“
“In terms of generating sustainable energy resources, the prospect of producing energy and other useful materials using cyanobacteria has been attracting increasing attention since these processes require only carbon dioxide and solar energy. Fedratinib To establish production processes with a high productivity, in silico models to predict the metabolic activity of cyanobacteria are highly desired. In this study, we reconstructed a genome-scale metabolic model of the

cyanobacterium Synechocystis sp. PCC6803, which included 465 metabolites and 493 metabolic reactions. Using this model, we performed constraint-based metabolic simulations to obtain metabolic flux profiles under various environmental conditions. We evaluated the simulated results by comparing these with experimental results from C-13-tracer metabolic flux analyses, which were obtained under heterotrophic and mixotrophic conditions. There was a good agreement of simulation and experimental results under both conditions. Furthermore, using our model, we evaluated the production of ethanol by Synechocystis sp. PCC6803, which enabled us to estimate quantitatively how its productivity Etomoxir depends on the environmental conditions. The genome-scale metabolic model provides useful information for the evaluation of the metabolic capabilities, and prediction

of the metabolic characteristics, of Synechocystis sp. PCC6803.”
“Reversible thiol oxidation is both a mark of hydrogen peroxide (H2O2) toxicity and an initiator of signalling events. H2O2 sensors contain exposed and reactive cysteine residues, which become transiently oxidized as an activation mechanism. In fission yeast, the Pap1 (pombe (AP) under bar -1) transcription factor is normally cytosolic, and upon H2O2 stress it undergoes post-translational modifications impairing its nuclear export; genetic evidences

suggested the formation of a disulphide bond in Pap1 as a triggering ABT-737 mw activation event. Nuclear Pap1 is then recruited to about 50-80 promoters and induces an adaptation response. We have now dissected the role of all seven cysteine residues in Pap1 using genetic and proteomic techniques, and we show that four of them are required for Pap1 to be activated by H2O2 stress. Thus, mutants lacking each one of these cysteine residues display sensitivity to peroxides. Furthermore, these mutant proteins do not become oxidized by H2O2 and cannot bind to promoters or trigger the Pap1-dependent gene expression program. We also demonstrate, by proteomic analysis of reduced and oxidized Pap1, that these four cysteine residues are reversibly oxidized upon H2O2 stress. Our study suggests that not just one but probably two disulphide bonds are required to promote the important conformational changes that trigger Pap1 activation and nuclear accumulation.

007). Patients with p16 overexpression

had poorer survival than patients with p16 underexpression (59.3% vs 83.8% 5-year survival rate, log-rank p=0.015). In univariate analysis, p16 expression was a significant predictor of survival (RR 2.76, p=0.02).\n\nConclusions Results suggest that p16 expression is an important predictive factor of LN metastasis in cervical cancer patients. Moreover, p16 overexpression is associated with a poor prognosis. Therefore, CT99021 manufacturer immunohistochemical evaluation of p16 expression is of potential value for treatment planning in cervical carcinomas.”
“Bronchial epithelial cells express xenobiotic-metabolizing enzymes (XMEs) that are involved in the biotransformation of inhaled toxic compounds. The activities of these XMEs in the lung may modulate respiratory toxicity and have been linked to several diseases of the airways. Arylamine N-acetyltransferases (NAT) are conjugating XMEs that play a key role in the biotransformation of aromatic amine pollutants such as the tobacco-smoke carcinogens 4-aminobiphenyl (4-ABP) and beta-naphthylamine (beta-NA).

We show here that functional human NAT1 or its murine counterpart Nat2 are present in different lung epithelial cells i.e. Clara cells, type II alveolar cells and bronchial epithelial cells, thus indicating that inhaled aromatic amines may undergo NAT-dependent biotransformation in lung epithelium. Exposure of these cells to pathophysiologically relevant amounts of oxidants selleck known to contribute to lung dysfunction, such as H(2)O(2) or peroxynitrite, was found to impair the

NAT1/Nat2-dependent cellular biotransformation LY2090314 of aromatic amines. Genetic and non genetic impairment of intracellular NAT enzyme activities has been suggested to compromise the important detoxification pathway of aromatic amine N-acetylation and subsequently to contribute to an exacerbation of untoward effects of these pollutants on health. Our study suggests that oxidative/nitroxidative stress in lung epithelia cells, due to air pollution and/or inflammation, could contribute to local and/or systemic dysfunctions through the alteration of the functions of pulmonary NAT enzymes. (C) 2009 Elsevier Inc. All rights reserved.”
“Vitiligo vulgaris is an autoimmune pigmentary disorder with no universally efficacious therapeutic options. Separate applications of calcipotriene ointment 0.005% and topical corticosteroid ointments have been successful in the repigmentation of vitiligo. We sought to examine the efficacy of a combination calcipotriene 0.005%-betamethasone dipropionate 0.064% ointment in the repigmentation of vitiligo. An institutional review board-approved retrospective chart review was conducted in 13 pediatric and adult patients with vitiligo treated with calcipotriene 0.005%-betamethasone dipropionate 0.064% ointment once daily for at least 2 months.

Here, we dissected the regulatory mechanisms underlying the activity of a conserved distal promoter element 1. We show that this element carries three Sox-binding sites, works as an enhancer in vivo, and allows promoter activation by the Sox5/6/9 chondrogenic trio. In early steps of chondrogenesis, declining Hmgb1 expression overlaps with the onset of Sox9 expression. Unlike repression in late steps, Hmgb1 overexpression in early chondrogenesis

increases Matn1 promoter activation by the Sox trio, and forced Hmgb1 expression in COS-7 cells facilitates induction of Matn1 expression by the Sox trio. The conserved Matn1 control elements bind Hmgb1 and SOX9 with opposite efficiency in vitro. They show higher HMGB1 than SOX trio

occupancy in established chondrogenic cell lines, and HMGB1 silencing greatly increases MATN1 and COL2A1 RG-7388 expression. Together, these data thus suggest a model whereby Hmgb1 helps recruit the Sox trio to the Matn1 promoter and thereby facilitates activation of the gene in early chondrogenesis. We anticipate that Hmgb1 may similarly affect transcription of other cartilage-specific genes. (C) 2013 Elsevier B.V. All rights reserved.”
“Yeast replication checkpoint mutants, lose viability following transient exposure to hydroxyurea, a replication-impeding drug. In all effort to understand the Fedratinib chemical structure basis for this lethality, we discovered that different events are responsible for inviability in checkpoint-deficient cells harboring mutations ill the mec1 and rad53 genes. By monitoring genomewide replication dynamics of cells exposed to hydroxyurea, we show that cells with a checkpoint deficient allele of RAD53, rad53K227A, fail to duplicate centromeres. Following removal of the drug, however, rad53K227A cells recover substantial

DNA replication, including replication through centromeres. Despite this recovery, the rad53K227A mutant fails to achieve biorientation of sister centromeres during recovery from hydroxyurea, leading to secondary activation of the spindle assembly checkpoint (SAC), aneuploidy, and lethal chromosome segregation errors. We demonstrate that cell lethality from this segregation defect could be partially remedied by reinforcing bipolar attachment. In contrast, cells with the mec1-1 sml1-1 mutations this website suffer from severely impaired replication resumption upon removal of hydroxyurea. mec1-1 sml1-1 cells call, however, duplicate at least some of their centromeres and achieve bipolar attachment, leading to abortive segregation and fragmentation of incompletely replicated chromosomes. Our results highlight the importance of replicating yeast centromeres early and reveal different mechanisms of cell death due to differences in replication fork progression.”
“Stem cells have become one of the “buzz” topics in the last decade or so. One of the best systems to study adult stem cells in vivo is in the model organism, Drosophila melanogaster.

(C) 2013 Elsevier Ltd. All rights reserved.”
“Gnetum (Gnetales: Gnetaceae) constitutes an evolutionarily isolated gymnosperm clade, comprising about 40 species that inhabit

tropical areas of the world. While its closest living relative, the monotypic Welwitschia, has a well-documented fossil record from the Early Cretaceous, Gnetum-like fossils are rare and poorly understood. The phylogeny of Gnetum has been studied previously but the distant relationship to outgroups and the difficulty of obtaining plant material mean it is not yet fully resolved. Most species are tropical lianas with an angiospermous vegetative habit that are difficult to find and identify. Here a new phylogeny is presented based on nuclear and chloroplast data from 58 Gnetum accessions, representing 27 putative Chk inhibitor species, and outgroup information from other seed plants. The results provide support for South American species being sister to the remaining species. The two African species constitute a monophyletic group, sister to an Asian clade, within which the two arborescent species of the genus are the earliest diverging. Estimated divergence times indicate, in contrast with previous results, that the major lineages of Gnetum diverged in the Late

Cretaceous. This result is obtained Dorsomorphin cost regardless of tree prior used in the BEAST analyses (Yule or birth-death). Together these findings suggest a correlation between early divergence events in extant Gnetum and the breakup of Gondwana in the Cretaceous. Compared to the old stem ages of major subclades of Gnetum, crown nodes date to the Cenozoic: the Asian crown group

dates to the Cretaceous-Paleogene (K-Pg) boundary, the African crown group to the mid-Paleogene, and the South American crown group Selleck ERK inhibitor to the Paleogene-Neogene boundary. Although dispersal must have contributed to the current distribution of Gnetum, e.g., within South America and from Southeast Asian islands to the East Asian mainland, dispersal has apparently not occurred across major oceans, at least not during the Cenozoic.”
“Lipocalins have been known for their several biological activities in blood-sucking arthropods. Recently, the identification and characterization of lipocalins from Ixodes ricinus (LIRs) have been reported and functions of lipocalins are well documented. In this study, we have characterized four Ixodes persulcatus lipocalins that were discovered while analyzing I. persulcatus tick salivary gland EST library. We show that the four I. persulcatus lipocalins, here after named LIPERs (lipocalin from I. persulcatus) are 28.8-94.4% identical to LIRs from I. ricinus. Reverse transcriptase-PCR analysis revealed that lipocalin genes were expressed specifically in the salivary glands throughout life cycle stages of the ticks and were up-regulated by blood feeding. The specific expressions were also confirmed by Western blotting analysis.

A total of 20 representative subjects were selected from the pool of patients, 5 subjects for each one of the grades of the scale, and a standardized photographic selleck chemicals llc record was made. One thousand dentists practicing in Spain were sent the survey by e-mail and 174 completed forms were received. We then calculated the concordance of the oral health status indicated by the respondents after visualising the photographs on comparison with the results of the oral health scale of infectious potential; concordance was termed correct grade allocation (CGA).\n\nResults: The majority of respondents (69.1%) achieved a CGA in 8 to

12 cases and none achieved more than 15 CGAs. The poorest CGA rates were found with grades 1 and 2, with a mean of 1.74 +/- 1.09 and 1.87 +/- 1.18, respectively, out of a maximum of 5. The concordance in terms of CGA was high for grade 0 (70.5%), very low for grade 1 (10.8%), low for grade 2 (37.3%), and moderate for grade YM155 order 3 (42.6%).\n\nConclusion: In comparison with visual examination of the oral cavity, the use of objective scale that establishes a reliable diagnosis of oral health in terms of infectious potential was found to

be advantageous.”
“Objectives: Illicit drug use peaks during late adolescence and young adulthood. Turkey has a young population, and, as an historical opium producing country, it has experienced a continual illicit drug abuse problem. This study aimed to estimate the prevalence of substance abuse, to determine the risk factors associated with drug abuse, and to compare the drug abuse between a metropolitan and a rural area.\n\nMethods: This was a cross-sectional study performed between March 2007 and May 2008 at 2 universities; 1 from a rural area (Gaziosmanpasa University) and 1 from a metropolitan area (Istanbul University).\n\nResults: We found that the most common drugs were minor

tranquilizers (5.7%), followed by inhalants (4.9%), and cannabis (3.6%). Cannabis and inhalant abuse were especially common among males. The major risk factors were contact with a person, such as a family member or a peer, who practiced substance abuse, a low level of success at school, being arrested or in selleck inhibitor trouble with the police, and burglary or theft.\n\nConclusions: These risk factors were similar those identified in developed countries. Similar risk factors were shared between different substances. Hence, preventive measures should target substance abuse in general, rather than focusing on controlling the abuse of individual substances.”
“The present study is aimed to assess age-related structural changes in corpus callosum with stereology in 21 postmortem a. brains without neuropathology, of age 65-75 (Group A. n = 7), 80-85 (Group B. n = 7), and 94-105 (Group C. n = 7) years.

Significant differences in quality of life were detected between patients with or without preoperative pain. Well-being was also significantly affected in patients having pain.\n\nConclusion. The pain severity and states of chronification not only explain a reduction in somatic and psychological well-being but also emphasize that preoperative pain should be identified thoroughly

prior to surgery.”
“This study aimed to determine the presence of pathogenic Vibrio spp., S. aureus and Salmonella in 100 seafood samples purchased from Bafilomycin A1 cell line retail outlets in Bursa city (Turkey). Of the samples examined including fish, mussel and shrimp, 67% were found to be contaminated with Vibrio. Presumed Vibrio spp. were identified

by standard biochemical tests, and further confirmed by API 20E system. Identified Vibrio spp. were V. parahaemolyticus (28%), V. vulnificus (1%) and V. cholerae (1%), with the most prevalent being V. alginolyticus (37%). Six (6%) of the samples analysed were positive for S. aureus. However, no contamination of the samples with Salmonella was observed. Our results showed that seafood from retail outlets can be a likely vehicle for infections with Vibrio spp. and S. aureus.”
“2-[(1-Methylpropyl)dithio]-1H-imidazole (IV-2) is a known inhibitor of the thioredoxin system. It causes the oxidation of cysteine residues from both thioredoxin reductase and thioredoxin, with only the latter leading to irreversible inhibition of protein function. Although IV-2 is considered to be the first specific inhibitor of thioredoxin to undergo evaluation ICG-001 datasheet in cancer patients (under the name PX-12), it is unclear whether the oxidative ability of IV-2 is limited to proteins of the thioredoxin family. The current study

investigated the specificity ACY-241 clinical trial of IV-2 by examining its interaction with tubulin, a protein in which cysteine oxidation causes loss of polymerization competence. The cellular effects of IV-2 were examined in MCF-7 breast cancer and endothelial cells (human umbilical vein endothelial cells). Immunocytochemistry revealed a loss of microtubule structure with Western blot analysis confirming that treated cells contained a higher proportion of unpolymerized tubulin. Cell-free tubulin polymerization assays showed a dose-dependent inhibition of tubulin polymerization and depolymerization of preformed microtubules, confirming a direct interaction between IV-2 and tubulin. Further investigation of the tubulin interaction, through analysis of sulfhydryl reactivity and disulfide bond formation, suggested that IV-2 acts through the oxidation of cysteines in tubulin. Biochemical assays indicated that the oxidative properties of IV-2 are not limited to thioredoxin and tubulin, as cysteine-dependent proteases were also inhibited.

\n\nConclusions: These studies validate the clinical usefulness of genomic signatures as potential biomarkers and highlight ADORA2B and GALNT13 as potential candidate genes in SCD-associated elevated TRV.”
“The sodium-phosphate cotransporter 2a (NPT2a) is the principal phosphate transporter expressed in the brush border of renal proximal tubules and is downregulated by parathyroid

hormone (PTH) through an endocytic mechanism. Apical membrane expression of NPT2a is dependent on interactions with the sodium-hydrogen exchanger regulatory factor 1 (NHERF-1). An LLC-PK1 renal cell line stably expressing the PTH receptor (PTH1R) and NHERF-1, termed B28-N1, fails to functionally express NPT2a. In B28-N1 cells, NHERF-1 and NPT2a are inappropriately HM781-36B in vitro localized to the cytoplasm. Ezrin, in the activated state, is capable at linking NHERF-1-assembled complexes to the actin cytoskeleton. Early-passage LLC-PK1 cells stably transfected with either empty vector

or wild-type ezrin express a comparable level of the active, T567 phosphorylated form of ezrin and are capable of functionally expressing NPT2a. Colocalization of the PTH1R, NPT2a, and ezrin exists and is prominently associated with actin-containing microvilli in apical domains of these cells. Upon PTH treatment, the PTH1R, NPT2a, NHERF-1, and ezrin colocalize to endocytic NU7441 mouse vesicles and NPT2a-dependent phosphate uptake is markedly inhibited. LLC-PK1 cells expressing the constitutively active ezrin (T567D) display enhanced

NPT2a functional expression and PTH-mediated regulation of phosphate. Expression of a dominant-negative ezrin, consisting of the NH(2)-terminal half of the protein, markedly disrupts NPT2a-dependent phosphate uptake. PTH does not appear to alter ezrin phosphorylation at T567. Instead, PTH perhaps initiates NPT2a endocytosis by inducing reorganization of the actin-containing microvilli in a process that is blocked by the actin-stabilizing compound jasplakinolide.”
“Background/Aims: The aim of this study is to highlight the variable clincoradiological spectrum of isolated cortical vein thrombosis (ICoVT), which seems to remain a challenge to clinicians. VS-6063 Cases Reports: We reported 3 patients with this diagnosis. One presented with only an epileptic seizure, one with worsening headache, seizures, mental disorder, speech disturbance and right-sided weakness, and the other with seizures and fluctuating paralysis in her left-sided limbs. Brain images were manifested with a strand-like abnormal signal, a large hemorrhagic infarction and a continuously enlarged space-occupying massive edema, respectively. Conclusions: Neurologic features and brain imaging of ICoVT are highly variable, which might be partly responsible for the underestimation of ICoVT. Clinical diagnosis should probably be evoked more often. Copyright (C) 2013 S.

Then, His-tagged truncated HA protein was expressed in Escherichia P5091 coli BL21 (DE3) under 1 mM IPTG induction. The protein expression was optimized under a time-course induction study and further purified using Ni-NTA agarose under

reducing condition. Migration size of protein was detected at 15 kDa by Western blot using anti-His tag monoclonal antibody and demonstrated no discrepancy compared to its calculated molecular weight.”
“Bismuth oxide may be a promising battery material due to the high gravimetric (690 mAh g(-1)) and volumetric capacities (6280 mAh cm(-3)). However, this intrinsic merit has been compromised by insufficient Li-storage performance due to poor conductivity and structural integrity. Herein, we engineer a heterostructure composed of bismuth oxide (Bi2O3) and bismuth sulphide (Bi2S3) through sulfurization of Bi2O3 nanosheets. Such a hierarchical Bi2O3-Bi2S3 nanostructure can be employed as efficient electrode material for Li storage, due to the high surface Selleck CH5424802 areas, rich porosity, and unique heterogeneous phase. The electrochemical results show that the heterostructure exhibits a high Coulombic

efficiency (83.7%), stable capacity delivery (433 mAhg(-1) after 100 cycles at 600 mAg(-1)) and remarkable rate capability (295 mAhg(-1) at 6 A g(-1)), notably outperforming reported bismuth based materials. Such superb performance indicates that constructing heterostructure could be a promising strategy towards high-performance electrodes for

rechargeable batteries.”
“A new, low-band-gap alternating copolymer consisting of terthiophene and isoindigo has been designed and synthesized. Solar cells based on this polymer and PC71BM show a power conversion efficiency of 6.3%, which is a record for polymer solar cells based on a polymer with an optical band gap below 1.5 eV. This work demonstrates the great potential of isoindigo moieties as electron-deficient units for building donor-acceptor-type polymers for high-performance polymer solar cells.”
“Objectives. This is a multicenter, collaborative study to accumulate cases of small cell carcinoma of the uterine GSK2126458 in vitro cervix (SmCC), to clarify its clinical and clinicopathologic features and prognosis, and to obtain findings to establish future individualized treatment.\n\nMethods. At medical centers participating in the Kansai Clinical Oncology Group/Intergroup, patients diagnosed with SmCC between 1997 and 2007 were enrolled. Clinicopathologic features and prognosis were retrospectively evaluated in patients with SmCC diagnosed at a central pathologic review.\n\nResults. A total of 71 patients were registered at 25 medical centers in Japan. Of these, 52 patients (73%) were diagnosed with SmCC based on a pathological review. These 52 patients diagnosed with SmCC were analyzed. The median follow-up period was 57 months. The 4-year progression-free survival (PFS) was: IB1, 59%; 182, 68%; IIB, 13%; and IIIB, 17%.

Their predictive performance can be characterized in two complementary ways: discrimination, the ability to distinguish between occupied and unoccupied sites, and calibration, the extent to which a model correctly predicts conditional probability of presence. The most common measures of model performance,

such as the area under the receiver operating characteristic curve (AUC), measure only discrimination. In contrast, we introduce a new tool for measuring model calibration: the presence-only this website calibration plot, or POC plot. This tool relies on presence-only evaluation data, which are more widely available than presence-absence evaluation data, to determine whether predictions are proportional to conditional probability of presence. We generalize the predicted/expected curves of Hirzel et al. to produce a presence-only analogue of traditional (presence-absence) calibration curves. POC plots facilitate visual exploration of model calibration, and can be

used to recalibrate badly calibrated models. We demonstrate buy Ruboxistaurin their use by recalibrating models made by the DOMAIN modeling method on a comprehensive set of 226 species from six regions of the world, significantly improving DOMAIN’s predictive performance.”
“Phenytoin (PHT), an anticonvulsant agent, widely used for the treatment of epilepsy has been reported to exhibit toxic side effects. The present study investigated the protective effects of kolaviron and vitamin E on hematotoxicity and neurotoxicity induced by phenytoin, in prepubertal

male rats. The animals were treated with PHT (75 mg/kg) separately or in combination with either kolaviron (200 mg/kg) or vitamin E (500 mg/kg) for 14 days. Phenytoin treatment significantly decreased the hemoglobin, white blood cells, lymphocytes and mean corpuscular volume levels without affecting red blood cell, packed cell volume, neutrophils, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration when compared with the control rats. There was a significant increase in lipid peroxidation and hydrogen peroxide levels with marked depletion in antioxidant status in brains of PHT-treated rats when click here compared with the control. Although PHT treatment had no effect on the granular layer, widest diameter of Purkinje cells and Purkinje layer of the cerebellum, it significantly reduced its molecular layer and the density of Purkinje cell. Administration of PHT significantly reduced the densities of the granule cells of the dentate gyrus and the pyramidal neurons of the cornu ammonis of hippocampus proper. Co-treatment with kolaviron and vitamin E effectively reversed the PHT-mediated alterations in the hematology, brain antioxidant status and histomorphometry when compared to PHT only.

journal of Endocrinology (2009) 201, 129-139″
“Primary bone cancers are extremely rare neoplasms, accounting for fewer Selleckchem Fer-1 than 0.2% of all cancers. The evaluation and treatment of patients with bone cancers requires a multidisciplinary team of physicians, including musculoskeletal, medical, and radiation oncologists, and surgeons and radiologists with demonstrated expertise in the management of these tumors. Long-term surveillance and follow-up are necessary for the management

of treatment late effects related to surgery, radiation therapy, and chemotherapy. These guidelines discuss the management of chordoma, giant cell tumor of the bone, and osteosarcoma.”
“Patients with rheumatoid arthritis (RA) tend to have a poor nutritional status. This study aimed to gather information on body composition in patients with RA in private and public health settings in the City of Cape Town, South Africa (SA). This cross-sectional study evaluated adults with RA. Information NCT-501 order on demographics, comorbidities and medication was gathered. Anthropometrical measurements included

weight, height, waist circumference and skinfolds and were used to calculate, interpret and classify body mass index (BMI), percentage body fat, waist circumference, fat mass index (FMI) and fat-free mass index (FFMI). Ethics approval for the execution of the study was obtained from the Health Research Ethics Committee of Stellenbosch University. The study included 251 participants [mean age, 54.7 years; +/- standard deviation (SD) 13.6]. The mean BMI was 30.3 kg/m(2) (+/- SD 6.7) and 26.6 kg/m(2) (+/- SD 6.1) for women and men,

respectively. BMI was used to classify obesity (45.9 %), overweight (26.8 %), normal weight (25.6 %) and underweight (1.6 %). Waist circumference classifications showed a substantially increased risk for metabolic complications in 127 participants (51.8 %) and an increased risk see more in 52 participants (21.2 %). Low fat-free mass (FFMI of < 10th percentile) was seen in 24 participants (21 %), and obesity (FMI of > 90th percentile) was seen in 31 (27 %). Rheumatoid cachexia was identified in 12 participants (10.3 %). Results indicate suboptimal nutritional status in patients with RA in the current setting. It highlights the importance of involving dietitians in the management of RA, with a view to reduce symptoms, improve quality of life, prevent cardiovascular disease and decrease overall medical costs.”
“In this study, we tested the ability of Baicalin to block Chlamydia trachomatis infection and found that the Baicalin blocked infection of Hep-2 cells. Then, we looked into the expression of RFX5 and CPAF gene in Chlamydia-infected cells. We found that RFX5 and CPAF were up-regulated and down-regulated respectively by Baicalin.