Search

It is vital to predicting the hidden behavior of complex systems, which is associated with the operation state of the system and cannot be directly observed. In recent research of hidden behavior prediction, one effective method called the semi-quantitative information-based method has received wide applications and become the main stream, where both the qualitative knowledge and the quantitative data are involved. Although some methods have been effectively applied to predict the hidden behavior, only the single behavior prediction has been achieved. It is shown that multiple hidden behaviors are not considered, which may not meet actual requirements of the system. Besides, the influence of perturbations on the system is not considered, which can indirectly affect the system's hidden behavior and reduce the hidden behavior prediction accuracy. As such, a new hidden behavior prediction model based on the evidential reasoning (ER) rule considering perturbations is proposed in this paper, which is typically a semi-quantitative information-based method and can deal with multiple hidden behaviors. A parameter estimation algorithm is proposed based on the expectation maximization (EM) to obtain more accurate model parameters. A case study is conducted to verify the effectiveness of the proposed model. [ABSTRACT FROM AUTHOR]

Neuregulin-1 (NRG1) and ErbB4 genes have been identified as candidate genes for schizophrenia. Post-mortem studies indicated that NRG1-ErbB4 signalling is impaired in schizophrenia subjects. This study investigated whether short- or long-term antipsychotic treatment has different effects on the expression of NRG1 and ErbB4 receptors. Female Sprague-Dawley rats were treated orally with either aripiprazole (0.75 mg/kg), haloperidol (0.1 mg/kg), olanzapine (0.5 mg/kg), or vehicle, 3 times/day for 1 or 12 weeks. Western blotting was performed to examine the expression of NRG1 isoforms (135 kDa, 70 kDa and 40 kDa) and ErbB4 receptors. Both 1-week haloperidol and olanzapine treatment increased NRG1-70 kDa expression in the hippocampus; haloperidol also up-regulated ErbB4 levels in the prefrontal cortex (PFC). In the 12-week group, aripiprazole decreased the expression of all three NRG1 isoforms and ErbB4 receptors in the PFC, NRG1-70 kDa and -40 kDa in the cingulate cortex (Cg), and NRG1-135 kDa, -70 kDa and ErbB4 receptors in the hippocampus; haloperidol reduced NRG1-135 kDa in the PFC, NRG1-40 kDa in all three brain regions, and ErbB4 receptor levels in the PFC and hippocampus; NRG1-40 kDa in the PFC and Cg was also down-regulated by olanzapine. These results suggest that the time-dependent and region-specific effects of antipsychotics on NRG1-ErbB4 signalling may contribute to the efficacy of antipsychotics to treat schizophrenia. [ABSTRACT FROM AUTHOR]

Hedscandines A-C (1 – 3), three undescribed indole alkaloids were isolated from Hedyotis scandens Roxb, a traditional Chinese medicine widely used in the treatment of respiratory ailments. Their structures were elucidated by extensive spectroscopic data and electronic circular dichroism calculation. Hedscandine A (1), possessed a unique carbon skeleton with a 1,4-oxazonin-2(3H)-one core system and displayed a rapid bactericidal activity against MRSA with a MIC value of 16 μg/mL. Mechanistic studies showed that compound 1 could disrupt the integrity of bacterial cell membranes and thus lead to bacterial death. Hedscandines A-C (1 – 3), three undescribed indole alkaloids were isolated from the traditional Chinese medicine Hedyotis scandens Roxb. Hedscandine A (1), possessed a unique carbon skeleton with a 1,4-oxazonin-2(3H)-one core system and displayed a rapid bactericidal activity against MRSA by disrupting the integrity of bacterial cell membranes, with a MIC value of 16 μg/mL. [Display omitted] • Three undescribed indole alkaloids were isolated from Hedyotis scandens. • Hedscandine A (1), possessed a unique carbon skeleton with a 1,4-oxazonin-2(3H)-one core system. • Hedscandine A (1), displayed a rapid bactericidal activity against MRSA by disrupting the integrity of bacterial cell membranes. [ABSTRACT FROM AUTHOR]

Lifetime prognostic based on the degradation data has been widely investigated and adopted for reliability assessment and maintenance policy. However, the measurement error (ME) is usually inevitable, which leads to the bias of lifetime estimation and erroneous evaluation of the safety risk. In this paper, we mainly focus on an inverse issue: how to specify the sensor's performance (i.e., the ME range) for satisfying a given requirement of the lifetime estimation. Under this consideration, we first analyze the probability distribution functions of the lifetime estimation with/without the ME based on Wiener process degradation model. Then a distance measure based on the relative entropy is formulated to evaluate the difference between these two lifetime estimations. Furthermore, the permissible ranges of the time-dependent and time-independent ME are attained under a given allowable bias of lifetime estimation according to the proposed distance measure. In addition, the influence of the ME on maintenance policy is discussed. Finally, numerical examples and a case study are provided to illustrate. [ABSTRACT FROM AUTHOR]

Long-term olanzapine treatment has been associated with serious metabolism disorders, such as abnormal body weight gain, hyperglycemia, and dyslipidemia. Recently, accumulated evidence points to a link between the metabolic disorders caused by olanzapine and thermogenetic impairment. Fibroblast growth factor 21 (FGF21), a pleiotropic protein, is a potent stimulator of thermogenesis in brown adipose tissue (BAT). However, the relationship between autocrine FGF21 in BAT and thermogenetic impairment induced by olanzapine has not been investigated. In this study, C57BL/6 mice and C3H10T1/2 (a brown adipocyte cell line) were used to investigate the role of FGF21 in modulating thermogenetic impairments caused by olanzapine. Our data found a fall in BAT temperature, with a decrease in the protein levels of uncoupling protein 1 (UCP1) and FGF21 in olanzapine-treatment mice. Olanzapine-induced deficits of mitochondrial activity and the expression of UCP1 and related thermogenetic factors could be improved by FGF21-overexpression in brown adipocytes. Furthermore, ChIP-sequencing showed the H3K9me3 modification in Fgf 21 was dramatically increased in BAT of mice with olanzapine treatment. Lysine-specific demethylase 4a (KDM4a), a histone demethylase responsible for site-specific erasure of H3K9me3, was decreased in olanzapine-treated C3H10T1/2 cells, whereas FGF21 and UCP1 expression and thermogenesis were upregulated in KMD2a-overexpressing brown adipocyte. We concluded that FGF21 was a crucial regulator mediating UCP1-dependent thermogenetic impairments by olanzapine-modulating histone methylations. Our results also provide novel insights into identifying a new therapeutic target for treating metabolic side effects caused by the antipsychotic drug. • Olanzapine might cause body weight gain via inhibiting thermogenesis. • FGF21 played a role in response to olanzapine-mediated UCP1-dependent thermogenetic impairments in BAT. • Olanzapine caused the enrichment of H3K9 trimethylation in the Fgf 21 gene of the mice BAT which could alter thermogenesis. [ABSTRACT FROM AUTHOR]

Aims Second-generation antipsychotic drugs (SGAs) have a high risk for serious metabolic side-effects including dyslipidemia. This study aimed to investigate the acute effects of oral olanzapine treatment on the expression of genes for fatty acid and cholesterol biosynthesis in rats. Main methods Female Sprague–Dawley rats were treated orally with olanzapine (1 mg/kg, equivalent to a human clinical dose of 10 mg) via self-administration aimed to measure pharmacokinetics. Based on the pharmacokinetic analysis, the acute effects of olanzapine on sterol regulatory element binding protein (SREBP)-related fatty acid/cholesterol metabolism genes were investigated in the liver and perirenal white adipose tissue (WAT) by Real-time quantitative PCR. Key findings A pharmacokinetic analysis demonstrated that the maximum concentration of olanzapine in plasma (C max ) occurred at 6 h with a peak concentration of 276.5 ng/ml after a single oral treatment and with a plasma elimination half-life of 3.5 h after peak. The mRNA expression of SREBP-2 and target genes for cholesterol synthesis and transport was increased 1.9 8.8 fold compared with the control at 6 h after olanzapine administration but returned to basal level at 12 h post-treatment, while the increased mRNA expression of SREBP-1c and its targeted fatty acid-related genes appeared at both 6 h and 12 h post-treatment. Significance The present study provided evidence that olanzapine at a clinically-relevant dose caused abnormal expression of genes involved in lipid metabolism in the liver and WAT. These results suggest that olanzapine may cause dyslipidemia side-effects through direct effects on lipid biosynthesis and efflux genes associated with SREBP-stimulated transcriptional changes. [ABSTRACT FROM AUTHOR]

In order to obtain an equivalent underwater explosion impulsive loading, the theoretical analysis is carried out for the impact of a flyer plate on a piston, which seals a conical target chamber filled with water, based on one-dimensional elastic wave propagation and a linear equation of state for water. The impact process is simulated by using AUTODYN software, and the decay times of shock waves for two pistons with different thicknesses are analyzed and compared. According to the theory and numerical simulation research, an equivalent equipment is designed, and the pressure-time curve is measured at the central point of chamber medial wall. The results show that it is feasible to obtain an equivalent underwater explosion shock waves in the laboratory through high speed impact, and the flyer speed and the piston thickness determine the peak pressure and decay time in the conical target chamber, respectively. The equivalent equipment can be used to investigate the shock response of typical structures and materials subjected to underwater explosion impulse loading. [ABSTRACT FROM AUTHOR]

As an effective way to enhance the system reliability, the standby redundancy technique has been widely applied in many industrial systems. Finding methods to determine the maintenance policy and spare-part inventory management is an interesting practical issue. However, due to the imperfect storage and inner mechanism, the spare parts usually deteriorate over time, which not only degrades their performance but also may lead to storage failure. In addition, the immediate burst failure caused by the external shock should not be neglected in storage. These two aspects make the joint optimization of preventive maintenance and inventory policies for a standby system more challenging. Thus, in this study, we first propose a general iterative approach for the lifetime estimation of standby systems with a hybrid spare-part degradation process, which includes both stochastic degradation and immediate burst failure. We then take an example of the Wiener-process-based model to explain how to obtain the analytical results of the lifetime estimation. On this basis, we further establish a joint optimization model, in which the preventive block replacement interval and the inventory number are treated as two decision variables to minimize the expected cost per unit time. Finally, a numerical example and practical case are provided for illustration. • Both spare-part storage degradation and immediate burst storage failure are considered. • A general iterative approach for the lifetime estimation of the standby system is proposed. • A joint optimization model of the maintenance interval and the inventory number is established. [ABSTRACT FROM AUTHOR]

• A general iterative method of SSL estimation for stochastic degradation processes is first proposed. • Analytical expressions of SSL's PDF based on Wiener-process-based model are obtained. • The unit-to-unit variability is described by a Gaussian Mixture Model. • Some analytical results of SSL's mean and variance are provided under a nonstorage-failure assumption. Standby redundancy is an effective fault-tolerant technique for enhancing reliability and prolonging the standby system's operating lifetime. How to estimate the total lifetime of a standby system with a predetermined number of standby components (i.e., spare parts) presents an interesting practical issue. Most existing studies, however, have mainly focused on the lifetime or remaining useful lifetime prediction of a single online product. Moreover, spare parts usually deteriorate in storage, which will worsen their performance and even lead to failure. This makes lifetime estimation for a standby system more challenging. This study, therefore, focused on how to estimate a standby system's lifetime (SSL) with deteriorating spare parts. Unlike prior work, we fully considered the uncertainty and randomness caused by the spare parts' storage degradation in the SSL estimation. By establishing the transition probability function of the storage degradation process, we first proposed a general iterative algorithm for SSL estimation under the concept of the first passage time (FPT) and provided the proof based on mathematical induction. Then, we extended this result to a Wiener-process-based model and obtained the iterative result in a single integral form. Moreover, we attained the analytical expressions of SSL mean and variance under a non-storage-failure hypothesis and further provided the requirement for the establishment of the hypothesis. Finally, a numerical case and a practical case of the gyroscope are introduced for illustration. [ABSTRACT FROM AUTHOR]

Olanzapine (OLZ) is a widely prescribed antipsychotic drug with a relatively ideal effect in the treatment of schizophrenia (SCZ). However, its severe metabolic side effects often deteriorate clinical therapeutic compliance and mental rehabilitation. The peripheral mechanism of OLZ-induced metabolic disorders remains abstruse for its muti-target activities. Endoplasmic reticulum (ER) stress is implicated in cellular energy metabolism and the progression of psychiatric disorders. In this study, we investigated the role of ER stress in the development of OLZ-induced dyslipidemia. A cohort of 146 SCZ patients receiving OLZ monotherapy was recruited, and blood samples and clinical data were collected at baseline, and in the 4th week, 12th week, and 24th week of the treatment. This case-control study revealed that OLZ treatment significantly elevated serum levels of endoplasmic reticulum (ER) stress markers GRP78, ATF4, and CHOP in SCZ patients with dyslipidemia. In HepG2 cells, treatment with OLZ (25, 50 μM) dose-dependently enhanced hepatic de novo lipogenesis accompanied by SREBPs activation, and simultaneously triggered ER stress. Inhibition of ER stress by tauroursodeoxycholate (TUDCA) and 4-phenyl butyric acid (4-PBA) attenuated OLZ-induced lipid dysregulation in vitro and in vivo. Moreover, we demonstrated that activation of PERK-CHOP signaling during ER stress was a major contributor to OLZ-triggered abnormal lipid metabolism in the liver, suggesting that PERK could be a potential target for ameliorating the development of OLZ-mediated lipid dysfunction. Taken together, ER stress inhibitors could be a potentially effective intervention against OLZ-induced dyslipidemia in SCZ., (© 2023. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

This study aimed to investigate the chemical constituents in the water extract of the whole herb of Hedyotis scandens by silica gel, ODS, and MCI column chromatographies together with preparative high-performance liquid chromatography(HPLC). The structures of isolated constituents were identified by NMR, HR-ESI-MS, etc. Thirteen compounds were isolated and identified as methyl 4-benzoyloxy-3-methoxybenzeneacetate(1), 4-benzoyloxy-3-methoxybenzeneacetic acid(2), 3-(4-hydroxy-3-methoxyphenyl)-propanoic acid(3), salicylic acid(4), 3-hydroxy-4-methoxypyridine(5), syringic acid(6), hydroxycinnamic acid(7),(R)-6-methyl-4,6-bis(4-methylpent-3-enyl)cyclohexa-1,3-dienecarbaldehyde(8), 1,2-bis(4-hydroxy-3-methoxyphenyl)-1,3-propanediol(9), 1H-indole-3-carboxaldehyde(10), isoscopoletin(11), syringaresinol(12), and pinoresinol(13). Among them, compounds 1 and 2 were new phenolic acid compounds, compounds 3-5, 8-11, and 13 were isolated from this genus for the first time, and compounds 6, 7, and 12 were obtained from H. scandens for the first time. The activity test showed that compounds 1 and 10 had a certain inhibitory effect on Mycobacterium smegmatis, with MIC_(50) values of 58.5 and 33.3 μg·mL~(-1), respectively.

Evidential reasoning (ER) rule has been widely used in dealing with uncertainty. As an important parameter to measure the inherent property of evidence, the evidence reliability makes the ER rule constitute a generalized reasoning framework. In current research of the ER rule, the evidence reliability tends to be expressed in the form of quantitative value by certain methods or expert knowledge. The single quantitative value lacks the ability to describe the statistical property of reliability, which leads to unreasonable results. In this article, a new ER rule with continuous probability distribution of reliability denoted by ERr-CR is proposed. The combination of two pieces of evidence is discussed in detail, where the reliability is profiled as random variables with specific probability distribution. To characterize the output of ERr-CR, a novel concept of expectation of the expected utility is proposed. In addition, the ERr-CR is expanded to multiple pieces of evidence to show its universality. Further, the basic performances of the ERr-CR are explored to illustrate the rationality. Moreover, a case study of safety assessment of natural gas storage tanks (NGSTs) is conducted to show the potential applications of ERr-CR, which makes the proposed method more practical.

Two new polyketides, lasobutone A(1) and lasobutone B(2), along with three known compounds, guignardianone C(3), guignardic acid(4), and 4-hydroxy-17R-methylincisterol(5), were isolated from the endophytic fungi Xylaria sp. by silica gel, MCI, and preparative HPLC, which was separated from the Chinese medicinal material Coptis chinensis and cultivated through solid fermentation with rice. Their structures were elucidated on the basis of spectroscopic methods, such as MS, NMR, IR, UV, and ECD. Compounds 2 and 4 showed inhibitory activities against the nitric oxide(NO) production in the LPS-induced macrophage RAW264.7 with IC_(50) values of 58.7 and 42.5 μmol·L~(-1) respectively, while compound 5 exhibited cytotoxic activities against HT-29 with IC_(50) value of 14.3 μmol·L~(-1).

A new polyketide, coptaspin A(1), along with two known compounds 4-acetyl-3,4-dihydro-6,8-dihydroxy-3-methoxy-5-methylisocoumarin(2), and cytochalasin Z_(12)(3), was isolated from the endophytic fungi Aspergillus sp. ZJ-58, which was isolated from the genuine medicinal plant Coptis chinensis in Chongqing after solid-state fermentation on rice and silica gel, MCI, and HPLC-based separation. Their structures were elucidated by MS, NMR, IR, UV, and ECD. The newly isolated compound 1 showed moderate inhibitory activities against LPS-induced NO production in RAW264.7 macrophages with the IC_(50) value of 58.7 μmol·L~(-1), suggesting its potential anti-inflammatory activity.

Brexpiprazole (Bre) is a new multi-target antipsychotic drug (APD) approved by the US FDA in 2015, and shows good therapeutic potential. But it lacks assessments on the metabolic side effects, which obstructs the treatment of schizophrenia. Glucagon-like peptide 1 (GLP1), an incretin associated with insulin action and metabolism, is involved in the metabolic syndrome (MS) caused by most APDs. In this study, we examined the adverse effects of Bre on glycolipid metabolism in rats and determined whether GLP1 was involved in Bre-caused MS. In the first part of experiments, rats were orally administered Bre (0.5 mg· kg -1 · d -1 ) for 28 days with aripiprazole (1.0 mg· kg -1 · d -1 ) or olanzapine (1.0 mg· kg -1 · d -1 ) as the controls. Compared to vehicle, Bre administration significantly increased the weight gain, serum lipid (TG, TC, LDL, FFA), and blood glucose levels accompanied by the hormonal (insulin, glucagon, GLP1) imbalance, and the impaired glucose tolerance and insulin sensitivity. Moreover, we demonstrated that Bre administration significantly decreased the protein and mRNA levels of GLP1 in pancreas and small intestine by suppressing CaMKIIα, AMPK, and β-catenin; Bre administration also caused islet dysfunction with decreased GLP1R, PI3K, IRβ expression in pancreas, and the interference of IRS1, PI3K, p-AKT, and GLUT4 expression in the liver and skeletal muscle that represented the insulin resistance. In the second part of experiments, rats were orally administered Bre (0.5 mg· kg -1 · d -1 ) for 42 days. We showed that co-administration with the GLP1 receptor (GLP1R) agonist liraglutide (0.125 mg· kg -1 · d -1 , ip) could ameliorate Bre-caused metabolic abnormalities. Our results demonstrate that GLP1/GLP1R signaling is involved in Bre-induced glycolipid metabolic disorders and co-treatment with liraglutide is an effective intervention against those abnormal metabolisms., (© 2021. The Author(s), under exclusive licence to CPS and SIMM.)

Protoberberine alkaloids belong to the quaternary ammonium isoquinoline alkaloids, and are the main active ingredients in traditional Chinese herbal medicines, like Coptis chinensis. They have been widely used to treat such diseases as gastroenteritis, intestinal infections, and conjunctivitis. Studies have shown that structural modification of the protoberberine alkaloids could produce derivative compounds with new pharmacological effects and biological activities, but the transformation mechanism is not clear yet. This article mainly summarizes the researches on the biotransformation and structure modification of protoberberine alkaloids mainly based on berberine, so as to provide background basis and new ideas for studies relating to the mechanism of protoberberine alkaloids and the pharmacological activity and application of new compounds.

Second-generation antipsychotic drug (SGA)-induced metabolic abnormalities, such as dyslipidemia, are a major clinical problem for antipsychotic therapy. Accumulated evidences have shown the efficacy of statins in reducing SGA-induced dyslipidemia, but the underlying mechanisms are unclear. In this study, we explored whether mTOR signaling was involved in olanzapine (OLZ)-induced dyslipidemia as well as the lipid-lowering effects of cotreatment of simvastatin (Sim) in rats. Model rats received OLZ (1.0 mg/kg, t.i.d.) for 7 weeks; from the third week a group of model rats were cotreatment of Sim (3.0 mg/kg, t.i.d.) for 5 weeks. We found that OLZ treatment significantly increased the plasma triglyceride (TG) and total cholesterol (TC) levels, and promoted lipid accumulation in the liver, whereas cotreatment of Sim reversed OLZ-induced dyslipidemia. Hepatic mTORC1 and p-mTORC1 expression was accelerated in the OLZ treatment group, with upregulation of mRNA expression of sterol regulatory element-binding protein 1c (SREBP1c) and its target genes, whereas these alterations were ameliorated by Sim cotreatment. In HepG2 cells, rapamycin (a mTOR inhibitor) significantly reduced the OLZ-stimulated hepatocellular lipid contents and weakened the ability of Sim to lower lipids via a mechanism associated with the upregulation of SREBP1c-mediated de novo lipogenesis. Our data suggest that OLZ induces lipid accumulation in both plasma and liver, and Sim ameliorates OLZ-induced lipid metabolic dysfunction through its effects on mTOR signaling via reducing SREBP1c activation and the downregulation of gene expression involved in lipogenesis. These data provide a new insight into the prevention of metabolic side effects induced by antipsychotic drugs.

It is important to predict both observable and hidden behaviors in complex engineering systems. However, compared with observable behavior, it is often difficult to establish a forecasting model for hidden behavior. The existing methods for predicting the hidden behavior cannot effectively and simultaneously use the hybrid information with uncertainties that include qualitative knowledge and quantitative data. Although belief rule base (BRB) has been employed to predict the observable behavior using the hybrid information with uncertainties, it is still not applicable to predict the hidden behavior directly. As such, in this paper, a new BRB-based model is proposed to predict the hidden behavior. In the proposed BRB-based model, the initial values of parameters are usually given by experts, thus some of them may not be accurate, which can lead to inaccurate prediction results. In order to solve the problem, a parameter estimation algorithm for training the parameters of the forecasting model is further proposed on the basis of maximum likelihood algorithm. Using the hybrid information with uncertainties, the proposed model can combine together with the parameter estimation algorithm and improve the forecasting precision in an integrated and effective manner. A case study is conducted to demonstrate the capability and potential applications of the proposed forecasting model with the parameter estimation algorithm.

Radix Ranuncoli Ternati is clinically effective traditional Chinese medicine for multidrug resistant tuberculosis. Its active components and mechanism of action remain unsolved. Two dimensional gel electrophoresis (2-DE) was employed to address this problem. Globlal proteome of Mycobacterium tuberculosis untreated and treated with Radix Ranuncoli Ternati were compared, and 22 protein spots were found to be expressed differentially. 3 protein spots which remarkably decreased in Mycobacterium tuberculosis treated with Radix Ranuncoli Ternati were subjected to matrix assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS) analysis. The data obtained from peptide mass finger printing were used for database search. The 3 protein spots in gel were identified as cysA2 (thiosulfate sulfurtransferase), tsf (elongation factor EF-Ts) and hspX (heat shock protein X). These data provide insights into the changed global protein patterns of Mycobacterium tuberculosis treated with Radix Ranuncoli Ternati and may prove useful for further study in the mechanism in how Radix Ranuncoli Ternati influence the life of Mycobacterium tuberculosis. The differentially expressed proteins may be potential novel antituberculosis drug targets.

Tuberculosis remains one of the major threats to public health. China is one of the heavy TB burden countries. Novel drugs and vaccines are urgently needed to combat the increasingly multidrug resistant TB. Mycobacteriophage is one of the hot topic in TB novel drugs discovery and drug susceptibility test. Phages can multiply via two alternative mechanisms: the lytic cycle or the lysogenic cycle. The lytic cycle ends with the lysis and death of the host cell, whereas the host cell remains alive in the lysogenic cycle. Lysogenic mycobacteriophages were intensively studied to elucidate the integration and lysis mechanisms of mycobacteriophage. The integration of mycobacteriophage requires for attP of bacteriopahge genome, attB of Mycobacterium genome, integrase and integration host factor. Some lysogenic phage, eg. mycobacteriophage Ms6, employ lytic cycle, form new phage, lysis host by the cooperation of lysin and holin, and release phages. There is no reports as to the mycobacteriophage unique to China clinical or environmental isolates. Studies on the integration and lysis molecular mechanism of mycobacteriophage might facilitate future new anti-TB drugs development.

156 actinomycetes were isolated from 10 soil samples collected in Tibet by the method of DDC(dispersion and differential centrifugation). The isolates were assigned to 32 different groups on the basis of their morphological characters and colors of substrate mycelium, aerial hyphae and pigment. The result of cell-wall DAP on 65 representative strains selected from these groups was that 9 strains were different from Streptomyces. The analysis of ARDRA and 16S rDNA sequeces showed that the isolates belonged to the genus Streptomyces and five different rare actinomycete genera respectively. Antimicrobial activity of the representative strains was also tested, with the result that 38.5% isolates were positive.

Tuberculosis(TB) remains one of the major problems in global health. Macrophage (MPhi) apoptosis, induced by Mycobacterium tuberculosis (Mtb), is a cornerstone of effective innate microbial defense mechanism. Elucidation of the complex apoptosis-related gene expression may facilitate understanding the mechanism and regulation of macrophage apoptosis in response to Mtb, and contribute to developing novel measures to counter TB. DNA microarray containing 19,200 gene or gene fragments was used to compare the macrophage cell line U937 gene expression response to the clinical and laboratory Mtb infection. Northern blotting and RT-PCR were used to confirm the microarray results. Mtb H37Rv infection were found to downregulate the bcl-2, vitamin D receptor, interferon regulatory factor 3, cytochrome c oxidase, gene expression by 2-, 3-, 3-, 2.5-fold, respectively, while the clinical strain infection leads to upregulate the SOD2, SOD3, serine protease, toll-like receptor 2, signal transducer and activator (STAT1), hypoxia-inducible factor 22, 2.9-, 2.5-, 2.5-, 2.2-, 2.4-, 5.9-fold respectively. The findings suggest that the clinical strain infection tends to override the macrophage apoptosis by which the host attempt to limit the growth of the invader. The research on the complex factors network involved in the interaction will benefit the vaccine and novel drug target development.

Expression microarray was employed in this study to investigate whether the ion channels and their regulatory elements encoding genes participate in the immune response to Mycobacterium tuberculosis infection. The results of a virulent strain were compared with those of the clinically isolated strains. The data demonstrate that K(+), Na(+), Ca(2+) and Cl(-) channels and their regulatory elements, such as the G protein, receptor and second messenger, protein kinase and protein phosphatase were involved in the immune reaction. The clinical strain affected more types of ion channels and respective regulatory elements. The data provides clues for further scrutiny into the role of ion channels and related elements in the interaction between Mycobacterium tuberculosis and host macrophage.