Combination Activity of Standard Antituberculosis Drugs and Extracts of Medicinal Plants Commonly Used in Traditional Treatment of Tuberculosis in Uganda

Introduction: Resistance to antituberculosis drugs and adverse drug reactions remain the leading causes of tuberculosis therapeutic failure globally. Despite the increasing acceptance of medicinal plant use in combination with conventional antituberculosis drugs in treatment of tuberculosis (TB) in Uganda, there is paucity of knowledge on their combination effect. Aim: This research aimed to determine combination activity of standard antituberculosis drugs with extracts of Zanthoxylum leprieurii Guill. & Perr. and Rubia cordifolia L., the two common antituberculosis medicinal plants in Uganda, against pansensitive (H37Rv) and multi-drug resistant (MDR) Mycobacterium tuberculosis strains. Materials and Methods: Two reference MTB strains (H37Rv and MDR strain) were inoculated on Middlebrook 7H11 medium containing a combination of standard antituberculosis drugs and methanol extracts of Z. leprieurii and R. cordifolia at varying concentrations. The number of colonies on the plates was observed and counted weekly for up to 8 weeks. In vitro combination activity was determined using proportion method. Mean percentage inhibition was calculated for the reduction of number of colonies on drug-extract combination medium in relation to drug-extract-free control medium. Results: Drug-extract combinations showed good combination activity against Mycobacterium tuberculosis strains when compared with individual standard anti-TB drugs. This was more exhibited against MDR strain. There was however a reduction in percentage inhibition when extracts were combined with ethambutol and streptomycin against H37Rv strain. Conclusions: Zanthoxylum leprieurii and Rubia cordifolia in combination with standard anti-TB drugs exhibited increased in vitro activity against Mycobacterium tuberculosis, especially MDR-TB strain. This justifies the local use of these plants in traditional treatment of tuberculosis especially in resistant cases in Uganda.

Control Effects of Bacillus subtilis DJ-6 and Pyraclostrobin Alone and in Combination Against Fusarium oxysporum

[Objective] This study was conducted to screen a synergistic biological fungicide complex to control Fusarium wilt, reducing the use of chemical pesticides. [Method] The inhibitory effects of Bacil us subtilis DJ-6 and pyraclostrobin alone or in combination at five ratios against Fusarium oxysporum were detected by mea-suring mycelium growth rate in laboratory tests. The growth promotion and disease control effect of combined or single use of 20% pyraclostrobin and 2 ×1011 cfu/g B. subtilis DJ-6 WP at 1∶1 000, 1∶2 000 and 1∶3 000 dilutions were detected in field trials. [Result] The EC50 values of combined use of B. subtilis DJ-6 and pyra-clostrobin at ratios of 1∶1, 1∶2, 1∶3, 1∶4 and 1∶5 against F. oxysporum were 5.311 5, 4.008 6, 3.570 6, 3.350 9 and 3.218 9 μg/ml, with the synergistic ratios （SR） of 2.28, 1.77, 1.53, 1.64, 1.11, among which the synergetic effect at 1∶1 was the best. The fungicidal activity of pyraclostrobin was greater than that of B. subtilis DJ-6 in laboratory tests. Field trials revealed that al the 1∶1 000, 1∶2 000 and 1∶3 000 dilu-tions of 20% pyraclostrobin·2×1011 cfu/g B. subtilis DJ-6 WP in combination, 1∶1 000 dilution of 1 ×1012 cfu/g B. subtilis DJ-6 WP and 1∶2 000 dilution of 250 g/L pyra-clostrobin EC promoted the growth of strawberry by increasing plant height, leaf petiole, leaf blade area and stem diameter. Among them, the treatments with 1∶1 000 and 1∶2 000 of 20% pyraclostrobin · 2×1011 cfu/g B. subtilis DJ-6 WP in combina-tion had better effects than other treatments. The control effects of al the treat-ments were measured 30 and 80 d after fungicide application. The control effects of 1∶1 000 dilution of 20% pyraclostrobin and 2×1011 cfu/g B. subtilis DJ-6 in combina-tion were up to 100% and 93.11%, which were higher than those in al other treat-ments. The second highest control effects were found in the treatment with 1∶ 2 000 dilution of 20% pyraclostrobin and 2×1011 cfu/g B. subtilis DJ-6 in combination, they were 92.49% and 86.49%, higher than those in other treatments except the 1∶1 000 dilution of 20% pyraclostrobin and 2 ×1011 cfu/g B. subtilis DJ-6 in combination. The control effects of 1∶3 000 dilution of 20% pyraclostrobin and 2×1011 cfu/g B. subtilis DJ-6 in combination were 82.61% and 72.42%, higher than those in treatment with 1∶1 000 dilution of 1×1012 cfu/g B. subtilis DJ-6 WP, but lower than those in treat-ment with 1∶2 000 dilution of 25% pyraclostrobin EC. [Conclusion] Al the results re-vealed that the combination use of 20% pyraclostrobin and 2 ×1011 cfu/g B. subtilis DJ-6 WP at 1∶1 000 to 1∶2 000 dilution had better control effect against strawberry Fusarium wilt.

哌拉西林与氧氟沙星联合抗菌活性的研究(摘要)

目前对于严重的难治性感染性疾病常采用抗菌药物联合治疗。本文根据棋盘法设计,应用微量稀释法研究了酰脲类青霉素哌拉西林(Piperacillin,PIP)与氟喹诺酮类药物氧氟沙星(Ofloxacin,OFLX)的体外联合抗菌活性。

Preparation and properties of pitch carbon based supercapacitor

Using the mesophase pitch as precursor, KOH and CO2 as activated agents, the activated carbon electrode material was fabricated by physical-chemical combined activated technique for supercapacitor. The influence of activated process on the pore structure of activated carbon was analyzed and 14 F supercapacitor with working voltage of 2.5 V was prepared. The charge and discharge behaviors, the properties of cyclic voltammetry, specific capacitance, equivalent serials resistance （ESR）, cycle properties, and temperature properties of prepared supercapacitor were examined. The cyclic voltammetry curve results indicate that the carbon based supercapacitor using the self-made activated carbon as electrode materials shows the desired capacitance properties. In 1 mol/L Et4NBF4/AN electrolyte, the capacitance and ESR of the supercapacitor are 14.7 F and 60 mΩ respectively, The specific capacitance of activated carbon electrode materials is 99.6 F/g; its energy density can reach 2,96 W.h/kg under the large current discharge condition, There is no obvious capacitance decay that can be observed after 5000 cycles, The leakage current is below 0,2 mA after keeping the voltage at 2.5 V for l h, Meanwhile, the supercapacitor shows desired temperature property; it can be operated normally in the temperature ranging from -40 ℃to 70 ℃,

A novel animal model for in vivo study of liver cancer metastasis

AIM:To establish an animal model with human hepatocyte-repopulated liver for the study of liver cancer metastasis.METHODS:Cell transplantation into mouse livers was conducted using alpha-fetoprotein(AFP)-producing hu-man gastric cancer cells(h-GCCs) and h-hepatocytes as donor cells in a transgenic mouse line expressing urokinase-type plasminogen activator(uPA) driven by the albumin enhancer/promoter crossed with a severe combined immunodeficient(SCID) mouse line(uPA/SCID mice).Host mice were divided into two groups(A and B).Group A mice were transplanted with h-GCCs alone,and group B mice were transplanted with h-GCCs and h-hepatocytes together.The replacement index(RI),which is the ratio of transplanted h-GCCs and h-hepatocytes that occupy the examined area of a histological section,was estimated by measuring h-AFP and h-albumin concentrations in sera,respectively,as well as by immunohistochemical analyses of h-AFP and human cytokeratin 18 in histological sections.RESULTS:The h-GCCs successfully engrafted,repopulated,and colonized the livers of mice in group A(RI = 22.0% ± 2.6%).These mice had moderately differentiated adenocarcinomatous lesions with disrupted glandular structures,which is a characteristics feature of gastric cancers.The serum h-AFP level reached 211.0 ± 142.2 g/mL(range,7.1-324.2 g/mL).In group B mice,the h-GCCs and h-hepatocytes independently engrafted,repopulated the host liver,and developed colonies(RI = 12.0% ± 6.8% and 66.0% ± 12.3%,respectively).h-GCC colonies also showed typical adenocarcinomatous glandular structures around the h-hepatocyte-colonies.These mice survived for the full 56 day-study and did not exhibit any metastasis of h-GCCs in the extrahepatic regions during the observational period.The mice with an h-hepatocyte-repopulated liver possessed metastasized h-GCCs and therefore could be a useful humanized liver animal model for studying liver cancer metastasis in vivo.CONCLUSION:A novel animal model of human liver cancer metastasis was established using the uPA/SCID mouse line.This model could be useful for in vivo testing of anti-cancer drugs and for studying the mechanisms of human liver cancer metastasis.

Late Quaternary Activity of the Central-North Segment of the Taihang Mountains Piedmont Fault Zone

The location and late Quaternary activity of the Central-North Segment of the Taihang Mountains Piedmont fault zone have been studied by shallow seismic survey and combined drill exploration.Our results show that the Baoding-Shijiazhuang fault and the Xushui fault were active in the late Pleistocene,but the south Xushui fault has been inactive since the late Pleistocene.The maximum magnitude of potential earthquake of the faults is 6.0.

A+P一体化5G设备的使用探讨

随着5G时代的到来,各地5G基站的建设如火如荼,同时5G网络建设存在工程投资大、5G天线部署需要关注覆盖性能及部署周期等问题。文章针对在利旧基站建设过程中存在的天面空间受限、5G低挂高、铁塔风荷载受限等问题,对A+P(Combination of active and passive antennas)一体化设备在中国电信和中国联通的5G基站建设中的使用方式提出一些建议,根据A+P设备在不同建设场景来进行工程建设、投资分析,说明A+P一体化设备的较高实用性。

A NEW EXPERIMENTAL AND CLINICAL APPROACH OF COMBINING USAGE OF HIGHLY ACTIVE TUMOR-INFILTRATING LYMPHOCYTES AND HIGHLY SENSITIVE ANTITUMOR DRUGS FOR THE ADVANCED MALIGNANT TUMOR

In recent years, tumor-nfiltrating lymphocytes (TILs) have been reported to be effective for tumors in experimental and clinical research. In order to increase the therapeutical effect, we modified some steps of Rosenberg's approach a. cold digestion with collagenase at 4C for 24 hours; b. sedimentation instead of centrifugation; c. elimination of tumor cells before the cultivation procedure. Compared with the original approach, the proliferation, activity and cytotoxicity of TILs obtained by the modified procedure were much improved. TILs' expansion-old was greater than that with the original approach. Cytotoxicity against rumor cells was more potent. Increased TILs' subsets were CD3 and CD8 cells. Meanwhile, we took tumor cells from tumor tissues to test their in vitro chemosensitivities to different drugs in order to select highly sensitive antitumor drugs for treatment of cases with advanced tumors. According to the design of using highly active TILs and highly sensitive drugs (H & H therapy), preliminary clinical results of 50 cases showed higher response rates than those in treatment with TIL / IL2, LAK / 1L2 and TIL+IL2+CTX. Less toxic side effects were observed in 14 patients.

Combined metabolic activators improve cognitive functions in Alzheimer’s disease patients:a randomised,double-blinded,placebo-controlled phase-II trial

Background Alzheimer’s disease(AD)is associated with metabolic abnormalities linked to critical elements of neurodegeneration.We recently administered combined metabolic activators(CMA)to the AD rat model and observed that CMA improves the AD-associated histological parameters in the animals.CMA promotes mitochondrial fatty acid uptake from the cytosol,facilitates fatty acid oxidation in the mitochondria,and alleviates oxidative stress.Methods Here,we designed a randomised,double-blinded,placebo-controlled phase-II clinical trial and studied the effect of CMA administration on the global metabolism of AD patients.One-dose CMA included 12.35 g L-serine(61.75%),1 g nicotinamide riboside(5%),2.55 g N-acetyl-L-cysteine(12.75%),and 3.73 g L-carnitine tartrate(18.65%).AD patients received one dose of CMA or placebo daily during the first 28 days and twice daily between day 28 and day 84.The primary endpoint was the difference in the cognitive function and daily living activity scores between the placebo and the treatment arms.The secondary aim of this study was to evaluate the safety and tolerability of CMA.A comprehensive plasma metabolome and proteome analysis was also performed to evaluate the efficacy of the CMA in AD patients.Results We showed a significant decrease of AD Assessment Scale-cognitive subscale(ADAS-Cog)score on day 84 vs day 0(P=0.00001,29%improvement)in the CMA group.Moreover,there was a significant decline(P=0.0073)in ADAS-Cog scores(improvement of cognitive functions)in the CMA compared to the placebo group in patients with higher ADAS-Cog scores.Improved cognitive functions in AD patients were supported by the relevant alterations in the hippocampal volumes and cortical thickness based on imaging analysis.Moreover,the plasma levels of proteins and metabolites associated with NAD+and glutathione metabolism were significantly improved after CMA treatment.Conclusion Our results indicate that treatment of AD patients with CMA can lead to enhanced cognitive functions and improved clinical parameters associated with phenomics,metabolomics,proteomics and imaging analysis.

Disinfection byproduct formation from algal organic matters after ozonation or ozone combined with activated carbon treatment with subsequent chlorination

Algal organic matter(AOM),including extracellular organic matter(EOM)and intracellular organic matter(IOM)from algal blooms,is widely accepted as essential precursors of disinfection byproducts(DBPs).This study evaluated the effect of ozonation or ozone combined with activated carbon(O_(3)-AC)treatment on characteristic alternation and DBP formation with subsequent chlorination of Chlorella sp..The effects of p H and bromide concentration on DBP formation by ozonation or O_(3)-AC treatment were also investigated.Results showed that the potential formation of DBPs might be attributed to ozonation,but these DBP precursors could be further removed by activated carbon(AC)treatment.Moreover,the formation of target DBPs was controlled at acidic pH by alleviating the reactions between chlorine and AOM.Besides,the bromide substitution factor(BSF)value of trihalomethanes(THMs)from EOM and IOM remained constant after AC treatment.However,THM precursors could be significantly decreased by AC treatment.The above results indicated that O_(3)-AC was a feasible treatment method for algal-impacted water.

Effect of Removing Toxic Substances Combined with Activating Blood Circulation on Stabilizing the Atherosclerotic Plaque and Unstable Angina

The therapeutic effects of activating blood circulation to remove stasis of Chinese medicine （CM） in the prevention and treatment of atherosclerotic diseases such as coronary artery disease and angina are generally acknowledged. In recent years, to further improve the therapeutic effects of those Chinese herbs on such diseases, we have carried out a series of studies of CM medications with the function of clearing heat and removing toxic substances combined with activating blood circulation to remove stasis.

Selective targeted adsorption and inactivation of antibiotic-resistant bacteria by Cr-loaded mixed metal oxides

Herein we provide a novel high-efficiency nanocomposite for bacterial capture based on mixed metal oxides(MMOs)with deleterious chromium properties.With both the layer structure of layered double hydroxides(LDHs)and the magnetic properties of Fe,MMOs enrich the location of ionic forms on the surface,providing a good carrier for adsorption of the heavy metal Cr(VI).The capacity for adsorption of Cr(VI)by MMOs can be as high as 98.80 mg/g.The prepared Cr(VI)-MMOs achieved extremely expeditious location of gram-negative antibiotic-resistant E.coliNDM-1 by identifying lipid bilayers.Cr-MMOs with a Cr loading of 19.70 mg/g had the best bactericidal effect,and the concentration of E.coliNDM-1 was decreased from~10^(8) to~10^(3) CFU/mL after 30 min of reaction.The binding of nitrogen and phosphorus hydrophilic groups to chromate generated realistic models for density functional theory(DFT)calculations.The specific selectivity of MMOs toward bacterial cells was improved by taking Cr(VI)as a transferable medium,thereby enhancing the antibacterial activity of Cr-MMOs.Under the combined action of chemical and physical reactions,Cr(VI)-MMOs achieved high capacity for inactivation of bacteria.Moreover,the metallic elements ratio in Cr-MMOs remained stable in their initial valence states after inactivation.This guaranteed high removal efficiency for both heavy metals and bacteria,allowing recycling of the adsorbent in practical applications.

Fabrication of high-performance non-doped OLEDs by combining aggregation-induced emission and thermally activated delayed fluorescence

Undoubtedly,the realization of"one stone and two birds"is ideal,which is also applicable to the molecular design in the pursuit of excellent performance.Recently,this standpoint has been confirmed again by an interesting story written from the lab of Zujin Zhao,Shi-Jian Su,and BenZhong Tang,at South China University of Technology and the Hong Kong University of Science and Technology,in the design of DBT-BZ-DMAC(Figure 1)[1].Despite its simple structure,DBT-BZ-DMAC exhibits wonderful characteristics,