Effects of schisandrin B on hypoxia-related cognitive function and protein expression in vascular dementia rats.

Vascular dementia (VD) a heterogenous group of brain disorders in which cognitive impairment is attributable to vascular risk factors and cerebrovascular disease. A common phenomenon in VD is a dysfunctional cerebral regulatory mechanism associated with insufficient cerebral blood flow, ischemia and hypoxia. Under hypoxic conditions oxygen supply to the brain results in neuronal death leading to neurodegenerative diseases including Alzheimer's (AD) and VD. In conditions of hypoxia and low oxygen perfusion, expression of hypoxia-inducible factor 1 alpha (HIF-1α) increases under conditions of low oxygen and low perfusion associated with upregulation of expression of hypoxia-upregulated mitochondrial movement regulator (HUMMR), which promotes anterograde mitochondrial transport by binding with trafficking protein kinesin 2 (TRAK2). Schisandrin B (Sch B) an active component derived from Chinese herb Wuweizi prevented ß-amyloid protein induced morphological alterations and cell death using a SH-SY5Y neuronal cells considered an AD model. It was thus of interest to determine whether Sch B might also alleviate VD using a rat bilateral common carotid artery occlusion (BCAO) dementia model. The aim of this study was to examine the effects of Sch B in BCAO on cognitive functions such as Morris water maze test and underlying mechanisms involving expression of HIF-1α, TRAK2, and HUMMR levels. The results showed that Sch B improved learning and memory function of rats with VD and exerted a protective effect on the hippocampus by inhibition of protein expression of HIF-1α, TRAK2, and HUMMR factors. Evidence indicates that Sch B may be considered as an alternative in VD treatment.

Mechanisms underlying LncRNA SNHG1 regulation of Alzheimer's disease involve DNA methylation.

Alzheimer's disease (AD) is a neurodegenerative disease associated with long non-coding RNAs and DNA methylation; however, the mechanisms underlying the role of lncRNA small nucleolar RNA host gene 1 (lncRNA SNHG1) and subsequent involvement of DNA methylation in AD development are not known. The aim of this study was to examine the regulatory mechanisms attributed to lncRNA SNHG1 gene utilizing 2 strains of senescence-accelerated mouse prone 8 (SAMP8) model of AD and compared to senescence-accelerated mouse resistant (SAMR) considered a control. Both strains of the mouse were transfected with either blank virus, psLenti-U6-SNHG1(low gene expression) virus, and psLenti-pA-SNHG1(gene overexpression) virus via a single injection into the brains for 2 weeks. At 2 weeks mice were subjected to a Morris water maze to determine any behavioral effects followed by sacrifice to extract hippocampal tissue for Western blotting to measure protein expression of p-tau, DNMT1, DNMT3A, DNMT3B, TET1, and p-Akt. No marked alterations were noted in any parameters following blank virus transfection. In SAMP8 mice, a significant decrease was noted in protein expression of DNMT1, DNMT3A, DNMT3B, and p-Akt associated with rise in p-tau and TET1. Transfection with ps-Lenti-U6-SNHG1 alone in SAMR1 mice resulted in a significant rise in DNMTs and p-Akt and a fall in p-tau and TET1. Transfection of SAMP8 with ps-Lenti-U6-SNHG1 blocked effects on overexpression noted in this mouse strain. However, knockdown of lncRNA SNHG1 yielded the opposite results as found in SAMR1 mice. In conclusion, the knockdown of lncRNA SNHG1 enhanced DNA methylation through the PI3K/Akt signaling pathway, thereby reducing the phosphorylation levels of tau in SAMP8 AD model mice with ameliorating brain damage attributed to p-tau accumulation with consequent neuroprotection.

Simulation of double resonant excitation of ions in an asymmetric linear ion trap mass analyzer.

RATIONALE: Improving the analytical performance of linear ion traps (LITs) is crucial for the advancement of high-performance LIT mass spectrometers. In this study, a double resonant excitation method was employed in an asymmetric LIT to achieve high ion unidirectional ejection efficiency and enhanced mass resolution. METHODS: The asymmetric trapping field was generated by stretching one x electrode with a distance α. The double resonant excitation was achieved by applying an alternating voltage out of phase and a supplementary alternating voltage in phase to the x and y electrode pairs of the LIT, respectively. Numerical simulations of ion trajectories were performed to validate the effectiveness of this method. RESULTS: The mass resolution of the asymmetric LIT with double resonant excitation could be improved to ~3800, which was over two times compared to that with only dipolar resonant excitation, while both reached ~90% in ion unidirectional ejection efficiency. CONCLUSIONS: By employing the double resonant excitation method, the mass resolution could be improved significantly in the asymmetric LIT, while maintaining a considerably high ion unidirectional ejection efficiency. This method might provide a general solution for enhancing ion detection efficiency and mass resolution of LIT mass spectrometers.

Association between maternal gestational diabetes and allergic diseases in offspring: a birth cohort study.

BACKGROUND: Previous studies have linked gestational diabetes (GDM) with allergies in offspring. However, the effect of specific glucose metabolism metrics was not well characterized, and the role of polyunsaturated fatty acids (PUFAs), a modifier of metabolism and the immune system, was understudied. We aimed to investigate the association between maternal GDM and allergic diseases in children and the interaction between glucose metabolism and PUFAs on allergic outcomes. METHODS: This prospective cohort study included 706 mother-child dyads from Guangzhou, China. Maternal GDM was diagnosed via a 75-g oral glucose tolerance test (OGTT), and dietary PUFAs were assessed using a validated food frequency questionnaire. Allergic disease diagnoses and the age of onset were obtained from medical records of children within three years old. RESULTS: Approximately 19.4% of women had GDM, and 51.3% of children had any allergic diseases. GDM was positively associated with any allergic diseases (hazard ratio [HR] 1.40; 95% confidence interval (CI) 1.05-1.88) and eczema (HR 1.44; 95% CI 1.02-1.97). A unit increase in OGTT after two hours (OGTT-2 h) glucose was associated with an 11% (95% CI 2%-21%) higher risk of any allergic diseases and a 17% (95% CI 1-36%) higher risk of food allergy. The positive associations between OGTT-2 h glucose and any allergic diseases were strengthened with decreased dietary a-linolenic acid (ALA) and increased n-6 PUFAs, linoleic acid (LA), LA/ALA ratio, and n-6/n-3 PUFA ratio. CONCLUSIONS: Maternal GDM was adversely associated with early-life allergic diseases, especially eczema. We were the first to identify OGTT-2 h glucose to be more sensitive in inducing allergy risk and that dietary PUFAs might modify the associations.

Genome-wide sequencing identifies a thermal-tolerance related synonymous mutation in the mussel, Mytilisepta virgata.

The roles of synonymous mutations for adapting to stressful thermal environments are of fundamental biological and ecological interests but poorly understood. To study whether synonymous mutations influence thermal adaptation at specific microhabitats, a genome-wide genotype-phenotype association analysis is carried out in the black mussels Mytilisepta virgata. A synonymous mutation of Ubiquitin-specific Peptidase 15 (MvUSP15) is significantly associated with the physiological upper thermal limit. The individuals carrying GG genotype (the G-type) at the mutant locus possess significantly lower heat tolerance compared to the individuals carrying GA and AA genotypes (the A-type). When heated to sublethal temperature, the G-type exhibit higher inter-individual variations in MvUSP15 expression, especially for the mussels on the sun-exposed microhabitats. Taken together, a synonymous mutation in MvUSP15 can affect the gene expression profile and interact with microhabitat heterogeneity to influence thermal resistance. This integrative study sheds light on the ecological importance of adaptive synonymous mutations as an underappreciated genetic buffer against heat stress and emphasizes the importance of integrative studies at a microhabitat scale for evaluating and predicting the impacts of climate change.

Tank-mixing adjuvants enhanced the efficacy of fludioxonil on cucumber anthracnose by ameliorating the penetration ability of active ingredients on target interface.

In this study, pot and field experiments showed that S903, Hasten and Gemini-31511 can significantly enhanced the control efficacy of fludioxonil on cucumber anthracnose. Then by studying the deposition and penetration interaction between active ingredients and cucumber leaves to revealed how the adjuvants influence the interaction process between pesticide active ingredients and target plants to improve the control efficacy. By analysis the effect of fludioxonil deposition to synergism of adjuvants, indicated that fludioxonil active ingredient deposition caused by adjuvants was not the main factor for the adjuvants synergistic effect. Fludioxonil + S903 yielded the lowest surface tension and contact angle, which also implying the best wetting ability. The mean diameters in Hasten + fludioxonil group were much smaller than those in only fludioxonil group (5.39 µm-90 g a.i. ha-1, 5.50 µm-180 g a.i. ha-1), the average particle size only had 3.45 µm (90 g a.i. ha-1) and 3.94 µm (180 g a.i. ha-1). And the result of spray droplets was consistent with the particles of fludioxonil crystals observed on glass slides and cucumber leaves. Therefore, S903 improved the penetrability of fludioxonil in the target plants by improving the wetting and dispersion of active ingredients on the target interface. Meantime, Hasten improved the penetrability of fludioxonil in the target plants by decreasing the particle size of active ingredients.

Temperature adaptations of the thermophilic snail Echinolittorina malaccana: insights from metabolomic analysis.

The periwinkle snail Echinolittorina malaccana, for which the upper lethal temperature is near 55°C, is one of the most heat-tolerant eukaryotes known. We conducted a multi-level investigation - including cardiac physiology, enzyme activity, and targeted and untargeted metabolomic analyses - that elucidated a spectrum of adaptations to extreme heat in this organism. All systems examined showed heat intensity-dependent responses. Under moderate heat stress (37-45°C), the snail depressed cardiac activity and entered a state of metabolic depression. The global metabolomic and enzymatic analyses revealed production of metabolites characteristic of oxygen-independent pathways of ATP generation (lactate and succinate) in the depressed metabolic state, which suggests that anaerobic metabolism was the main energy supply pathway under heat stress (37-52°C). The metabolomic analyses also revealed alterations in glycerophospholipid metabolism under extreme heat stress (52°C), which likely reflected adaptive changes to maintain membrane structure. Small-molecular-mass organic osmolytes (glycine betaine, choline and carnitine) showed complex changes in concentration that were consistent with a role of these protein-stabilizing solutes in protection of the proteome under heat stress. This thermophilic species can thus deploy a wide array of adaptive strategies to acclimatize to extremely high temperatures.

Living on the upper intertidal mudflat: Different behavioral and physiological responses to high temperature between two sympatric cerithidea snails with divergent habitat-use strategies.

Temperature plays a major role in controlling species' distributions, and small-scale variation in the thermal environment are potentially an important factor that governs distributions on a local scale. For untangling the roles of behavioral and physiological adaptations on species' distribution at a small-scale level, we carried out a comparative study of two mudflat snails (genus Cerithidea) by determining these congeners' burying behavior, lethal temperature, cardiac performance and heat-shock protein (hsp70) gene expression. These two sympatric snails occupy different microhabitats on the upper intertidal mudflat. During periods of emersion, C. cingulata inhabits the open mudflat and C. largillierti usually aggregates around small rocks on the upper intertidal mudflat. Our results indicate that the two Cerithidea congeners show different behavioral and physiological responses to high temperature. Compared to C. largillierti, C. cingulata prefers to bury into the mud, has a higher thermal limit and a higher level of inducible expression of hsp70 mRNA, implying important roles of behavioral and physiological adaptations to the harsh thermal environment on the open mudflat. Furthermore, results of generalized additive modelling (GAM) analysis of cardiac performance and coefficient of variation (CV) of hsp70 mRNA expression showed high inter-individual variation in C. cingulata. These results highlight the importance of behavioral and physiological adaptions in sympatric species' distributions on the mudflat and help to shed light on the mechanisms of how small-scale differences in the thermal environment shape sympatric species' distributions.

Fungicide Formulations Influence Their Control Efficacy by Mediating Physicochemical Properties of Spray Dilutions and Their Interaction with Target Leaves.

In this study, three types of pyraclostrobin formulations (including emulsifiable concentrate (EC), suspension concentrate (SC), and microcapsules (MCs)) were used to control cucumber anthracnose. Pyraclostrobin EC had the highest inhibitory activity against Colletotrichum orbiculare in vitro. Much different from the bioactivity in vitro, pyraclostrobin MCs exhibited the highest control efficacy on cucumber anthracnose both in pot and field experiments. The physicochemical properties (particle size, surface tension) of the spray dilution, their interaction with target leaves (contact angle, adhesional tension, work of adhesion, retention, crystallization) and dissipation dynamic of the active ingredient were found to be highly potential factors that would significantly influence the control efficacy of pesticide formulations. Results showed that the control efficacies of different formulations of pyraclostrobin were determined mainly by the final behavior of the pesticides at the target interface, namely, the retention, crystallization, and dissipation dynamics of active ingredients. This study had revealed crucial factors that would influence the efficacy of different formulations of pyraclostrobin and thus could guide the rational and efficient use of different formulations of pesticides on target crops.

Clinical trials, progression-speed differentiating features and swiftness rule of the innovative targets of first-in-class drugs.

Drugs produce their therapeutic effects by modulating specific targets, and there are 89 innovative targets of first-in-class drugs approved in 2004-17, each with information about drug clinical trial dated back to 1984. Analysis of the clinical trial timelines of these targets may reveal the trial-speed differentiating features for facilitating target assessment. Here we present a comprehensive analysis of all these 89 targets, following the earlier studies for prospective prediction of clinical success of the targets of clinical trial drugs. Our analysis confirmed the literature-reported common druggability characteristics for clinical success of these innovative targets, exposed trial-speed differentiating features associated to the on-target and off-target collateral effects in humans and further revealed a simple rule for identifying the speedy human targets through clinical trials (from the earliest phase I to the 1st drug approval within 8 years). This simple rule correctly identified 75.0% of the 28 speedy human targets and only unexpectedly misclassified 13.2% of 53 non-speedy human targets. Certain extraordinary circumstances were also discovered to likely contribute to the misclassification of some human targets by this simple rule. Investigation and knowledge of trial-speed differentiating features enable prioritized drug discovery and development.

Impact of Kuntai Capsules on LIF, IGF-1 and EGF expression in the implantation window of endometrium in mice / Impacto de cápsulas de Kuntai en la expresión de LIF, IGF-1 y EGF en la ventana de implantación de endometrio en ratones

To investigate the influence of Kuntai capsules on the expression level of leukemia inhibitory factor (LIF), insulin-like growth factor-I (IGF-1)and epidermal growth factor (EGF) during the mouse's implantation window of superovulation period and controlled ovarian hyperstimulation period. 90 female mice were randomly divided into six groups in control, superovulation and controlled ovarian hyperstimulation (COH) conditions. The RNA expression of EGF, LIF and IGF-1 in the endometrium on the 4th day of pregnancy was detected, and the relative expression was compared. mRNA expression of these three factors in endometrium was significantly lower in superovulation and COH groups than control group (p<0.001). mRNA expression of these three factors in endometrium remained obviously lower in superovulation plus kuntai capsule group and COH plus kuntai capsule group than control group (p<0.01). mRNA expression of these three factors in endometrium was lower in control group than in the NS plus kuntai capsule group (p<0.05). Kuntai capsule cannot completely reverse the endometrial damages caused by superovulation and COH. Thus Kuntai capsule could partially improve a mouse's endometrial receptivity during the implantation window.

Para investigar la influencia de las cápsulas de Kuntai en el nivel de expresión del factor inhibidor de la leucemia (LIF), el factor de crecimiento similar a la insulina I (IGF-1) y el factor de crecimiento epidérmico (EGF) durante la ventana de implantación del ratón del período de superovulación y la hiperestimulación ovárica controlada período, se dividieron aleatoriamente 90 ratones hembra en seis grupos en condiciones de control, superovulación e hiperestimulación ovárica controlada (COH). Se detectó la expresión de ARN de EGF, LIF e IGF-1en el endometrio al cuarto día de embarazo, y se comparó la expresión relativa. La expresión de ARNm de estos tres factores en el endometrio fue significativamente menor en los grupos de superovulación y COH que en el grupo control (p<0,001). La expresión de ARNm de estos tres factores en el endometrio permaneció más baja en el grupo de cápsulas de superovulación más Kuntai y en el grupo de cápsulas de COH más Kuntai respecto del grupo control (p<0,01). La expresión de ARNm de estos tres factores en el endometrio fue menor en el grupo control que en el grupo de cápsula NS más Kuntai (p<0,05). La cápsula de Kuntai no pudo revertir completamente los daños endometriales causados por la superovulación y la COH. Por lo tanto, se sugiere que la cápsula de Kuntai podría mejorar parcialmente la receptividad endometrial de un ratón durante la ventana de implantación.

[Effects of notoginseng and ginkgo leaf tablets on cardiac function and serum inflammatory factors in hypoxia deacclimatized rats and its mechanism].

OBJECTIVE: To study the effects of notoginseng, gingko leaf and rhodiola on cardiac functions and the serum inflammatory factors interleukin-6,interleukin-10, and TNF-α of rats with hypoxia deacclimatization, to explore the mechanism of hypoxia detoxification. METHODS: Forty SD rats were randomly divided into notoginseng group(n=10), gingko leaf group(n=10), rhodiola group(n=10) and high altitude control group(n=10) after fed in a hypobaric hypoxia chamber(simulated altitude of 5 000 m) for 3 month, while 10 rats fed at normal pressure and oxygen environment for 3 month were used as the plain control group. Rats in notoginseng group, gingko leaf group and rhodiola group were treated with notoginseng, gingko leaf tablets or rhodiola suspension through intragastric administration (200 mg/kg,twice a day, for 10 days). After the rats got intraperitoneal anesthesia with 10% urethane, 5 min pulmonary artery pressure curve were traced continuously while pulmonary artery pressure (PAP). Left and right ventricular systolic pressure (VSP) and ventricular diastolic pressure (VEDP), the hemodynamic parameters were detected through a multi-channel physiological recorder. Serum tumor necrosis factor-α(TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10), superoxide dismutase (SOD) and malondialdehyde (MDA) were measured. RESULTS: Right ventricular systolic pressure (RVSP), right ventricular end-diastolic pressure (RVEDP), mean pulmonary artery pressure (mPAP), left vent-ricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP),IL-6,and IL-10 were higher in notoginseng group, gingko leafgroup, rhodiola group and high altitude control group than those in plain control group(P＜0.05 or P＜0.01). The contents of MDA and TNF-α were higher while the level of SOD was lower in rhodiola group and high altitude control group than those in plain control group(P＜0.01). The contents of MDA and TNF-α were lower while the level of SOD was higher in notoginseng group, gingko leaf group and rhodiola group than those in high altitude control group(P＜0.01). The levels of RV,RVHI,RVSP,RVEDP,LVSP,LVEDP,IL-10 and TNF-α were statistically changed in notoginseng group than those in gingko leaf group and rhodiola group(P＜0.05orP＜0.01). CONCLUSION: Notoginseng, gingkoleaf and rhodiola can enhance antioxidant capacity of body and improve ventricular functions and Notoginseng, gingko leaf and rhodiola can effectively enhance the functions of ventricular and hypoxia tolerance and inhibit the expressions of inflammatory factors in rats during the hypoxia deacclimatization.

Selection of organosilicone surfactants for tank-mixed pesticides considering the balance between synergistic effects on pests and environmental risks.

In this study, the bioactivities of binary mixtures of organosilicone surfactants and indoxacarb against two Lepidopteran pests were investigated along with their environmental risks. All of the tested organosilicone surfactants had obvious synergistic effects on the contact toxicity of indoxacarb against Spodoptera exigua and Agrotis ipsilon. However, all of the organosilicone surfactants exhibited certain antagonism for indoxacarb against S. exigua in terms of stomach & contact toxicity; both Silwet-408 and Silwet-806 exhibited additivity against A. ipsilon, whereas Silwet-618 and Silwet-DRS-60 exhibited synergism and slight antagonism, respectively. All of the tested chemicals were highly toxic to Daphnia magna, among which Silwet-DRS-60 had the lowest acute toxicity (EC50 of 94.91 µg/L). However, these chemicals were less toxic to Brachydanio rerio. Silwet-DRS-60 had a low toxicity to B. rerio, while Silwet-408, Silwet-806 and Silwet-618 were moderately toxic to B. rerio. For the joint toxicity evaluation of organosilicone surfactants and indoxacarb to D. magna and B. rerio, the additive index method, concentration addition method and toxicity unit method were robust in judging synergism or antagonism, whereas other methods were more conservative; the V-value method and equilibrium curve method exhibited high robustness and viability in evaluating the combined effects of binary mixtures. Overall, we should carefully select organosilicone surfactants for premixed or tank-mixed pesticides in agriculture to obtain a balance between synergistic effects on pests and environmental risks.

Determining the Balance Between Drug Efficacy and Safety by the Network and Biological System Profile of Its Therapeutic Target.

One of the most challenging puzzles in drug discovery is the identification and characterization of candidate drug of well-balanced profile between efficacy and safety. So far, extensive efforts have been made to evaluate this balance by estimating the quantitative structure-therapeutic relationship and exploring target profile of adverse drug reaction. Particularly, the therapeutic index (TI) has emerged as a key indicator illustrating this delicate balance, and a clinically successful agent requires a sufficient TI suitable for it corresponding indication. However, the TI information are largely unknown for most drugs, and the mechanism underlying the drugs with narrow TI (NTI drugs) is still elusive. In this study, the collective effects of human protein-protein interaction (PPI) network and biological system profile on the drugs' efficacy-safety balance were systematically evaluated. First, a comprehensive literature review of the FDA approved drugs confirmed their NTI status. Second, a popular feature selection algorithm based on artificial intelligence (AI) was adopted to identify key factors differencing the target mechanism between NTI and non-NTI drugs. Finally, this work revealed that the targets of NTI drugs were highly centralized and connected in human PPI network, and the number of similarity proteins and affiliated signaling pathways of the corresponding targets was much higher than those of non-NTI drugs. These findings together with the newly discovered features or feature groups clarified the key factors indicating drug's narrow TI, and could thus provide a novel direction for determining the delicate drug efficacy-safety balance.

Easily Tunable Membrane Thickness of Microcapsules by Using a Coordination Assembly on the Liquid-Liquid Interface.

A model solvent, 1,3,5-trimethylbenzene, was encapsulated using coordination assembly between metal ions and tannic acid to reveal the deposition of coordination complexes on the liquid-liquid interface. The deposition was confirmed by zeta potential, energy dispersive spectroscopy and X-ray photoelectron spectroscopy. Scanning electron microscopy and transmission electron microscopy were integrated to characterize the microcapsules (MCs). According to atomic force microscopy height analysis, membrane thickness of the MCs increased linearly with sequential deposition. For MCs prepared using the Fe3+-TA system, the average membrane thicknesses of MCs prepared with 2, 4, 6, and 8 deposition cycles were determined as 31.3 ± 4.6, 92.4 ± 15.0, 175.4 ± 22.1, and 254.8 ± 24.0 nm, respectively. Dissolution test showed that the release profiles of all the four tested MCs followed Higuchi kinetics. Membrane thicknesses of MCs prepared using the Ca2+-TA system were much smaller. We can easily tune the membrane thickness of the MCs by adjusting metal ions or deposition cycles according to the application requirements. The convenient tunability of the membrane thickness can enable an extensive use of this coordination assembly strategy in a broad range of applications.

Assessing the Performances of Protein Function Prediction Algorithms from the Perspectives of Identification Accuracy and False Discovery Rate.

The function of a protein is of great interest in the cutting-edge research of biological mechanisms, disease development and drug/target discovery. Besides experimental explorations, a variety of computational methods have been designed to predict protein function. Among these in silico methods, the prediction of BLAST is based on protein sequence similarity, while that of machine learning is also based on the sequence, but without the consideration of their similarity. This unique characteristic of machine learning makes it a good complement to BLAST and many other approaches in predicting the function of remotely relevant proteins and the homologous proteins of distinct function. However, the identification accuracies of these in silico methods and their false discovery rate have not yet been assessed so far, which greatly limits the usage of these algorithms. Herein, a comprehensive comparison of the performances among four popular prediction algorithms (BLAST, SVM, PNN and KNN) was conducted. In particular, the performance of these methods was systematically assessed by four standard statistical indexes based on the independent test datasets of 93 functional protein families defined by UniProtKB keywords. Moreover, the false discovery rates of these algorithms were evaluated by scanning the genomes of four representative model organisms (Homo sapiens, Arabidopsis thaliana, Saccharomyces cerevisiae and Mycobacterium tuberculosis). As a result, the substantially higher sensitivity of SVM and BLAST was observed compared with that of PNN and KNN. However, the machine learning algorithms (PNN, KNN and SVM) were found capable of substantially reducing the false discovery rate (SVM < PNN < KNN). In sum, this study comprehensively assessed the performance of four popular algorithms applied to protein function prediction, which could facilitate the selection of the most appropriate method in the related biomedical research.

Clinical Success of Drug Targets Prospectively Predicted by In Silico Study.

The selection of the right drug targets is critically important for the successful and cost-effective development and clinical testing of drugs. A 2009 paper reported an in silico prospective prediction of the clinical potential of 156 targets of clinical trial drugs (all of these targets were without an approved drug at the time of the paper's publication). Eight years later, the assessment of the clinical status of these targets revealed impressive capability of the in silico method in prospectively predicting the clinical success of drug targets.

Alcohol ethoxylates significantly synergize pesticides than alkylphenol ethoxylates considering bioactivity against three pests and joint toxicity to Daphnia magna.

Seeking alternatives for alkylphenol ethoxylates (APEOs) have been a heavily researched topic in the surfactant industry and agricultural systems. In this study, the combined effects of different ethoxylates and pesticides on the bioactivity against three pests and toxicological risks to Daphnia magna were investigated. Results showed that alcohol ethoxylates (AEOs) had higher synergistic effects on the bioactivity of pesticides against Spodoptera exigua, Agrotis ipsilon and Aphis citricola than did APEOs. In terms of the joint toxicity of the ethoxylates and pesticides to D. magna, additive index method, toxicity unit method, V value method and isobologram method were used in the tests. All of these methods indicated that the joint effects of APEOs + acetamiprid and APEOs + indoxacarb upon D. magna turned from synergism to antagonism with the increasing EO (ethylene oxide) numbers. Those of AEOs exhibited similar trends. Overall, AEOs may be potential alternatives for APEOs in agriculture as they synergize pesticides against three pests significantly more than do APEOs. However, further research should investigate the compounds' environmental risks to aquatic organisms because the AEOs were highly toxic to D. magna.

Therapeutic target database update 2018: enriched resource for facilitating bench-to-clinic research of targeted therapeutics.

Extensive efforts have been directed at the discovery, investigation and clinical monitoring of targeted therapeutics. These efforts may be facilitated by the convenient access of the genetic, proteomic, interactive and other aspects of the therapeutic targets. Here, we describe an update of the Therapeutic target database (TTD) previously featured in NAR. This update includes: (i) 2000 drug resistance mutations in 83 targets and 104 target/drug regulatory genes, which are resistant to 228 drugs targeting 63 diseases (49 targets of 61 drugs with patient prevalence data); (ii) differential expression profiles of 758 targets in the disease-relevant drug-targeted tissue of 12 615 patients of 70 diseases; (iii) expression profiles of 629 targets in the non-targeted tissues of 2565 healthy individuals; (iv) 1008 target combinations of 1764 drugs and the 1604 target combination of 664 multi-target drugs; (v) additional 48 successful, 398 clinical trial and 21 research targets, 473 approved, 812 clinical trial and 1120 experimental drugs, and (vi) ICD-10-CM and ICD-9-CM codes for additional 482 targets and 262 drugs against 98 disease conditions. This update makes TTD more useful for facilitating the patient focused research, discovery and clinical investigations of the targeted therapeutics. TTD is accessible at http://bidd.nus.edu.sg/group/ttd/ttd.asp.