A Systematic Review and Meta-analysis of the Distress Thermometer for Screening Distress in Asian Patients with Cancer.

The distress thermometer (DT) is a commonly used tool for screening distress in Asian patients with cancer. However, the optimal cut-off score and discriminative accuracy remain unclear. Hence, this meta-analysis aimed to examine its diagnostic value and optimal cut-off score in Asia. A systematic search was conducted in the PubMed, EMBASE and Cochrane Library databases. The pooled sensitivity, specificity, positive and negative predictive values, and diagnostic odds ratio were calculated. The area under the curve (AUC) was computed from the summary receiver-operating characteristic (SROC) curve. All analyses were performed using STATA 12.0 software. Finally, 10 studies describing 2851 patients were included. After pooling all the results from the 10 studies, the optimal DT cut-off score was 4 with a pooled sensitivity of 0.78 (95% confidence intervals (CI) 0.68-0.86), specificity of 0.73 (95% CI 0.65-0.80) and AUC of 0.82 (95% CI 0.78-0.85). When the DT was compared to the hospital anxiety and depression scale-total (HADS-T), the cut-off score of 4 showed the best balance between the pooled sensitivity (0.81, 95% CI 0.69-0.89) and specificity (0.74, 95% CI 0.59-0.84), and the AUC was 0.84 (95% CI 0.81-0.87). In conclusion, the DT with a cut-off score of 4 was an effective screening tool in Asian patients with cancer.

Cancer-related fatigue and biochemical parameters among cancer patients with different stages of sarcopenia.

PURPOSE: Cancer-related fatigue (CRF) is a pervasive symptom experienced by cancer patients. Sarcopenia has been suggested as a treatment target of CRF. This study aims to assess the differences of CRF and biochemical markers among different stages of sarcopenia which remain poorly delineated. METHODS: A total of 187 patients were included in this cross-sectional study. Based on muscle mass (skeletal muscle index, SMI), muscle strength (handgrip strength), and physical performance (SARC-F score), patients were divided into four groups (non-sarcopenia, pre-sarcopenia, sarcopenia, and severe sarcopenia). Cancer-related fatigue was measured by the Brief Fatigue Inventory (BFI). Biochemical markers were measured by routine blood tests. RESULTS: The BFI score was significantly associated with sarcopenia stage (r=0.500; P<0.001). Cancer patients in severe sarcopenia group suffered from worse CRF than those in non-sarcopenia, pre-sarcopenia, and sarcopenia groups (P<0.001). In the multivariate linear regression model (R2=0.542), CRF was significantly correlated with SARC-F score (standardized B=0.519; P<0.001) and high-sensitivity C-reactive protein (standardized B=0.389; P=0.004). Serum albumin and cholinesterase were statistically correlated with both sarcopenia stage and CRF. CONCLUSIONS: The significantly increased occurrence and severity of CRF in cancer patients with sarcopenia suggest that sarcopenia may be a crucial target to improve the management of CRF. Circulating albumin and cholinesterase have the potential to predicting sarcopenia as biomarkers.

Inducing Intermediates in Biotransformation of Natural Polyacetylene and A Novel Spiro-γ-Lactone from Red Ginseng by Solid Co-Culture of Two Gut Chaetomium globosum and The Potential Bioactivity Modification by Oxidative Metabolism.

The ω-hydroxyl-panaxytriol (1) and ω-hydroxyl-dihydropanaxytriol (2)-are rare examples of polyacetylene metabolism by microbial transformation, and these new metabolites (1, 2) from fermented red ginseng (FRG) by solid co-culture induction of two Chaetomium globosum should be the intermediates of biotransformation of panaxylactone (metabolite A). The metabolic pathway of panaxylactone was also exhibited. The ingredients of red ginseng (RG) also induced the production of rare 6/5/5 tricyclic ring spiro-γ-lactone skeleton (3). The ω-hydroxylation of new intermediates (1, 2) decreases cytotoxicity and antifungal activity against C. globosum compared with that of its bioprecursor panaxytriol. Additionally, compounds 1 and 2 indicated obvious inhibition against nitric oxide (NO) production, with ratios of 44.80 ± 1.37 and 23.10 ± 1.00% at 50 µM. 1 has an equivalent inhibition of NO production compared with the positive drug. So, the microbial biotransformation that occurred in FRG fermented by gut C. globosum can change the original bioactivity of polyacetylene, which gave a basis about the metabolic modification of red ginseng by intestinal fungus fermentation.

Coix seed oil ameliorates cancer cachexia by counteracting muscle loss and fat lipolysis.

BACKGROUND: Cancer cachexia is a cancer-induced multifactorial debilitating syndrome directly accounting for 20% of cancer deaths without effective therapeutic approaches. It is extremely urgent to explore effective anti-cachexia drugs to ameliorate muscle and fat loss in cachexia patients. METHODS: Lewis lung carcinoma bearing C57BL/6 mice were applied as the animal model to examine the therapeutic effect of Coix seed oil (CSO) on cancer cachexia. The food intake and body weight change were monitored every 3 days throughout the experiment. The IL-6 and TNF-α levels in serum were detected by ELISA assay. Several key proteins involved in muscle wasting and fat lipolysis were tested by Western blot to identify the potential mechanism of CSO. RESULTS: Administration of CSO through gavage significantly prevented body weight loss and ameliorated systemic inflammation without affecting food intake and tumor size. The weight and histological morphology of gastrocnemius muscle and epididymal adipose tissue in CSO-treated mice were also improved. In mechanism, we found that CSO decreased the expression of MuRF1 and the ratio of phospho-p65 (Ser536) to p65 in muscle tissue. Meanwhile, cancer-induced activation of HSL and AMPK was also inhibited by CSO administration. CONCLUSION: Coix seed oil exerts an anti-cachexia pharmaceutical effect by counteracting muscle and adipose tissue loss most likely through regulating NF-κB-MuRF1 and AMPK-HSL pathway.

Identification and functional analysis of a potential key lncRNA involved in fat loss of cancer cachexia.

Cancer cachexia is a devastating, multifactorial, and irreversible syndrome characterized by skeletal muscle reduction with or without fat loss. Although much attention has been focused on muscle wasting, fat loss may occur earlier and accelerate muscle wasting in cachexia. The cause of 20% of cancer related death makes it urgent to discover molecular mechanisms behind cancer cachexia. Here we applied weighted gene co-expression network analysis (WGCNA) to identify cachexia related gene modules using differentially expressed 3289 genes and 59 long non-coding RNAs based on microarray data of cachectic and non-cachectic subcutaneous adipose tissue. Subsequently, 16 independent modules were acquired and GSAASeqSP Toolset confirmed that black module was significantly associated with fat loss in cancer cachexia. Top 50 hub-genes in black module contained only one lncRNA, VLDLR antisense RNA 1 (VLDLR-AS1). We then explored the function of black module from the view of VLDLR-AS1-connected genes in the network. GO enrichment and KEGG pathways analysis revealed LDLR-AS1-connected genes were involved in Wnt signaling pathway, small GTPase mediated signal transduction, epithelial-mesenchymal transition and so on. Through construction of competing endogenous RNAs (ceRNAs) regulation network, we showed that VLDLR-AS1 may function with hsa-miR-600 to regulate gene GOLGA3, DUSP14, and UCHL1, or interact with hsa-miR-1224-3p to modulate the expression of gene GOLGA3, ZNF219, RNF141, and CALU. After literature validation, we predicted that VLDLR-AS1 most likely interacted with miR-600 to regulate UCH-L1 through Wnt/ß-catenin signaling pathway. However, further experiments are still required to validate mechanisms of VLDLR-AS1 in fat reduction of cancer cachexia.

New Azaphilones from Nigrospora oryzae Co-Cultured with Beauveria bassiana.

In this study, the co-culture of Nigrospora oryzae and Beauveria bassiana, the endophytes in the seeds of Dendrobium officinale, were examined for metabolite diversity. Five new azaphilones were isolated, and their structures were determined by spectral analysis. In terms of azaphilones, compound 2 had an unprecedented skeleton, with a bicyclic oxygen bridge. The antifungal selectivities of the metabolite produced by N. oryzae against its co-culture fungus, B. bassiana, and common pathogens exhibited competitive interaction in this mix-culture. Compounds 1 and 2 showed obvious nitric oxide (NO) inhibitory activity with ratios of 37%, and 39%, respectively, at a concentration of 50 µM.

Genomic dynamics of the Lower Yellow River Valley since the Early Neolithic.

The Yellow River Delta played a vital role in the development of the Neolithic civilization of China. However, the population history of this region from the Neolithic transitions to the present remains poorly understood due to the lack of ancient human genomes. This especially holds for key Neolithic transitions and tumultuous turnovers of dynastic history. Here, we report genome-wide data from 69 individuals dating to 5,410-1,345 years before present (BP) at 0.008 to 2.49× coverages, along with 325 present-day individuals collected from 16 cities across Shandong. During the Middle to Late Dawenkou period, we observed a significant influx of ancestry from Neolithic Yellow River farmers in central China and some southern Chinese ancestry that mixed with local hunter-gatherers in Shandong. The genetic heritage of the Shandong Longshan people was found to be most closely linked to the Dawenkou culture. During the Shang to Zhou Dynasties, there was evidence of genetic admixture of local Longshan populations with migrants from the Central Plain. After the Qin to Han Dynasties, the genetic composition of the region began to resemble that of modern Shandong populations. Our genetic findings suggest that the middle Yellow River Basin farmers played a role in shaping the genetic affinity of neighboring populations in northern China during the Middle to Late Neolithic period. Additionally, our findings indicate that the genetic diversity in the Shandong region during the Zhou Dynasty may be linked with their complex ethnicities.

Performance of a continuous flow reactor on bio-reducing vanadium with straw.

Vanadium (V) in groundwater could cause a serious threat to the environment and health. Continuous flow reactors were applied to reduce V(V) with straw being a solid carbon. The reduced efficiency of V(V) in the reactor with straw and inoculated sludge reached to 71.8%-99.9% for two months' operation (after 44 d). However, a long-term operation with only straw was not satisfied, achieving the reduced efficiency of 39.2-66.6%. The SEM images clearly revealed some traces of straw surface by utilized by microbes, which implied that microbes had a stronger capacity to hydrolyze straw. The introducing external microbes were essential to achieve a better bio-reduction performance on V(V). Treponema (5.3%) with metal reduction ability and Prevotellaceae (3.3%) able to specifically degrade complex plant-derived polysaccharides were found to be dominant in the microbial community. Utilizing agricultural biomass can save a lot of normal carbon like acetate, which is of benefit for carbon emissions.

Optimizing the added ratio of mixed auxiliary packings for enhancing the biological vanadium (V) removal.

Developing sustainable and low-cost bio-reduction technologies is essential for vanadium (V) bioremediation in groundwater. With both agricultural waste (wheat stalk) being a solid carbon source and ceramsite and medical stone being auxiliary packings, V(V) removal was confirmed and optimized in this study. The ratio of ceramsite to medical stone was maintained at 1:3 in Group I, which accomplished a V(V) removal efficiency up to 97.5% within 120 h and an average removal rate was around 0.305 mg/(L·h). The dissolution and utilization of carbon and trace elements (Mg, Fe, Mo and Ni) by microbes also contributed to the V(V) bio-reduction enhancement. The main components of DOM (tryptophan and humic acid-like substances) were vital in the V(V) binding and electron transfer processes. This study could promote the current knowledge on the sustainable V(V) bioremediation by using agricultural waste and auxiliary packings.

A Comprehensive and Modularized Statistical Framework for Gradient Norm Equality in Deep Neural Networks.

The rapid development of deep neural networks (DNNs) in recent years can be attributed to the various techniques that address gradient explosion and vanishing. In order to understand the principle behind these techniques and develop new methods, plenty of metrics have been proposed to identify networks that are free of gradient explosion and vanishing. However, due to the diversity of network components and complex serial-parallel hybrid connections in modern DNNs, the evaluation of existing metrics usually requires strong assumptions, complex statistical analysis, or has limited application fields, which constraints their spread in the community. In this paper, inspired by the Gradient Norm Equality and dynamical isometry, we first propose a novel metric called Block Dynamical Isometry, which measures the change of gradient norm in individual blocks. Because our Block Dynamical Isometry is norm-based, its evaluation needs weaker assumptions compared with the original dynamical isometry. To mitigate challenging derivation, we propose a highly modularized statistical framework based on free probability. Our framework includes several key theorems to handle complex serial-parallel hybrid connections and a library to cover the diversity of network components. Besides, several sufficient conditions for prerequisites are provided. Powered by our metric and framework, we analyze extensive initialization, normalization, and network structures. We find that our Block Dynamical Isometry is a universal philosophy behind them. Then, we improve some existing methods based on our analysis, including an activation function selection strategy for initialization techniques, a new configuration for weight normalization, a depth-aware way to derive coefficients in SeLU, and initialization/weight normalization in DenseNet. Moreover, we propose a novel normalization technique named second moment normalization, which has 30 percent fewer computation overhead than batch normalization without accuracy loss and has better performance under micro batch size. Last but not least, our conclusions and methods are evidenced by extensive experiments on multiple models over CIFAR-10 and ImageNet.

Performance and Enhancement of Various Fillers Guiding Vanadium (V) Bioremediation.

Bioremediation of vanadium (V) pollution in groundwater is an emerging topic. However, knowledge of V in a biogeochemical process is limited and long-term effective removal methods are lacking. V(V) remediation processes by various kinds of auxiliary fillers (maifanite-1, maifanite-2, volcanic rock, green zeolite and ceramsite), agricultural biomass and microbial enhancing were explored in this study. In tests without inocula, the V(V) removal efficiencies of ceramsite (inert filler) and maifanite-2 (active filler) were 84.9% and 60.5%, respectively. When inoculated with anaerobic sludge, 99.9% of V(V) could be removed with the synergistic performance of straw and maifanite-2. TOC (Total Organic Carbon), trace elements and three-dimensional fluorescence analyses confirmed that maifanite-2 was the most suitable among various fillers in biological V(V) removal systems with straw. This study provides a collaborative method (adsorption-biology) by using straw with maifanite-2 in V(V)-contaminated groundwater. The knowledge gained in this study will help develop permeable reactive barrier technology to repair polluted groundwater to put forward a reasonable, effective and sustainable environmental treatment strategy.

Corrigendum to "Performance of Distress Thermometer and Associated Factors of Psychological Distress among Chinese Cancer Patients".

[This corrects the article DOI: 10.1155/2020/3293589.].

Performance of Distress Thermometer and Associated Factors of Psychological Distress among Chinese Cancer Patients.

OBJECTIVE: We aimed to examine the performance of the distress thermometer (DT) and identify the prevalence and risk factors associated with psychological distress (PD) in heterogeneous cancer patients. METHODS: This cross-sectional study enrolled 1496 heterogeneous cancer patients from the inpatient and outpatient departments. Receiver operating characteristic analysis (ROC) of DT was evaluated against the Hospital Anxiety and Depression Scale-Total (HADS-T ≥15). An area under the curve (AUC), sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and clinical utility index were calculated. Multiple binary logistic regression was used to identify the factors associated with PD. RESULTS: Referring to ROC analysis, DT showed good discriminating accuracy (AUC = 0.88). A cutoff score of 4 was established, and it yielded sensitivity (0.81), specificity (0.88), PPV (0.87), NPV (0.82), and clinical utility indexes (screening utility = 0.71 and case-finding utility = 0.73). 46.5% of our participants was distressed. Lower education levels (odd ratio (OR) = 1.39), advanced stage (OR = 1.85), active disease status (OR = 1.82), lack of exercise (OR = 3.03), diagnosis known (OR = 0.64), emotional problems (OR = 3.54), and physical problems (OR = 8.62) were the predictive factors for PD. CONCLUSION: DT with a cutoff score (≥4) is a comprehensive, appropriate, and practical initial screener for PD in cancer patients. Predicting factors should be considered together for effective management of PD in such population.

Inducing secondary metabolite production from Daldinia eschscholzii JC-15 by red ginseng medium.

Red ginseng (RG) is one of the most popular herbal medicines and used as a dietary supplement in recent years. The bioactive ingredient in RG can induce the production of novel microbial metabolite from fermented RG. Using the one strain-many compounds strategy, the reinvestigation of the metabolites from Daldinia eschscholzii JC-15 cultured in red ginseng medium led to the isolation of an unprecedented benzopyran-naphthalene hybrid, daldinsin (1) and a new lactone (2). In this research, a new lactone, 8-hydroxylhelicascolide A (2) instead of helicascolide A was produced by the D. eschscholzii JC-15 induced by the red ginseng medium. Compound 1 showed anti-acetylcholinesterase activity with the inhibition ratio of 38.8% at 50 µM. Compound 2 indicated antimicrobial activities against Fusarium Solani, F. oxysporum, and Escherichia coli with MICs at 128 µg/mL. RG is therefore a promising activator in production of novel microbial metabolite.

Biotransformation of natural polyacetylene in red ginseng by Chaetomium globosum.

BACKGROUND: Fermentation has been shown to improve the biological properties of plants and herbs. Specifically, fermentation causes decomposition and/or biotransformation of active metabolites into high-value products. Polyacetylenes are a class of polyketides with a pleiotropic profile of bioactivity. METHODS: Column chromatography was used to isolate compounds, and extensive NMR experiments were used to determine their structures. The transformation of polyacetylene in red ginseng (RG) and the production of cazaldehyde B induced by the extract of RG were identified by TLC and HPLC analyses. RESULTS: A new metabolite was isolated from RG fermented by Chaetomium globosum, and this new metabolite can be obtained by the biotransformation of polyacetylene in RG. Panaxytriol was found to exhibit the highest antifungal activity against C. globosum compared with other major ingredients in RG. The fungus C. globosum cultured in RG extract can metabolize panaxytriol to Metabolite A to survive, with no antifungal activity against itself. Metabolites A and B showed obvious inhibition against NO production, with ratios of 42.75 ± 1.60 and 63.95 ± 1.45% at 50 µM, respectively. A higher inhibitory rate on NO production was observed for Metabolite B than for a positive drug. CONCLUSION: Metabolite A is a rare example of natural polyacetylene biotransformation by microbial fermentation. This biotransformation only occurred in fermented RG. The extract of RG also stimulated the production of a new natural product, cazaldehyde B, from C. globosum. The lactone in Metabolite A can decrease the cytotoxicity, which was deemed to be the intrinsic activity of polyacetylene in ginseng.

Benzopyran derivatives from endophytic Daldinia eschscholzii JC-15 in Dendrobium chrysotoxum and their bioactivities.

Five new benzopyran derivatives (2-6) and a new natural product (1) were isolated from endophytic Daldinia eschscholzii in Dendrobium chrysotoxum and determined as (R)-2,3-dihydro-2,5-dihydroxy-2-methylchromen-4-one (1), (2R, 4S)-2,3-dihydro-2-methyl-benzopyran-4,5-diol (2), (R)-3-methoxyl-1-(2,6-dihydroxy phenyl)-butan-1-one (3), 7-O-α-d-ribosyl-5-hydroxy-2-methyl-4H-chromen-4-one (4), 7-O-α-d-ribosyl-2,3-dihydro-5-hydroxy-2-methyl-chromen-4-one (5), daldinium A (6). These compounds were evaluated for their antimicrobial activity, anti-acetylcholinesterase, nitric oxide inhibition, anticoagulant, photodynamic antimicrobial activities and glucose uptake of adipocytes. Some compounds showed photoactive antimicrobial activities and glucose uptake stimulating activities.

Five extracellular matrix-associated genes upregulated in oral tongue squamous cell carcinoma: An integrated bioinformatics analysis.

Despite advancements in treatment regimens, the mortality rate of patients with oral tongue squamous cell carcinoma (OTSCC) is high. In addition, the signaling pathways and oncoproteins involved in OTSCC progression remain largely unknown. Therefore, the aim of the present study was to identify specific prognostic marker for patients at a high risk of developing OTSCC. The present study used four original microarray datasets to identify the key candidate genes involved in OTSCC pathogenesis. Expression profiles of 93 OTSCC tissues and 76 normal tissues from GSE9844, GSE13601, GSE31056 and GSE75538 datasets were investigated. Differentially expressed genes (DEGs) were determined, and gene ontology enrichment and gene interactions were analyzed. The four GSE datasets reported five upregulated and six downregulated DEGs. Five upregulated genes (matrix metalloproteinase 1, 3, 10 and 12 and laminin subunit gamma 2) were localized in the extracellular region of cells and were associated with extracellular matrix disassembly. Furthermore, analysis for The Cancer Genome Atlas database revealed that the aforementioned five upregulated genes were also highly expressed in OTSCC and head and neck squamous cell carcinoma tissues. These results demonstrated that the five upregulated genes may be considered as potential prognostic biomarkers of OTSCC and may serve at understanding OTSCC progression. Upregulated DEGs may therefore represent valuable therapeutic targets to prevent or control OTSCC pathogenesis.

Development and validation of a clinically applicable score to classify cachexia stages in advanced cancer patients.

BACKGROUND: Cachexia is a multifactorial syndrome that is highly prevalent in advanced cancer patients and leads to progressive functional impairments. The classification of cachexia stages is essential for diagnosing and treating cachexia. However, there is a lack of simple tools with good discrimination for classifying cachexia stages. Therefore, our study aimed to develop a clinically applicable cachexia staging score (CSS) and validate its discrimination of clinical outcomes for different cachexia stages. METHODS: Advanced cancer patients were enrolled in our study. A CSS comprising the following five components was developed: weight loss, a simple questionnaire of sarcopenia (SARC-F), Eastern Cooperative Oncology Group, appetite loss, and abnormal biochemistry. According to the CSS, patients were classified into non-cachexia, pre-cachexia, cachexia, and refractory cachexia stages, and clinical outcomes were compared among the four groups. RESULTS: Of the 297 participating patients, data from 259 patients were ultimately included. Based on the CSS, patients were classified into non-cachexia (n = 69), pre-cachexia (n = 68), cachexia (n = 103), and refractory cachexia (n = 19) stages. Patients with more severe cachexia stages had lower skeletal muscle indexes (P = 0.002 and P = 0.004 in male and female patients, respectively), higher prevalence of sarcopenia (P = 0.017 and P = 0.027 in male and female patients, respectively), more severe symptom burden (P < 0.001), poorer quality of life (P < 0.001 for all subscales except social well-being), and shorter survival times (P < 0.001). CONCLUSIONS: The CSS is a simple and clinically applicable tool with excellent discrimination for classifying cachexia stages. This score is extremely useful for the clinical treatment and prognosis of cachexia and for designing clinical trials.

Potential antihyperlipidemic polyketones from endophytic Diaporthe sp. JC-J7 in Dendrobium nobile.

Eleven new polyketones named diaporthsins A-K (1-11) were isolated from the fermentation of Diaporthe sp. JC-J7. The chemical structures of compounds (1-11) were elucidated by spectroscopic methods including HRESIMS, 2DNMR, NMR and chemical methods. Compound 11 features an unusual acyclic polyketone-phenolic polyketone hybrid structure that integrates the characteristics of different fungal metabolites (cytosporone and multiplolide). Compound 3 was the only C12-polyketone obtained in this research. These new polyketones showed inhibitory activity on triglycerides (TG) in steatosis hepatocyte L-02 cells. Among them, compound 5 and (4E)-6,7,9-trihydroxydec-4-enoic acid displayed inhibitory activities on TG in steatotic L-02 cells with inhibition ratios of 26% and 21% at concentration of 5 µg mL-1; also, inhibition ratios of 8-O-acetylmultiplolide A and phomopsisporone A at concentration of 5 µg mL-1 were calculated to be about 24% and 16%, respectively, which were equivalent to the antihyperlipidemic activity of lovastatin. The preliminary structure-activity relationship indicated that acetyl at C-8 can increase the antihyperlipidemic activity of multiplolide A and the glycol ester and hydroxyl at C-6 can also increase the corresponding activity of diaporthsin B.

New azaphilones and tremulane sesquiterpene from endophytic Nigrospora oryzae cocultured with Irpex lacteus.

Five new metabolites belonging to two backbones of pulvilloric acid-type azaphilone and tremulane sesquiterpene were obtained and their structures were determined by spectral analysis. Based on the biogenesis analysis, tremulane sesquiterpenes were obtained from Irpex lacteus by the stimulation of mixed-culture. The antifungal selectivities of metabolites produced by fungus against their co-culture fungus and common pathogens, exhibited competitive interaction of this mix-culture. The tremulane sesquiterpene conocenol B produced by I. lacteus through the induction of Nigrospora oryzae showed selectivity of anti-fungal activity against its co-culture fungus, N. oryzae, with MICs at 16 µg/mL and 128 µg/mL against I. lacteus. The fungus can metabolize these new compounds to inhibit the growth of co-culture fungus while not inhibiting its own growth. Compound 5 was active against acetylcholinesterase (AChE) with a ratio of 35% at the concentration of 50 µM.