微生物来源的Azole类抗真菌活性增强剂——FKI-0076A、B和C的研究

FKI- 0 0 76 A、B和 C是从真菌培养液中筛选 Azole类抗真菌活性增强剂过程中获得的 ,每 6 mm纸片 10μg FKI- 0 0 76 A、B或 1.0μg FKI- 0 0 76 C就显示增强活性。真菌 Talaromyces sp.FKI- 0 0 76培养 5 d后 ,经有机溶媒提取 ,常压 ODS柱层析和制备 HPL C柱层析分离 ,得到 FKI- 0 0 76 A、B和 C纯品。又经过测定其HR- MS、UV、IR、1 H- NMR、1 3C- NMR、DEPT、1 H- 1 H COSY、HMQC和 HMBC等光谱数据。将 FKI- 0 0 76 A的结构定为 BK 2 2 3- A,FKI- 0 0 76 B的结构定为 vermistatin,FKI- 0 0 76 C的结构定为 deoxyfunicone。

Azole derivatives embedded in montmorillonite clay nanocarriers as corrosion inhibitors of mild steel

Azole derivatives such as 2-mercaptobenzothiazole(MBT) and 2-mercaptobenzimidazole(MBI) were introduced as corrosion inhibitors into the interlayer space of sodium montmorillonite clay(Na+-MMT). The corrosion protection behavior of mild steel in solutions containing MBT, MBI, MMT + MBT, MMT + MBI, Na^+-MMT, and NaCl(3.5 wt%) was evaluated using polarization and electrochemical impedance spectroscopy(EIS). Also, the release of penetrated species into the medium from the clay nanocarriers was evaluated using ultraviolet-visible(UV-Vis) spectroscopy. Small-angle X-ray scattering(SAXS) confirmed the insertion of MBT and MBI into the inner space of the clay layers and the interaction between two organic and inorganic phases. Scanning electron microscopy(SEM) was used to assess the morphology of the surface of the steel samples after the samples had been immersed for 24 h in the extraction solution. The corrosion protection in the solutions with clay nanocarriers containing MBT and MBI was better than that in solutions without MMT. The UV-Vis results showed that the release of MBI species from Na+-MMT nanocarriers in neutral pH was far lower than that of MBT species.

Nitrogen-rich azoles as trifunctional electrolyte additives for high-performance lithium-sulfur battery

Rechargeable lithium-sulfur(Li-S)batteries are considered one of the most promising energy storage techniques owing to the high theoretical energy density.However,challenges still remain such as the shuttle effect of lithium polysulfides(LPSs)and the instability of lithium metal anode.Herein,we propose to use nitrogen-rich azoles,i.e.,triazole(Ta)and tetrazole(Tta),as trifunctional electrolyte additives for Li-S batteries.The azoles afford strong lithiophilicity for the chemisorption of LPSs.The density functional theory and experimental analysis verify the presence of Li bonds between the azoles and LPSs.The azoles can also interact with lithium salt in the electrolyte,leading to increase ionic conductivity and lithiumion transference number.Moreover,the azoles render particle-like lithium deposition on the lithium metal anode,leading to superlong cycling of a Li symmetric cell.The Li-S batteries with Ta and Tta exhibit the initial discharge capacity of 1425.5 and 1322.2 m Ah g^(-1),respectively,at 0.2 C rate,and promising cycling stability.They also enable enhanced cycling performance of a Li-organosulfide battery.

Cardiac Toxicity of Azole Antifungals

Cardiac toxicity is an uncommon side effect of anti-fungal therapy. Until the recent reports of itraconazole (ITZ) associated cardiac failure, amphotericin was the antifungal most frequently reported with arrhythmias. We evaluated the cardiac effect of azole antifungals, specifically ITZ, and possible mechanisms of toxicity. Ex vivo live-heart studies were performed utilizing Sprague Dawley rats. Short exposure (<5 minutes), random crossover, dose ranging studies were performed with each pharmacologic agent. ITZ focused trials also included dose ranging utilizing a non-crossover design. The only azole found to have significant toxicity was ITZ. At ITZ ~ ED25 (2 - 2.5 ug/mL) exposures, contractility decreased by 22.2% ± 15.7% and amplitude of left ventricular pressure decreased by 11% ± 0.17%. Electron micrograph and alterations in mitochondrial respiration suggest mitochondrial toxicity as an underlying mechanism. In conclusion, ITZ was associated with reductions in contractility, possibly secondary to mitochondrial dysfunction and dilated cardiomyopathy.

Azole selenourea disrupted the midgut and caused malformed development of Plutella xylostella

Chemical insecticides targeting the digestive system of diamondback moth(DBM),Plutella xylostella,have not been developed.The discovery of an insecticide with novel mode of action is a challenge for the control of DBM.In this study,a class of selenium-and difluoromethyl-modified azoles(fluoroazole selenoureas,FASU)were designed and synthesized for the control of DBM.Of these azoles,compound B4 showed the highest insecticidal activity against DBM.The LC50of third-and second-instar larvae reached 32.3 and 4.6μg mL^(–1),respectively.The midgut tissue of larvae was severely disrupted,and the larval intestinal tissue was dotted with unique red spots after treatment with compound B4.Compound B4 led to disintegration of the peritrophic matrix,swelling of the midgut epithelium,fracture of the microvilli,and extensive leakage of cellular debris in the midgut lumen.Surviving larvae grew very slowly,and the larval duration was significantly prolonged after exposure to compound B4 at sublethal doses(LC10,LC25and LC50).Furthermore,the pupation rate,emergence rate and pupae weight were significantly decreased.Compound B4 also induced abnormal pupae,causing adults to be trapped in the cocoon or failure to fly due to twisted wings.These results demonstrated that FASU could reduce the population of DBM in sublethal doses.FASU is the first synthetic insecticidal lead compound that has been shown to disrupt the midgut tissue of the larvae of DBM,and its mode of action totally differs from that of commercial chemical insecticides.

Cis-2-dodecenoic Acid Mediates Its Synergistic Effect with Triazoles by Interfering with Efflux Pumps in Fluconazole-resistant Candida albicans

Objective To evaluate the synergy of the Burkholderia signaling molecule cis-2-dodecenoic acid(BDSF) and fluconazole(FLU) or itraconazole(ITRA) against two azole-resistant C. albicans clinical isolates in vitro and in vivo. Methods Minimum inhibitory concentrations(MICs) of antibiotics against two azole-resistant C. albicans were measured by the checkerboard technique, E-test, and time-kill assay. In vivo antifungal synergy testing was performed on mice. Analysis of the relative gene expression levels of the strains was conducted by quantitative reverse-transcription polymerase chain reaction(qR T-PCR). Results BDSF showed highly synergistic effects in combination with FLU or ITRA with a fractional inhibitory concentration index of ≤ 0.08. BDSF was not cytotoxic to normal human foreskin fibroblast cells at concentrations of up to 300 μg/mL. The qR T-PCR results showed that the combination of BDSF and FLU/ITRA significantly inhibits the expression of the efflux pump genes CDR1 and MDR1 via suppression of the transcription factors TAC1 and MRR1, respectively, when compared with FLU or ITRA alone. No dramatic difference in the mR NA expression levels of ERG1, ERG11, and UPC2 was found, which indicates that the drug combinations do not significantly interfere with UPC2-mediated ergosterol levels. In vivo experiments revealed that combination therapy can be an effective therapeutic approach to treat candidiasis. Conclusion The synergistic effects of BDSF and azoles may be useful as an alternative approach to control azole-resistant Candida infections.

Efficacy of voriconazole on leishmaniasis by Leishmania major: An in vitro and in vivo study

Objective: To appraise the activity of voriconazole against Leishmania major(L. major) in vitro and its effectiveness on wound regeneration in cutaneous leishmaniasis in BALB/c mice Methods: The IC_(50) of voriconazole against promastigotes and intra-macrophage amastigotes of L. major was investigated in vitro. The in vivo study was performed by treating the L. major infected BALB/c mice. When the wounds appeared in the base of tail, treatment was started by administration of 30 mg/kg voriconazole for 28 consecutive days orally. Results: The IC_(50) of voriconazole against promastigotes and intra-macrophage amastigotes were 0.74 and 0.89μM, respectively. Voriconazole decreased lipid peroxidation and IL-6 level. Histopathologica findings indicated accelerated healing in the voriconazole treated group compared to other groups. Conclusions: Our results demonstrate that voriconazole can be an option in treating the cutaneous leishmaniasis by L. major.

ERG11 mutations associated with azole resistance in Candida albicans isolates from vulvovaginal candidosis patients

Objective: To investigate the azole susceptibility of Candida albicans(C.albicans)from vulvovaginal candidosis patients and to analyze the relationship between ERG11 gene mutations in these isolates and azole resistance.Methods: Three hundred and two clinical isolates of Candida species were collected.Azole susceptibility was tested in vitro in microdilution studies. The ERG11 genes of 17 isolates of C. albicans(2 susceptibles, 5 dose-dependent resistants and 10 resistants) were amplified and sequenced.Results: Of the 302 isolates collected, 70.2% were C. albicans, of which 8.5%, 3.8% and4.2% were resistant to fluconazole, itraconazole and voriconazole, respectively. In total,27 missense mutations were detected in ERG11 genes from resistant/susceptible dosedependent isolates. Among them, Y132 H, A114 S, and Y257 H substitutions were most prevalent and were known to cause fluconazole resistance. G464 S and F72 S also have been proved to cause fluconazole resistance. Two novel substitutions(T285A, S457P) in hotspot regions were identified.Conclusions: Twenty seven mutations in the ERG11 gene were identified in azoleresistant C. albicans isolates, which indicated a possible relation with the increase in resistance to azole drugs and the recurrence of vulvovaginal candidosis. The relationship of two novel substitutions(T285A, S457P) with fluconazole resistance needs to be further verified by site-directed mutagenesis.

<i>In-Vitro</i>Comparison of Antifungal Activity of Herbs (Darehald and Pomegranate) with Azoles

Aim: Candida, an opportunistic organism is one of the commonest causes of hospital acquired infections among fungi. Currently available antifungal drugs have numerous adverse effects and drug-drug interactions (DDIs) along with increase in resistance over the time. Therefore, it is highly emergent to consider alternative treatments for candidal infections, having fewer adverse effects and is cost-effective. The current in-vitro study is undertaken to assess and compare the antifungal effects of the herbs, Berberis aristata (B. aristata, Darehald/Darhald) and Punica granatum (P. granatum, Pomegranate) with fluconazole and voriconazole, based on culture and sensitivity of candidal isolates. Materials and Methods: Ethanolic extracts of herbs (Berberis aristata and Punica granatum) and concentrations were formulated as per standard procedure. 130 samples were obtained for the study from in and out patients reported in clinical subsets of Ziauddin Hospital, Karachi from March to May, 2018. Samples were collected and grown according to the standard procedures like, wet mount test and gram’s staining. Species were identified by CHROM agar candida and API 20 C AUX methods. Sensitivity tests were performed by Kirby Bauer’s disc diffusion method according to CLSI guide lines M-44 A2, 2009. Data analysis was done by one-way ANOVA to compare the antifungal activities of drugs and herbs. Results: Mean inhibitory zones of herbs, B. aristata and P. granatum were highly significant against clinical candidal isolates with respective p-values of 0.00 and 0.02. Both of the herbs, B. aristata and P. granatum were found to be more sensitive, 98.5% and 97.7% respectively in comparison to fluconazole showing 42.3% and voriconazole showing 29.2% sensitivity against candidal isolates. The most resistant candidal specie was C. tropicalis that showed resistance against both fluconazole and voriconazole, contrary to that, this specie was highly sensitive to both of the herbs, showing sensitivity of 100% respective for Darehald and Pomegranate. Conclusion: In comparison to azoles: Culture sensitivity of both herbs (B. aristata and P. granatum) displayed more sensitivity against candidal isolates of patients having non-invasive and invasive candidiasis. These herbs can be considered as substitute or alternative antifungal agents to the conventional antifungal therapy, particularly in cases of treating candidemia patients, which is a life threating condition.

Contribution to a Comparative Study of the Corrosion Inhibiting Effect of Some Azoles, to Protect the Cu70-30Ni Alloy in Aerated NaCl 3% in Presence of Ammonia

Some azoles were tested such as 3-amino-1,2,4-triazole (ATA), 3-4’-bitriazole -1,2,4 (BiTA)and 2-Mercaptobenzimidazole (MBI) against Cu-30Ni alloy corrosion in 3%NaCl polluted by ammonia using potentiodynamic measurements and electrochemical impedance spectroscopy and non-electrochemical techniques (scanning Electron Microscopy (SEM)) studied surface morphology has been used to characterize electrode surface. This study permitted to follow the evolution of the inhibitory effect of some azoles, on Cu-30Ni alloy corrosion in 3%NaCl polluted by ammonia and indicate that the tested inhibitors act as a good mixed-type inhibitor retarding the anodic and cathodic reactions. An increase of the inhibitors concentration leads to a decrease of corrosion rate and inhibition efficiency increase.

Arylated analogues of cypronazole: fungicidal effect and activity on human fibroblasts. Docking analysis and molecular dynamics simulations

Triadimefon(TDM)and cyproconazole(CPZ)are two triazoles widely used as fungicides.Several azoles were synthe-sised starting from commercial TDM and CPZ.The compounds were evaluated against phytopathogenic filamentous fungi,including Aspergillus fumigatus(AF),A.niger(AN),A.ustus(AU),A.japonicus(AJ),A.terreus(AT),Fusarium oxyspo-rum and Botrytis cinerea isolated from grapevine in the province of San Juan,Argentina.Three of the synthesised compounds(1-(Biphenyl-4-yloxy)-3,3-dimethyl-1-(1H-1,2,4-triazol-1-yl)butan-2-one,1;2-(Biphenyl-4-yl)-3-cyclopropyl-1-(1H-1,2,4-triazol-1-yl)butan-2-ol,3;3-Cyclopropyl-2-(4’-fluorobiphenyl-4-yl)-1-(1H-1,2,4-triazol1-yl)butan-2-ol,4)presented remarkable in vitro fungicidal properties,with better effects than TDM and CPZ on some of the target fungi.Cytotoxicity was assessed using human lung fibroblasts MRC5.Derivative 1,with IC50 values of 389.4μM,was less toxic towards MRC-5 human lung fibroblasts than commercial TDM(248.5μM)and CPZ(267.4μM).Docking analysis and molecular dynamics simulations suggest that the compounds present the same interaction in the binding pocket of the CYP51B enzyme and with the same amino acids as CPZ.The derivatives investigated could be considered broad-spectrum but with some selectivity towards imperfect fungi.

Multi-effect distillation system for seawater desalination driven by tidal energy and low grade energy

A multi-effect distillation technology for seawater desalination driven by tidal energy and low grade energy is presented.In the system,tidal energy is utilized to supply power instead of coventional electric pumps during the operation,resulting in the decrease of dependence on steady electric power supply and a reduction in the running costs.According to the technological principle,a testing unit is designed and built.The effects of the feed seawater temperature and the heat source temperature on the unit performance are tested and analyzed.The experimental results show that the fresh water output is 27 kg/h when the heating water temperature is 65 ℃ and the absolute pressure is 25 kPa.The experimental and theoretical analysis results indicate that the appropriate heating water temperature is a key factor in ensuring the steady operation of the system.

Chemical dehydration coupling multi-effect evaporation to treat waste sulfuric acid in titanium dioxide production process

In order to concentrate the diluted sulfuric acid from the titanium dioxide(TiO2)production of sulphate process,a new concentration process was proposed by coupling chemical dehydration and multi-effect evaporation.The ferrous sulfate monohydrate(FeSO4·H2O),as the dehydrant,was added to the diluted sulfuric acid to form ferrous sulfate heptahydrate(FeSO4·7H2O)according to the H2SO4-FeSO4-H2O phase diagrams,which partially removes the water.This process was named as Chemical Dehydration Process.The residual water was further removed by two-effect evaporation and finally 70 wt%sulfuric acid was obtained.The FeSO4·H2O can be regenerated through drying and dehydration of FeSO4·7H2O.The results show that FeSO4·H2O is the most suitable dehydrant,the optimal reaction time of chemical dehydration process is 30 min,and low temperature is favorable for the dehydration reaction.45.17%of the entire removed water can be removed by chemical dehydration from the diluted sulfuric acid.This chemical dehydration process is also energy efficient with 24.76%saving compared with the direct evaporation process.Furthermore,51.21%of the FeSO4 dissolved originally in the diluted sulfuric acid are precipitated out during the chemical dehydration,which greatly reduces the solid precipitation and effectively alleviates the scaling in the subsequent multi-effect evaporation process.

Selecting Suitable Heat Source in Refinery for Multi-effect Distillation Based on Grey System Theory

For dealing with high-salinity wastewater in the refinery, the high cost of driving heat source is the disadvantage of multi-effect distillation (MED) so it is of great importance to evaluate the performance of low-temperature heat source for conducting MED and select the optimal temperature for it. Both the MED and the low-temperature heat sources studied in this paper were from a typical refinery located in northwestern China. Besides, a new methodology to evaluate heat sources as the optimal candidate was proposed for MED based on the grey system theory. Five process units, which included 18 fluids of the refinery, were named as the evaluation projects. Three factors, which included safety effects, total costs and characteristics of low-temperature heat sources were determined as the evaluation indexes, the values of which were established through the analyses. The results obtained through the grey correlation analyses have revealed that the grey correlation degrees of these units were 0.661(AVDU), 0.732 (#1 FCCU), 0.618 (#2 FCCU), 0.535 (#1 DCU), and 0.572 (#2 DCU), respectively. Thus, the optimal heat source was provided from #1 FCCU. Through further analyses of the fluids from #1 FCCU, the grey correlation degrees of the fluids were 0.597 (oil and gas at top of tower), 0.714 (recycle oil and gas), and 0.512 (diesel), respectively. Thus, the optimal heat source was the oil and gas recycle stream.

Study on Multi-effect Time Parameters of Ergonomic Validity Index in Low-carbon Residential Kitchen

In the study on functional low-carbon ergonomic validity in buildings,ergonomic validity is different from resource validity which is easy for quantitative analysis. To eliminate the complexity and uncertainty impacts of human factors on quantitative study,it proposes a method of building a parameter of ergonomic validity—multi-effect time by using cardiotachometer to record heart rate change,being used to evaluate the functional low-carbon ergonomic validity targeting at the ontological characteristics of kitchen. This method is used to determine the physical consumption intensity( multi-effect) through heart rate incremental relation based on the principles of physiology and ergonomics,and to confirm the ergonomic validity of environmental factors by the time to complete standard work as well as multi-effect quantitative analysis. The test results show that,under the kitchen operating conditions,the multi-effect( ME) can properly reflect the real-time status of the operator and is easily operated; the parameters obtained are not significantly related to the physiological status of the operator,and multi-effect time( MT) is sensitive to the physical consumption brought about to the operator due to kitchen environmental factors; thus,it can be taken as an objective index,which is simple and easy to operate in residential kitchen functional low-carbon evaluation.

Simulation of Countercurrent Multi-Effect Drying System

The paper bulids a countercurrent multi-effect drying process model which can be expressed as a linear programming(LP) problem with the minimum total energy consumption as target function. Based on the model it can be conventient to solve the heat load , degree of drying and other drying parameters of each effect. And it realizes the mathematical simulation an analysis of multi-effect drying process. Such process not only reuses the secondary steam but also utilizes the high energy grade. Drying silica sand using 1-effect drying to 5-effect drying is presented as an example. The energy consumption and energy saving rate are compared by using co-current multi-effect drying and countercurrent multi-effect drying. As a summary, the countercurrent multi-effect drying is better than co-current drying. Considered the equipment investment and energy conservation, the study also concluded that the countercurrent 4-effect drying is the optimum selection, and it can save 57.6% energy compared to countercurrent 1-effect drying.

Multi-effects and Mechanism of Broad Beau M_1 Root-tip Cells Implanted by Low Energy N^+ Beam

Broad beans were divided into six groups and implanted with N+ beam of 30 KeV, 8 × 1016/cm2 per time for various radiating times respectively. Besides the statistics of its vigor of germination, the M1 root-tip cells of these broad beans were systematically analyzed on their changes in mitotic percentage, morphology and behavior of chromosomes, along with the structure o f cytoskeletons, including microtubule and intermediate filament. Based on all results of these studies, our opinions have been expressed in the report on the mechanism of low-energy N+ beams effecting on higher dicotyledons such as broad beau.

基于定位校正指数的嘧啶类含能材料爆轰性能

为研究嘧啶类含能化合物的爆轰性能与其分子结构的构效关系,根据嘧啶类含能化合物分子中原子相互连接的空间特性,提出了一种新的分子结构指数——定位校正指数B;此外还计算了19个含能化合物分子的电拓扑态指数,并优化筛选出其中的E 13作为分子结构描述符,将E 13与定位校正指数B结合,与嘧啶类含能化合物的爆轰性能进行回归分析;将B和E 13这两种结构指数作为BP神经网络的输入变量,神经网络结构采用2-3-1的结构方式,构建了预测嘧啶类含能化合物爆轰性能好的神经网络法模型。结果表明,每个模型的总相关系数均超过0.99,达优级相关,计算得到的氧平衡、爆热、爆速和爆压的预测值与文献值的平均相对误差分别为1.59%、1.05%、0.37%和1.28%;如将指数扩展到与噁三唑稠环类含能材料分子、含氟唑类含能化合物分子的爆轰性能等进行分析预测,同样能得到令人满意的结果。说明嘧啶类含能材料分子的爆轰性能与定位校正指数、电拓扑态指数有良好的非线性关系。

基于一种唑类羧酸配体的两种配合物的合成、结构及染料吸附性能研究

以1-(3,5-二羧基苄基)-1,2,4-1H-三唑-3-羧酸(H_(3)L1)为有机配体,选择Cu^(2+)和Pb^(2+)为金属中心,通过溶剂热反应制备得到两种新的配合物[Cu(L1)·(CH_(3)CN)_(2)]·H_(2)O(1)和[Pb(L2)](2),H_(2)L_(2)为H_(3)L1原位脱羧产物,并通过单晶X-射线衍射、红外光谱、X-射线粉末衍射、热重分析等对配合物进行表征和分析.染料吸附实验结果表明,配合物1对亚甲基蓝的吸附效率为84.0%,而配合物2对结晶紫的吸附效率为60.2%.

唑类杂合体的抗鲍曼不动杆菌活性研究进展

鲍曼不动杆菌,广泛存在于自然界中,是一种条件致病革兰阴性菌,可引起呼吸道感染、菌血症、泌尿系感染、继发性脑膜炎、手术部位感染和呼吸机相关性肺炎等多种致命性院内感染,严重威胁人类健康。鲍曼不动杆菌已对几乎所有现有抗菌药产生了耐药性,但是近半个世纪以来鲜有抗鲍曼不动杆菌药物上市。因此,亟须开发新型抗鲍曼不动杆菌药物。唑类化合物可与多种生物靶点形成各种非共价键和共价键作用,广泛存在于各种药物中。其中,唑类杂合体可同时作用于多个细菌靶点,具有增强抗菌活性和克服耐药性的潜力,对各种难治性和耐药鲍曼不动杆菌感染具有潜在的体内、外疗效。本文将归纳自2020年以来所发现的具有抗鲍曼不动杆菌活性的唑类杂合体的最新研究进展,以期为今后发现新型药物候选物提供理论支持。