Revealing the contribution of basilar membrane's biological activity to the mechanism of the cochlear phonosensitive amplification

Explaining the mechanism of the cochlear active phonosensitive amplification has been a major problem in medicine.The basilar membrane(BM)is the key infrastructure.In 1960,Nobel Laureate von B′ek′esy first discovered BM's traveling wave motion.Since that time,BM's models only have considered the traveling wave but not the biological activity.Therefore,a new model considering changes of BM's stiffness in space and time is established based on the immersed boundary method to describe its biological activity.It not only reproduces the results of traveling wave motion but also explains the mechanization on the generation of traveling wave.An important discovery is that changes of BM's stiffness in space and time will cause the unstable global resonance,which will induce amplification of sounds in cochlea.An important inference is that biological activity shall be included in the application of mechanical principles to the analysis of life,which is the essential difference between biomechanics and general mechanics.

Overview of Research on Citral in Lauraceae Plants and Its Biological Activity

Citral is a monoterpene aldehyde,which is the main chemical component of essential oils from Litsea cubeba and Cymbopogon citratus,as well as one of the most important representatives of open-chain monoterpene compounds.The lemon flavor released by citral is very strong,and thus,it is widely used in essence,spices,manufacturing of various foods and beauty and other industries.It has antibacterial,anti-inflammatory,antioxidant,anti-tumor,insecticidal and other biological activity.This paper reviewed citral in Lauraceae plants and its biological activity,in order to provide reference for the development and utilization of citral in Lauraceae plants and its diversified applications.

Bioactive compounds in Hericium erinaceus and their biological properties:a review

Hericium erinaceus is a nutritious edible and medicinal fungi,rich in a variety of functional active ingredients,with various physiological functions such as antioxidation,anticancer,and enhancing immunity.It is also effective in protecting the digestive system and preventing neurodegenerative diseases.In this review paper,we summarize the sources,structures and efficacies of the main active components in H.erinaceus fruiting body,mycelium,and culture media,and update the latest research progress on their biological activities and the related molecular mechanisms.Based on this information,we provide detailed challenges in current research,industrialization and information on the active ingredients of H.erinaceus.Perspectives for future studies and new applications of H.erinaceus are proposed.

Construction of recombinant plasmid and prokaryotic expression in E. Coli and biological activity analysis of human placenta arresten gene

BACKGROUND: The proliferation and metastasis of cancers depend on angiogenesis. This property provides the feasibility for the treatment of cancer by inhibition of angiogenesis, and many angiogenic inhibitors have been demonstrated to effectively inhibit angiogenesis and consequently the growth of solid cancer. As for the newly identified angiogenesis inhibitor, arresten, some studies have found its high activity on restrainting tumor vessel. This study was to assess the anti-angiogenic activity of arresten. METHODS: The arresten gene was obtained from a healthy puerpera's placenta tissue by the reverse transcriptase-polymerase chain reaction (RT-PCR) method, and molecular cloning to prokaryotic expression plasmid pBV220 by recombination strategy. The prokaryotic expression plasmid pBV220/arr was identified by restriction enzyme digestion and sequenced. The pBV220/arr was transformed into E. coli JM109, DH5α, BL21 and BL21 (DE3) by the CaCl_2 transformation method. The arresten expression level was detected by SDS-PAGE. The expressed product was purlfled, re-naturalized and detected for its biological activity of inhibiting the angiogenesis of chorioallantoic membrane (CAM). RESULTS: The arresten gene was cloned and pBV220/arr was constructed. The arresten expression level of protein was highly increased after pBV220/arr was transformed into E. coli BL21 (DE3). SDS-PAGE showed that the expressed arresten proteins were mainly inclusion bodies and had a molecular weight of 26 kDa. The expressed arresten protein showed evident biological activities. CONCLUSIONS: The successful construction of recombinant plasmid pBV220/arr and the effective expression in E. coil have laid a foundation for further study of its anti-angiogenic function and may pave the way for future antitumor application.

Biological Mode of Action of Dimethomorph on Pseudoperonospora cubensis and Its Systemic Activity in Cucumber

Dimethomorph is a fungicide with high activity against Peronosporomycetes plant pathogens. The present study showed that dimethomorph is effective on controlling the oomycete fungal pathogen Pseudoperonospora cubensis causing downy mildew on cucumber. The fungicide did not affect zoospores discharge from sporangia of P. cubensis, but it strongly inhibited mycelial growth and sporangial production in vitro and increased lysis of zoospores. Dose of 2 mg L^-1 of dimethomorph was sufficient to inhibit mycelial growth and sporangial production of P. cubensis on leaf disks, 5 mg L^-1 was enough to lyse zoospores of P. cubensis, and 25 mg L^-1 was required to inhibit sporangial production on detached leaves. In whole plant tests, dimethomorph exhibited strong protective and curative activity. Dimethomorph when applied at a dose of 300 mg L^-1 for 1, 3, 5, 7 days before inoculation exhibited 100% efficacy on disease control. On the other hand, efficacies of 67.1 and 31.5% were obtained when the same dose of dimethomorph was applied for 1 and 3 days after inoculation, respectively. So dimethomorph had persistence effect on leaves for 7 days at least and exhibited strong protective and curative activity. Bioassay analyses showed that dimethomorph could be translocated in the xylem system, redistributed in the leaf, and penetrated from the upper surface to the lower surface of the leaf but could not be translocated in phloem system or transferred from the roots to leaves of cucumber plants in sufficient amounts for disease control. The biocharacteristics of dimethomorph make it well suitable for integration of a control programme against downy mildew disease on cucumber and as a component to delay other peronosporomycetes fungicide-resistance development.

Synthesis,Crystal Structure and Biological Activity of N-(2,6-Difluorobenzoyl)-N'-[5-(4-trifluoromethyl-phenyl)-1,3,4-thiadiazol-2-yl]ure

The title compound N-（2,6-difluorobenzoyl）-N＇-[5-（4-trifluoromethylphenyl）-1,3,4-thiadiazol-2-yl]urea（C17H9F5N4O2S,Mr = 428.34） has been synthesized by the reaction of 2-amino-5-（4-trifluoromethylphenyl）-1,3,4-thiadiazole with 2,6-difluorobenzoyl isocyanate,and its crystal structure was determined by single-crystal X-ray diffraction.The crystal belongs to monoclinic,space group P21/n with a = 10.7316（13）,b = 10.5617（13）,c = 16.037（2） ,β = 106.408（2）°,V = 1743.6（4） 3,Z = 4,Dc = 1.632 g/cm3,μ = 0.260 mm-1,F（000） = 864,the final R = 0.0599 and wR = 0.1420 for 3467 observed reflections with I〉 2σ（I）.The urea group,which adopts a planar configuration mediated by the intramolecular N-H...O hydrogen bond,is nearly coplanar with the thiadiazole and 4-trifluoromethylbenzene rings.The title compound was found to exhibit good fungicidal activity against Rhizoctonia solani and Botrytis cinerea.

Synthesis, Crystal Structure and Biological Activity of a Novel Amino Acid Salt (HGly)_4[HPMo_(12)O_(40) ]_2·22H_2O

A novel compound, (HGly) 4[HPMo 12 O 40 ] 2·22H 2O, was synthesized and characterized by means of elemental analysis, IR and X ray diffraction. The compound crystallized in a monoclinic space group Cc with a =4 0060(0 8) nm, b =1 2527(0 3) nm, c =1 9930(0 4) nm, β =96 36(3)°, V =9 940(3) nm 3, Z =2, R 1=0 0576, wR 2 =0 1746. The anti tumor activity of this compound was tested in two human tumor cell lines in vitro .

Prokaryotic Expression and Biological Activity Analysis of Human Arresten Gene

To express recombinant arresten in Escherichia coli (E.Coli) and investigate its biological activity, prokaryotic expression vector of human arresten gene was constructed by gene engineering. Human arresten gene was amplified from recombinant plasmid pGEMArr by polymerase chain reaction (PCR), and inserted into prokaryotic expression vector pRSET containing T7 promoter. Restriction analysis and DNA sequencing verified that the arresten gene was correctly cloned into the expression vector. The recombinant plasmid pRSETAt was subsequently transformed into E.coli BL21 (DE3), and the target gene was expressed under induction of IPTG. SDS-PAGE analysis revealed that the recombinant protein with a molecular weight of 29 kD (1 kD=0.992 1 ku) amounted to 29 % of the total bacterial proteins. After purification and renaturation, the recombinant protein could significantly suppress the proliferation of human umbilical vein endothelial cells (HUVECs). These results suggested that the expression of a biologically active form of human arresten in the pRSET expression system laid a foundation for further study on the mechanistic insight into arresten action on angiogenesis and the development of powerful anti-cancer drugs.

Synthesis, Crystal Structure, and Biological Activity of 4-Chlorobenzaldehyde (2-trifluoromethylTrifluoromethyl-5,6,7,8-tetrahydrobenzo[4 ,5]-thieno[2,3-d]pyrimidin-4-yl)hydrazone Monohydrate

The novel title compound 4-chlorobenzaldehyde （2-trifluoromethyl-5,6,7,8- tetrahydro- benzo[4,5]thieno[2,3-d]pyrimidin-4-yl）hydrazone monohydrate （C18H14C1F3N4S.H20, Mr = 428.86） has been synthesized by a condensation reaction of 4-chlorobenzaldehyde with （2-trifuoromethyl-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4-yl）hydrazine, and its crystal structure was determined by single-crystal X-ray diffraction. The crystal belongs to monoclinic, space group P21/c with a = 7.4252（7）, b = 26.344（2）, c = 10.3095（9） A, /3 = 109.407（2）~, V= 1902.0（3） A3, Z = 4, Dc = 1.498 g/cm^3, p = 0.356 mm-1, F（000） = 880, the final R = 0.0564 and wR = 0.1681 for 2343 observed reflections with I 〉 2o（/）. X-ray diffraction analysis reveals that the title hydrazone molecule is nearly planar except for the cyclohexene and trifluoromethyl moieties. In the crystal packing, the molecules form stacks by a three-dimensional framework, which results from intermolecular N（3）-H（3）...O（1）, O（1）-H（1B）...N（2）, O（1）- H（1B）...N（4） and O（1）-H（1A）...F（1） hydrogen bonds via water molecules together with π-π stacking interactions. Molecular geometry of the title compound in the ground state optimized by B3LYP functional with 6-311G＊＊ basis sets indicates that the calculations are in agreement with the experimental data. The preliminary bioassay suggested that the title compound exhibits relatively good fungicidal activity against Fusarium oxysporium fsp.vasinfectum and Dothiorella gregaria.

Synthesis,Crystal Structure and Biological Activity of 2-(1-(3-Bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carbonyl)piperidin-4-yl)-N-isopropyl-1,3-thiazole-4-carboxamide

The title compound 2-（1-（3-bromo-1-（3-chloropyridin-2-yl）-1H-pyrazole-5-carbonyl）piperidin-4-yl）-N-isopropylthiazole-4-carboxamide（C21H22Br Cl N6O2 S,Mr = 536.04） has been synthesized,and its structure was characterized by IR spectra,1H-NMR,13C-NMR,EA,and single-crystal X-ray diffraction.The crystal of the title compound belongs to monoclinic system,space group P/c with a = 15.146（3）,b = 11.573（2）,c = 26.937（5） A,β = 103.64（3）°,V = 1839.0（6） A^3,Z = 4,Dc = 1.557 g/cm^3,μ（Mo Ka） = 0.71073 mm^-1,F（000） = 2192,R = 0.0601 and w R = 0.1392.There exist one intramolecular hydrogen bond at N–H···N and four intermolecular weak interactions at O（2）···H（1）,Cl（1）···H（12）,O（1）···Cl（1） and S（1）···O（2）.Bioassay results indicated that the title compound had good fungicidal and antiviral activities against tobacco mosaic virus.

Synthesis, Crystal Structure and Biological Activity of 2-(3,4-Dichloroisothiazol-5-yl)-4-(trifluoromethyl)-4,5-dihydrothiazol-4-yl-3-methylbenzoate

The title compound diethyl 2-（3,4-dichloroisothiazol-5-yl）-4-（trifluoromethyl）-4,5- dihydrothiazol-4-yl-3-methylbenzoate （C15H9C12F3N202S2, Mr = 441.26） was prepared from methyl 3,4-dichloroisothiazole-5-carboxylate as the starting material by four steps of reaction. Its structure was characterized by IR, 1H-NMR, 13C-NMR, EA and single-crystal X-ray diffraction. The crystal of the title compound belongs to the monoclinic system, space group P2dc with a = 8.8437（18）, b = 16.128（3）, c = 12.305（3） A, β = 91.68（3）°, V= 1754.4（6） A3, Z = 4, Dc = 1.671 g/cm3,μ（MoKa） = 0,71073 mm^-1, F（000） = 888, R = 0.0384 and wR = 0.0778. Weak π-π interactions occur between the isothiazole rings and phenyl rings of adjacent molecules to form a one-dimensional chain and stabilize the crystal structure. Bioassay indicates that the title compound has good activity against the fungi and TMV tested.

Synthesis,Crystal Structure and Biological Activity of N-cyanosulfoximine Derivative Containing 1,2,3-Thiadiazole

The title compound N-cyanosulfoximine derivative containing 1,2,3-thiadiazole （C6HsN4OS2, Mr = 216.28） has been synthesized using 4-（chloromethyl）-5-methyl-1,2,3-thiadiazole as the starting material, and its structure was characterized by IR, 1H NMR, HRMS, elemental analysis and single-crystal X-ray diffraction. The crystal of the title compound belongs to orthorhombic, space group Pna21 with a = 14.730（6）, b = 5.478（2）, c = 22.619（9） A, Z = 8, V = 1825.0（13） A3, Dc = 1.574 g/cm3,/a = 0.547 mm-1, F（000） = 896, R = 0.0767 and wR （I〉 2o（/）） = 0.2064. X-ray analysis indicates that in this crystal double enantiomers are found as the basically asymmetrical unit and interactions between S（1）...N（3）, S（3）...N（4） and S（3）...N（7） are observed. This kind of interactions extends the molecules into a one-dimensional double chain. The preliminary biological test showed that the title compound had insecticidal activity against Myzus persicae in a certain degree and also presented moderate potential bioactivity against tobacco mosaic virus （TMV）.

Synthesis,Crystal Structure and Biological Activity of 2-(Anthracen-9-yl)-5-p-tolyl-1,3,4-oxadiazole

A novel compound,2-（anthracen-9-yl）-5-p-tolyl-1,3,4-oxadiazole（C23H16N2O）,has been synthesized by the condensation of 4-methylbenzohydrazide and anthracene-9-carbaldehyde in an ethanol solution with chloramine-T.The compound was characterized by 1H-NMR,13C-NMR,MS and single-crystal X-ray diffraction.The crystal belongs to the triclinic system,space group P with a = 7.7817（4）,b = 8.8544（5）,c = 12.4726（8） ,β = 92.8520（10）°,Z = 2,V = 826.58（8） 3,Dc = 1.352 g/cm3,Mr = 336.38,λ（MoKα） = 0.71073 ,μ = 0.084 mm-1,F（000） = 352,R = 0.0381 and wR = 0.1099.The dihedral angle between anthracene skeleton and phenyl ring is 64.19°.A total of 6354 unique reflections were collected,of which 3172 with I 〉 2σ（I） were observed.X-ray analysis indicated an offset face-to-face π-π stacking interaction between anthracene skeletons and an offset face-to-face π-π stacking interaction between phenyl ring planes.The novel compound molecules are connected through the offset face-to-face π-π stacking interactions to generate a three-dimensional network.The preliminary bioassay results showed that the novel compound exhibited significant insect growth inhibitory activity against Spodoptera litura Fabricius larvae.

Synthesis, Characterization and Biological Activity of Transition Metals with Schiff Base Derived from Adamantaneamineand o-Vanillin

Five new solid complexes were synthesized about transition metals with Schiff base（ L, C18H23NO2 ） derived from adamantaneamine and o-vanillin, and characterized by elemental analysis, molar conductance, infrared spectra, UV-vis spectra, thermal analysis. Their chemical formula are [ML2]（ClO4）2 （ M= Mn, Co, Ni, Cu, Zn）, and the coordination numbers are four, The antibacterial activity of Schiff base ligand and its complexes was studied.

Synthesis,Crystal Structure and Biological Activity of N-tert-butyl-N-(4-methyl-1,2,3-thiadiazole)-5-yl-N’-(4-methyl-1,2,3-thiadiazole)-5-formyl-N’-3,5-dichloropyridin-2-yl-diacylhydrazine

The title compound N-tert-butyl-N-（4-methyl-1,2,3-thiadiazole）-5-yl-N＇-（4-me-thyl-1,2,3-thiadiazole）-5-formyl-N＇-3,5-dichloropyrid-2-yl-diacylhydrazines （C18H17Cl2N7O3S2, Mr = 514.41） has been synthesized by the reaction of N-tert-butyl-N＇-3,6-dichloropyridine-2-formyl hydrazine with 4-methyl-1,2,3-thiadiazole-5-carbonyl chloride and triethylamine, and its structure was characterized by 1H NMR, HR MS, and single-crystal X-ray diffraction. The crystal of the title compound belongs to monoclinic, space group C2/c with a = 27.726（8）, b = 11.045（3）, c = 14.507（4）A, β = 96.758（4）°, Z = 8, V = 4412（2） A^3, Dc = 1.549 g/cm^3, μ = 0.521 mm^-1, F（000） = 2112, R = 0.0405 and wR = 0.1153. X-ray analysis indicates that all rings are non-planar in this molecule. The bioassay results indicate that both the title compound and the positive control RH-5992 have weak fungicide activities, while the title compound has good insecticidal activity against Plutella xylostella L. and no insecticidal activity against Culex pipiens pallens.

Synthesis,Crystal Structure and Biological Activity of a Planar Copper Complex Derived from S-benzyldithiocarbazate

A planar transition metal complex Cu（L）2 （L = （E）-benzyl-2-（4-nitrobenzylidene）-hydrazinecarbodithioate） has been prepared and determined by X-ray single-crystal diffraction. The crystal belongs to the monoclinic system,space group P21/c with a = 6.7101（11）,b = 16.952（3）,c = 13.962（3） ,β = 92.458（4）°,V = 1586.7（5） 3,Z = 4,Mr = 724.33,Dc = 1.516 g·m-3,μ = 0.998 mm-1,F（000） = 742,S = 1.021,R = 0.0634 and wR = 0.1077 for 813 observed reflections with Ⅰ〉 2σ（Ⅰ） and 205 parameters. In the molecular structure of the title complex,the copper atom exhibits a slightly distorted square-planar geometry in which the basal plane is defined by two N and two S atoms from two bidentate ligands. The complex was evaluated for its antitumor activity against two kinds of cell lines （MKN45 and HepG2） by MTT method. The preliminary bioassay indicates that the complex exhibits weak antitumor activity.

Synthesis, Crystal Structure and Biological Activity of Diethyl 1,4-dihydro-2,6-dimethyl-4-(4-methyl-1,2,3-thiadi azol-5-yl)pyridine-3,5-dicarboxylate

The title compound diethyl 1,4-dihydro-2,6-dimethyl-4-（4-methyl-1,2,3-thiadiazol- 5-yl） pyridine-3,5-dicarboxylate （C16H21N3O4S, Mr = 351.42） was prepared by the Hantszch reaction with 4-methyl-1,2,3-thiadiazole-5-formaldehyde, ethyl acetoacetate and ammonium acetate in the presence of aluminum chloride in alcohol, and its structure was characterized by IR spectra, 1H-NMR, EA, and single-crystal X-ray diffraction. The crystal of the title compound belongs to monoclinic system, space group P21/n with α= 11.300（2）, b = 12.771（3）, c = 12.826（3） ？, β = 96.55（3）o, V = 1839.0（6） ？3, Z = 4, Dc = 1.296 g/cm3, μ（MoKa） = 0.71073 mm-1, F（000） = 744, R = 0.0981 and wR = 0.1994. X-ray diffraction result shows that the torsion angles of N（1）–C（2）– C（3）–C（4） and C（2）–C（3）–C（4）–C（8） are 178.9（3）° and –130.3（3）°, respectively. All rings in the title compound are non-planar. The bioassay results indicate that the title compound has good fungicidal activity, good antivirus activity against tobacco mosaic virus and certain extent of insecticidal activity against Mythimna separata.

Synthesis,Crystal,Computational Study and Biological Activity of N-(1-(2,4-Dichlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-4-(N,N-dipropylsulfamoyl)benzamide

The title compound N-（1-（2,4-dichlorophenyl）-1 H-pyrazolo[3,4-d]pyrimidin-4-yl）-4-（N,N-dipropylsulfamoyl）benzamide was synthesized by the condensation of 4-（dipropylsulfamoyl）benzoic acid with 1-（2,4-dichlorophenyl）-1 H-pyrazolo[3,4-d]pyrimidin-4-amine. This intermediate was prepared from 5-amino-1-（2,4-dichlorophenyl）-1 H-pyrazole-4-carbonitrile by the condensation with triethyl orthoformate and then cyclisation with ammonium hydroxide solution in tetrahydrofuran at room temperature. The crystal structure of the title compound was determined. The optimized geometric bond lengths and bond angles obtained by using density functional theory（DFT） have been compared with X-ray diffraction values. In addition, the preliminary biological test showed that the compound possesses distinct effective inhibition on the proliferation of some cancer cell lines.

Synthesis and Biological Activity of N-[N'-(4,5,6-Trisubstitued pyrimidin-2-yl)acetylureido] Benzoic Sulfimide Derivatives

Fourteen N'- (4,5,6-Trisubstitued pyrimidin-2-y1) -2-chloroacetylureas and fourteen N-[N'- (4,5,6-trisubstitued pyrimidin-2-yl) acetylureido] benzoic sulfimide derivatives were synthesized. Among them twenty-seven are new compounds and their structures have been confirmed by 1HNMR, IR, MS and elemental analysis. The preliminary biological tests showed that some of the target compounds have excellent inhibitory activities against barnyard grass and rape, and the others have a good regulating activity for plant growth.

Synthesis, Crystal Structure and Biological Activity of N-(tert-butyl)-N'-(2-(4-chlorophenyl)acetyl)-5-methyl-1,2,3-thiadiazole-4-carbohydrazide

The title compound N-（tert-butyl）-N＇-（2-（4-chlorophenyl）acetyl）-5-methyl-1,2,3-thiadiazole-4-carbohydrazide （C16H19ClN4NaO2S, Mr = 366.86） has been synthesized, and its structure was characterized by IR, 1H NMR, H RMS and single-crystal X-ray diffraction. The crystal of the title compound belongs to triclinic, space group Pī with a = 8.464（2）, b = 10.192（2）, c = 11.757（2）, α = 68.48（3）, β = 76.31（3）, γ = 80.86（3）°, Z = 2, V = 2024.6（10） 3, Dc = 1.333 g/cm3, μ = 0.339 mm-1, F（000） = 384, R = 0.0450 and wR （Ⅰ 〉 2σ（Ⅰ）） = 0.1234. X-ray analysis indicates one N-H…N intermolecular hydrogen bond and no π-π stacking interactions are observed in this crystal structure. The preliminary biological test shows that the title compound has fungicidal activity and antivirus activities against tobacco mosaic virus.