Taraxasterol attenuates zearalenone-induced kidney damage in mice by modulating oxidative stress and endoplasmic reticulum stress.

Taraxasterol is one of the bioactive ingredients from traditional Chinese herb Taraxacum, which exhibits multiple pharmacological activities and protective effects. However, the underlying influence and mechanism of its use against kidney damage caused from zearalenone (ZEA) remain unexplored. The ZEA-induced kidney damage model of mice was established by feeding diets containing ZEA (2 mg/kg), and taraxasterol (5 and 10 mg/kg) was administered by gavage for 28 days. Results demonstrated taraxasterol increased average daily gain (ADG) and average daily feed intake (ADFI), reduced feed-to-gain ratio (F/G) and kidney index of mice induced by ZEA. Taraxasterol alleviated histopathological changes of kidney, reduced ZEA residue and the levels of blood urea nitrogen (BUN), uric acid (UA), and creatinine (CRE). Concurrently, taraxasterol reduced the contents of oxidative stress indicator reactive oxygen species (ROS) and malondialdehyde (MDA), and increased the activities of antioxidant enzymes catalase (CAT), total superoxide dismutase (T-SOD), and glutathione peroxidase (GSH-Px). Further, taraxasterol up-regulated the mRNA and protein expression of nuclear factor erythroid-2-related factor 2 (Nrf2), GSH-Px, NAD(P)H quinone oxidoreductase 1 (NQO1), and heme oxygenase-1 (HO-1), and down-regulated the mRNA and protein expression of KELCH like ECH associated protein (Keap1) in Nrf2/Keap1 pathway. Taraxasterol down-regulated the mRNA and protein expression of immunoglobulin binding protein (Bip), C/EBP homologous protein (CHOP), Bcl-2 associated X (Bax), cysteine protease (Caspase)-12, and Caspase-3, and up-regulated B-cell lymphoma 2 (Bcl-2) expression in endoplasmic reticulum stress pathway. This study suggests that taraxasterol attenuates ZEA-induced mouse kidney damage through the modulation of Nrf2/Keapl pathway to play antioxidant role and endoplasmic reticulum stress pathway to enhance anti-apoptotic ability. It will provide a basis for taraxasterol as a potential drug to prevent and treat ZEA-induced kidney damage.

The actin cytoskeleton is important for pseudorabies virus infection.

Viruses are dependent on the host factors for their replication and survival. Therefore, identification of host factors that druggable for antiviral development is crucial. The actin cytoskeleton plays an important role in the virus infection. The dynamics change of actin and its function are regulated by multiple actin-associated proteins (AAPs). However, the role and mechanism of various AAPs in the life cycle of virus are still enigmatic. In this study, we analyzed the roles of actin and AAPs in the replication of pseudorabies virus (PRV). Using a library of compounds targeting AAPs, our data found that multiple AAPs, such as Rho-GTPases, Rock, Myosin and Formin were involved in PRV infection. Besides, our result demonstrated that the actin-binding protein Drebrin was also participated in PRV infection. Further studies are necessary to elucidate the molecular mechanism of AAPs in the virus life cycle, in the hope of mining host factors for antiviral developments.

Monoterpene-chalcone conjugates and diarylheptanoids isolated from the seeds of Alpinia katsumadai Hayata with cytotoxic activity.

Five undescribed monoterpene-chalcone conjugates (1-5), one undescribed hypothetical precursor of diarylheptanoid (6), two undescribed diarylheptanoids (7-8), and fourteen known compounds (9-22) were isolated from the seeds of Alpinia katsumadai. Their structures were elucidated through the interpretation of HRESIMS, NMR, ECD, and X-ray diffraction data. MTT assays on human cancer cell lines (HepG2, A549, SGC7901, and SW480) revealed that compounds 3-8, 11, and 13 exhibited broad-spectrum antiproliferative activities with IC50 values ranging from 3.59 to 21.78 µM. B cell lymphoma 2 was predicted as the target of sumadain C (11) by network pharmacology and verified by homogeneous time-resolved fluorescence assay and molecular docking.

Terpenoids from Alpinia galanga and their acetylcholinesterase inhibitory activity.

A new labdane diterpene (1), two new norsesquiterpenoids (2-3), as well as eight known terpenoids (4-11) were isolated from the seeds of Alpinia galanga (Zingiberaceae). Their structures and absolute configurations were elucidated by 1D, 2D NMR, MS, and comparison of their experimental and calculated electronic circular dichroism (ECD). The acetylcholinesterase (AChE) inhibitory activities of all the isolated compounds (1-11) were evaluated and the result showed that compounds 6 and 9 had inhibitory activity against AChE, with IC50 values at 295.70 and 183.91 µM, whereas other compounds did not show any inhibitory activity.

Prediction of cytochrome P450-mediated bioactivation using machine learning models and in vitro validation.

Cytochrome P450 (P450)-mediated bioactivation, which can lead to the hepatotoxicity through the formation of reactive metabolites (RMs), has been regarded as the major problem of drug failures. Herein, we purposed to establish machine learning models to predict the bioactivation of P450. On the basis of the literature-derived bioactivation dataset, models for Benzene ring, Nitrogen heterocycle and Sulfur heterocycle were developed with machine learning methods, i.e., Random Forest, Random Subspace, SVM and Naïve Bayes. The models were assessed by metrics like "Precision", "Recall", "F-Measure", "AUC" (Area Under the Curve), etc. Random Forest algorithms illustrated the best predictability, with nice AUC values of 0.949, 0.973 and 0.958 for the test sets of Benzene ring, Nitrogen heterocycle and Sulfur heterocycle models, respectively. 2D descriptors like topological indices, 2D autocorrelations and Burden eigenvalues, etc. contributed most to the models. Furthermore, the models were applied to predict the occurrence of bioactivation of an external verification set. Drugs like selpercatinib, glafenine, encorafenib, etc. were predicted to undergo bioactivation into toxic RMs. In vitro, IC50 shift experiment was performed to assess the potential of bioactivation to validate the prediction. Encorafenib and tirbanibulin were observed of bioactivation potential with shifts of 3-6 folds or so. Overall, this study provided a reliable and robust strategy to predict the P450-mediated bioactivation, which will be helpful to the assessment of adverse drug reactions (ADRs) in clinic and the design of new candidates with lower toxicities.

Human dental pulp stem cells have comparable abilities to umbilical cord mesenchymal stem/stromal cells in regulating inflammation and ameliorating hepatic fibrosis.

Hepatic fibrosis, also called cirrhosis, have wide prevalence worldwide for long yeas. Recently, many treatments for liver cirrhosis made marked progress, especially the umbilical cord-derived mesenchymal stromal cells (UCMSC) therapy. However, limited recourses and potential immune-related issues become the obstacles on UCMSC popularization in clinic. Therefore, we took dental pulp stem cells (DPSCs) into the consideration, since autologous DPSCs can be easily obtained without any ethnic or immune-related issues that heterogenous UCMSCs could encounter. We systematically compared the effects of both cell types and found that DPSCs had similar results to UCMSCs in regulating inflammation and reversing hepatic fibrosis. In our study, co-culturing T cells and PBMSCs showed that DPSCs have the ability to inhibit the proliferation of inflammatory cells and downregulate relevant inflammatory factors. In vitro and in vivo sterility tests confirmed the bio-safety of DPSCs. Moreover, the 1 year-aged mouse model demonstrated that DPSCs successfully reversed hepatic fibrosis. Overall, DPSCs demonstrated comparable effectiveness to UCMSCs in regulating inflammation and reversing hepatic fibrosis, particularly in the aged mouse model that represents middle-aged and elderly humans. Since autologous DPSCs avoid potential immune-related issues that heterogenous UCMSCs could encounter, they may be a better choice for stem cell-related therapies.

RhoA suppresses pseudorabies virus replication in vitro.

The porcine pseudorabies virus (PRV) is one of the most devastating pathogens and brings great economic losses to the swine industry worldwide. Viruses are intracellular parasites that have evolved numerous strategies to subvert and utilize different host processes for their life cycle. Among the different systems of the host cell, the cytoskeleton is one of the most important which not only facilitate viral invasion and spread into neighboring cells, but also help viruses to evade the host immune system. RhoA is a key regulator of cytoskeleton system that may participate in virus infection. In this study, we characterized the function of RhoA in the PRV replication by chemical drugs treatment, gene knockdown and gene over-expression strategy. Inhibition of RhoA by specific inhibitor and gene knockdown promoted PRV proliferation. On the contrary, overexpression of RhoA or activation of RhoA by chemical drug inhibited PRV infection. Besides, our data demonstrated that PRV infection induced the disruption of actin stress fiber, which was consistent with previous report. In turn, the actin specific inhibitor cytochalasin D markedly disrupted the normal fibrous structure of intracellular actin cytoskeleton and decreased the PRV replication, suggesting that actin cytoskeleton polymerization contributed to PRV replication in vitro. In summary, our data displayed that RhoA was a host restriction factor that inhibited PRV replication, which may deepen our understanding the pathogenesis of PRV and provide further insight into the prevention of PRV infection and the development of anti-viral drugs.

Computational prediction for the metabolism of human UDP-glucuronosyltransferase 1A1 substrates.

UDP-glucuronosyltransferase (UGT) 1A1, one of the most important isoforms in UGTs superfamily, has attracted increasing concerns for its special role in the clearance and detoxification of endogenous and exogenous substances. To avoid the clinical drug-drug interactions, it is of great importance to have the knowledge of the metabolic profile of UGT1A1 substrates early. Herein, we purposed to establish machine learning models to predict the metabolic propeties of UGT1A1 substrates. On the basis of the literature-derived substrates database of UGT1A1, automatic metabolism prediction models for the aromatic hydroxyl (ArOH) and carboxyl (COOH) groups were developed with eight machine learning methods, among which, three methods, i.e. Random Forest, Random Subspace and J48, illustrated the best performance either for the aromatic hydroxyl and the carboxyl model. The models illustrated good robustness when they were evaluated with functions like "Precision", "Recall", "F-Measure", "AUC", "MCC", etc. Nice accuracy was observed for the aromatic hydroxyl and carboxyl model of these methods, whose AUCs ranged from 0.901 to 0.997. Additionally, the ArOH model was applied to predict the UGT1A1-mediated metabolism of an external set. Two new unknown substrates, cytochrome P450 (CYPs)-mediated metabolites of gefitinib, were predicted and identified, which were validated by in vitro assays. In summary, this study provides a reliable and robust strategy to predict UGT1A1 metabolites, which will be helpful either in rational-optimization of drug metabolism or in avoiding drug-drug interactions in clinic.

Highly efficient blue quantum-dot light-emitting diodes based on a mixed composite of a carbazole donor and a triazine acceptor as the hole transport layer.

Solution-processed thermally activated delayed fluorescence (TADF) exciplexes were employed as the hole transport layer (HTL) of blue quantum dot (QD) light-emitting diodes (QLEDs) by blending polymer donors of poly(N-vinylcarbazole) (PVK) with small molecular acceptors of 2,4,6-tris(biphenyl-3-yl)-1,3,5-triazine (T2T). As a result, the PVK:T2T HTL can harvest holes and electrons leaking from the QD active layer to form exciplex excitons and then this harvested exciton energy can be effectively transferred to the adjacent QD emitters through the Förster resonance energy-transfer process. Furthermore, the TADF exciplexes can enhance the hole mobility of the HTL due to the charge transfer process from the PVK donor to the T2T acceptor under an external electric field. The maximum current efficiency (CE) and external quantum efficiency (EQE) of the fabricated blue ZnCdS/ZnS core/shell QLEDs increase from 4.14 cd A-1 and 7.33% for the PVK HTL to 7.73 cd A-1 and 13.66% for the PVK:(5 wt%)T2T HTL, respectively. Our results demonstrate that the TADF exciplex HTL would be a facile strategy to design high-performance blue QLEDs.

Patients with ankylosing spondylitis have high risk of irritable bowel syndrome: a long-term nationwide population-based cohort study.

OBJECTIVE: Ankylosing spondylitis (AS) is a chronic inflammatory disease, might carry a high risk of irritable bowel syndrome (IBS) due to abnormal gut microbiota or inflammatory reaction. METHODS: We conducted a 14-year retrospective cohort study based on Taiwan's National Health Insurance Research Database (NHIRD). A total of 4007 patients with newly diagnosed AS (outpatient visits≧3 times, or hospitalization≧1 time) and 988,084 non-AS comparisons were enrolled during 2000-2012. To ensure baseline comparability, the propensity score was matched by age, gender, comorbidities, and other possible confounders. The outcome was the incidence of IBS, followed up to the end of 2013. Cox proportional hazard model calculated adjusted hazard ratio (aHR) and the cumulative incidence of both groups was analyzed by the Kaplan-Meier method. RESULT: After propensity score matching, baseline demographic characteristics were comparable between AS patients and the comparison group. The crude HR for IBS in the AS group was significantly higher 2.41 (95%C.I. = 1.84-3.16) than comparison group. After adjusting for possible confounders, adjusted HR was 2.50 (95%C.I. = 1.91-3.29). The cumulative incidence of IBS in AS was significantly higher than non-AS comparisons during the 14-year follow-up (P < 0.001). CONCLUSION: This nationwide population-based cohort study showed that patients with AS have higher risks of IBS than those of the non-AS comparison group.

Development of a nomogram for predicting nasogastric tube-associated pressure injuries in intensive care unit patients.

Here, we aimed to build a nomogram model to estimate the probability of nasogastric tube-associated pressure injuries (NTAPIs) in intensive care unit(ICU)patients. This prospective cohort study included 219ICU patients with nasogastric tube between September 2019 and January 2020.Univariate and multivariate logistic regression analyses were used to develop the nomogram model. The resulting nomogram was tested for calibration, discrimination, and clinical usefulness. Of the included patients, 58 developed NTAPIs, representing an incidence rate of 26.5%. Binary logistic regression analysis revealed that the prediction nomogram included C-reactive protein, vasopressor use, albumin level, nasogastric tube duration, and Sequential Organ Failure Assessment score. The value of these predictors was again confirmed using theLasso regression analysis. Internal validation presented a good discrimination of the nomogram, with an area under the curve value of 0.850, and good calibration (Hosmer-Lemeshow test, P = 0.177). The decision curve analysis also demonstrated preferable net benefit along with the threshold probability in the prediction nomogram. The nomogram model can accurately predict the risk factors for NTAPIs, to formulate intervention strategies as early as possible to reduce NTAPI incidence.

Prevalence of suicidal ideation, suicide attempt, and suicide plan among HIV/AIDS: A systematic review and meta-analysis.

BACKGROUND: Suicidality is common in people living with HIV/AIDS. However, the prevalence estimates of the suicidality vary between studies. Here, we performed a systematic review and estimated the prevalence of suicidal behavior in this population. METHODS: Systematic search of PubMed, Embase, Web of Science, CINAHL, Scopus and PsycINFO for relevant studies published before August 29, 2020. A random-effects model was used to pool the estimates of the prevalence of suicidal ideation, attempts and plans, which were also stratified by continent or region and screening instrument from the studies included in this meta-analysis. RESULTS: Suicide prevalence data were extracted from 36 studies(n=32,818) from 15 countries. The overall pooled crude prevalence estimates of suicidal ideation, plans, and attempts were 20.9% [95% confidence interval (CI) 16.5-21.6%],8.1% (95% CI 5.4-11.3%), and 7.5% (95% CI 5.7-9.5%), respectively. For lifetime suicidal ideation and attempts prevalence, this was 22.4% (95% CI 15.9-29.8%), and 12.0% (95% CI 6.9- 18.1%), respectively. Summary prevalence estimates ranged across assessment modalities from 6.5% to 33.7%. Pooled estimates were generally higher for females, as compared with males (risk ratios in the range 1.48-1.85). The leave-one-out analysis showed that no single study significantly affected the final pooled results.

Knowledge, attitude, and practice of nurses in intensive care unit on preventing medical device-related pressure injury: A cross-sectional study in western China.

The knowledge, attitude, and practice of nurses in intensive care units (ICUs) are determinants for the efficacy of preventing the medical device-related pressure injury (MDRPI). The aim of this study was to determine the level and factors of knowledge, attitude, and practice of nurses' ICUs on preventing medical MDRPI in western China. An annual cross-sectional study was conducted in hospitals of western China from May 2020 to September 2020. Nurses' knowledge and attitudes were assessed using Clinical Nurses Prevention MDRPI of Critically Ill Patients for the Knowledge, Attitude, Practice Assessment Scale. SPSS software version 25.0 and independent t-test, Chi-square, Fisher exact, one-way analysis of variance, and multiple linear regression tests were used for data analysis. A total of 1002 nurses in ICUs from 37 hospitals in Gansu Province, China, participated in this study. The scores of overall KAP, knowledge, attitudes, and practice were 149.17 ± 24.62, 53.83 ± 12.23, 37.24 ± 6.35 and 58.10 ± 9.83, respectively. There was a positive and significant relationship between three variables. Findings revealed that nurses' knowledge score in the Tertiary hospital was higher than scores of other hospitals as 3.840 units. Moreover, the knowledge score and practice score of nurses with bachelor's degree or above were higher than other nurses and are 0.978 and 1.106 units, respectively. Based on the findings, practice of nurses increased by 0.992 units, with a 1-year increase in work experience of nurses in the ICU. The levels of knowledge, attitude, and practice of nurse in ICUs on preventing MDRPI were acceptable. The findings of the study highlight that a comprehensive approach should be conducted for raising the level of knowledge, attitude, and practice of nurses' ICUs on preventing medical MDRPI, as well as improving the quality of care for critically ill patients.

Effects of long-term right ventricular apex pacing on left ventricular dyssynchrony, morphology and systolic function.

BACKGROUND: Right ventricular apex (RVA) is still the most common implanted site in the world. There are a large number of RVA pacing population who have been carrying dual-chamber permanent pacemaker (PPM) over decades. Comparison of left ventricular dyssynchrony, morphology and systolic function between RVA pacing population and healthy population is unknown. METHOD: This case-control study enrolled 61 patients suffered from complete atrioventricular block (III°AVB) for replacement of dual-chamber PPM. Then, 61 healthy controls matched with PPM patients in gender, age, follow-up duration and complications were included. The lead impedance, pacing threshold and sensing were compared between at implantation and long-term follow-up. Left ventricular (LV) dyssynchrony, morphology and systolic function were compared between RVA pacing population (RVA group) and healthy population (healthy group) at implantation (baseline) and follow-up. And clarify the predictors of LV systolic function in RVA group at follow-up. RESULTS: After 112.44 ± 34.94 months of follow-up, comparing with parameters at implantation, atrial lead impedance decreased significantly (690 ± 2397 Ω vs 613 ± 2257 Ω， p = 0.048); atrial pacing threshold has a increased trend and P-wave amplitude has a decreased trend, but there was no statistical differences; while, RVA ventricular lead threshold increased significantly (0.50 ± 0.23 V vs 0.91 ± 0.47 V， p < 0.001), impedance (902 ± 397 Ω vs 680 ± 257 Ω，p < 0.001) and R-wave amplitude (11.71 ± 9.40mv vs 7.00 ± 6.91 mv， p < 0.001) decreased significantly. Compared with healthy group, long-term RVA pacing significantly increased ventricular dyssynchrony (mean QRS duration, 156.21 ± 29.80 ms vs 97.08 ± 15.70 ms， p < 0.001), left atrium diameter (LAD, 40.61 ± 6.15 mm vs 37.49 ± 4.80 mm，p = 0.002), left ventricular end-diastolic diameter (LVEDD, 49.15 ± 5.93 mm vs 46.41 ± 3.80 mm，p = 0.003), left ventricular hypertrophy (LVMI, 121.86 ± 41.52 g/m2 vs 98.41 ± 25.29 g/m2，p < 0.001), significantly deteriorated degree of tricuspid regurgitation (p < 0.001), and significantly decreased left ventricular ejection fraction (LVEF, 61.38 ± 8.10% vs 64.64 ± 5.85%, p = 0.012), but after long-term RVA pacing, the mean LVEF was still more than 50%. Long-term RVA group LVEF was negatively correlated with preimplantation LVMI (B = -0.055，t = -2.244，p = 0.029), LVMI at follow-up (B = -0.081，t = -3.864，p = 0.000) and tricuspid regurgitation at follow-up (B = -3.797，t = -3.599，p = 0.001). CONCLUSION: In conclusion, although long-term RVA pacing has significantly effects on left ventricular dyssynchrony, morphology and systolic function in III°AVB patients, the mean LVEF is still >50%. High preimplantation LVMI can predict the decline of LVEF.

Mindfulness-Based Cognitive Therapy for Treating Chronic Pain A Systematic Review and Meta-analysis.

Chronic pain is a significant public health problem with emotional and disabling factors, which may not completely respond to current medical treatments such as opioids. The systematic review and meta-analysis aimed to examine the effectiveness and safety of MBCT for patients with chronic pain. Database searches of PubMed, Medline, EMBASE, the Cochrane Library, PsycINFO, Web of Science, Scopus and CINAHL up to 15 October 2019. Included studies assessed with the Cochrane risk-of-bias tool. Eight RCTs involved 433 patients, including chronic low back pain, fibromyalgia, migraine, rheumatoid arthritis and mix etiology. MBCT intervention demonstrated a short-term improvement on depression mood [standardized mean difference -0.72; 95% confidence interval = -1.22 to -0.22, p = 0.005] compared with usual care and was associated with short-term improvement in mindfulness compared with non-MBCT [SMD 0.51; 95% CI = 0.01 to 1.01, p = 0.04]. Between-group differences in pain intensity, pain inference and pain acceptance were not significant at short- or long-term follow-up. Compared to active treatments, MBCT intervention not found significant differences in either short- or long-term outcomes. MBCT showed short-term efficacious on depressed mood and mindfulness of chronic pain patients. Longer follow-ups, large sample and rigorous RCTs that can be best understand remaining uncertainties needed.

Prevalence of suicidal ideation and suicide attempt in patients with migraine: A systematic review and meta-analysis.

BACKGROUND: Suicidality is common in patients with migraine. Here, we performed a systematic review and estimated the prevalence of suicidal ideation (SI) and suicide attempt (SA) in patients with migraine. METHODS: We searched Pubmed, Embase, Web of Science, Cochrane database library, CINAHL, and PsycINFO for relevant publications. A random-effects model was used to pool the estimates of the prevalence of SI and SA, which were also stratified by the geographical location of the research institutions from the studies included in this meta-analysis. RESULTS: Fifteen studies involving 2,247,648 participants with migraine were selected. Pooled prevalence estimates of SI and SA were 15.5% [95% confidence interval (CI) 10.4-21.3%] and 3.9% (95% CI 0.9-8.8%), respectively, and the prevalence of SI was higher in Asian countries (21.5%, 95%CI 16.8-26.6%) compared with non-Asian countries (11.0%, 95%CI 6.1-17.2%). Measures of heterogeneity between studies were high for all outcomes (I2 = 89-100%), indicating that the substantial between-study heterogeneity in estimated proportions was not attributed to sampling error. The leave-one-out analysis showed that no single study significantly affected the final pooled results. CONCLUSIONS: This meta-analysis indicated a high prevalence of SI and SA in migraine patients. Thus, it is necessary to design targeted preventive measures for the management of migraine-related suicide.

Advance in Risk Assessment Tools for Pressure Injury of Patients with Spinal Cord Injury / 中国康复理论与实践

Spinal cord injury (SCI) is a common traumatic disease. Patients with limited mobility are prone to pressure injuries, which seriously affect the patient's rehabilitation process. The use of risk assessment scale can effectively predict the occurrence of pressure injuries. This article reviewed the pathogenesis, risk factors, and use of different risk assessment tools for patients with spinal cord injury, compared the content, assessment methods, applicable population, reliability and validity of each risk assessment scale, summarized the advantages and disadvantages of different assessment scales, and provided reference to choose the best risk assessment tool.

Aspiration Screening Tools after Stroke: A Systematic Review / 中国康复理论与实践

Objective:To systematically review the relevant researches on aspiration screening tools for stroke patients. Methods:Literatures aboute stroke aspiration screening tools till December, 2018 were recalled from PubMed, Cochrane Library, Web of Science, EMbase, CNKI, Wanfang Database and China Biomedical Literature Database. Two researchers independently screened the literatures and extracted the basic information, such as the content, screening format, scoring standard and measurement characteristics. Results:A total of 25 studies were included, involving ten aspiration screening tools. The content, screening format, scoring standard and measurement characteristics of the aspiration screening tools were analysed. There was no evidence to support the tools. Conclusion:Tools would be selected according to the patient's condition, age and swallowing related characteristics.

Antidiabetic potential of the ethyl acetate extract of Physalis alkekengi and chemical constituents identified by HPLC-ESI-QTOF-MS.

ETHNOPHARMACOLOGICAL RELEVANCE: The edible plant Physalis alkekengi (PA) is used in traditional medicine to treat diabetes. However, the anti-diabetic effects and constituents of the fruit and aerial parts of this plant have not been studied extensively. AIM OF THE STUDY: The purpose of this study was to investigate the antidiabetic potential of Physalis alkekengi and identify its chemical constituents. MATERIALS AND METHODS: In the present study, the in vitro glucose uptake capacity was tested using the 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-d-glucose (2-NBDG) assay in HepG2 cells. Secondly, the anti-diabetes effects of the ethyl acetate extracts of the aerial parts/fruit (EAP/EAF) of P. alkekengi were evaluated in high-fat diet-fed and streptozotocin-induced diabetic rats (seven groups, n = 7) daily at doses of 300 and 600 mg/kg for 28 days. Fasting blood glucose (FBG) was measured with a glucometer and the levels of total cholesterol (TC), triglyceride (TG), glycated serum protein (GSP), and fasting insulin (FINS) were measured by ELISA. Furthermore, insulin sensitivity index (ISI) and homeostasis model assessment-insulin resistance index (HOMA-IR) were calculated based on FBG and FINS. Changes in blood glucose concentration were assessed after an oral glucose challenge in diabetic rats treated with EAF and EAP extracts. In all assays, rosiglitazone, a current antidiabetic drug and insulin sensitizer, was also tested. Finally, the compounds in EAP were identified by HPLC-ESI-QTOF-MS analysis. RESULTS: EAP increased the uptake of 2-NBDG, a measure of direct glucose uptake, in HepG2 cells. Next, in diabetic rats treated with P. alkegenki extracts for 28 days, the levels of FBG, TC, TG and GSP and were lowered effectively, while FINS was increased significantly. EAP/EAF enhanced insulin sensitivity significantly as measured by ISI and HOMA-IR along with oral glucose tolerance test analysis. The EAP generally exerted the greatest effects. Lastly, a HPLC-ESI-Q-TOF-MS analysis identified 50 compounds, including 26 physalins, 10 flavonoids, and 9 phenolic acids, with 21 compounds found for the first time in P. alkekengi. CONCLUSIONS: The results support the merit of P. alkekengi as an antidiabetic herbal medicine or dietary supplement.

FPGASW: Accelerating Large-Scale Smith-Waterman Sequence Alignment Application with Backtracking on FPGA Linear Systolic Array.

The Smith-Waterman (SW) algorithm based on dynamic programming is a well-known classical method for high precision sequence matching and has become the gold standard to evaluate sequence alignment software. In this paper, we propose fine-grained parallelized SW algorithms using affine gap penalty and implement a parallel computing structures to accelerating the SW with backtracking on FPGA platform. We analysis the dynamic parallel computing features of anti-diagonal elements and storage expansion problem resulting from backtracking stage, and propose a series of optimization strategies to eliminate data dependency, reduce storage requirements, and overlap memory access latency. Our implementation is capable of supporting multi-type, large-scale biological sequence alignment applications. We obtain a speedup between 3.6 and 25.2 over the typical SW algorithm running on a general-purpose computer configured with an Intel Core i5 3.2 GHz CPU. Moreover, our work is superior to other FPGA implementations in both array size and clock frequency, and the experiment results show that it can get a performance closed to that of the latest GPU implementation, but the power consumption is only about 26% of that of the GPU platforms.