is mediated through the trans and/or cis co-regulations of resistance genes. [ABSTRACT FROM AUTHOR]

Background: Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality worldwide, and novel treatment modalities to improve the prognosis of patients with advanced disease are highly desirable. Oncolytic virotherapy is a promising approach for the treatment of advanced NSCLC. MicroRNAs (miRNAs) may be a factor in the regulation of tumor-specific viral replication. The purpose of this study was to investigate whether miRNA-145 regulated oncolytic herpes simplex virus-1 (HSV-1) can selectively kill NSCLC cells with reduced collateral damage to normal cells. Methods: We incorporated 4 copies of miRNA-145 target sequences into the 3'-untranslated region of an HSV-1 essential viral gene, ICP27, to create AP27i145 amplicon viruses and tested their target specificity and toxicity on normal cells and lung cancer cells in vitro. Results: miRNA-145 expression in normal cells was higher than that in NSCLC cells. AP27i145 replication was inversely correlated with the expression of miRNA-145 in infected cells. This oncolytic HSV-1 selectively reduced cell proliferation and prevented the colony formation of NSCLC cells. The combination of radiotherapy and AP27i145 infection was significantly more potent in killing cancer cells than each therapy alone. Conclusions: miRNA-145-regulated oncolytic HSV-1 is a promising agent for the treatment of NSCLC. [ABSTRACT FROM AUTHOR]

Background: One of the key genes that regulate human brain size, MCPH1 has evolved under strong Darwinian positive selection during the evolution of primates. During this evolution, the divergence of MCPH1 protein sequences among primates may have caused functional changes that contribute to brain enlargement. Results: To test this hypothesis, we used co-immunoprecipitation and reporter gene assays to examine the activating and repressing effects of MCPH1 on a set of its down-stream genes and then compared the functional outcomes of a series of mutant MCPH1 proteins that carry mutations at the human- and great-ape-specific sites. The results demonstrate that the regulatory effects of human MCPH1 and rhesus macaque MCPH1 are different in three of eight down-stream genes tested (p73, cyclinE1 and p14ARF), suggesting a functional divergence of MCPH1 between human and non-human primates. Further analyses of the mutant MCPH1 proteins indicated that most of the human-specific mutations could change the regulatory effects on the down-stream genes. A similar result was also observed for one of the four great-ape-specific mutations. Conclusions: Collectively, we propose that during primate evolution in general and human evolution in particular, the divergence of MCPH1 protein sequences under Darwinian positive selection led to functional modifications, providing a possible molecular mechanism of how MCPH1 contributed to brain enlargement during primate evolution and human origin. [ABSTRACT FROM AUTHOR]

Background Recently several reports have indicated that elevated expression of DKK1 is tightly associated with the progression of hepatocellular carcinoma (HCC). However, the biological function of DKK1 in HCC has not yet been well documented. Methods In this study, the role of DKK1 in tumor cell proliferation, migration and invasion was investigated using MTT, colony formation, wound scratch, transwell assays, and also human HCC samples. Results Both gain- and loss-of-function studies showed that DKK1 did not influence the tumor cell proliferation and colony formation, while dramatically promoted HCC cell migration and invasion. Subsequent investigations revealed that β-catenin was an important target of DKK1. The blocking of β-catenin by pharmacological inhibitor antagonized the function of DKK1, whereas introduction of β-catenin by transfection with plasmids or treatment with GSK3β inhibitor phenocopied the pro-migration and pro-invasion effects of DKK1. We further disclosed that DKK1 exerted its pro-invasion function, at least in part, by promoting β- catenin expression, in turn, upregulating the expression of matrix metalloproteinase 7 (MMP7), which was independent of the canonical Wnt signaling pathway. Moreover, introduction of MMP7 significantly enhanced the ability of HCC cells to invade extracellular matrix gel in vitro. Consistently, in human HCC tissues, DKK1 level was positively correlated with β-catenin expression, as well as tumor metastasis. Conclusion Taken together, these results demonstrated that DKK1 is overexpressed in HCC; moreover, ectopic expression DKK1 promotes HCC cell migration and invasion at least partly through β-catenin/MMP7 signaling axis, suggesting that DKK1 may be a promising target for HCC therapy. [ABSTRACT FROM AUTHOR]

Background: HuR is an RNA-binding protein that post-transcriptionally modulates the expressions of various target genes implicated in carcinogenesis, such as CCNA2 encoding cyclin A. No prior study attempted to evaluate the significance of HuR expression in a large cohort with upper urinary tract urothelial carcinomas (UTUCs). Methods: In total, 340 cases of primary localized UTUC without previous or concordant bladder carcinoma were selected. All of these patients received ureterectomy or radical nephroureterectomy with curative intents. Pathological slides were reviewed, and clinical findings were collected. Immunostaining for HuR and cyclin A was performed and evaluated by using H-score. The results of cytoplasmic HuR and nuclear cyclin A expressions were correlated with disease-specific survival (DSS), metastasis-free survival (MeFS), urinary bladder recurrence-free survival (UBRFS), and various clinicopathological factors. Results: HuR cytoplasmic expression was significantly related to the pT status, lymph node metastasis, a higher histological grade, the pattern of invasion, vascular and perineurial invasion, and cyclin A expression (p = 0.005). Importantly, HuR cytoplasmic expression was strongly associated with a worse DSS (p < 0.0001), MeFS (p < 0.0001), and UBRFS (p = 0.0370) in the univariate analysis, and the first two results remained independently predictive of adverse outcomes (p = 0.038, relative risk [RR] = 1.996 for DSS; p = 0.027, RR = 1.880 for MeFS). Cyclin A nuclear expression was associated with a poor DSS (p = 0.0035) and MeFS (p = 0.0015) in the univariate analysis but was not prognosticatory in the multivariate analyses. High-risk patients (pT3 or pT4 with/without nodal metastasis) with high HuR cytoplasmic expression had better DSS if adjuvant chemotherapy was performed (p = 0.015). Conclusions: HuR cytoplasmic expression was correlated with adverse phenotypes and cyclin A overexpression and also independently predictive of worse DSS and MeFS, suggesting its roles in tumorigenesis or carcinogenesis and potentiality as a prognostic marker of UTUC. High HuR cytoplasmic expression might identify patients more likely to be beneficial for adjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. Current therapies are insufficient, making HCC an intractable disease. Our previous studies confirmed that inhibition of protein phosphatase 2A (PP2A) may provide a promising therapeutic strategy for cancer. Unfortunately, constitutive expression of PP2A in normal tissues limits the application of PP2A inhibition. Thus, a HCC-specific gene delivery system should be developed. The a-fetoprotein (AFP) promoter is commonly used in HCC-specific gene therapy strategies; however, the utility of this approach is limited due to the weak activity of the AFP promoter. It has been shown that linking the AFP enhancer with the promoter of the non-tissue-specific, human housekeeping phosphoglycerate kinase (pgk) gene can generate a strong and HCC-selective promoter. Methods: We constructed a HCC-specific gene therapy system to target PP2A using the AFP enhancer/pgk promoter, and evaluated the efficiency and specificity of this system both in vitro and in vivo. Results: AFP enhancer/pgk promoter-driven expression of the dominant negative form of the PP2A catalytic subunit α (DN-PP2Acα) exerted cytotoxic effects against an AFP-positive human hepatoma cell lines (HepG2 and Hep3B), but did not affect AFP-negative human hepatoma cells (SK-HEP-1) or normal human liver cells (L-02). Moreover, AFP enhancer/pgk promoter driven expression of DN-PP2Acα inhibited the growth of AFP-positive HepG2 tumors in nude mice bearing solid tumor xenografts, but did not affect AFP-negative SK-HEP-1 tumors. Conclusions: The novel approach of AFP enhancer/pgk promoter-driven expression of DN-PP2Acα may provide a useful cancer gene therapy strategy to selectively target HCC. [ABSTRACT FROM AUTHOR]

Background: HIV-negative, CD20-negative de novo diffuse large B-cell lymphoma (DLBCL) patients has rarely been reported. To elucidate the nature of this entity, we retrospectively reviewed the data of 1,456 consecutive de novo DLBCL patients who were treated at Sun Yat-Sen University Cancer Center between January 1999 and March 2011. Methods: The pathologic characteristics of CD20-negative patients, clinical features, response to initial treatment, and outcomes of 28 patients with available clinical data (n = 21) were reviewed. Then, a matched case-control (1:3) analysis was performed to compare patients with CD20-negative and -positive DLBCL. Results: The median age of the 28 CD20-negative DLBCL patients was 48 years, with a male-female ratio of 20:8. Seventeen of 22 (77.3%) CD20-negative DLBCL cases were of the non-germinal centre B-cell (non-GCB) subtype. High Ki67 expression (≥80%), an index of cell proliferation, was demonstrated in 17 of 24 (70.8%) cases. Extranodal involvement (≥ 1 site) was observed in 76.2% of the patients. Following initial therapy, 9 of 21 (42.9%) cases achieved complete remission, 4 (19%) achieved partial remission, 1 (4.8%) had stable disease, and 7 (33.3%) had disease progression. The median overall survival was 23 months. The 3-year progression-free survival (PFS) and overall survival (OS) rates were 30.5% and 35%, respectively. A matched case-control analysis showed that patients with CD20-negative and -positive DLBCL did not exhibit a statistically significant difference with respect to the main clinical characteristics (except extranodal involvement), whereas the patients with CD20-positive DLBCL had a better survival outcome with 3-year PFS (P = 0.008) and OS (P = 0.008) rates of 52% and 74.1%, respectively. Conclusions: This study suggests that HIV-negative, CD20-negative de novo DLBCL patients have a higher proportion of non-GCB subtype, a higher proliferation index, more frequent extranodal involvement, a poorer response, and a poorer prognosis to conventional treatment compared to patients with CD20-positive DLBCL. Further studies are warranted to investigate new target and optimal therapy of CD20-negative de novo DLBCL. [ABSTRACT FROM AUTHOR]

We propose a novel aggregating U-test for gene-based association analysis. The method considers both rare and common variants. It adaptively searches for potential disease-susceptibility rare variants and collapses them into a single "supervariant." A forward U-test is then used to assess the joint association of the supervariant and other common variants with quantitative traits. Using 200 simulated replicates from the Genetic Analysis Workshop 17 mini-exome data, we compare the performance of the proposed method with that of a commonly used approach, QuTie. We find that our method has an equivalent or greater power than QuTie to detect nine genes that influence the quantitative trait Q1. This new approach provides a powerful tool for detecting both common and rare variants associated with quantitative traits. [ABSTRACT FROM AUTHOR]

Background: Our previous studies revealed that a new disease form of streptococcal toxic shock syndrome (STSS) is associated with specific Streptococcus suis serotype 2 (SS2) strains. To achieve a better understanding of the pathogenicity and evolution of SS2 at the whole-genome level, comparative genomic analysis of 18 SS2 strains, selected on the basis of virulence and geographic origin, was performed using NimbleGen tiling arrays. Results: Our results demonstrate that SS2 isolates have highly divergent genomes. The 89K pathogenicity island (PAI), which has been previously recognized as unique to the Chinese epidemic strains causing STSS, was partially included in some other virulent and avirulent strains. The ABC-type transport systems, encoded by 89K, were hypothesized to greatly contribute to the catastrophic features of STSS. Moreover, we identified many polymorphisms in genes encoding candidate or known virulence factors, such as PlcR, lipase, sortases, the pilus-associated proteins, and the response regulator RevS and CtsR. On the basis of analysis of regions of differences (RDs) across the entire genome for the 18 selected SS2 strains, a model of microevolution for these strains is proposed, which provides clues into Streptococcus pathogenicity and evolution. Conclusions: Our deep comparative genomic analysis of the 89K PAI present in the genome of SS2 strains revealed details into how some virulent strains acquired genes that may contribute to STSS, which may lead to better environmental monitoring of epidemic SS2 strains. [ABSTRACT FROM AUTHOR]

Background: The halophilic archaeon Haloferax mediterranei is able to accumulate large amounts of poly(3- hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) with high molar fraction of 3-hydroxyvalerate (3HV) from unrelated carbon sources. A Polyhydroxyalkanoate (PHA) synthase composed of two subunits, PhaCHme and PhaCHme, has been identified in this strain, and shown to account for the PHBV biosynthesis. Results: With the aid of the genome sequence of Hfx. mediterranei CGMCC 1.2087, three additional phaC genes (designated phaC1, phaC2, and phaC3) were identified, which encoded putative PhaCs. Like PhaCHme (54.8 kDa), PhaC1 (49.7 kDa) and PhaC3 (62.5 kDa) possessed the conserved motifs of type III PHA synthase, which was not observed in PhaC2 (40.4 kDa). Furthermore, the longer C terminus found in the other three PhaCs was also absent in PhaC2. Reverse transcription PCR (RT-PCR) revealed that, among the four genes, only PhaEHme was transcribed under PHA-accumulating conditions in the wild-type strain. However, heterologous coexpression of PhaEHme with each phaC gene in Haloarcula hispanica PHB-1 showed that all PhaCs, except PhaC2, could lead to PHBV accumulation with various 3HV fractions. The three kinds of copolymers were characterized using gel-permeation chromatography (GPC), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA). Their thermal properties changed with the variations in monomer composition as well as the different molecular weights (Mw), thus might meet various application requirements. Conclusion: We discover three cryptic phaC genes in Hfx. mediterranei, and demonstrate that genetic engineering of these newly identified phaC genes has biotechnological potential for PHBV production with tailor-made material properties. [ABSTRACT FROM AUTHOR]

Background: The interaction between overweight/obesity and alcohol intake on liver enzyme concentrations have been demonstrated. No studies have yet examined the interaction between metabolic syndrome or multiple metabolic risk factors and alcohol intake on liver enzymes. The aim of this study was to examine if alcohol consumption modifies the effect of metabolic risk on elevated serum GGT in Indigenous Australians. Methods: Data were from N = 2609 Indigenous Australians who participated in a health screening program in rural far north Queensland in 1999-2000 (44.5% response rate). The individual and interactive effects of metabolic risk and alcohol drinking on elevated serum GGT concentrations (≥50 U/L) were analyzed using logistic regression. Results: Overall, 26% of the population had GGT≥50 U/L. Elevated GGT was associated with alcohol drinking (moderate drinking: OR 2.3 [95%CI 1.6 -3.2]; risky drinking: OR 6.0 [4.4 -8.2]), and with abdominal obesity (OR 3.7 [2.5-5.6]), adverse metabolic risk cluster profile (OR 3.4 [2.6-4.3]) and metabolic syndrome (OR 2.7 [2.1 - 3.5]) after adjustment for age, sex, ethnicity, smoking, physical activity and BMI. The associations of obesity and metabolic syndrome with elevated GGT were similar across alcohol drinking strata, but the association of an adverse metabolic risk cluster profile with elevated GGT was larger in risky drinkers (OR 4.9 [3.7 - 6.7]) than in moderate drinkers (OR 2.8 [1.6 - 4.9]) and abstainers (OR 1.6 [0.9 - 2.8]). Conclusions: In this Indigenous population, an adverse metabolic profile conferred three times the risk of elevated GGT in risky drinkers compared with abstainers, independent of sex and ethnicity. Community interventions need to target both determinants of the population's metabolic status and alcohol consumption to reduce the risk of elevated GGT. [ABSTRACT FROM AUTHOR]

Background: The genetic etiology of complex diseases in human has been commonly viewed as a complex process involving both genetic and environmental factors functioning in a complicated manner. Quite often the interactions among genetic variants play major roles in determining the susceptibility of an individual to a particular disease. Statistical methods for modeling interactions underlying complex diseases between single genetic variants (e.g. single nucleotide polymorphisms or SNPs) have been extensively studied. Recently, haplotypebased analysis has gained its popularity among genetic association studies. When multiple sequence or haplotype interactions are involved in determining an individual's susceptibility to a disease, it presents daunting challenges in statistical modeling and testing of the interaction effects, largely due to the complicated higher order epistatic complexity. Results: In this article, we propose a new strategy in modeling haplotype-haplotype interactions under the penalized logistic regression framework with adaptive L1-penalty. We consider interactions of sequence variants between haplotype blocks. The adaptive L1-penalty allows simultaneous effect estimation and variable selection in a single model. We propose a new parameter estimation method which estimates and selects parameters by the modified Gauss-Seidel method nested within the EM algorithm. Simulation studies show that it has low false positive rate and reasonable power in detecting haplotype interactions. The method is applied to test haplotype interactions involved in mother and offspring genome in a small for gestational age (SGA) neonates data set, and significant interactions between different genomes are detected. Conclusions: As demonstrated by the simulation studies and real data analysis, the approach developed provides an efficient tool for the modeling and testing of haplotype interactions. The implementation of the method in R codes can be freely downloaded from http://www.stt.msu.edu/∼cui/software.html. [ABSTRACT FROM AUTHOR]

It has been reported that consolidation of motor skill, a type of non-declarative memories, requires protein synthesis, as hippocampus-dependent declarative memory does. However, little is known about the importance of protein synthesis in maintenance and especially post-retrieval reconsolidation of acrobatic motor skill. Here, we show that protein synthesis is essential not only for the consolidation but also for the maintenance and reconsolidation of a rotarod-running skill. Intra-ventricle infusion of the protein synthesis inhibitor anisomycin 0 h but not 2 h post-training caused a severe deficit in the acquisition of the rotarod-running skill. Protein synthesis inhibition (PSI) also caused a deficit in the maintenance of the rotarod-running skill, as well-trained rats demonstrated a deficit in the rotarod-running performance upon treatment with anisomycin. Similarly, PSI impaired the post-retrieval reconsolidation of the rotarod-running skill: well-trained rats treated with anisomycin 0 h but not 0.5, 2 and 4 h after the task performance exhibited amnesia for the running skill later on. Interestingly, rats treated with anisomycin 6 and 12 h post-retrieval exhibited amnesia for the running skill. Thus, protein synthesis is essential not only for the consolidation but also for the maintenance and post-retrieval reconsolidation of rotarod-running acrobatic motor skill. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to characterize thumb motor dysfunction resulting from simulated lower median nerve lesions at the wrist. Methods: Bupivacaine hydrochloride was injected into the carpal tunnel of six healthy subjects to locally anesthetize the median nerve. Motor function was subsequently evaluated by measuring maximal force production in all directions within the transverse plane perpendicular to the longitudinal axis of the thumb. Force envelopes were constructed using these measured multidirectional forces. Results: Blockage of the median nerve resulted in decreased force magnitudes and thus smaller force envelopes. The average force decrease around the force envelope was 27.9%. A maximum decrease of 42.4% occurred in a direction combining abduction and slight flexion, while a minimum decrease of 10.5% occurred in a direction combining adduction and slight flexion. Relative decreases in adduction, extension, abduction, and flexion were 17.3%, 21.2%, 41.2% and 33.5%, respectively. Areas enclosed by pre- and post-block force envelopes were 20628 ± 7747 N.N, and 10700 ± 4474 N.N, respectively, representing an average decrease of 48.1%. Relative decreases in the adduction, extension, abduction, and flexion quadrant areas were 31.5%, 42.3%, 60.9%, and 52.3%, respectively. Conclusion: Lower median nerve lesion, simulated by a nerve block at the wrist, compromise normal motor function of the thumb. A median nerve block results in force deficits in all directions, with the most severe impairment in abduction and flexion. From our results, such a means of motor function assessment can potentially be applied to functionally evaluate peripheral neuropathies. [ABSTRACT FROM AUTHOR]

Background Neddylation, an important post-translational modifcation (PTM) of proteins, plays a crucial role in follicular development. MLN4924 is a small-molecule inhibitor of the neddylation-activating enzyme (NAE) that regulates various biological processes. However, the regulatory mechanisms of neddylation in rabbit ovarian cells have not been emphasized. Here, the transcriptome and metabolome profles in granulosa cells (GCs) treated with MLN4924 were utilized to identify diferentially expressed genes, followed by pathway analysis to precisely defne the altered metabolisms. Results The results showed that 563 upregulated and 910 downregulated diferentially expressed genes (DEGs) were mainly enriched in pathways related to cancer, cell cycle, PI3K-AKT, progesterone-mediated oocyte maturation, and PPAR signaling pathway. Furthermore, we characterized that MLN4924 inhibits PPAR-mediated lipid metabolism, and disrupts the cell cycle by promoting the apoptosis and proliferation of GCs. Importantly, we found the reduction of several metabolites in the MLN4924 treated GCs, including glycerophosphocholine, arachidic acid, and palmitic acid, which was consistent with the deregulation of PPAR signaling pathways. Furthermore, the increased metabolites included 6-Deoxy-6-sulfo-D-glucono-1,5-lactone and N-Acetyl-D-glucosaminyldiphosphodolichol. Combined with transcriptome data analyses, we identifed genes that strongly correlate with metabolic dysregulation, particularly those related to glucose and lipid metabolism. Therefore, neddylation inhibition may disrupt the energy metabolism of GCs. Conclusions These results provide a foundation for in-depth research into the role and molecular mechanism of neddylation in ovary development. [ABSTRACT FROM AUTHOR]

The large numbers of human intestinal microorganisms have a highly co-evolved relationship with the immune system. Dysbacteriosis of intestinal microbiota induces alterations of immune responses, and is closely related to disease development. Peyer's patches are immune sensors in intestine which exert essential functions during development of inflammatory disease. However, interactions between commensal bacteria and PPs have been poorly characterized. In this study, changes of lymphocyte subpopulations and production of cytokines in PPs of mice with intestinal dysbacteriosis were investigated. The ceftriaxone-induced dysbacteriosis caused a notable change in populations of T lymphocytes, their subpopulations in PPs and expressions of various cytokines. Our results suggest intestinal dysbacteriosis in mice reduces immune tolerance in PPs and orients immune response towards humoral immunity. [ABSTRACT FROM AUTHOR]

Background: Amomum compactum is one of the basic species of the traditional herbal medicine amomi fructus rotundus, with great pharmacology effect. The system position of A. compactum is not clear yet, and the introduction of this plant has been hindered by many plant diseases. However, the correlational molecular studies are relatively scarce. Methods: The total chloroplast (cp) DNA was extracted according to previous studies, and then sequenced by 454 GS FLX Titanium platform. Sequence assembly was complished by Newbler. Genome annotation was preformed by CPGAVAS and tRNA-SCAN. Then, general characteristics of the A. compactum cp genome and genome comparsion with three Zingiberaceae species was analyzed by corresponding softwares. Additionally, phylogenetical trees were reconstructed, based on the shared protein-coding gene sequences among 15 plant taxa by maximum parsimony (MP) and maximum likelihood (ML) methods. Results: The A. compactum cp genome with a classic quadripartite structure, consisting of a pair of reverse complement repeat regions (IRa/IRb) of 29,824 bp, a large single copy (LSC, 88,535 bp) region as well as a small single copy (SSC, 15,370 bp) region, is 163,553 bp in total size. The total GC content of this cp genome is 36.0%. The A. compactum cp genome owns 135 functional genes, that 113 genes are unique, containing eighty protein-coding genes, twenty-nine tRNA (transfer RNA) genes and four rRNA (ribosomal RNA) genes. Codon usage of the A. compactum cp genome is biased toward codons ending with A/T. Total 58 SSR loci and 24 large repeats are detected in the A. compactum cp genome. Relative to three other Zingiberaceae cp genomes, the A. compactum cp genome exhibits an obvious expansion in the IR regions. In A. compactum cp genome, the ycf1 pseudogene is 2969 bp away from the IRa/SSC border, whereas in other Zingiberaceae species, it is only 4–5 bp away from the IRa/SSC border. Comparative cp genome sequences analysis of A. compactum with other Zingiberaceae reveals that the gene order and gene content differ slightly among Zingiberaceae species. The phylogenetic analysis based on 67 protein-coding gene sequences supports the phylogenetic position of A. compactum. Conclusions: The study has identified unique features of the A. compactum cp genome which would be helpful for us to understand the cp genome evolution and offer useful information for phylogenetics and further studies of this traditional medicinal plant. [ABSTRACT FROM AUTHOR]

An abstract of the article "Left ventricular twist, but not circumferentiallongitudinal shear angle, increases with increasing age in normal subjects," by Meral Reyhan and colleagues is presented.

Background: The purpose of this study is to investigate the clinical effectiveness of staging radioactive particle implantation guided by computed tomography (CT) and fiber-optic bronchoscopy in treating cancerous large airway stenosis. Methods: A total of 102 patients were included; 57 had undergone staging radioactive particle implantation guided by CT and fiber bronchoscopy and 45 did not. Patients were evaluated by CT and fiber-optic bronchoscopy to determine the feasibility of the implantation of radioactive seeds for the treatment of cancerous large airway stenosis. The treatment planning system (TPS) was used to plan the doses. Radioactive seeds were implanted using fiber-optic bronchoscopy. One week later, CT-guided implantation of radioactive seeds was performed. Results: The clinical evaluation showed complete, partial, slight, and non-response in 38, 14, 5, and 0 patients, respectively. None of the patients were found with serious complications. The diameter of the affected airway, Karnofsky score, dyspnea index, survival, and quality of life of the patients in both groups was significantly higher and significantly different after the treatment (P < 0.05). The dyspnea index was significantly lower in the treatment group as compared with the control group (P < 0.001). Conclusion: CT- and fiber bronchoscopy-guided staging radioactive particle implantation has definite treatment effectiveness in treating cancerous large airway stenosis. It should be widely used in clinical practices. [ABSTRACT FROM AUTHOR]