Natural Products as Potential Lead Compounds for Drug Discovery Against SARS-CoV-2

For the past 2 years,the coronavirus responsible for the COVID-19 infection has become a world pandemic,ruining the lives and economies of several nations in the world.This has scaled up research on the virus and the resulting infection with the goal of developing new vaccines and therapies.Natural products are known to be a rich source of lead compounds for drug discovery,including against infectious diseases caused by microbes(viruses,bacteria and fungi).In this review article,we conducted a literature survey aimed at identifying natural products with inhibitory concentrations against the coronaviruses or their target proteins,which lie below 10μM.This led to the identification of 42 compounds belonging to the alkaloid,flavonoid,terpenoid,phenolic,xanthone and saponin classes.The cut off concentration of 10μM was to limit the study to the most potent chemical entities,which could be developed into therapies against the viral infection to make a contribution towards limiting the spread of the disease.

Growth and Application of Chalcogenides of Lead and Related Compounds

Large grain, low-dislocation, high-quality single crystals of various Pb-salt compounds have been grown reproducibly by the Horizontal Unseeded Vapor Growth (HUVG) technique. The Tunable Diode Lasers with better performance have been made with such crystals. The annealing feature, dislocations and diffusion in the crystals have also been investigated.

Marine soft corals as source of lead compounds for anti-inflammatories

Marine soft corals are known to produce a wide array of secondary metabolites,particularly diterpenoids and steroids,and often characterized by uncommon structural features and potent bioactivities.The remarkable abundance and diversity of bioactive small molecule which have been isolated from soft corals have made these organisms an important source of new drug candidates for human diseases,particularly for their anti-inflammatory activity.In this paper,the authors reported anti-inflammatory marine natural products isolated from diverse species of soft corals determined in vitro by their inhibition of lipopolysaccharide-induced expression of inducible NO synthase and cyclooxygenase-2 in murine macrophage cells(RAW 264.7).

Formation of Bulk Intermetallic Compound AgaSn in Slowly-Cooled Lead-Free Sn-4.0 wt pct Ag Solders

Sn-Ag alloy system has been regarded as one of the most promising lead-free solder to substitute conventional Sn- Pb eutectic solder. But the formation of bulk Ag3Sn intermetallic compounds （IMCs） during reflow and post heat treatment significantly influences the performance of the solder joints. With an effort to clarify its microstructural evolution as a function of slow cooling rates, the fraction of bulk IMCs within the slowly solidified Sn-4.0 wt pct Ag solder was investigated by standard metallographic and compared with that detected by thermal analysis. It was found that the bulk IMCs fraction determined by thermal analysis corresponds quite well with the microstructure observation results. In accordance with the conventional solidification theory, the lower the applied cooling rate, the fewer the amount of bulk Ag3Sn IMCs formed in Sn-4.0 wt pct Ag alloy. In addition, Vickers hardness measurement results indicated that the relative coarse eutectic Ag3Sn IMCs distributing in the lamellar eutectic structure favored the improvement of the mechanical performance.

Solvothermal Synthesis,Crystal Structure and Luminescent Property of a Two-dimensional Lead(Ⅱ) Compound：[Pb(bmzbc)2]n

A two-dimensional coordination polymer, [Pb（bmzbc）2]n（1）（Hbmzbc =4-benzimidazole-1-yl-benzoic acid）, has been synthesized by the solvothermal reaction of Pb（NO3）2 with Hbmzbc at 120 ℃ in ethanol solvent. Compound 1 has been characterized by single-crystal X-ray diffraction, powder X-ray diffraction, thermogravimetry analysis, and IR spectrum. Compound 1 crystallizes in the orthorhombic system, space group Pccn, with a = 12.5801（7）, b = 20.0795（11）, c = 9.1830（6） ？, V = 2319.6（2） A^3, Z = 4, C（28）H（18）N4O4Pb, Mr = 681.65, Dc = 1.952 g/cm^3, μ = 7.319 mm^-1, F（000） = 1312, the final R = 0.0336 and wR = 0.0965 for 1699 observed reflection with I 〉 2σ（I）. In 1, the bmzbc^– ligands bridge the Pb（Ⅱ） ions to generate a 2-D sheet with（4, 4） topology. The complex exhibits turquoise photoluminescent emission with a maximum at 480 nm upon excitation at 300 nm.

Solderability and intermetallic compounds formation of Sn-9Zn-xAg lead-free solders wetted on Cu substrate

The eutectic Sn-9Zn alloy was doped with Ag （0 wt.%-1 wt.%） to form Sn-9Zn-xAg lead-free solder alloys. The effect of the addition of Ag on the microstructure and solderability of this alloy was investigated and intermetallic compounds （IMCs） formed at the solder/Cu interface were also examined in this study. The results show that, due to the addition of Ag, the microstructure of the solder changes. When the quantity of Ag is lower than 0.3 wt.%, the needle-like Zn-rich phase decreases gradually. However, when the quantity of Ag is 0.5 wt.%-1 wt.%, Ag-Zn intermetallic compounds appear in the solder. In particular, adding 0.3 wt.% Ag improves the wetting behavior due to the better oxidation resistance of the Sn-9Zn solder. The addition of an excessive amount of Ag will deteriorate the wetting property because the gluti- nosity and fluidity of Sn-9Zn-（0.5, 1）Ag solder decrease. The results also indicate that the addition of Ag to the Sn-Zn solder leads to the precipitation of ε-AgZn3 from the liquid solder on preformed interracial intermetallics （CusZn8）. The peripheral AgZn3, nodular on the Cu5Zn8 IMCs layer, is likely to be generated by a peritectic reaction L ＋ γ-Ag5Zns→AgZn3 and the following crystallization of AgZn3.

<i>In Silico</i>Pharmacological Analysis of a Potent Anti-Hepatoma Compound of Mushroom Origin and Emerging Role as an Adjuvant Drug Lead

Mushrooms are well-known to possess a continuum of anticancer metabolites that are vital in the development of anticancer adjuvant drug leads based on natural products. Owing to the fact that conventional cancer therapeutic methods were failed to lessen mortality caused by cancer to the estimated level with occurrence of adverse side effects, anticancer agents isolated from natural mushroom sources unarguably make an experimental research area worth mass focus today. The current study was targeted on in vitro cytotoxicity and in silico predictive pharmacological analysis of a flavonoid compound isolated from Fulvifomes fastuosus mushroom. Targeted compound was isolated from the mushroom using different chromatographic methods and identified by NMR spectrometry and mass spectrometry. Cytotoxicity experiments were carried out using MTT assay and apoptotic cells were identified by ethidium bromide/acridine orange staining. The SwissADME tool, BOILED-Egg construction model and Swiss target protein prediction software have been used to perform in silico predictive pharmacological analysis. The isolated compound has been identified as 2-(3,4-dihydroxyphenyl)-6-[(E)-2-(3,4-dihydroxyphenyl)ethenyl]-5'-methylspiro[2H-furo[3,2-c]pyran-3,2'-furan]-3',4-dione by spectrometric methods. The result of MTT assay showed that 2-(3,4-dihydroxyphenyl)-6-[(E)-2-(3,4-dihydroxyphenyl)ethenyl]-5'-methylspiro[2H-furo[3,2-c]pyran-3,2'-furan]-3',4-dione has potent anticancer activity for hepatoma against Hep-G2 cell line (IC50 = 20.8 μg/ml) being less toxic to normal CC-1 epithelial cells (IC50 = 167.00 μM). The cells treated with compound ex-hibited apoptotic features such as cellular shrinkage, nuclear fragmentation and condensed cytoplasm. In summary, 2-(3,4-dihydroxyphenyl)-6-[(E)-2-(3,4-dihydroxyphenyl)ethenyl]-5'-methylspiro[2H-furo[3,2-c]pyran-3,2'-furan]-3',4-dione has shown potent anticancer properties against hepatoma with less cytotoxicity effect on normal cells. Furthermore, in silico study has revealed that properties of 2-(3,4-dihydroxyphenyl)-6-[(E)-2-(3,4-dihydroxyphenyl)ethenyl]-5'-methylspiro[2H-furo[3,2-c]pyran-3,2'-furan]-3',4-dione may contribute to making a high absorption and clearance of the test compound as not interfering with the therapeutic failure of the compound. The properties of 2-(3,4-dihydroxyphenyl)-6-[(E)-2-(3,4-dihydroxyphenyl)ethenyl]-5'-methylspiro[2H-furo-[3,2-c]pyran-3,2'-furan]-3',4-dione were compatible with well-known anticancer drug lapatinib. In conclusion, 2-(3,4-dihydroxyphenyl)-6-[(E)-2-(3,4-dihydroxyphenyl)ethenyl]-5'-methylspiro[2H-furo[3,2-c]pyran-3,2'-furan]-3',4-dione has a high tendency to act as a good anticancer adjuvant drug in the treatment of hepatoma.

<i>In-Silico</i>Identification of Anticancer Compounds;Ligand-Based Pharmacophore Approach against EGFR Involved in Breast Cancer

Objective: Breast cancer is a public health challenge on a global scale that is caused by environmental or genetic factors. Breast cancer is affecting both males and females, but there is still a lack of effective drugs with improved potency and admissibility against breast cancer as many of the breast cancer drugs have severe side effects. Methods: The docking approach has been used to find a new compound for breast cancer with more efficacy and tolerance and with lesser side effects. A ligand-based pharmacophore approach has been generated for 39 anticancer compounds with significance for the development of new drugs. Result: Through docking, the approach found new lead compounds for breast cancer. The proposed pharmacophore model in this study contains two HBAs and one HYD, one hydrophobic domain and two Aromatic rings and the estimated distance range is minimum to maximum of derived pharmacophore features. Conclusion: Based on this research, it is proposed that these two lead compounds may be able to be used against EGFR in breast cancer. New compounds can be identified based on common features in the Pharmacophore model. 3D pharmacophore triangle could be used for further studies because this pharmacophore has better merging and in the future for more studies can suggest the same distance range of pharmacophore features as this pharmacophore.

Alkaline leaching of metal melting industry wastes and separation of zinc and lead in the leach solution

In this work, a thorough examinations on the extractability of zinc and lead present in the steelmaking dusts using alkaline leaching process and the effectiveness of the zinc and lead separation in the resultant leaching solutions using sulfide precipitation method were made. It was found that only about 53% of zinc and over 70% of the lead could be leached out of the dusts, while the other 47% of zinc and 30% of lead were left in the leaching residues. The zinc and lead in the resultant leaching solution can be effectively and selectively separated. When the weight ratio of sodium sulfide (M.W. = 222-240) to Pb was kept at 1.8, the lead in the solution could be precipitated out quantitatively while all the zinc was remained in the solution. The zinc left in the solution can be further recovered by the addition of extra sodium sulfide with a weight ratio of sodium sulfide to the zinc over 2.6. The resultant filtrate can be recycled to the leaching of dust in the next leaching process.

Effects of Ga,Al,Ag,and Ce multi-additions on the wetting characteristics of Sn-9Zn lead-free solder

An orthogonal method was used to evaluate the effects of Ga, Al, Ag, and Ce multi-additions on the wetting characteristics of Sn-9Zn lead-free solders by wetting balance method. The results show that the optimal loading of Ga, Al, Ag, and Ce was 0.2 wt.%, 0.002 wt.%, 0.25 wt.%, and 0.15 wt.%, respectively. Intermetallic compounds （IMCs） formed at the interface between Sn-9Zn-0.2Ga-0.002Al-0.25Ag- 0.15Ce solder and Cu substrate were investigated by scanning electron microscope （SEM） and energy dispersive spectroscopy （EDS） analysis. The SEM images illustrate that the IMCs can be divided into two portions from the substrate side to the solder side： a planar CusZns layer and an additional continuous scallop-like AgZn3 layer. The EDS analysis also shows that Ga segregates in the solder abutting upon the interface. X-ray photoelectron spectroscopy （XPS） and Auger electron spectroscopy （AES） of the surface components of Sn-9Zn-0.2Ga-0.002Al- 0.25Ag-0.15Ce solder indicate that Al aggregates at the surface in the form of Al203 protective fdm, which prevents the further oxidation of the solder surface. On the other hand, Ce aggregates at the subsurface, which may reduce the surface tension of the solder and improve the wettability in consequence.

Effects of rapid solidification on the microstructure and microhardness of a lead-free Sn-3.5Ag solder

A lead-free Sn-3.5Ag solder was prepared by rapid solidification technology. The high solidification rate, obtained by rapid cooling, promotes nucleation, and suppresses the growth of Ag3Sn intermetallic compounds （IMCs） in Ag-rich zone, yielding fine Ag3Sn nanoparticulates with spherical morphology in the matrix of the solder. The large amount of tough homogeneously-dispersed IMCs helps to improve the surface area per unit volume and obstructs the dislocation lines passing through the solder, which fits with the dispersion-strengthening theory. Hence, the rapidly-solidified Sn-3.5Ag solder exhibits a higher rnicrohardness when compared with a slowly-solidified Sn-3.5Ag solder.

邻苯二甲酸二异丁酯——新型的ANO2通道开放剂

目的筛选ANO2的特异性配体药物,为医药行业开发靶向ANO2新药提供先导化合物的结构信息。方法构建ANO2过表达的HEK293细胞株,应用共聚焦显微镜-膜片钳全细胞记录模式技术筛选ANO2的特异性配体。结果在胞内外钳制电压100 mV及含1μmol·L^(-1)钙离子电极内液的记录条件下,邻苯二甲酸二异丁酯(diisobutyl phthalate,DIBP)给药前ANO2介导的氯电流密度为(14.67±2.87)pA/pF,给药后ANO2介导的氯电流电导为(28.75±4.05)pA/pF,差异具有统计学意义(P<0.01);钙荧光成像实验结果表明DIBP无调节胞内游离钙信号的作用;在0μmol·L^(-1)钙离子条件下,DIBP对静息状态的ANO2通道不具有直接的激活作用。结论DIBP通过直接作用增强已活化ANO2通道的电导,其作为一种新型的促ANO2通道开放剂为开发靶向ANO2的药物提供结构信息,同时也为研究其他邻苯二甲酸酯类物质的毒理作用提供一定的理论基础。

The Kinetics of Pb Removal from Brass Scrap Using Compound Separation

2 wt% Ca was added to molten brass containing 3.2 wt% Pb. The composition and grain size of the formed Ca-Pb compound were examined in detail using SEM-EDS and XRD. This revealed that the composition of the Ca-Pb compound depends on the grain size of the liquid phase Pb and the diffusion phenomenon of the Ca in the Ca-Pb compound formed on the surface of the Pb. When the Pb has a fine grain, a compound composed only of Ca-Pb compounds is formed. When the grain size of the Pb is several μm, Ca-Pb compounds containing unreacted Pb in the center are formed. These compounds aggregate into a larger compound grain. From the evaluation of the floating force (the resultant force of the weight and buoyancy of the Ca-Pb compounds formed) and the rising terminal velocity of the Ca-Pb compound within the molten brass, it was found that the floating force and rising terminal velocity depend on the composition and grain size of the Ca-Pb compound. It was found that since Ca-Pb compounds with a floating force greater than 10-6 g ·cm/s2 have a very large rising terminal velocity, they reach the surface of the molten brass in a short time after compound formation and then continue to float on the surface of the molten brass. Thus they can be removed by skimming. The effects of the grain size of the Ca-Pb compound on the floating force and the rising terminal velocity were greater than those of the composition of the Ca-Pb compound.

Characteristics of Laser Reflow Bumping of Sn3.5Ag and Sn3.5Ag0.5Cu Lead-Free Solder Balls

ead-free Sn3.5Ag and Sn3.5Ag0.5Cu solder balls were reflowed by laser to form solder bumps. Shear test was performed on the solder bumps, and SEM/EDX （scanning electron microscopy/energy dispersive X-ray spectrometer） was used to analyze the formation of intermetallic compounds （IMCs） at interface region. A finite element modeling on the temperature gradient and distribution at the interface of solder bump during laser reflow process was conducted to elucidate the mechanism of the IMCs growth direction. The results show that the parameters window for laser reflow bumping of Sn3.5Ag0.5Cu was wider than that of Sn3.5Ag. The shear strength of Sn3.5Ag0.5Cu solder bump was comparable to that of Sn3.5Ag solder bump, and was not affected obviously by laser power and irradiation time when appropriate parameters were used. Both laser power and heating time had a significant effect on the formation of IMCs. A continuous AuSn4 intermetallic compound layer and some needle-like AuSn4 were observed at the interface of solder and Au/Ni/Cu metallization layer when the laser power is small. The formation of needle-like AuSn4 was due to temperature gradient at the interface, and the direction of temperature gradient was the preferred growth direction of AuSn4. With increasing the laser power and heating time, the needle-like AuSn4 IMCs dissolved into the bulk solder, and precipitated out once again during solidification along the grain boundary of the solder bump.

Identification of Rare Earth Phase in the Deformed High Lead-Brasses

Deformed high lead-brasses have excellent machining characteristics and good mechanical and physicalproperties.They are widely used in mechanical,clock-watch and pen-making field.Especially,they are suit-able for deep-hole machining.Because of their worse hot-working characteristics,there exists trouble inproduction process.It is reported that the rare earth metals could improve the hot-rolling property,but themechanism is still unclear.

高校党建引领复合型基层治理人才培养路径探索

我国基层治理逐渐迈向复杂化、多元化与专业化,亟需一批素质过硬、能力多元、服务专业的复合型基层治理人才。党建与人才培养深度融合是我国高等教育的重要特征,但在培养复合型基层治理人才中,高校党建在发挥引领学科交叉、科研育人、实践育人、活动育人等方面的作用仍有待加强。因此,高校需加强党建引领并深度嵌入到人才培养的各个环节,充分发挥高校党建在思想引领、能力培养、道德提升等多方面的作用,进一步完善复合型基层治理人才的培养路径。

Effects of cooling rates on microstructure and microhardness of lead-free Sn-3.5%Ag solders

The microstructure and microhardness of Sn-3.5%Ag solders were explored in the cooling rate ranging from 0.08 to 104 K/s. Under rapid cooling condition, the strong kinetic undercooling effect leads to the actual solidification process starting at the temperature lower than the equilibrium eutectic point, and the actual metastable eutectic point shifts to the higher Ag concentration. Hence, the higher the applied cooling rate is, the more the volume fraction of primary β-Sn crystal forms. At the same time, the separation of primary β-Sn crystal favors restraining the formation of bulk Ag3Sn intermetallic compounds (IMCs) in solder due to the mismatch crystalline orientation relationship, those Ag3Sn phase separating through the eutectic reaction could hardly cling to the primary β-Sn crystal and grow up. Additionally, the Vickers hardness test shows that fine β-Sn and spherical Ag3Sn phase in the rapidly solidified alloy strongly improves the microhardness of the Sn-3.5%Ag solder.

Rapid directional solidification in Sn-Cu lead-free solder

An experimental study on the microstructures of a rapid directionally solidified metallo-eutectic Sn-Cu alloy was carried out. This material is an important alloy that is used as a lead-free solder. The results showed that the kinetic undercooling due to the rapid solidification process led to the formation of a pseudoeutectic zone, whereas the hypereutectic reaction produced the regular lamellar structure in the hypereutectic Sn-1.0Cu alloy. The corresponding arm spacing in the obtained lamellar phases decreased gradually with the increase of the applied cooling rate, which corresponded well with the prediction of a rapid directional solidification model.

Synthesis and Crystal Structure of Salicylyl-4-phenyl Thiosemicarbazide Lead with a Two-dimensional Network

A two-dimensional lead complex, [Pb（C14N3O2H12S）（NO3）]n·nH2O, was prepared by the reaction of salicylyl-4-phenyl thiosemicarbazide and lead nitrate. The compound （C14H13N4O6PbS, Mr = 572.53） crystallizes in the monoclinic space group P21/c with a = 11.2984（2）, b = 15.6628（7）, c = 11.1118（2）A,β= 113.564（2）°, V = 1802.43（10）A3, Dc= 2.110 g/cm3, Z = 4,μt（MoKα） = 9.515 mm-1, F（000） = 1084, the final R = 0.0394 and wR = 0.0701 for 2552 observed reflections with I 〉 2σ（I）. The Pb（Ⅱ） ion displays a distorted octahedron in which the hypothesized stereochemically active lone pair occupies the apex. The compound exhibits a two-dimensional network structure formed by the zigzag one-dimensional chains joined by two μ-O of two nitrate groups in overlapping. A large ring exists in the two-dimensional layers. The TGA of the title compound has been studied.

Mechanism of Pb Removal from Brass Scrap by Compound Separation Using Ca and NaF

The Mechanism of Pb removal from brass scrap by compound separation using Ca and NaF addition was investigated. Because large Ca-Pb compound particles formed by Ca addition rise to the surface of the molten brass, they can be skimmed off from the molten brass. However, fine Ca-Pb compound particles remain in the molten brass because of low buoyancy. By subsequent NaF addition, the reaction between Ca-Pb compound and NaF takes place at their contact regions, resulting in the formation of solid CaF2, liquid Pb and Na gas. Pb is mainly present at the Ca-Pb compound-CaF2 interface. CaF2 acts as a binder for aggregation of fine Ca-Pb compound particles, resulting in the formation of light and large composite compounds, which rise to the surface of the molten brass. A high Pb removal rate is achieved by skimming off.