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The failure of endogenous repair is the main feature of neurological diseases that cannot recover the damaged tissue and the resulting dysfunction. Currently, the range of treatment options for neurological diseases is limited, and the approved drugs are used to treat neurological diseases, but the therapeutic effect is still not ideal. In recent years, different studies have revealed that neural stem cells (NSCs) have made exciting achievements in the treatment of neurological diseases. NSCs have the potential of self-renewal and differentiation, which shows great foreground as the replacement therapy of endogenous cells in neurological diseases, which broadens a new way of cell therapy. The biological functions of NSCs in the repair of nerve injury include neuroprotection, promoting axonal regeneration and remyelination, secretion of neurotrophic factors, immune regulation, and improve the inflammatory microenvironment of nerve injury. All these reveal that NSCs play an important role in improving the progression of neurological diseases. Therefore, it is of great significance to better understand the functional role of NSCs in the treatment of neurological diseases. In view of this, we comprehensively discussed the application and value of NSCs in neurological diseases as well as the existing problems and challenges., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yang, Liu, Liu, Zhu, Xiong, Hu and Zhang.)

Spinal cord injury (SCI) can lead to severe motor, sensory and autonomic nervous dysfunction, cause serious psychosomatic injury to patients. There is no effective treatment for SCI at present. In recent years, exciting evidence has been obtained in the application of cell-based therapy in basic research. These studies have revealed the fact that cells transplanted into the host can exert the pharmacological properties of treating and repairing SCI. Olfactory ensheathing cells (OECs) are a kind of special glial cells. The application value of OECs in the study of SCI lies in their unique biological characteristics, that is, they can survive and renew for life, give full play to neuroprotection, immune regulation, promoting axonal regeneration and myelination formation. The function of producing secretory group and improving microenvironment. This provides an irreplaceable treatment strategy for the repair of SCI. At present, some researchers have explored the possibility of treatment of OECs in clinical trials of SCI. Although OECs transplantation shows excellent safety and effectiveness in animal models, there is still lack of sufficient evidence to prove the effectiveness of their clinical application in clinical trials. There has been an obvious stagnation in the transformation of OECs transplantation into routine clinical practice, and clinical trials of cell therapy in this field are still facing major challenges and many problems that need to be solved. Therefore, this paper summarized and analyzed the clinical trials of OECs transplantation in the treatment of SCI, and discussed the problems and challenges of OECs transplantation in clinical trials., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Although current computational biology software is available and has prompted the development of enzyme-substrates simulation, they are difficult to install and inconvenient to use. This makes the time-consuming and error-prone process. By far there is still a lack of a complete tool which can provide a one-stop service for the enzyme-substrates simulation process. Hence, in this study, several computational biology software was extended development and integrated as a website toolbox named Atomevo. The Atomevo is a free web server providing a user-friendly interface for enzyme-substrates simulation: (1) protein homologous modeling; (2) parallel docking module of Autodock Vina 1.2; (3) automatic modeling builder for Gromacs molecular dynamics simulation package; and (4) Molecular Mechanics/Poisson-Boltzmann Surface Area (MMPBSA) analysis module for receptor-ligand binding affinity analysis. We officially launched the web server and provided instructions through a case for the design and simulation of Candida antarctica lipase B (CalB) fusion protein called Maltose Binding Protein-Thioredoxin A-Candida antarctica lipase B (MBP-TrxA-CalB)., (© 2022. The Author(s).)

Pheochromocytoma is a relatively uncommon tumor, and the histomorphologic and biochemical features that may portend malignant behavior have poor overall consensus across various proposed classification systems. Steroid receptor coactivator-1 (SRC-1) is a nuclear protein that mediates transcriptional activity. Current diagnostic applications of SRC-1 are limited, and include distinguishing adrenocortical carcinoma (ACC) from renal cell carcinoma, and other mimickers. SRC-1 expression in pheochromocytoma has not been previously studied. Pheochromocytoma cases were retrieved from our Urological Pathology database and expert consultation files of the senior author, from 2015 to 2019. Clinicopathological data were obtained. SRC-1 expression was scored systematically. Thirty-eight cases were included, with a female predominance, and a mean age of 52 years (range, 16 to 75 y). Seven patients had heritable mutations including RET (n=3), VHL (2), SDHB (1), and ATM and PDGFRA (1). Two patients developed clinical metastasis, who individually had ATM and PDGFRA mutations, and SDHB p.V140F mutation. All heritable tumors were positive for SRC-1, including diffuse/strong staining and intensity in the VHL cases, and diffuse staining with variable intensity in RET cases. Diffuse positivity was seen in most of our heritable cases, providing evidence for a putative link between RET and downstream SRC-1 signaling. An inverse relationship was observed between SRC-1 expression and Pheochromocytoma of the Adrenal Gland Scaled Score/tumor size, suggesting that SRC-1 phenotype may become muted in pheochromocytomas that have malignant potential. SRC-1 expression in aggressive pheochromocytomas, may also be a potential diagnostic pitfall in view of the fact that these tumors may be misinterpreted as ACC in the primary or metastatic setting.

Objectives: The purpose of this study was to determine the effect of microencapsulated olfactory ensheathing cells (MC-OECs) transplantation on neuropathic pain (NPP) caused by sciatic nerve injury in rats, and its relationship with the expression levels of P2X2 receptor (P2X2R) in the L4-5 spinal cord segment., Methods: Olfactory bulb tissue was removed from a healthy Sprague-Dawley (SD) rat for culturing olfactory ensheathing cells (OECs). Forty-eight SD rats were randomly divided into four groups (12 per group): the sham, chronic constriction injury (CCI), olfactory ensheathing cells (OECs), and MC-OECs groups. On days 7 and 14 after surgery, the mechanical withdrawal thresholds (MWT) were measured by using behavioral method. The expression levels of P2X2R in the L4-5 spinal cord segment were detected by in situ hybridization and Western blotting., Results: On days 7 and 14 post-surgical, the MWT of rats from high to low were the sham, MC-OECs, OECs, and CCI groups, the MWT of rats in the MC-OECs groups were higher than that in OECs groups. The expression levels of P2X2R in the L4-5 spinal cord segment from high to low were the CCI, OECs, MC-OECs, and sham groups, the expression levels of P2X2R were lower than that in OECs groups. All differences between groups were statistically significant (p value <.05 )., Conclusions: OECs and MC-OECs transplantation can reduce the expression levels of P2X2R genes in the L4-5 spinal cord segment, and relieve NPP. The therapeutic efficacy of MC-OECs transplantation was better than the transplantation of OECs.

Hot spring ecosystems are analogous to some thermal environments on the early Earth and represent ideal models to understand life forms and element cycling on the early Earth. Denitrification, an important component of biogeochemical nitrogen cycle, is highly active in hot springs. Nitrite (NO 2 - ) reduction to nitric oxide (NO) is the significant and rate-limiting pathway in denitrification and is catalyzed by two types of nitrite reductases, encoded by nirS and nirK genes. NirS and NirK were originally considered incompatible in most denitrifying organisms, although a few strains have been reported to possess both genes. Herein, we report the functional division of nirS and nirK in Thermus, a thermophilic genus widespread in thermal ecosystems. Transcriptional levels of nirS and nirK coexisting in Thermus antranikianii DSM 12462 T were measured to assess the effects of nitrite, oxygen, and stimulation time. Thirty-nine Thermus strains were used to analyze the phylogeny and distribution of nirS and nirK; six representative strains were used to assess the denitrification phenotype. The results showed that both genes were actively transcribed and expressed independently in T. antranikianii DSM 12462 T . Strains with both nirS and nirK had a wider range of nitrite adaptation and revealed nir-related physiological adaptations in Thermus: nirK facilitated adaptation to rapid changes and extended the adaptation range of nitrite under oxygen-limited conditions, while nirS expression was higher under oxic and relatively stable conditions.

This paper investigates the conformational stability of porcine pancreatic lipase (PPL) in three non-aqueous organic solvents, including dimethyl sulfoxide (DMSO), propylene glycol (PRG), and ethanol (EtOH) through molecular dynamic (MD) simulation. The root mean square deviations (RMSDs), radius of gyration (Rg), solution accessible surface area (SASA), radial distribution function (RDF), hydrogen bond (H-bond), Ramachandran plot analysis, secondary structure, and enzyme substrate affinity of the PPL in the various organic solvents were comparatively investigated. The results showed that the backbone and active pocket RMSD, and hydrophilic ASA of PPL in three solvents increase with the increase in the solvent LogP, while the Rg, hydrophobic ASA, and H-bond between the solvent and PPL decrease. Among the three organic solvents, DMSO acts as a better solvent, in which the PPL can be loose and extended, and retains its native backbone in DMSO compared to PRG and EtOH. Moreover, Ramachandran plot analysis indicated that the PPL structure quality in DMSO was higher than that in PRG and EtOH. Also, the molecular docking results showed that PPL in DMSO exhibited the highest enzyme-substrate affinity., (Copyright © 2020 Chen, Wu, Hao, Liu, He, Jiang, Xiong, Lv, Cao and Zhu.)

The group Nitriliruptoria, recently classified as a separate class of phylum Actinobacteria, has five members at present, which belong to halophilic or halotolerant Actinobacteria. Here, we sequenced the genomes of Egicoccus halophilus EGI 80432 T and Egibacter rhizosphaerae EGI 80759 T , and performed a comparative genomics approach to analyze the genomic differences and salt adaptation mechanisms in Nitriliruptoria. Phylogenetic analysis suggested that Euzebya tangerina F10 T has a closer phylogenetic relationship to Euzebya rosea DSW09 T , while genomic analysis revealed highest genomic similarity with Nitriliruptor alkaliphilus ANL-iso2 T and E. halophilus EGI 80432 T . Genomic differences of Nitriliruptoria were mainly observed in genome size, gene contents, and the amounts of gene in per functional categories. Furthermore, our analysis also revealed that Nitriliruptoria possess similar synthesis systems of solutes, such as trehalose, glutamine, glutamate, and proline. On the other hand, each member of Nitriliruptoria species possesses specific mechanisms, K + influx and efflux, betaine and ectoine synthesis, and compatible solutes transport to survive in various high-salt environments.

Background: Inflammatory bowel disease (IBD) is characterised by acute intestinal mucosal inflammation with chronic inflammatory features. Various degrees of mucosal eosinophilia are present along with the typical acute (neutrophil-predominant) inflammation. The effect of intestinal eosinophils on IBD outcomes remains unclear., Methods: This is a retrospective study. Archived intestinal mucosal biopsy specimens of treatment-naïve IBD patients were examined by two pathologists. The number of eosinophils per high-power field was counted, and the mucosal inflammation was classified according to the eosinophilic inflammatory patterns. Clinical outcomes during the follow-up period were recorded., Results: 142 treatment-naïve IBD patients were included. Mean age was 39 years. 83% of patients had ulcerative colitis, and median follow-up was 3 years. 41% of patients had disease flare(s) and 24% required hospitalisation. Eosinophil count was not associated with risk of disease flare or hospitalisation. Patients with neutrophil-predominant inflammation (>70% neutrophils) had greater risk of disease flare(s): 27(55%) versus 24(36%) and 7(28%) in patients with mixed and eosinophil-predominant inflammation, respectively (p=0.04). Overall, patients with neutrophil-predominant inflammation were more likely to have a disease flare; HR: 2.49, 95% CI (1.0 to 5.6). Hospitalisation rate was higher in patients with neutrophil-predominant inflammation: 17(35%) compared to 17(19%) in patients with eosinophil-rich inflammation (p=0.04). Kaplan-Meier analysis showed higher flare-free survival in patients with eosinophil-predominant inflammation compared to mixed and neutrophil-predominant inflammation., Conclusion: IBD patients with eosinophil-predominant inflammation phenotype might have reduced risk of disease flares and hospitalisation. Larger prospective studies to assess IBD outcomes in this subpopulation are warranted., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective To evaluate the instant effects and five-year clinical outcomes of coronary artery disease patients complicated with diabetes mellitus after StentBoost-optimized percutaneous coronary intervention (PCI). Methods From March 2009 to July 2010, 184 patients undergoing PCI at our hospital were found stent underexpansion or malapposition by StentBoost after stents implantation and were divided into the diabetic ( n =73, 39.67%) and the non-diabetic group ( n =111, 60.33%). All patients received StentBoost-guided post-dilatation after stent implantation. The instant procedural results were measured and clinical outcome after five-year follow-up was analyzed in each group. Between-group comparisons were performed using Chi-square test or Student's t test. Multivariate logistic regression analysis was carried out to reveal the independent predictors for long-term clinical outcomes of StentBoost-optimized PCI . Results After StentBoost-guided post-dilatation, the minimum diameter (MinLD), maximum diameter (MaxLD) and average diameter in both groups increased significantly than before ( P <0.001), the (MaxLD-MinLD)/MaxLD ratio and the in-stent residual stenosis decreased accordingly ( P <0.001). The five-year follow-up showed similar mortality rate (4.92% vs . 2.86%, P =0.67) and major adverse cardiac event rate (11.48% vs . 11.43%, P = 1.0) between the diabetic and the non-diabetic group, whereas the recurrence of angina pectoris was higher in the diabetic group compared to the non-diabetic group (47.54% vs . 29.52%; P =0.02). A multivariate logistic regression analysis revealed that age and left ventricular ejection fraction rather than diabetes mellitus were independent predictors for long-term clinical outcomes. Conclusions StentBoost could effectively improve instant PCI results; the long-term clinical outcomes of StentBoost-optimized PCI were similar between diabetic and non-diabetic patients. Age and left ventricular ejection fraction were the independent predictors for long-term clinical outcomes.

Phytoplankton classification is the foundation for revealing the succession rules of phytoplankton communities and for conducting water ecology investigation. At present, the classification methods of functional group (FG), morpho-functional group (MFG), and morphology-based functional group (MBFG) are widely used, although great differences occur among the classification methods of different FGs. In order to compare the differences among FG, MFG and MBFG classification methods, FG classification and redundant analysis (RDA) were used to sample and analyze the phytoplankton community structures and the physical and chemical indicators of water environment in April 2017 (normal seasons) and August 2017 (wet seasons). The following results were noted. ①The MFG and FG had overlapping parts, whereas the MBFG was differed significantly from FG and MFG. ②The FG considers the physiological and ecological characteristics of phytoplankton, which can better explain the correlation with the environment and can accurately reflect the relationship between environmental factors and the phytoplankton niche. Moreover, the environmental factors and eutrophication status of the reservoir can be predicted according to the dominant FGs of phytoplankton; however, the FG needs to have systematic knowledge of phytoplankton identification and a large workload. The MFG classification method is simple and easily understood, which can better explain the relationship between phytoplankton and environmental factors; however, it is weakly connected with environmental factors. The MBFG classification method is the simplest and most efficient, although its interpretation degree to the environment is not sufficient. ③Each of the three classification methods has advantages and disadvantages; therefore, appropriate classification methods are selected according to different research purposes and their actual needs.

Cav1.2 is the pore-forming subunit of L-type voltage-gated calcium channel (LTCC) that plays an important role in calcium overload and cell death in Alzheimer's disease. LTCC activity can be regulated by estrogen, a sex steroid hormone that is neuroprotective. Here, we investigated the potential mechanisms in estrogen-mediated regulation of Cav1.2 protein. We found that in cultured primary neurons, 17β-estradiol (E2) reduced Cav1.2 protein through estrogen receptor α (ERα). This effect was offset by a proteasomal inhibitor MG132, indicating that ubiquitin-proteasome system was involved. Consistently, the ubiquitin (UB) mutant at lysine 29 (K29R) or the K29-deubiquitinating enzyme TRAF-binding protein domain (TRABID) attenuated the effect of ERα on Cav1.2. We further identified that the E3 ligase Mdm2 (double minute 2 protein) and the PEST sequence in Cav1.2 protein played a role, as Mdm2 overexpression and the membrane-permeable PEST peptides prevented ERα-mediated Cav1.2 reduction, and Mdm2 overexpression led to the reduced Cav1.2 protein and the increased colocalization of Cav1.2 with ubiquitin in cortical neurons in vivo. In ovariectomized (OVX) APP/PS1 mice, administration of ERα agonist PPT reduced cerebral Cav1.2 protein, increased Cav1.2 ubiquitination, and improved cognitive performances. Taken together, ERα-induced Cav1.2 degradation involved K29-linked UB chains and the E3 ligase Mdm2, which might play a role in cognitive improvement in OVX APP/PS1 mice., (© 2019 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.)

Conflicting reports regarding whether high tumor-associated neutrophils (TAN) are associated with outcomes in colorectal cancer (CRC) exist. Previous investigators have counted TAN using non-neutrophil-specific immunohistochemistry (IHC) stains. We examined whether TAN levels as determined by multi-field manual counting would predict prognosis. IRB approval was obtained and two pathologists, blinded to stage/outcome, counted TAN in 20 high power fields (HPF) per specimen. TAN score was defined as the mean of these counts. High TAN was defined as at or greater than the median score for that stage. Demographics, tumor characteristics, and overall survival (OS) were obtained from the records and examined for association with TAN score. IHC for arginase expression was performed in a subset of samples. 221 patients were included. Stage II patients with high TAN scores had an OS of 232 months as compared to those with low TAN (OS = 85 months, p = 0.03). The survival benefit persisted in multivariable analysis (HR 0.48, CI 0.25-0.91, p = 0.026) controlling for age and sex. Women had increased survival as compared to men, and there were no significant prognostic associations with TAN count in stage III/IV patients, although there were only 12 stage IV patients. Arginase staining did not provide additional information. Stage II colorectal cancer patients with high TAN live nearly 3 times longer than those with low TAN. Women with stage II disease and high TAN counts appear to be driving the survival benefit seen in the stage II patients and have increased overall survival in all stages.

Conjunctival myxoma is an exceptionally rare, slow-growing, benign neoplasm of primitive mesenchyme origin. Forty-one cases of conjunctival myxoma from a literature review, including the authors' case, are listed. The usual clinical history is a painless mass appearing during months to years. Grossly, the tumor is a well-circumscribed, cystlike, gelatinous, yellow-to-pink, translucent-to-solid mass. Microscopically, the hypocellular tumor contains stellate- and spindle-shaped cells in a mucoid stroma with abundant hyaluronic acid mucopolysaccharides. Vimentin and α-smooth muscle actin highlight the spindle and stellate cells. S100 protein and desmin are negative for the tumor cells. Treatment is complete surgical excision, with no recurrence reported in the follow-up period. Notably, conjunctival myxoma may be associated with Carney complex, an autosomal-dominant disorder associated with skin pigmentation, endocrine abnormalities, and myxoma of the heart and eye. Physicians should appreciate this unique ocular tumor because of its potential association with Carney complex.

Felty's syndrome (FS) is characterized by the three conditions of rheumatoid arthritis (RA), neutropenia and splenomegaly, and occurs in few cases of longstanding erosive RA. Discriminating between rare occurrences of autoimmune diseases and malignancies is crucial. The present study describes the case of a 17-year-old female with a two-year history of RA, presenting with an irregular fever, hepatosplenomegaly and enlarged lymph nodes. The antinuclear antibody titer was 1:320, while antibody results for anti-dsDNA, anti-Sm and rheumatoid factor were negative. The clinical presentation was similar to that of lymphoma. However, the fluorodeoxyglucose-positron emission tomography and biopsy examinations of the liver and cervical lymph node did not support the diagnosis of lymphoma. According to the laboratory results and clinical symptoms, the differential diagnosis indicated FS, and immunosuppressive agents were administered. Two weeks later, the patient no longer had a fever, and the transaminase levels were normal, associated with shrinkage of the liver and spleen.

The mitogen-activated protein kinase (MAPK) pathway has a protective function on the management of hematologic malignancies. The aim of this study was to assess whether the induction of MAPK-mediated effects contributes to the therapeutic value of combination sorafenib and daunorubicin (DNR) treatment. Herein, we found that DNR increased phosphorylation of extracellular signal-regulated kinases (ERK1/2) in K562 cells. ERK1/2 activity was blocked by either the mitogen-induced extracellular kinase (MEK) inhibitor U0126 or a multi-kinase inhibitor sorafenib. Of note, sorafenib sensitized K562 to DNR by inhibiting proliferation and inducing apoptosis in a dose-dependent manner which was through blocking the RAF/MEK/ERK pathway. Moreover, K562 cells transfected with a constitutively active MEK2DD plasmid showed increasing IC50 values following DNR treatment compared with control cells. Combination of DNR with MEK inhibitor U0126 synergistically inhibited K562 cell growth. In conclusion, our results indicated that sorafenib sensitized K562 cells to DNR-induced cytotoxicity by downregulating p-ERK1/2 expression. DNR in combination with sorafenib may represent a new and potential therapeutic strategy in treating acute leukemia with high p-ERK1/2 levels.

A previously healthy 34-year-old female presented with a 5-month history of progressive backache and weakness in the left fingers. Magnetic resonance imaging (MRI) showed soft tissue masses in the spinal canal distributed along the nerve course. The patient's baseline laboratory data were normal. Surgical intervention was performed and histological examination identified isolated spinal granulocytic sarcoma (GS). A bone marrow biopsy also presented normal findings. However, the patient developed numbness and pain in the right lower limb two months later. Fluorodeoxyglucose (FDG)-positron emission tomography (PET) showed FDG uptake in the left trapezius muscle, cervix uteri, iliac bone, lymphadenectasis of the pelvic wall and left axillary fossa. Cerebrospinal fluid (CSF) examination allowed a diagnosis of central nervous system leukemia (CNSL). The patient underwent chemotherapy and intrathecal injection, resulting in the elimination of the residual lesion. Correct diagnosis and adequate treatment are essential to achieve optimal results in patients with isolated spinal GS.

The aim of this study was to investigate the proliferation-inhibitory and inducing apoptotic effects of decitabine (DAC) on acute promyelocytic leukemia NB4-R2 cells. Cell inhibitory rate was determined by cell proliferation and cytotoxicity assay (WST-1 assay) after NB4-R2 cells were treated with 0.01 - 0.5 µmol/L DAC for 24, 48 and 72 h. Apoptosis of NB4-R2 cells treated with 0.05 - 5 µmol/L DAC for 48 h was detected by flow cytometry with PI staining and AnnexinV/PI staining. Reverse transcription-PCR (RT-PCR) was used to determine the mRNA expression level of MDR1 gene encoding P-glycoprotein (P-gp). The results indicated that DAC (0.01 - 0.5 µmol/L) inhibited the proliferation of NB4-R2 cells in both time- and concentration-dependent manners. The IC(50) of DAC on the viability of NB4-R2 cells after treatment for 48 and 72 h were 0.089 and 0.064 µmol/L respectively. DAC (0.05 - 5 µmol/L) induced NB4-R2 cell apoptosis in dose-dependent manner with down-regulation of MDR 1 gene expression. It is concluded that a low concentration of DAC (< 0.5 µmol/L) inhibits cell proliferation, while higher concentration of DAC (1 or 5 µmol/L) induces apoptosis on NB4-R2 cells, accompanied with reduction of MDR1 levels.

This study was aimed to investigate the effect of multikinase inhibitor sorafenib on the proliferation and apoptosis of U937 cells and its possible mechanism. U937 cells were treated with different concentrations of sorafenib for 48 hours. Cell viability was determined by Cell Counting Kit-8; cell apoptosis and cell ratio in cell cycle were detected by flow cytometry with Annexin V/PI staining and PI staining respectively; expressions of GSK-3β, β-catenin and cyclin-D1 were assayed by Western blot. The results showed that the proliferation of U937 cells was inhibited by sorafenib in a dose-dependent manner (p < 0.05). Sorafenib induced cell apoptosis and cell cycle G(1)/G(0) arrest. Compared with results of Western blot before treatment, expression of inactivated GSK-3β, β-catenin and Cyclin-D1 down-regulated in a dose-dependent manner after treatment with sorafenib, this same changes were observed after up-regulation of inactivated GSK-3β by LiCl (p < 0.05). It is concluded that sorafenib inhibits the proliferation of U937 cells and induces cell apoptosis through reducing negative regulation of WNT signal pathway on inactivated GSK-3β and down-regulating β-catenin and cyclin-D1 level, which result in U937 cell cycle G(1)/G(0) arrest.

A 18-year-old female patient after cleft lip and palate surgery with an uncommon complication-precardium area pain were reported. The psychological treatment and nursing along with routine clinical treatment to the patient were applied. The patient had recovered from the precardium area pain after one week treatment.

Biopartitioning micellar chromatography (BMC) is a mode of micellar liquid chromatography that uses micellar mobile phases of Brij35 under adequate experimental conditions and can simulate biopartioning process of many kinds of drugs and describe their biological behavior. The capability of BMC to describe and estimate pharmacokinetic and pharmacodynamic parameters of angiotensin-converting enzyme inhibitors (ACEIs) had been studied in this paper. The correlation between retention factors of ACEIs obtained using BMC and bioactivity parameters (half-life, volume of distribution, clearance, and IC(50)) was investigated utilizing a second-order polynomial model. The P-values obtained for half-life, volume of distribution, clearance, and IC(50) models were less than 0.05, and the r(2) of those four models were 0.89, 0.98, 0.94, and 0.97, with r(2)(adj) (adjusted for freedom degrees) being 0.85, 0.98, 0.91, and 0.95, respectively. The predictive and interpretative ability of the chromatographic models was evaluated in terms of cross-validated data [root mean squared error of calibration (RMSEC), root mean squared error of cross-validation (leave-one-out) (RMSECV), and root mean squared error of cross-validation (leave-one-out) for interpolated data (RMSECVi)]. The quantitative retention-activity relationship (QRAR) models of ACEIs developed in this paper may be a useful approach to screening new chemicals in the early stage of development.

The capability of biopartitioning micellar chromatography (BMC), using pure Brij35 solution and mixed micellar system of Brij35-SDS (85:15) as mobile phase, to describe and estimate bioactivities of angiotensin converting enzyme inhibitors at different pH has been studied. Quantitative retention-activity relationships (QRAR) in BMC were investigated for these compounds. The obtained BMC(Brij35-SDS)-QRAR models were compared with the traditional BMC(Brij35)-QRAR, and better statistically models were obtained using Brij35-SDS retention data. The superiority of BMC(Brij35-SDS)-QRAR is due to the fact that the mixed micellar mobile phase can simulate the resting membrane potential and the conformation of the long hydrophilic polyoxyethylene chains remains unchanged.

Biological fluid cell membranes are barriers for the uptake of many kinds of drugs and their metabolites, along with passive transport across membranes and bioaccumulation. Biopartitioning micellar chromatography (BMC) is a mode of micellar liquid chromatography that uses micellar mobile phases of Brij35 under adequate experimental conditions and can be useful to simulate the drug's passive absorption and the transport in biological systems. The use of micellar aqueous solutions of Brij35 as mobile phases in reversed-phase liquid chromatography has proven to be valid to predict the biological activities of barbiturates, benzodiazepines, catecholamines, local anesthetics, non-steriodal anti-inflammatory drugs and tricyclic antidepressants. In this study, the relationships between the capacity factor in BMC and some pharmacokinetic and pharmacodynamic parameters of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors are studied. Predictive quantitative retention-activity relationship (QRAR) models describing some of the biological activities and pharmacokinetic properties of HMG-CoA reductase inhibitors are obtained. The results indicate that QRAR model may be a useful tool during the drug discovery process.

In this study, we examined the hypothesis that semantic judgment tasks share overlapping processes if they require processing on common dimensions but not if they require processing on orthogonal dimensions in semantic space (Osgood, Suci, & Tannenbaum, 1957). We tested the hypothesis with the implicit association test (IATl Greenwald, McGhee, & Schwartz, 1998) in three experiments. Consistent with the hypothesis, IAT effects (costs in reaction time because of incompatible response mapping between associated judgment tasks) occurred consistently when judgment tasks tapped into common semantic dimensions, whereas no IAT effect appeared when judgment tasks entailed processing on orthogonal semantic dimensions.

In the present study, the specificity of repetition priming between semantic classification tasks was examined using Osgood's (Osgood, Suci, & Tannenbaum, 1957) semantic space as a heuristic for determining the similarity between classifications. The classification tasks involved judging the meaning of words on semantic scales, such as pleasant/unpleasant. The amount of priming across classifications was hypothesized to decrease with increasing distance (decreasing similarity) between semantic scales in connotative semantic space. The results showed maximum repetition priming when the study and the test classifications were the same, intermediate degrees of priming when the study and the test classification scales shared loadings on semantic factors, and little priming when the study and the test classification scales loaded primarily on orthogonal semantic factors--that is, when the distance between scales was maximized. Consistent with the transfer-appropriate processing framework, repetition priming in semantic classifications was highly task specific, decreasing with increasing distance between classification scales.