Lightweight Deep Neural Network Embedded with Stochastic Variational Inference Loss Function for Fast Detection of Human Postures.

Fusing object detection techniques and stochastic variational inference, we proposed a new scheme for lightweight neural network models, which could simultaneously reduce model sizes and raise the inference speed. This technique was then applied in fast human posture identification. The integer-arithmetic-only algorithm and the feature pyramid network were adopted to reduce the computational complexity in training and to capture features of small objects, respectively. Features of sequential human motion frames (i.e., the centroid coordinates of bounding boxes) were extracted by the self-attention mechanism. With the techniques of Bayesian neural network and stochastic variational inference, human postures could be promptly classified by fast resolving of the Gaussian mixture model for human posture classification. The model took instant centroid features as inputs and indicated possible human postures in the probabilistic maps. Our model had better overall performance than the baseline model ResNet in mean average precision (32.5 vs. 34.6), inference speed (27 vs. 48 milliseconds), and model size (46.2 vs. 227.8 MB). The model could also alert a suspected human falling event about 0.66 s in advance.

CSC-3436 sensitizes triple negative breast cancer cells to TRAIL-induced apoptosis through ROS-mediated p38/CHOP/death receptor 5 signaling pathways.

Tumor necrosis factor-related apoptosis-induced ligand (TRAIL) shows little or no toxicity in most normal cells and preferentially induces apoptosis in a variety of malignant cells. However, patients develop resistance to TRAIL, therefore, sensitizing agents that can sensitize the tumor cells to TRAIL-mediated apoptosis are necessary. In this study, we investigated the effect of 2-(3-hydroxyphenyl)-5-methylnaphthyridin-4-one (CSC-3436), an useful flavonoid, to overcome the TRAIL-resistant triple negative breast cancer (TNBC) cells. We found that CSC-3436 potentiated TRAIL-induced apoptosis in TRAIL-resistant TNBC cells and this correlated with the upregulation of death receptors (DR)-5 and down-regulation of decreased decoy receptor (DcR)-1 expression. When examined for its mechanism, we found that the decreased expression of anti-apoptotic proteins c-FLIPS/L, Bcl-Xl, Bcl-2, Survivin, and XIAP. CSC-3436 would increase the expression of Bax and promoted the cleavage of bid. In addition, the induction of DR5 by CSC-3436 was found to be dependent on the modulation of reactive oxygen species (ROS)/p38/C/EBP-homologous protein (CHOP) signaling pathways. Overall, our results indicated that CSC-3436 could potentiate the apoptotic effects of TRAIL through down-regulation of cell survival proteins and upregulation of DR5 via the ROS-mediated upregulation of CHOP protein.

Demethoxycurcumin induces apoptosis in HER2 overexpressing bladder cancer cells through degradation of HER2 and inhibiting the PI3K/Akt pathway.

Bladder cancer is the most common malignancy of the urinary tract and arising from the epithelial lining of the urinary bladder. Resistance to cytotoxic therapies is associated with overexpression of oncogenic proteins; including HER2, and Akt in chemotherapy resistance of bladder cancer. Various studies demonstrated that curcuminoids, the most important active phenolic compounds of turmeric (Curcuma longa), have anti-tumor activities in a wide range of human malignant cell lines. The aim of this study is to evaluate whether curcuminoids (curcumin, demethoxycurcumin (DMC), and bisdemethoxycurcumin) could repress the expression of HER2 in HER2-overexpressing bladder cancer cells. Among the test compounds, DMC significantly suppressed the expression of HER2, and preferentially inhibited cell proliferation and induced apoptosis in HER2-overexpressing bladder cancer cells. DMC decreases HER2 level through inhibiting the interaction of HER2 and Hsp90. Our study also indicated that DMC showed additive activity in combination with chemotherapeutic agents, including paclitaxel and cisplatin. These findings show that DMC should be developed further as a new antitumor drug candidate for treatment of HER2-overexpressing bladder cancer.

Transcriptomics comparison reveals the diversity of ethylene and methyl-jasmonate in roles of TIA metabolism in Catharanthus roseus.

BACKGROUND: The medicinal plant, Catharanthus roseus (C. roseus), accumulates a wide range of terpenoid indole alkaloids (TIAs). Ethylene (ET) and methyl-jasmonate (MeJA) were previously reported as effective elicitors for the production of various valuable secondary metabolites of C. roseus, while a few ET or MeJA induced transcriptomic research is yet reported on this species. In this study, the de-novo transcriptome assembly of C. roseus is performed by using the next-generation sequencing technology. RESULTS: The result shows that phenolic biosynthesis genes respond specifically to ET in leaves, monoterpenoid biosynthesis genes respond specifically to MeJA in roots. By screening the database, 23 ATP-binding cassette (ABC) transporter partial sequences are identified in C. roseus. On this basis, more than 80 key genes that encode key enzymes (namely TIA pathway, transcriptional factor (TF) and candidate ABC transporter) of alkaloid synthesis in TIA biosynthetic pathways are chosen to explore the integrative responses to ET and MeJA at the transcriptional level. Our data indicated that TIA accumulation is strictly regulated by the TF ethylene responsive factor (ERF) and bHLH iridoid synthesis 1 (BIS1). The heatmap, combined with principal component analysis (PCA) of C. roseus, shows that ERF co-expression with ABC2 and ABC8 specific expression in roots affect the root-specific accumulation of vinblastine in C. roseus. On the contrast, BIS1 activities follow a similar pattern of ABC3 and CrTPT2 specific expression in leaves, which affects the leaf-specific accumulation of vindoline in C. roseus. CONCLUSIONS: Results presented above illustrate that ethylene has a stronger effect than MeJA on TIA induction at both transcriptional and metabolite level. Furthermore, meta-analysis reveals that ERF and BIS1 form a positive feedback loop connecting two ABC transporters respectively and are actively involved in TIAs responding to ET and MeJA in C. roseus.

Genome-wide association study identifies novel susceptibility loci for migraine in Han Chinese resided in Taiwan.

Background Susceptibility genes for migraine, despite it being a highly prevalent and disabling neurological disorder, have not been analyzed in Asians by genome-wide association study (GWAS). Methods We conducted a two-stage case-control GWAS to identify susceptibility genes for migraine without aura in Han Chinese residing in Taiwan. In the discovery stage, we genotyped 1005 clinic-based Taiwanese migraine patients and 1053 population-based sex-matched controls using Axiom Genome-Wide CHB Array. In the replication stage, we genotyped 27 single-nucleotide polymorphisms with p < 10-4 in 1120 clinic-based migraine patients and 604 sex-matched normal controls by using Sequenom. Variants at LRP1, TRPM8, and PRDM, which have been replicated in Caucasians, were also genotyped. Results We identified a novel susceptibility locus (rs655484 in DLG2) that reached GWAS significance level for migraine risk in Han Chinese ( p = 1.45 × 10-12, odds ratio [OR] = 2.42), and also another locus (rs3781545in GFRA1) with suggestive significance ( p = 1.27 × 10-7, OR = 1.38). In addition, we observed positive association signals with a similar trend to the associations identified in Caucasian GWASs for rs10166942 in TRPM8 (OR = 1.33, 95% confidence interval [CI] = 1.14-1.54, Ppermutation = 9.99 × 10-5; risk allele: T) and rs1172113 in LRP1 (OR = 1.23, 95% CI = 1.04-1.45, Ppermutation = 2.9 × 10-2; risk allele: T). Conclusion The present study is the first migraine GWAS conducted in Han-Chinese and Asians. The newly identified susceptibility genes have potential implications in migraine pathogenesis. DLG2 is involved in glutamatergic neurotransmission, and GFRA1 encodes GDNF receptors that are abundant in CGRP-containing trigeminal neurons. Furthermore, positive association signals for TRPM8 and LRP1 suggest the possibility for common genetic contributions across ethnicities.

Identifying rare and common disease associated variants in genomic data using Parkinson's disease as a model.

BACKGROUND: Genome-wide association studies have been successful in identifying common genetic variants for human diseases. However, much of the heritable variation associated with diseases such as Parkinson's disease remains unknown suggesting that many more risk loci are yet to be identified. Rare variants have become important in disease association studies for explaining missing heritability. Methods for detecting this type of association require prior knowledge on candidate genes and combining variants within the region. These methods may suffer from power loss in situations with many neutral variants or causal variants with opposite effects. RESULTS: We propose a method capable of scanning genetic variants to identify the region most likely harbouring disease gene with rare and/or common causal variants. Our method assigns a score at each individual variant based on our scoring system. It uses aggregate scores to identify the region with disease association. We evaluate performance by simulation based on 1000 Genomes sequencing data and compare with three commonly used methods. We use a Parkinson's disease case-control dataset as a model to demonstrate the application of our method. Our method has better power than CMC and WSS and similar power to SKAT-O with well-controlled type I error under simulation based on 1000 Genomes sequencing data. In real data analysis, we confirm the association of α-synuclein gene (SNCA) with Parkinson's disease (p = 0.005). We further identify association with hyaluronan synthase 2 (HAS2, p = 0.028) and kringle containing transmembrane protein 1 (KREMEN1, p = 0.006). KREMEN1 is associated with Wnt signalling pathway which has been shown to play an important role for neurodegeneration in Parkinson's disease. CONCLUSIONS: Our method is time efficient and less sensitive to inclusion of neutral variants and direction effect of causal variants. It can narrow down a genomic region or a chromosome to a disease associated region. Using Parkinson's disease as a model, our method not only confirms association for a known gene but also identifies two genes previously found by other studies. In spite of many existing methods, we conclude that our method serves as an efficient alternative for exploring genomic data containing both rare and common variants.

Screening rate constants in the simulation of rapid kinetics of chlorophyll a fluorescence using the Morris method.

Chlorophyll a fluorescence, a sensitive and cost-effective probe, is widely used in photosynthetic research. Its rapid phase, occurring within 1 second under intense illumination, displays complex O-J-I-P transients, providing valuable insights into various aspects of photosynthesis. In addition to employing experimental approaches to measure the rapid Fluorescence Induction (FI) kinetics, mathematical modeling serves as a crucial tool for understanding the underlying mechanisms that drive FI dynamics. However, the significant uncertainty and arbitrary nature of selecting model parameters amplify concerns about the effectiveness of modeling tools in aiding photosynthesis research. Therefore, there is a need to gain a deeper understanding of how these models operate and how arbitrary parameter choices may influence their outcomes. In this study, we employed the Morris method, a global Sensitivity Analysis (SA) tool, to assess the significance of rate constants employed in an existing fluorescence model, particularly those linked to the entire electron transport chain, in shaping the rapid FI dynamics. In summary, utilizing the insights gained from the Morris SA allows for targeted refinement of the photosynthesis model, thereby improving our understanding of the complex processes inherent in photosynthetic systems.

Using maximal segmental score in genome-wide association studies.

Genome-wide association studies (GWAS) have become the method of choice for identifying disease susceptibility genes in common disease genetics research. Despite successes in these studies, much of the heritability remains unexplained due to lack of power and low resolution. High-density genotyping arrays can now screen more than 5 million genetic markers. As a result, multiple comparison has become an important issue especially in the era of next-generation sequencing. We propose to use a two-stage maximal segmental score procedure (MSS) which uses region-specific empirical P-values to identify genomic segments most likely harboring the disease gene. We develop scoring systems based on Fisher's P-value combining method to convert locus-specific significance levels into region-specific scores. Through simulations, our result indicated that MSS increased the power to detect genetic association as compared with conventional methods provided type I error was at 5%. We demonstrated the application of MSS on a publicly available case-control dataset of Parkinson's disease and replicated the findings in the literature. MSS provides an efficient exploratory tool for high-density association data in the current era of next-generation sequencing. R source codes to implement the MSS procedure are freely available at http://www.csjfann.ibms.sinica.edu.tw/EAG/program/programlist.htm.

Effectiveness of Teriparatide for Spine Fusion in Osteoporotic Patient: A Systematic Review and Meta-Analysis of Comparative Studies.

OBJECTIVE: Our goal was to assess teriparatide's (TP) effectiveness in improving radiographic and functional outcomes after spinal fusion surgery. This meta-analysis included randomized controlled trials (RCTs) and comparative cohort studies. The findings provide valuable insights and guidance for surgeons treating osteoporotic patients undergoing spinal fusion surgery. METHODS: We conducted a systematic review to assess TP's efficacy in spinal fusion surgery for osteoporosis. Through thorough selection, data extraction, and quality assessment, we employed network meta-analysis to evaluate radiographic outcomes (fusion rate, screw loosening, vertebral fracture) and changes in bone mineral density measured by Hounsfield units. Functional outcomes were assessed using the Oswestry Disability Index scales. Our study aims to comprehensively understand TP's impact and effectiveness in spinal fusion surgery. RESULTS: A total of 868 patients were included in the analysis. All patients underwent thoracolumbar internal fixation fusion surgery and were divided into following 2 groups: the TP treatment group and the control group. The results revealed significant differences in radiological outcomes. The fusion rate showed a significant difference, as well as screw loosening, and bone mineral density measured in Hounsfield units. However, there was no significant difference in vertebral fracture. The TP group demonstrated favorable effects with statistical significance. In terms of functional outcomes, there was no significant difference in the assessment of Oswestry Disability Index scores between the 2 treatment groups. CONCLUSIONS: The meta-analysis demonstrated that the TP group exhibited significantly better outcomes, particularly in radiological measures, when compared to the control group. The use of TP in spinal fusion surgery shows promise in reducing postoperative complications and providing overall benefits.

Potassium accumulation characteristics and expression of related genes involved in potassium metabolism in a high-potassium variety: tobacco (Nicotiana tabacum) as a model.

We investigated potassium (K) accumulation characteristics and expression of K metabolism related genes in one high-K variety (ND202) and a common variety (NC89) of tobacco (Nicotiana tabacum L.). Results showed that K accumulation and leaf K content in ND202 were higher than those in NC89. The distribution rate and K accumulation in the leaves of ND202 increased significantly, while the distribution rate in the roots and stems had lower values. In addition, the maximum K accumulation rate and high-speed K accumulation duration in ND202 were found to be better than those in NC89. The expression of NKT1 in the upper and middle leaves of ND202 had an advantage, and the relative expression of NtKC1 and NtTPK1 in both the upper and middle leaves, as well as the roots, was also significantly upregulated. Conversely, the expression of NTRK1 in the lower leaves and roots of ND202 was weaker. ND202 had significantly greater expression levels of NtHAK1 than NC89 in the upper and middle leaves and roots; moreover, the expression of NtKT12 in the upper leaves and roots of ND202 was also higher. In comparison with common varieties, high-K varieties had a stronger ability to absorb and accumulate K. They also possessed higher expression of K+ channel- and transporter-related genes and showed a superior K accumulation rate and longer duration of high-speed K accumulation. Furthermore, K accumulation rate at 40-60days can be suggested as an important reference for the selection of high-K tobacco varieties.

Intrathecal lemnalol, a natural marine compound obtained from Formosan soft coral, attenuates nociceptive responses and the activity of spinal glial cells in neuropathic rats.

The investigators previously found that the administration of lemnalol, a natural marine compound isolated from the Formosan soft coral Lemnalia cervicorni, produced anti-inflammatory and analgesic effects in carrageenan-injected rats. Recently, several studies have demonstrated that the development and maintenance of neuropathic pain are accompanied by releasing of proinflammatory mediators from activated glial cells in the spinal cord. In this study, we investigated the antinociceptive properties of lemnalol, a potential anti-inflammatory compound, on chronic constriction injury (CCI) in a well-established rat model of neuropathic pain. Our results demonstrated that a single intrathecal administration of lemnalol (0.05-10 µg) significantly attenuated CCI-induced thermal hyperalgesia and mechanical allodynia, 14 days postsurgery. Furthermore, immunohistofluorescence analyses showed that lemnalol (10 µg) also significantly inhibits CCI-induced upregulation of microglial and astrocytic immunohistochemical activation markers in the dorsal horn of the lumbar spinal cord. Double immunofluorescent staining demonstrated that intrathecal injection of lemnalol (10 µg) markedly inhibited spinal proinflammatory mediator tumor necrosis factor-α expression in microglial cells and astrocytes in neuropathic rats. Collectively, our results indicate that lemnalol is a potential therapeutic agent for neuropathic pain, and that further exploration of the effects of lemnalol on glial proinflammatory responses is warranted.

Bisdemethoxycurcumin Promotes Apoptosis and Inhibits the Epithelial-Mesenchymal Transition through the Inhibition of the G-Protein-Coupled Receptor 161/Mammalian Target of Rapamycin Signaling Pathway in Triple Negative Breast Cancer Cells.

Triple negative breast cancer (TNBC) is one of the leading causes of cancer death in the world and lacks an effective targeted therapy. G-protein-coupled receptor 161 (GPR161) has been demonstrated to perform the functional regulations on TNBC progression and might be a potential new target for TNBC therapy. This study showed the effects of bisdemethoxycurcumin (BDMC) on GPR161 regulation, indicating that BDMC effectively inhibited GPR161 expression and downregulated GPR161-driven signaling. BDMC showed the potent inhibitory effects on TNBC proliferation through suppressing GPR161-mediated mammalian target of rapamycin (mTOR)/70 kDa ribosomal protein S6 kinase (p70S6K) activation. Besides, in this study, we discover the mechanism of GPR161-driven TNBC metastasis, linking to GPR161-mediated twist-related protein 1 (Twist1)/matrix metallopeptidase 9 (MMP9) contributing to the epithelial-mesenchymal transition (EMT). BDMC effectively repressed GPR161-mediated TNBC metastasis via inhibiting Twist1/MMP9-induced EMT. The three-dimensional invasion assay also showed that BDMC significantly inhibited TNBC invasion. The combination treatment of BDMC and rapamycin enhanced the inhibition of TNBC proliferation and metastasis through increasing the blockage of mTOR activation. Furthermore, this study also observed that BDMC activated the caspase 3/9 signaling pathway to induce TNBC apoptosis. Therefore, BDMC could be applicable to anticancer therapy, especially targeting on the GPR161-driven cancer type.

A genome-wide survey of copy number variations in Han Chinese residing in Taiwan.

Copy number variation (CNV) is a form of DNA sequence variation in the human genome. CNVs can affect expression of nearby and distant genes, and some of them might cause certain phenotypic differences. CNVs vary slightly in location and frequency among different populations. Because currently-available CNV information from Asian population was limited to fewer small-scale studies with only dozens of subjects, a high-resolution CNV survey was conducted using a large number of Han Chinese in this study. The Illumina HumanMap550K single-nucleotide polymorphism array was used to identify CNVs from 813 unrelated Han Chinese residing in Taiwan. A total of 365 CNV regions were identified in this population, and the average size of the CNV regions was 235 kb (covering a total of 2.86% of the human genome), and 67 (18.4%) were newly-discovered CNV regions. Two hundred and seventy-nine CNV regions (76%) were verified from 304 randomly-selected samples by Affymetrix 500K GeneChip and qPCR experiments. These regions contain 1029 genes, some of which are associated with diseases. Consistent with previous studies, most CNVs were rare structural variations in the human genome, and only 64 regions (17.5%) had a CNV allele frequency greater than 1%. Our discovery of 67 new CNV regions indicates that previous CNV coverage of the human genome is incomplete and there is diversity among different ethnic populations. The comprehensive knowledge of CNVs in the human genome is very important and useful in further genetic studies.

Activation of potassium released from soil by root-secreted organic acids in different varieties of tobacco (Nicotiana tabacum).

Organic acids secreted from the roots of plants play important roles in nutrient acquisition and metal detoxification; however, the precise underlying mechanisms of these processes remain poorly understood. In the present study we examined the content of organic acids exuded from roots and the effects of these organic acids on the activation of slowly available potassium (K) at different K levels, including normal K supply and K-deficient conditions. In addition, the study system also comprised a high-K tobacco variety (ND202) and two common ones (K326 and NC89). Our results showed that high-K varieties exhibited significantly higher contents of organic acids in its root exudates and available K in both rhizosphere and non-rhizosphere soils than the other varieties. This research also suggested that a cyclic process in which soil was acidified after being complexed by organic acids was involved in the release of slowly available K, and that this process primarily depended on the soil pH at high organic acids concentrations, but the complexation of organic ligands became dominant at low concentrations. In conclusion, tobacco roots secrete organic acids to increase available K content and improve the utilisation rate of soil K. High-K varieties probably enhance slowly available K activation by secreting relatively high amounts of organic acids, thus leading to more available K in soil for absorption by plants.

[Vehicle Emission Inventory and Scenario Analysis in Liaoning from 2000 to 2030].

Vehicle emissions have become a major source of air pollution in urban cities. The vehicle emission inventory of the Liaoning province from 2000 to 2030 was established based on the COPERT model and ArcGIS, and the temporal and spatial distribution characteristics of six pollutants (CO, NMVOC, NOx, PM10, SO2, and CO2) were analyzed. Taking 2016 as the base year, eight scenarios of control measures were designed based on scenario analysis, and the effects of different scenarios on emission reduction were assessed. Results showed that during 2000-2016, CO, NMVOC, NOx, and PM10 emissions at first exhibited increasing trends, after which they decreased. Emissions of SO2 exhibited fluctuating trends, while the emissions of CO2 showed a continuous increase. Passenger cars and motorcycles were the main contributors of CO and NMVOC emissions. Heavy-duty trucks and buses were the main sources of NOx and PM10 emissions. Passenger cars were the major contributors to SO2 and CO2 emissions. Vehicle emissions were significantly higher in the central and southern in Liaoning Province. At the city level, vehicle emissions were mainly concentrated in Shenyang and Dalian. The scenario analysis showed that the implementation of stricter vehicle emission standards can enhance the emission reduction effect. Moreover, accelerating the implementation of new emission standards was beneficial to reduce emissions. The integrated scenario would achieve the maximum emission reduction, with reduction rates of CO, NMVOC, NOx, PM10, CO2, and SO2 at 30.7%, 14.3%, 81.7%, 29.4%, 12.3%, and 12.1%, respectively.

Correction: Aloe-emodin inhibits HER-2 expression through the downregulation of Y-box binding protein-1 in HER-2-overexpressing human breast cancer cells.

[This corrects the article DOI: 10.18632/oncotarget.10410.].

[Pollution Characteristics and Emission Factors of VOCs from Vehicle Emissions in the Tianjin Tunnel].

The pollution characteristics and emission factors (EFs) of the volatile organic compounds (VOCs) of vehicles were investigated using the tunnel test method on weekdays and weekends in the Wujinglu Tunnel in Tianjin, China. Gas samples in the tunnel were collected with 3.2 L stainless steel canisters and 99 VOCs species were analyzed by gas chromatography-mass spectrometry (GC-MS). The concentration levels, variation characteristics, and EFs of the VOCs were analyzed. The ozone formation potentials (OFPs) and secondary organic aerosol formation potentials (SOAFPs) of the VOCs in the tunnel were calculated. Moreover, a comparison of the study results with current literature was conducted. The total concentrations of VOCs at the inlet and midpoint are (190.85±51.15) µg·m-3 and (257.44±62.02) µg·m-3, respectively. The total EFs are (45.12±10.97) mg·(km·veh)-1 and the EFs for alkanes, alkenes, alkynes, aromatics, halocarbons, and oxygenated volatile organic compounds (OVOCs) are (22.79±7.15), (5.04±1.20), (0.78±0.34), (9.86±2.81), (0.26±0.17), and (6.25±2.27) mg·(km·veh)-1, respectively. They are notably smaller than the values obtained in a previous test in 2009. Isopentane, toluene, ethylene, methyl tert-butyl ether (MTBE), and ethane were the top five species among the VOC EFs. The ratios of methyl tert-butyl ether/benzene (MTBE/B) and methyl tert-butyl ether/toluene (MTBE/T) are 1.07 and 0.77, respectively. This implies that the contribution of evaporative emissions from vehicles to VOCs emissions cannot be ignored. The OFPs and SOAFPs in the tunnel are (145.50±37.85) and (43.87±12.75) mg·(km·veh)-1, respectively. Compared with the test in 2009, the OFPs and SOAFPs are 94.23% and 90.88% smaller, respectively. The sharp decrease of the OFPs and SOAFPs is closely related to stricter emission standards and the upgrade of oil products.

Using the longest significance run to estimate region-specific p-values in genetic association mapping studies.

BACKGROUND: Association testing is a powerful tool for identifying disease susceptibility genes underlying complex diseases. Technological advances have yielded a dramatic increase in the density of available genetic markers, necessitating an increase in the number of association tests required for the analysis of disease susceptibility genes. As such, multiple-tests corrections have become a critical issue. However the conventional statistical corrections on locus-specific multiple tests usually result in lower power as the number of markers increases. Alternatively, we propose here the application of the longest significant run (LSR) method to estimate a region-specific p-value to provide an index for the most likely candidate region. RESULTS: An advantage of the LSR method relative to procedures based on genotypic data is that only p-value data are needed and hence can be applied extensively to different study designs. In this study the proposed LSR method was compared with commonly used methods such as Bonferroni's method and FDR controlling method. We found that while all methods provide good control over false positive rate, LSR has much better power and false discovery rate. In the authentic analysis on psoriasis and asthma disease data, the LSR method successfully identified important candidate regions and replicated the results of previous association studies. CONCLUSION: The proposed LSR method provides an efficient exploratory tool for the analysis of sequences of dense genetic markers. Our results show that the LSR method has better power and lower false discovery rate comparing with the locus-specific multiple tests.

Banana Flower Extract Suppresses Benign Prostatic Hyperplasia by Regulating the Inflammatory Response and Inducing G1 Cell-cycle Arrest.

BACKGROUND/AIM: The banana flower is used for ameliorating urinary disturbance. However, there is limited evidence to support the efficacy or mechanism of action of banana flower against benign prostatic hyperplasia (BPH). In the present study, the anti-BPH activity and mechanisms of banana flower extracts were investigated in vitro and in vivo. MATERIALS AND METHODS: The banana flower extract is a water-soluble extract obtained by sonication. MTT assay was used to examine whether banana flower extract exhibited cytotoxic effects on BPH-1 cells. The effect of banana flower extract on cell-cycle distribution was examined by flow cytometry. The expression of cell-cycle-regulatory molecules was determined by western blot analysis. Testosterone propionate (TP)-induced rat model of BPH was used to evaluate the anti-BPH activity of banana flower extract in vivo. RESULTS: Banana flower extract reduced epithelial cell line BPH-1 cell viability through cell-cycle arrest at G1 phase. Moreover, banana flower extract reduced the expression of cyclin D1 and cyclin-dependent kinase 6, while it increased the expression of p53 and p27. Interestingly, banana flower extract suppressed BPH-related inflammatory responses through suppressing cyclo-oxygenase-2 expression and prostaglandin E2 production. Finally, banana flower extract administered orally to male rats reduced prostatic weight and serum dihydrotestosterone level, and improved prostate gland morphology. High-performance liquid chromatography revealed that banana flower extract contains citric acid, taurine, pantothenic acid and nicotinic acid components. In summary, banana flower extract may be used as a therapeutic agent for BPH via anti-proliferative and anti-inflammatory activities.

CHM-1, a novel microtubule-destabilizing agent exhibits antitumor activity via inducing the expression of SIRT2 in human breast cancer cells.

Breast cancer is a major public health problem throughout the world. In this report, we investigated whether CHM-1, a novel synthetic antimitotic agent could be developed into a potent antitumor agent for treating human breast cancer. CHM-1 induced growth inhibition in MDA-MB-231, MDA-MB-453 and MCF-7 cells in a concentration-dependent manner. Importantly, CHM-1 is less toxic to normal breast (HBL-100) cells. CHM-1 interacted with tubulin, markedly inhibited tubulin polymerization, and disrupted microtubule organization. Proteins from control and CHM-1-treated animal tumor specimens were analyzed by two-dimensional electrophoresis and MALDI-TOF mass spectrometry. Our results indicated that CHM-1 increased the expression of SIRT2 protein, an NAD-dependent tubulin deacetylase. A prodrug strategy was also investigated to address the problem of low aqueous solubility and low bioavailability of the antitumor agent CHM-1. The water-soluble prodrug of CHM-1 (CHM-1-P) was synthesized. After oral and intravenous administration, CHM-1-P induced a dose-dependent inhibition of tumor growth. The aforementioned excellent anti-tumor activity profiles of CHM-1 and its prodrug CHM-1-P, suggests that CHM-1-P deserves to further develop as a clinical trial candidate for treating human breast carcinoma.