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A pair of new oxindole alkaloids, named macrophyllines C (1) and D (2), together with two known oxindole alkaloids isorhynchophylline (3) and corynoxine (4) were isolated from Uncaria macrophylla. Their structures were elucidated based on detailed spectroscopic analysis and by comparison with literature data. In addition, all the isolates were tested for their anti-HIV activities and cytotoxicities in C8166 cells and compounds 2-4 showed weak anti-HIV activities with EC50 values of 11.31 ± 3.29 μM, 18.77 ± 6.14 μM and 30.02 ± 3.73 μM, respectively.

Background: Cuscutae Semen (CS) is reported to show a hepatoprotective effect. Chlorogenic acid, hyperoside and astragalin are three major biologically active components from CS. Objective: A sensitive method based on ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was developed and validated to quantify the three components in rat plasma and was successfully used to study pharmacokinetics in liver injury rats. Methods: Plasma samples were prepared with protein precipitation by acetonitrile. Chromatographic separation was achieved on ACQUITY-XBridge BEH C18 column with gradient elution using the mobile phase containing 0.05% formic acid in water (A) and acetonitrile (B). The three components were quantified using Electrospray Ionization (ESI) source in the negative multiple Reaction Monitoring (MRM) mode. Results: Calibration curves of each analyte showed good linearity with correlation coefficients over 0.99. Accuracies (RE%) and precisions (RSD%) were within 15%. The method was stable. Recovery of the target compounds in plasma samples ranged from 87.00% to 102.29%. No matrix effect was found to influence the quantitative method. Conclusion: The UPLC-MS/MS method met the acceptance criteria and was successfully applied to the simultaneous determination of chlorogenic acid, hyperoside and astragalin in rat plasma for the first time. It is suitable for pharmacokinetic application in liver injury rats. It provides the foundation for further development and utilization of the hepatoprotective effect of cuscutae semen.

A series of 2-(((5-akly/aryl-1H-pyrazol-3-yl)methyl)thio)-5-alkyl-6-(cyclohexylmethyl)-pyrimidin-4(3H)-ones were synthesized and their anti-HIV-1 activities were evaluated. Most of these compounds were highly active against wild-type (WT) HIV-1 strain (IIIB) with EC50 values in the range of 0.0038–0.4759 μmol/L. Among those compounds, I-11 had an EC50 value of 3.8 nmol/L and SI (selectivity index) of up to 25,468 indicating excellent activity against WT HIV-1. In vitro anti-HIV-1 activity and resistance profile studies suggested that compounds I-11 and I-12 displayed potential anti-HIV-1 activity against laboratory adapted strains and primary isolated strains including different subtypes and tropism strains (EC50s range from 4.3 to 63.6 nmol/L and 18.9–219.3 nmol/L, respectively). On the other hand, it was observed that those two compounds were less effective with EC50 values of 2.77 and 4.87 μmol/L for HIV-1A17 (K103N + Y181C). The activity against reverse transcriptase (RT) was also evaluated for those compounds. Both I-11 and I-12 obtained sub-micromolar IC50 values showing their potential in RT inhibition. The pharmacokinetics examination in rats indicated that compound I-11 has acceptable pharmacokinetic properties and bioavailability. Preliminary structure–activity relationships and molecular modeling studies were also discussed. Key words: HIV-1, NNRTIs, S-DABOs, Antiviral activity, SAR, Molecular modeling

Eight new sulfur-bridged pyranonaphthoquinone (PNQ) dimers, naquihexcins C-J (1-8), a new PNQ monomer, naquihexcin K (10), and three known analogues (9, 11, and 12) were isolated from Streptomyces sp. KIB3133. The new structures were elucidated by interpretation of spectroscopic data. Dimer 4 was synthesized via a cascade SN2 reactions between two monomers and sodium sulfide, an approach motivated by the proposed biosynthetic pathway of dimeric pyranonaphthoquinones. Naquihexcin E (3) exhibited moderate HIV-1 inhibitory activity. Naquihexcins C (1), E (3), and I (7) showed inhibitory effects against two tumor cell lines (HL-60 and MCF-7) with IC50 values ranging from 1.4 to 16.1 μM.

CaAl-LDH has its special application such as crystal seeds in mortar to improve the early strength. But it is hard to prepare pure phase CaAl-LDH by traditional coprecipitation method and to avoid the byproducts like aluminum hydroxide and calcium carbonate. In this paper, pure phase Ca2Al-LDH nanosheets could be obtained by controlling Rb/s (mole ratio between base and salt solution) of 1.5 using a T-type microchannel reactor. The so-obtained Ca2Al-LDH nanosheets had a two-dimensional structure with lateral size of 30–100 nm and thickness of 2–3 nm. By correlating characterizations of pH titration with zeta potential, detailed information was obtained during the formation process of LDH prepared by the microchannel reactor and traditional coprecipitation, respectively. Tracking zeta potential of LDH prepared by microchannel reactor revealed that Ca2Al-LDH nanosheets were formed through one-step reaction between salts and base solutions in microspace. While for the case of traditional coprecipitation method, results revealed LDH formed through three stages: Al(OH)3 formation, mixing of trace Ca2+ into Al(OH)3, and their transformation into LDH. As a hardening accelerator for mortar, a dosage of only 0.35 wt % Ca2Al-LDH nanosheets prepared using microchannel reactor exhibited greatly enhanced performances in both the early tensile strength and compressive strength of the mortar, which increased by 62% and 36%, respectively.

Naturally abundant quinones are important molecules, which play essential roles in various biological processes due to their reduction potential. In contrast to their universality, the investigation of reactions between quinones and proteins remains sparse. Herein, we report the development of a convenient strategy to protein modification via a biomimetic quinone-mediated oxidation at the N-terminus. By exploiting unique reactivity of an ortho-quinone reagent, the α-amine of protein N-terminus is oxidized to generate aldo or keto handle for orthogonal conjugation. The applications have been demonstrated using a range of proteins, including myoglobin, ubiquitin and small ubiquitin-related modifier 2 (SUMO2). The effect of this method is further highlighted via the preparation of a series of 17 macrophage inflammatory protein 1β (MIP-1β) analogs, followed by preliminary anti-HIV activity and cell viability assays, respectively. This method offers an efficient and complementary approach to existing strategies for N-terminal modification of proteins., Methods for selective modification of the N-terminus of proteins are of high interest, but mostly require specific amino acid residues. Here, the authors report a selective and fast method for N-terminal modification of proteins based on quinone-mediated oxidation of the alpha-amine to aldehyde or ketone, and apply it to diverse proteins.

In order to discover and develop the new HIV-1 NNRTIs, a series of 5-alkyl-6-(benzo[d][1,3]dioxol-5-ylalkyl)-2-mercaptopyrimidin-4(3H)-ones was synthesized and screened for their in vitro cytotoxicity against HIV-1. Most of the compounds we synthetized showed high activity against wild-type HIV-1 strain (IIIB) while IC50 values are in the range of 0.06–12.95 μM. Among them, the most active HIV-1 inhibitor was compound 6-(benzo[d][1,3]dioxol-5-ylmethyl)-5-ethyl-2-((2-(4-hydroxyphenyl)-2-oxoethyl)thio)pyrimidin-4(3H)-one (5b), which exhibited similar HIV-1 inhibitory potency (IC50 = 0.06 μM, CC50 = 96.23 μM) compared with nevirapine (IC50 = 0.04 μM, CC50 >200 μM) and most of compounds exhibited submicromolar IC50 values indicating they were specific RT inhibitors. The compounds 5b, 6-(benzo[d] [1,3]dioxol-5-yl)-5-ethyl-2-((2-(4-hydroxyphenyl)-2-oxoethyl)thio)pyrimidin-4(3H)-one (5c) and 4-(2-((4-(benzo[d][1,3]dioxol-5-ylmethyl)-5-ethyl-6-oxo-1,6-dihydropyrimidin-2-yl)thio)acetyl)phenylbenzo[d][1,3]dioxole-5-carboxylate (5r) were selected for further study. It was found that all of them had little toxicity to peripheral blood mononuclear cell (PBMC), and had a good inhibitory effect on the replication of HIV-1 protease inhibitor resistant strains, fusion inhibitor resistant strains and nucleosides reverse transcriptase inhibitor resistant strains, as well as on clinical isolates. Besides, compound 5b and 5c showed inhibition of HIV-1 RT RNA-dependent DNA polymerization activity and DNA-dependent DNA polymerization activity, while compound 5r only showed inhibition of HIV DNA-dependent DNA polymerization activity, which was different from classical reverse transcriptase inhibitors. Our study which offered the preliminary structure-activity relationships and modeling studies of these new compounds has provided the valuable avenues for future molecular optimization.

Mechano-optical materials are of great importance in smart window, security, display and camouflages. However, fabricating ultrasensitive optical devices with wide range still remains great challenging. Inspired from the fast tail amputation of gecko utilizing weak non-ossificated septum, herein, we report an ultrasensitive mechano-optical membrane based on weak dye layer between silica nanoparticles and soft polydimethylsiloxane matrix. Owing to the light scattering from dye-induced internal cavitation, the transmittance dramatically decreases by ～44% at initial small strain level (15%) and a high sensitivity (S > 2) is kept within an abroad strain range (0～35%). Moreover, a high total transmittance tuning range of ～75% is exhibited. Simulation and experimental monitoring demonstrate the effective weakening of interface energy. The potential applications in smart window, sensor, anti-counterfeiting also exhibit the multifunctionality of our smart membranes. This facile and low-cost approach enables the large-scale production and applications of mechano-optical membranes and this interface design provides a general way to develop ultrasensitive mechano-responsive materials.

Both HIV and DENV are serious threats to human life, health and social economy today. So far, no vaccine for either HIV or DENV has been developed successfully. The research on anti-HIV or DENV drugs is still of great significance. In this study we developed a series of novel 2-Aryl-1H-pyrazole-S-DABOs with C6-strucutral optimizations as potent NNRTIs, among which, 8 compounds had low cytotoxicity and EC50 values in the range of 0.0508 ∼ 0.0966 μM, and their selectivity index was SI > 1415 ∼ 3940. In particular, two compounds 4a and 4b were identified to have good inhibitory effects on DENV of four serotypes. The EC50 of compound 4a and 4b against DENV-II (13.2 μM and 9.23 μM, respectively) were better than that of the positive control ribavirin (EC50 = 40.78 μM). In addition, the effect of C-6 substituents on the anti-HIV or anti-DENV activity of these compounds was also discussed.

ZIF-8 nanoparticle-doped polyvinyl alcohol (PVA)-S-MC films were prepared via casting method. The effect of different concentrations of ZIF-8 on the physical properties and structural characterization of the films were investigated. The results indicated that ZIF-8 could increase the water resistance and mechanical property of the membrane. Through FTIR, scanning electron microscope (SEM), atomic force microscope (AFM), and TGA analysis, it was found that ZIF-8 changed the phenomenon of macromolecule agglomeration and improved the thermal stability of the membrane. The breathable behavior of the film was also studied through oxygen permeability and water vapor permeability analysis. The result illustrated that the breathability of the film improved significantly by adding ZIF-8. The maximum reached when the weight ratio of ZIF-8 was 0.01 wt %. The property expands the application of PVA/starch blend film in the postharvest technology of fruits and vegetables.

Among the perovskite-type oxides with symmetrical structure applied in oxygen permeable membranes, cubic phase structure is the most favorable for oxygen permeation.In order to stabilize the cubic perovskite structure of BaFeO3-δ material at room temperature, iron was partially substituted by praseodymium.BaFe1-yPryO3-δ powders were synthesized by a solid state reaction method, and sintered samples were prepared from the synthesized BaFe1-yPryO3-δ powders.X-ray diffraction results reveal that the BaFe1-yPryO3-δ samples remain cubic structure at praseodymium substitution amount of y=0.05, 0.075, 0.1.Scanning electron microscope observation indicates that the sintered samples contain only a small amount of enclosed pores and the grain size of BaFe1-yPryO3-δ increase monotonically with the increase of the praseodymium doping amount, praseodymium doping promotes the grain size growth.Tests of electrical conductivity and oxygen permeation flux show that praseodymium doping improves the conduction properties of BaFe1-yPryO3-δ and BaFe0.9Pr0.1O3-δ composition has an electrical conductivity of 6.5 S/cm and an oxygen permeation of 1.112 mL/(cm2·min) at 900 ℃, respectively.High temperature XRD investigation shows that the crystal structure of BaFe0.975Pr0.025O3-δ membrane completely transform to cubic phase at 700 ℃.The present test results have shown that partially substitution of Fe by praseodymium in BaFeO3 can stabilize the cubic structure and improve the properties.

Background The human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) has always been a global health threat and leading cause of deaths. However, due to the emergence of drug-resistant HIV, an inevitable consequence of increasing use of antiretroviral drugs posed a major threat to antiretroviral therapy success. Objective The discovery of anti-HIV-1 agents will be used for the effective treatment of HIV/AIDS. Method In continuation of our program aimed to discover anti-HIV-1 agents, twelve matrine derivatives, such as 14-formyl-15-aryloxy/methoxymatrines (3a-j) and 14-aryloxymethylidenylmatrines (3k,l), were semi-prepared from matrine, and evaluated against HIV-1 IIIB replication in acutely infected C8166 cells in vitro. Results Among them, compound 3j showed the most potent anti-HIV-1 activity with EC50 and therapeutic index (TI) values of 1.79 µg/mL, and 98.2, respectively. Conclusion It has been demonstrated that the positions of methyl on the phenyl ring and 14- formylmatrine-15-oxy on the naphthyl ring were very important for the activity. It will lay the foundation for further structural modification and application of matrines as HIV-1 inhibitors.

A promising approach for the development of effective full-color displays is to combine blue microLEDs (μLEDs) with color conversion layers. Perovskite nanocrystals (PNCs) are notable for their tolerance to defects and provide excellent photoluminescence quantum yields and high color purity compared to metal chalcogenide quantum dots. The stability of PNCs in ambient conditions and under exposure to blue light can be improved using a SiO 2 coating. This study proposes a device that could be used for both display and visible light communication (VLC) applications. The semipolar blue μLED array fabricated in this study shows a negligible wavelength shift, indicating a significant reduction in the quantum confined Stark effect. Owing to its shorter carrier lifetime, the semipolar μLED array exhibits an impressive peak 3 dB bandwidth of 655 MHz and a data transmission rate of 1.2 Gb/s corresponding to an injection current of 200 mA. The PNC–μLED device assembled from a semipolar μLED array with PNCs demonstrates high color stability and wide color-gamut features, achieving 127.23% and 95.00% of the National Television Standards Committee standard and Rec. 2020 on the CIE 1931 color diagram, respectively. These results suggest that the proposed PNC–μLED device is suitable for both display-related and VLC applications.

In the present study, flavor profiles of Chinese spiced beef in the cooking process were comparatively analyzed by electronic nose, gas chromatography–mass spectrometry (GC–MS) with a thermal desorption system (TDS), and solid-phase microextraction (SPME). A total of 82 volatile compounds were identified, and 3-methyl-butanal, pentanal, hexanal, ρ-xylene, heptanal, limonene, terpinene, octanal, linalool, 4-terpinenol, α-terpineol, and ( E )-anethole were identified as the characteristic flavor compounds in Chinese spiced beef. Variation in the content of volatile components produced by different cooking processes was observed. In general, a cooking time of 4 h resulted in optimal flavor quality and stability. Results indicated that the electronic nose could profile and rapidly distinguish variation among different cooking time. The volatile profiling by TDS-GC–MS and responses from the electronic nose, in combination with multivariate statistical analysis, are a promising tool for control the cooking process of spiced beef.

Pathogenesis-related (PR) proteins are generally involved in the defense of plants and are important contributors in the disease resistance of plants. Among the 17 PRs that are currently recognized, the PR4 family of proteins is divided into two classes and features a conserved barwin domain. In this study, we isolated two Class II PR4s from the oriental hybrid lily cultivar Sorbonne using the rapid amplification of the cDNA ends (RACE) method, and designated these two PR4s LhSorPR4a and LhSorPR4b. LhSorPR4a and LhSorPR4b were 627 and 617 bp in length, respectively, and encoded two corresponding PR4s of 141 and 143 amino acids. These deciphered LhSorPR4a and LhSorPR4b protein sequences shared a sequence similarity of 90.7%, but their theoretical isoelectric points were distinctively different (7.74 and 4.08, respectively). The three-dimensional structures of LhSorPR4a and LhSorPR4b predicted by homology modeling showed high similarity to their corresponding papaya barwin-like protein template. Analysis of expression by qPCR revealed that both LhSorPR4a and LhSorPR4b were responsive to methyl jasmonate and ethephon treatments. The LhSorPR4b expression was also significantly induced by sodium salicylate (SS); however, LhSorPR4a was unresponsive to the SS treatment. Both LhSorPR4a and LhSorPR4b were expressed in Escherichia coli (E. coli) and successfully purified. The PR4s characterized in this study (LhSorPR4a and LhSorPR4b) are the first two PR4 family genes isolated from the Lilium genus, and they could therefore play an important role in lily disease resistance.

Background: Although a number of agents can achieve high response in acquired immunodeficiency syndrome (AIDS) patients, safer and more active HIV inhibitors are still needed for the growing number of patients infected with resistant HIV virus strains. GW678248 is one of the most potent benzophenone derivatives, exhibiting high potency against a panel of HIV- 1 virus (wild-type, K103N mutant, Y181C, etc.) at 1 nmol/L concentrations. However, the safety issues associated with rash and liver metabolic enzymes ultimately led to discontinue its further deve-lopment. As a continuation of our structural modifications on this template, in this manuscript, a new series of benzophenones are described as potential HIV inhibitors. Methods: All the title molecules were synthesized according to the routes in Scheme 1 and Scheme 2, and were tested for anti-HIV-1 activity using the MTT method. In the molecular simulation, the docking program of AutoDock 4.0.1 in parallel with the default parameters were used. Results: A series of novel benzophenone derivatives (BPs) with nanomolar anti-HIV-1 activity were identified. Of these inhibitors, analogue 10i (EC50 = 2.9 nmol/L), the most active inhibitor, was comparable to the lead compound GW678248 in inhibiting the wild-type HIV-1 virus. Additionally, analogue 13b, which not only exhibited strong inhibitory activity against the HIV-1 virus (EC50 = 4.2 nmol/L), but also has very low cytotoxicity with a TI value of more than 219178.1 was also discovered. Conclusion: This study led to the identification of a series of benzophenone derivatives with nanomolar level of anti-HIV-1 activity. Analogues 10i and 13b, with low cytotoxicity along with high activity are worthy of further development.

The development of pure-phase semi-conducting buffering materials as the substitution of conventional cadmium sulfide (CdS) is extremely important for the large-scale application of solar cells. Herein, we demonstrated a facile approach to deposit pure-phase indium sulfide (In2S3) thin films on the indium tin oxide (ITO) substrates by sulfurizing the co-electrodeposited In2S3 films. The effect of sulfurization temperatures (200–550 °C) on the surface morphologies, crystal structures, optical and electrical properties of In2S3 films was investigated. The results showed that the highly-oriented pure β-In2S3 thin films were obtained as the sulfurization temperature exceeded 250 °C. The obtained β-In2S3 films possessed a relatively ideal S/In atomic ratio and a continuous and densely packed surface feature. The optical band gaps of the β-In2S3 films have been determined in the range of 1.93 ± 0.01–2.06 ± 0.01 eV, which can be controlled by adjusting the sulfurization temperature. The electrical properties tests demonstrated that the pure β-In2S3 films obtained by sulfurizing at 550 °C exhibited the characteristic n-type semiconductors with a low electrical resistivity of 38.8 Ω cm, a carrier concentration of 3.8 × 1015 cm−3 and a carrier mobility of 42.3 cm2 V−1 s−1. This facile synthetic route is promising for the preparation of pure-phase In2S3 films, and then gives the guidance for future design and synthesis of other metal sulfide films for high-performance solar cells.

Antiretroviral therapy (ART) can effectively suppress human immunodeficiency virus type 1 (HIV-1) replication and limit the disease progression. However, ART is unable to eradicate the virus, and the requirement for lifelong treatment may have side effects and poses a risk of the development of resistance. New approaches to prevent and treat HIV-1 infection should therefore be developed. HIV-1 capsid (CA) protein is an unexploited but attractive target for antiviral drug development. The hydrophobic cavity of C-terminal domain of CA (CA CTD) has been validated as a potential target for antiviral drugs. Binding of compounds to this conserved nonpolar groove in CA CTD allosterically disrupts the CA assembly. In the study described here, we screened 2,080 natural products to identify potential antiviral agents for further development to combat HIV-1 infection. From the primary screen at a fixed concentration of 50 µM, 16 compounds were found to be effective against this target. Then, 6 compounds observed in the primary screen were confirmed in dose-response experiments. Finally, the 6 selected compounds were tested against HIV-1-induced cytopathic effects. Two compounds showed inhibitory effect on HIV-1 replication, and the most active one, rubranol, inhibited viral replication at a moderate micromolar concentration (EC50 = 15.85 μM). The binding mode of rubranol and hirsutanonol to CA CTD were analyzed by molecular docking respectively, providing insight for design of drug targeting HIV-1 capsid. The research reports, for the first time, identification of natural products that showed potential as anti-HIV-1 agents by targeting conserved hydrophobic cavity of HIV-1 CA CTD.

Background Plant glycerol-3-phosphate dehydrogenase (GPDH) catalyzes the reduction of dihydroxyacetone phosphate (DHAP) to produce glycerol-3-phosphate (G-3-P), and plays a key role in glycerolipid metabolism as well as stress responses. Results In this study, we report the cloning, enzymatic and physiological characterization of a cytosolic NAD+-dependent GPDH from maize. The prokaryotic expression of ZmGPDH1 in E.coli showed that the enzyme encoded by ZmGPDH1 was capable of catalyzing the reduction of DHAP in the presence of NADH. The functional complementation analysis revealed that ZmGPDH1 was able to restore the production of glycerol-3-phosphate and glycerol in AtGPDHc-deficient mutants. Furthermore, overexpression of ZmGPDH1 remarkably enhanced the tolerance of Arabidopsis to salinity/osmotic stress by enhancing the glycerol production, the antioxidant enzymes activities (SOD, CAT, APX) and by maintaining the cellular redox homeostasis (NADH/NAD+, ASA/DHA, GSH/GSSG). ZmGPDH1 OE Arabidopsis plants also exhibited reduced leaf water loss and stomatal aperture under salt and osmotic stresses. Quantitative real-time RT-PCR analyses revealed that overexpression of ZmGPDH1 promoted the transcripts accumulation of genes involved in cellular redox homeostasis and ROS-scavenging system. Conclusions Together, these data suggested that ZmGPDH1 is involved in conferring salinity and osmotic tolerance in Arabidopsis through modulation of glycerol synthesis, stomatal closure, cellular redox and ROS homeostasis. Electronic supplementary material The online version of this article (10.1186/s12870-018-1597-6) contains supplementary material, which is available to authorized users.

A compact accelerator-driven deuterium–deuterium neutron source using a heavy water jet target is under development at the Institute of Nuclear Physics and Chemistry. The neutrons are generated by bombarding a 0.45 mm-thick heavy water jet target with 11 MeV/0.33 mA deuterons. The angular neutron yield between 10–14 MeV is about 6.5 × 1011 n/s/sr at 0 degree. The D(d,n)3 reaction is adopted to generate high energy neutrons for its relatively high angular neutron yield, outstanding forward directional characteristics and convenient for obtaining, operating and maintaining. To minimize the length of the neutron source, an IH-DTL is adopted for its high accelerating gradient, low input energy and low power consumption. The design of the deuteron accelerator, consisting of a deuteron injector, a four vane Radio-Frequency Quadrupole (RFQ) and an Interdigital H-mode Drift Tube Linac (IH-DTL), is introduced in this paper. The heavy water jet target, which suffers high deuteron beam power density, is also introduced in this paper.

As our ongoing work on research of gelatinase inhibitors, an array of hydrazide-containing peptidomimetic derivatives bearing quinoxalinone as well as spiro-heterocyclic backbones were designed, synthesized, and assayed for their in vitro enzymatic inhibitory effects. The results demonstrated that both the quinoxalinone (series I and II) and 1,4-dithia-7-azaspiro[4,4]nonane-based hydrazide peptidomimetics (series III) displayed remarkably selectivity towards gelatinase A as compared to APN, with IC50 values in the micromole range. Structure-activity relationships were herein briefly discussed. Given evidences have validated that gelatinase inhibition may be contributable to the therapy of HIV-1 infection, all the target compounds were also submitted to the preliminary in vitro anti-HIV-1 evaluation. It resulted that gelatinase inhibition really has positive correlation with anti-HIV-1 activity, especially compounds 4m and 7h, which gave enhanced gelatinase inhibition in comparison with the positive control LY52, and also decent anti-HIV-1 potencies. The FlexX docking results provided a straightforward insight into the binding pattern between inhibitors and gelatinase, as well as the selective inhibition towards gelatinase over APN. Collectively, our research encouraged potent gelatinase inhibitors might be used in the development of anti-HIV-1 agents. And else, compounds 4m and 7h might be promising candidates to be considered for further chemical optimization.

CC-chemokine receptor 5 (CCR5) is an attractive target for preventing the entry of human immunodeficiency virus 1 (HIV-1) into human host cells. Maraviroc is the only CCR5 antagonist, and it was marketed in 2007. To overcome the shortcomings of maraviroc, structure-based drug design was performed to minimize CYP450 inhibition and to enhance anti-HIV potency and bioavailability. Thirty-four novel 1-heteroaryl-1,3-propanediamine derivatives (1-34) were synthesized, displaying CCR5-antagonist activities in the 2.3-296.4 nM range. Among these, compounds 21 and 34 were the most potent CCR5 antagonists, with excellent in vitro anti-HIV-1 activity, low cytotoxicity, and an acceptable pharmacokinetic profile. Furthermore, the X-ray crystal structures of compounds 21 and 34 bound to CCR5 were determined at 2.8 Å resolution. Compound 34 exhibited no CYP450-inhibition activity at 25 μM, which overcomes the potential drug-drug interaction of maraviroc. Compound 34 represents a promising drug candidate for HIV-infection treatment.

In a previous study the small molecule SJP-L-5 that inhibits HIV replication, has been shown to block uncoating of the viral capsid. Continued study showed that SJP-L-5 might hinder HIV capsid uncoating by blocking the completion of reverse transcription. However, to date, the mechanism has not been fully elucidated. Here, the effects of SJP-L-5 for reverse transcription were explored via quantitative PCR, DIG-labelled ELISA, fluorescent resonance energy transfer, and Southern blot assays. We also analyzed the resistance profile of this compound against reverse transcriptase. Our results show that SJP-L-5 preferentially inhibits PPT primed plus-strand DNA synthesis (EC50 = 13.4 ± 3.0 μM) over RNA primed minus-strand DNA synthesis (EC50 > 3,646 μM), resulting in formation of five segmented plus-strand DNA and loss of HIV DNA flap, suggesting failure of both nuclear import and integration. Moreover, resistance study evidenced that SJP-L-5 requires the amino acid residues Val108 and Tyr181 to exert an inhibitory effect. These results indicate SJP-L-5 as a new non-nucleoside reverse transcriptase inhibitor that inhibits HIV-1 polypurine tract primed plus-strand DNA synthesis, initiating HIV-1 down-stream plus-strand DNA synthesis at multiple sites under drug pressure.

Organic solvent upgrading Indonesian lignite was performed in a 1 L autoclave under moderate temperature. The chemical structure and functional groups transformation of lignite upgraded by two organic solvents (ethanol and n-hexane) were analyzed to explore the upgrading mechanism of solvent thermal treatment by using Fourier transform infrared (FTIR) and 13 C nuclear magnetic resonance (NMR). In addition, the characteristics of pyrolysis of treated samples were investigated using thermo gravimetric (TG) to clarify the variance of pyrolysis reactivity. Results showed that the carbon content and calorific value of upgraded lignite were significantly improved, and H/C and O/C ratios of treated samples were significantly reduced with the temperature increasing. The relative percentage of carbonyl and carboxyl carbon, oxygenated aliphatic carbon and methoxyl carbon of lignite upgraded at 300 °C decreased by 20–30%. However, the carbon-substituted and protonated aromatic carbon at 120–135 ppm and protonated aromatic carbon at 90–120 ppm were significantly increased after lignite was upgraded by the two solvents at above 200 °C. These transformations indicated that oxygen-containing functional group was substituted by hydrogen or carbon-substituent as temperature increased, and were intensified at above 200 °C. In addition, oxygen-loss in the treated samples was attributed to the loss of carbonyl group at 175 ppm, dihydric phenol at 147 ppm, and methoxyl group at 55 ppm. The activation energy of upgraded lignite at 300 °C were higher than those of raw lignite and upgraded lignite at 100 and 200 °C, indicating the low reactivity of pyrolysis of the treated lignite with the temperature increasing.

Individual carbon fibers, calcium carbonate (CaCO 3 ) whiskers and their hybrid combination were used to reinforce the oil well cement, and the reinforced cement was analyzed by means of scanning electron microscopy (SEM) and mechanical testing. Compared with individual CaCO 3 whiskers or carbon fibers, the hybrid combination of 10% CaCO 3 whiskers and 0.3% carbon fibers can more effectively improve the strength and toughness. This is likely attributed to the carbon fibers pulling out from the cement matrix, better stress transfer in the presence of CaCO 3 whiskers, finer dispersion of CaCO 3 whiskers and good miscibility of CaCO 3 whiskers with cement phases.

Searching for more safe and effective agents for HIV treatments is still an urgent topic worldwide. Based on our continuous modifications on the benzophenone derivatives as HIV-1 reverse transcriptase (RT) inhibitors, a new template bearing N-phenylbenzenesulfonamide (PBSA) structure was designed to enhance the interactions with HIV-1 RT. In this manuscript, a series of PBSA derivatives were synthesized and evaluated for their anti-HIV-1 activity. The preliminary test showed that these compounds were potent to inhibit wild-type HIV-1 with EC50 values ranging of 0.105–14.531 μmol/L. In particular, compound 13f not only has high anti-HIV-1 activity (0.108 μmol/L), but also possesses low toxicity with a TI value of 1816.6. Furthermore, the major interactions of the inhibitor 13f with HIV-1 RT were also investigated using the molecular modelling. Our discovered structure-activity relationships (SARs) of these analogues may serve as an important clue for further optimizations.

Collagen, as an important biomedical material, has been widely used in medical industry. Fish waste (scales, skins, bones, fins and swim bladders) is a kind of newly developed alternative collagen raw material.This paper uesd papain as enzyme and local bighead fish scales as raw material to extract collagen. More attention was paid to the study on enzymatic reaction kinetics of papain-extracted collagen. The results showed that two kinds of kinetic models(Michaelis-Menten equations and exponential type dynamic equations) at 20, 25 and 28°C were established, respectively and experimentally proved to be basically in agreement with the actual values. These models have a great significance to predict, adjust and control the reaction rate and production output under different conditions.

Collagen is an important biomedical material. Enzyme (papain) extracted collagen (EEC) and acid (citric acid) extracted collagen (AEC) were isolated from the scale of bighead carp. The process conditions of EEC and AEC were optimized, by orthogonal test method , to be: liquid/solid ratio 20 mL/g, extraction time 48 min, papain concentration 9.52×10-5 mol/L, temperature 28°C for EEC and liquid/solid ratio 20 mL/g, extraction time 36 min, citric acid concentration 0.5 mol/L, temperature 28°C for AEC.Under the optimal conditions the maximum extraction rates were 31.20% for EEC and 9.22% for AEC, respectively. Both EEC and AEC were characterized basically as type I collagen by UV spectra, infrared spectra and amino acid compositions.

A series of small-molecule Plk1 inhibitors targeting the substrate-binding pocket were designed through rational drug design for the first time. The designed compounds were synthesized and their activities were evaluated in vitro. Some of the targeted compounds showed potent Plk1 inhibitory activities and anti-proliferative characters. Particularly, 5i showed Plk1 inhibitory activity with an IC50 value of 0.68 µM. Compound 5i also showed cell growth inhibitory activity on HeLa cells with an IC50 value of 0.51 µM, which is about four times more potent compared to thymoquinone. The mechanism of action suggested that 5i was an ATP-independent and substrate-dependent Plk1 inhibitor. Compound 5i demonstrated excellent Plk1 inhibitory selectivity against Plk2, Plk3, and five serine/threonine and tyrosine kinases. Our discovery and structure–activity relationship study may provide useful lead compounds for further optimization of non-ATP-competitive Plk1 inhibitors.

As an organochlorine insecticide, endosulfan has been widely banned or restricted, but it is still largely used in many developing countries. Previous studies have shown multiple adverse health effects of endosulfan. However, the neurotoxicity of endosulfan has not been fully elucidated. In this study, endosulfan isomers (α-/β-endosulfan) and their major metabolites (endosulfan sulfate, endosulfan diol, and endosulfan lactone) were, respectively, exposed to human neuroblastoma SH-SY5Y cells. Results showed that both α-endosulfan and β-endosulfan caused decrease of cell viability and morphological damages in a dose-dependent manner. Their median effective concentrations (EC50s) were respectively 79.6 μM (α-endosulfan) and 50.37 μM (β-endosulfan) for 72 h exposure. EC50s of α/β-endosulfan mixture were lower than that of the single isomer. However, EC50s of its metabolites were higher than that of technical endosulfan. Endosulfan and its metabolites caused increases of reactive oxygen species and the lipid peroxidation, but decrease of superoxide dismutase in a dose-dependent manner. These results indicate that α-endosulfan exhibits higher neurotoxicity than β-endosulfan. Mixture of endosulfan isomers shows stronger cytotoxicity than the single isomer. After endosulfan is degraded, cytotoxicity of its metabolites decreases gradually. The neurotoxicity of endosulfan and its metabolites is closely related to oxidative damage and antioxidative deficit.

[Cd2(C13H15N5)2I4], triclinic, P1̄ (no. 2), a = 8.1348(16) Å, b = 10.1716(17) Å, c = 11.645(3) Å, α = 76.485(18)°, β = 77.750(19)°, γ = 74.030(16)°, V = 889.4(3) Å3, Z = 1, R gt(F) = 0.0597, wR ref(F 2) = 0.1251, T = 293(2) K.

Novel fluorinated polyhedral oligomeric silsesquioxane (POSS) acrylic copolymers were synthesized by the radical solution polymerization. The superhydrophobic coating was prepared using a one-step breath figure method. Chemical constitution, morphology, hydrophobicity, and anticorrosion ability of as-prepared coatings were investigated by the corresponding equipment. The addition of proper fluorinated POSS can synchronously promote the formation of the micro-nano convex structure and the enrichment of fluorinated groups on the surface. Compared to commercial acrylic coating, the fluorinated POSS coating presented enhanced anticorrosion performance. The impedance was the highest and the corrosion current density was the lowest for superhydrophobic coating with 25 wt % fluorinated POSS.

Triple-negative breast cancer (TNBC) lacks major effective target molecules and chemotherapy remains the current main treatment. However, traditional chemotherapy drugs, such as doxorubicin (DOX), cause serious side effects and have a poor prognosis. Piperlongumine (PL), a natural alkaloid, has showed selective anticancer effects and is expected to become a new strategy against TNBC. In our research, cell viability, colony formation, flow cytometry, Western blot, and tumor xenograft model assays were established to evaluate the suppression effect of PL and DOX alone and in combination. Data showed that PL could effectively inhibit cell growth and induce apoptosis in two TNBC cell lines. We also demonstrated for the first time that the combination treatment of PL and DOX synergistically inhibited cell growth and induced apoptosis in TNBC cells. The suppression of STAT3 activation was indicated to be a mechanism of the anticancer effect. Moreover, the effectiveness of this combination was confirmed in a tumor xenograft model. These results revealed that inhibition of the JAK2-STAT3 pathway was a key anticancer mechanism when treated with PL alone or combined with DOX, suggesting that the combination of PL and chemotherapy drugs may be a potential strategy for the clinical treatment of TNBC.

Objective: Acquired immunodeficiency syndrome (AIDS) was first identified in the Western world in 1981. Since then, AIDS has been increasingly wide spreading, its rapid worldwide dissemination brought about by modern mass tourism. Isatin (1 H-indole-2, 3-Dione), an endogenous compound identified in many organisms, shows a wide range of biological activities. In view of the above details, we wish to report the synthesis and evaluation of novel isatin analogs, as promising anti-human immunodeficiency (HIV) agents.Methods: A series of novel isatin analogs (3a-3p) were synthesized, and their chemical structures were confirmed by nuclear magnetic resonance:1H, 13C, ESI-MS spectral data, and CHNS.Results: The compounds were evaluated as inhibitors of HIV type-1 in MT-4 cell cultures. Of these sixteen compounds, only 5 compounds showed potent anti-HIV activity.Conclusion: Evaluation of compound properties in silico showed that they possess significant drug-like characteristics.

A series of N -phenylarylformamide derivatives (PAFAs) with anti-wild-type HIV-1 activity (EC 50 values) ranging from 0.3 nM to 5.1 nM and therapeutic index (TI) ranging from 10 616 to 271 000 were identified as novel non-nucleoside reverse transcriptase inhibitors. Among them, compound 13g (EC 50 = 0.30 nM, TI = 184 578), 13l (EC 50 = 0.37 nM, TI = 212 819), 13m (EC 50 = 0.32 nM, TI = 260 617) and 13r (EC 50 = 0.27 nM, TI = 271 000) displayed the highest activity against this type virus nearly as potent as lead compound GW678248. Moreover, all of them were also active to inhibit the double mutant strain A 17 (K103N + Y181C) with EC 50 values of 0.29 μM, 0.14 μM, 0.10 μM and 0.27 μM, respectively. In particular, compound 13m , which showed broad-spectrum anti-HIV activity, was also effective to inhibit the HIV-2 ROD replication within 4.37 μM concentration.

The search for new molecular constructs that resemble the critical two-metal binding pharmacophore and the halo-substituted phenyl functionality required for HIV-1 integrase (IN) inhibition represents a vibrant area of research within drug discovery. As reported herein, we have modified our recently disclosed 1-[2-(4-fluorophenyl)ethyl]-pyrrole-2,5-dione scaffolds to design 35 novel compounds with improved biological activities against HIV-1. These new compounds show single-digit micromolar antiviral potencies against HIV-1 and low toxicity. Among of them, compound 9g and 15i had potent anti-HIV-1 activities (EC50 < 5 μM) and excellent therapeutic index (TI, CC50/EC50 > 100). These two compounds have potential as lead compounds for further optimization into clinical anti-HIV-1 agents.

BN based composites were prepared by hot-pressing using h-BN as main material in ceramic preparation process. The bulk density, bending strength, vickers’ hardness, thermal expansion coefficient, phase composition and microstructure were tested and analyzed by using modern testing technology. The results indicate that the best formula is H1, the bulk density is 2.77 g.cm−3, the bending strength is 231.7MPa, the hardness is HV5 182.73 and the thermal expansion coefficient is 6.75×10–6°C−1 at 1400°C. XRD phase composition analysis showed that the main crystal phase of the sample is magnesium aluminium spinel and boron nitride. SEM. and EPMA microstructure and element analysis showed that the porosity apertures diameters are under 3 m, the phase distribution are uniformly as well.

Carbon assimilation by submerged plants is greatly reduced due to low light levels. It is hypothesized that submergence reduces carbohydrate contents and that plants recover from submergence in the same way as darkness-treated plants. To test this hypothesis, the responses of plants to submergence and darkness were studied and compared. Plants of a submergence-tolerant species, Alternanthera philoxeroides, were exposed to well drained and illuminated conditions, complete submergence conditions or darkness conditions followed by a recovery growth period in a controlled experiment. The biomass maintenance and accumulation, carbohydrate content dynamics and respiration rate in the plants were assessed to quantify the carbohydrate utilization rate and regrowth. The submerged plants maintained higher chlorophyll contents, more green leaf tissue and more biomass; recovered more quickly; and accumulated more carbohydrates and biomass than darkness-treated plants. The respiration rate was continuously reduced in the same pattern under both stress conditions but was maintained at a significantly lower level in the submerged plants; the total soluble sugar and total fructan contents were decreased at approximately the same rate of decrease, reaching similar low levels, in the two stress treatments. The A. philoxeroides plants were more tolerant of submergence than darkness. The faster recovery of desubmerged plants could not be explained by the similar carbohydrate contents at the start of recovery. Other types of carbon reserves besides carbohydrates or other mechanisms such as higher post-stress photosynthetic performance might be involved.

Twenty-one 2-(N-arylsulfonylindol-3-yl)-3-aryl-1,3-thiazolidin-4-ones (4a-u) were synthesized and evaluated as HIV-1 inhibitors in vitro. Among all compounds, compounds 4n and 4p displayed the potent anti-HIV-1 activities with EC50 values of 3.48 and 8.61 mu g/mL, and TI values of 34.08 and g 23.22, respectively. It demonstrated that, to a series of 2-(N-arylsulfonyl-6-methylindol-3-yl)-3-aryl-1,3-thiazolidin-4-one derivatives, introduction of R-2 as 4-Cl and R-3 as H or 3-Cl could afford the more promising and potent compounds.

Employing unsymmetrical 2-mercapto-5-methyl-1,3,4-thiadiazole and 2,2′-bipyridine as mixed ligands, a new low-dimensional coordination polymer [Zn(MMTA)2(2,2′-bipy)]n (MMTA = 2-mercapto-5-methyl-1,3,4-thiadiazole, 2,2′-bipy = 2,2′-bipyridine), as been synthesized under solvothermal condition and characterized by single crystal X-ray diffraction. This compound crystallizes in the noncentrosymmetric space group Cc, with cell parameters: a = 8.291(4) A, b = 15.483(9) A, c = 15.620(6) A, β = 96.00(5)°, V = 1994.1(2) A3, and Z = 4. The mixed ligands link the zinc center into a mononuclear unit, which is futher linked by weak C-H…N and C-H…S hydrogen bonds into a three-dimensional noncentrosymmetric framework. The compound exhibits intense photoluminescence and distinct NLO properties at room temperature. The intensity of the green light produced by the powder sample of the compound is about 3.2 times that produced by KDP powder. On the basis of the results of TG analysis, the structure is thermally stable up to ∼260 °C.

In continuation of our program to find compounds with potent anti-human immunodeficiency virus type 1 (HIV-1) activities, seventeen 5,6-dihydro-indolo[1,2-a]quinoxaline derivatives (1-17) were preliminarily evaluated as HIV-1 inhibitors in vitro. Among all the derivatives, especially compounds 10 and 17 showed the most potent anti-HIV-1 activities with EC50 values of 2.42 and 3.39 mu g/mL, and TI values of 63.76 and 53.60, respectively.

A novel series of naphthyl phenyl ether analogues (NPEs) have been synthesized and evaluated for their in vitro activities against HIV in C8166 cells. Most of the compounds exhibited moderate to excellent anti-HIV activities. Among them the most active compound 12o showed excellent activities against wild-type HIV-1 with an EC 50 value of 4.60 nM, along with moderate activities against the double mutant strain HIV-1 IIIB A17 (K103N+Y181C) and HIV-2 strain ROD with an EC 50 value of 0.82 and 4.40 μM, respectively. Preliminary structure–activity relationship (SAR) among the newly synthesized NPEs was also investigated.

Four highly oxygenated daphnane diterpenoids, trigonothyrins D-G (1-4), were isolated from the stems of Trigonostemon thyrsoideum, and their structures were elucidated on the basis of extensive spectroscopic studies. Inhibitory activity against HIV-1 was assessed for compounds 1,3 and 4, wherein, 3 showed activity with an EC(50) value of 0.13 mu g/mL and a therapeutic index (TI) of 75.1. (C) 2010 Elsevier Ltd. All rights reserved.

Three new dibenzocyclooctadiene lignans, wilsonilignans A-C (1-3), together with nine known ones, were isolated from the fruits of Schisandra wilsoniana. The structures of 1-3 were elucidated by spectroscopic methods including extensive 1D and 2D NMR techniques. Compounds 1-3 were also evaluated for their anti-HIV-1 activities and showed bioactivity with EC50 values of 3.26, 6.18, and 2.87g/ml, respectively.