[Phenotypic drug discovery promotes research and development of innovative drugs based on traditional Chinese medicine].

Traditional Chinese medicine with rich resources in China and definite therapeutic effects on complex diseases demonstrates great development potential. However, the complex composition, the unclear pharmacodynamic substances and mechanisms of action, and the lack of reasonable methods for evaluating clinical safety and efficacy have limited the research and development of innovative drugs based on traditional Chinese medicine. The progress in cutting-edge disciplines such as artificial intelligence and biomimetics, especially the emergence of cell painting and organ-on-a-chip, helps to identify and characterize the active ingredients in traditional Chinese medicine based on the changes in model characteristics, thus providing more accurate guidance for the development and application of traditional Chinese medicine. The application of phenotypic drug discovery in the research and development of innovative drugs based on traditional Chinese medicine is gaining increasing attention. In recent years, the technology for phenotypic drug discovery keeps advancing, which improves the early discovery rate of new drugs and the success rate of drug research and development. Accordingly, phenotypic drug discovery gradually becomes a key tool for the research on new drugs. This paper discusses the enormous potential of traditional Chinese medicine in the discovery and development of innovative drugs and illustrates how the application of phenotypic drug discovery, supported by cutting-edge technologies such as cell painting, deep learning, and organ-on-a-chip, propels traditional Chinese medicine into a new stage of development.

Thermo-responsive properties driven by hydrogen bonding in aqueous cationic gemini surfactant systems.

A series of unexpected thermo-responsive phenomena were discovered in an aqueous solution of the cationic gemini surfactant, 2-hydroxypropyl-1,3-bis(alkyldimethylammonium chloride) (n-3(OH)-n(2Cl), n = 14, 16), in the presence of an inorganic salt. The viscosity change trend for the 14-3(OH)-14(2Cl) system was investigated in the 20-40 °C temperature range. As the temperature increased, the viscosity of the solution first decreased to a minimum point corresponding to 27 °C, and then increased until a maximum was reached, after which the viscosity decreased again. In the 16-3(OH)-16(2Cl) system, the gelling temperature (T(gel)) and viscosity changes upon heating were similar to those in the 14-3(OH)-14(2Cl) system above 27 °C. The reversible conversion of elastic hydrogel to wormlike micelles in the aqueous solution of the 16-3(OH)-16(2Cl) system in the presence of an inorganic salt was observed at relatively low temperatures. Various techniques were used to study and verify the phase-transition processes in these systems, including rheological measurements, cryogenic transmission electron microscopy (cryo-TEM), electric conductivity, and differential scanning calorimetry. The abovementioned phenomena were explained by the formation and destruction of intermolecular hydrogen bonds, and the transition mechanisms of the aggregates were analyzed accordingly.

A Scd1-mediated metabolic alteration participates in liver responses to low-dose bavachin.

Hepatotoxicity induced by bioactive constituents in traditional Chinese medicines or herbs, such as bavachin (BV) in Fructus Psoraleae, has a prolonged latency to overt drug-induced liver injury in the clinic. Several studies have described BV-induced liver damage and underlying toxicity mechanisms, but little attention has been paid to the deciphering of organisms or cellular responses to BV at no-observed-adverse-effect level, and the underlying molecular mechanisms and specific indicators are also lacking during the asymptomatic phase, making it much harder for early recognition of hepatotoxicity. Here, we treated mice with BV for 7 days and did not detect any abnormalities in biochemical tests, but found subtle steatosis in BV-treated hepatocytes. We then profiled the gene expression of hepatocytes and non-parenchymal cells at single-cell resolution and discovered three types of hepatocyte subsets in the BV-treated liver. Among these, the hepa3 subtype suffered from a vast alteration in lipid metabolism, which was characterized by enhanced expression of apolipoproteins, carboxylesterases, and stearoyl-CoA desaturase 1 (Scd1). In particular, increased Scd1 promoted monounsaturated fatty acids (MUFAs) synthesis and was considered to be related to BV-induced steatosis and polyunsaturated fatty acids (PUFAs) generation, which participates in the initiation of ferroptosis. Additionally, we demonstrated that multiple intrinsic transcription factors, including Srebf1 and Hnf4a, and extrinsic signals from niche cells may regulate the above-mentioned molecular events in BV-treated hepatocytes. Collectively, our study deciphered the features of hepatocytes in response to BV insult, decoded the underlying molecular mechanisms, and suggested that Scd1 could be a hub molecule for the prediction of hepatotoxicity at an early stage.

Seasonal and spatial variations of air concentrations of polycyclic aromatic hydrocarbons in Northeastern Chinese urban region.

Polyurethane foam disk passive air samplers were deployed along an urban-rural-background transect in a northeastern Chinese region (Harbin) to investigate the spatial and seasonal variations of polycyclic aromatic hydrocarbons (PAHs). The ∑16PAHs concentrations [ng/(sample·day)] were high at urban sites (315 ± 206), followed by rural sites (222 ± 160), suburban site (142 ± 114) and background site (128 ± 107). The urban fractionation effect was observed along the transect with increasing proportions for low molecular weight PAHs and decreasing proportions for high molecular weight PAHs. PAHs were found to be higher in winter and spring than in summer and autumn, most likely due to the combustion of coal and biomass for domestic heating. Sources of PAHs were investigated by principal component analysis in combination with diagnostic ratios, which both indicated that pyrogenic sources were the main sources of PAHs in the air of Harbin, China.

Poly[[(1,10-phenanthroline){µ(3)-2,2',2''-[1,3,5-triazine-2,4,6-triyltris(sulfane-diyl)]triacetato}-cadmium] 0.42-hydrate].

The asymmetric unit of the title complex, {[Cd(C(9)H(7)N(3)O(6)S(3))(C(12)H(8)N(2))]·0.42H(2)O}(n), contains a Cd(II) atom, one doubly deprotonated 2,2',2''-[1,3,5-triazine-2,4,6-triyltris(sulfanediyl)]triacetic acid ligand (HTTTA(2-)), a 1,10-phenanthroline (phen) ligand and a fractionally occupied water mol-ecule [site occupancy = 0.421 (15)]. The Cd(II) atom is six-coordinated within a distorted octa-hedral coordination geometry. Six coordination arises from four O atoms derived from three different HTTTA(2-) ligands, and two N atoms of the chelating phen mol-ecule. The incompletely deprotonated triazine ligand adopts a µ(3)-η(1):η(1):η(2) coordination mode, resulting in the formation of chains along the c axis based on Cd(2)O(2) dimeric units. Adjacent chains are stacked through π-π stacking [3.533 (2) Šbetween phen and triazine rings] and C-H⋯O inter-actions, forming supra-molecular sheets in the ab plane. Intra-and intermolecular O-H⋯O hydrogen bonds are also observed.

3-(Pyridin-4-yl-thio)-pentane-2,4-dione.

In the title compound, C(10)H(11)NO(2)S, the acetyl-acetone group crystallizes in the keto form with all the non-hydrogen atoms in the acetyl-acetone group approximately co-planar with a maximum atomic deviation 0.055 (2) Å; the dihedral angle between the acetyl-acetone group and the pyridine ring is 85.90 (6)°. An intra-molecular O-H⋯O hydrogen bond involving the acetyl-acetone group forms a six-membered ring.

5-(Pyridin-4-yl)isophthalic acid.

In the title compound, C(13)H(9)NO(4), the two carb-oxy-lic groups and the benzene ring are approximately co-planar with a maximum atomic deviation 0.175 (4) Å, while the pyridine ring is oriented at a dihedral angle of 31.07 (18)° with respect to the benzene ring. In the crystal, mol-ecules are linked by O-H⋯O, O-H⋯N and weak C-H⋯O hydrogen bonds, forming a three-dimensional supra-molecular framework.

Polycyclic aromatic hydrocarbons and polychlorinated biphenyls in topsoils of Harbin, China.

Levels of polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs) in 17 topsoil samples collected in and around the city of Harbin, an industrial center in Northeast China for decades, are presented. Total concentrations (ng/g dry weight [dw]) ranged from 17 to 3,260 (mean: 508) for PAHs and 0.30 to 6.17 (mean: 1.63) for PCBs. As expected, large differences of the concentration levels of PAHs and PCBs in topsoil were found among the samples from urban, suburban, and background/rural sites. Total PCB and PAH concentrations were higher in industrialized areas than those at the other sites, with a ratio of up to one order of magnitude, possibly indicating the urban source of these chemicals. The PAH profiles were similar among samples, with high percentages of high molecular weight (HMW) PAHs and domination of four-ring PAHs. Compositions of PCB homologues showed that tri-CBs and tetra-CBs were abundant in all soil samples. There was also a higher abundance of low molecular weight (LMW) PCBs and lower abundance of HMW PCBs at background sites than other areas, indicating the urban fractionation phenomenon. Pyrogenic origins were the dominant PAH sources in surface soil at most urban sites, whereas petrogenic origins were the major PAH sources in surface soil at all the rural and background sites. The TEQ concentrations (pg/g dw) of all four dioxin-like PCBs (CBs 77, 81, 105, and 118) were 0.009 for humans and mammals, 0.005 for fish, and 1.42 for birds. Strong correlations were found between PAH and PCB concentrations and soil organic matter and, also, between PAH and PCB concentrations.

Formaldehyde degradation by UV/TiO2/O3 process using continuous flow mode.

The degradation of formaldehyde gas was studied using UV/TiO2/O3 process under the condition of continuous flow mode. The effects of humidity, initial formaldehyde concentration, residence time and ozone adding amount on degradation of formaldehyde gas were investigated. The experimental results indicated that the combination of ozonation with photocatalytic oxidation on the degradation of formaldehyde showed a synergetic action, e.g., it could considerably increase decomposing of formaldehyde. The degradation efficiency of formaldehyde was between 73.6% and 79.4% while the initial concentration in the range of 1.84-24 mg/m3 by O3/TiO2/UV process. The optimal humidity was about 50% in UV/TiO2/O3 processs and degradation of formaldehyde increases from 39.0% to 94.1% when the ozone content increased from 0 to 141 mg/m3. Furthermore, the kinetics of formaldehyde degradation reaction could be described by Langmuir-Hinshelwood model. The rate constant k of 46.72 mg/(m3 x min) and Langmuir adsorption coefficient K of 0.0268 m3/mg were obtained.

Isothermal titration calorimetry and 1H NMR studies on host-guest interaction of paeonol and two of its isomers with beta-cyclodextrin.

Thermodynamic parameters of inclusion complex of beta-cyclodextrin (beta-CD) with paeonol and two of its isomers in aqueous solution have been determined with nano-watt-order isothermal titration calorimetry (ITC) and the host-guest inclusion structure has been investigated by using 1H NMR spectra at 298.2 K. The analysis of thermodynamic data reveals that stoichiometry of beta-CD complex with paeonol (Pae) or acetovanillone (Ace) is 1:1 whereas the inclusion complex of beta-CD with 2-hydroxyl-5-methoxyacetophone (Hma) is in 1:1 coexistence with 2:1 stoichiometry. Further analysis indicates that formation of all the complexes is simultaneously driven by enthalpy and entropy, the inclusion complexation of Pae.beta-CD, Ace.beta-CD and Ham.beta-CD2 is predominantly driven by entropy while Ham.beta-CD by enthalpy. The 1H NMR spectra data provide clear evidence of the inclusion phenomena, which shows that the aromatic ring of the guest molecule insert itself into the torus from the narrow side of the cavity.

Kinetics study on photochemical oxidation of polyacrylamide by ozone combined with hydrogen peroxide and ultraviolet radiation.

An investigation on the process of ozone combined with hydrogen peroxide and ultraviolet radiation has been carried out in order to establish the kinetics for photochemical oxidation of polyacrylamide (PAM) in aqueous solution. Effects of operating parameters, including initial PAM concentration, dosages of ozone and hydrogen peroxide, UV radiation and pH value on the photochemical oxidation of PAM, have been studied. There was an increase in photochemical oxidation rate of PAM with increasing of dosages of O3, H2O2 and ultraviolet radiation. Upon increasing of the initial PAM concentration, the photochemical oxidation rate of PAM decreased. Slight effect of pH value on the photochemical oxidation rate of PAM was observed in the experiments. The kinetics equation for the photochemical oxidation of PAM by the system has been established.

Functions and behaviors of activated sludge extracellular polymeric substances (EPS): a promising environmental interest.

Extracellular polymeric substances (EPS) are the predominant constituents of activated sludge and represent up to 80% of the mass of activated sludge. They play a crucial role in the flocculation, settling and dewatering of activated sludge. Furthermore, EPS also show great efficiency in binding heavy metals. So EPS are key factors influencing reduction in sludge volume and mass, as well as activity and utilization of sludge. EPS are of considerable environmental interest and hundreds of articles on EPS have been published abroad, while information on EPS in China is limited. In this paper, results of over 60 publications related to constituents and characteristics of EPS and their influences on flocculation, settling and dewatering of sludge are compiled and analyzed. Metal-binding ability of EPS is also discussed, together with a brief consideration of possible research interests in the future.

Preparation and characterization of Fe2O3-CeO2-TiO2/gamma-Al2O3 catalyst for degradation dye wastewater.

In order to develop a catalyst with high activity for catalytic wet oxidation (CWO) process at room temperature and atmospheric pressure, Fe2O3-CeO2-TiO2/gamma-Al2O3 catalyst was prepared by consecutive impregnation method and the prepared parameters were optimized. The structure of the catalyst was characterized by BET, XRF, SEM and XPS technologies, and the actual wastewater was used to investigate the catalytic activity of Fe2O3-CeO2-TiO2/gamma-Al2O3 in CWO process. The experimental results showed that the prepared catalyst exhibited good catalytic activity when the doping amount of Ti was 1.0 wt%/o (the weight ratio of Ti to carriers), and the middle product, CeO2-TiO2/gamma-Al2O3, was calcined in 450'C for 2 h. The CWO experiment for treating actual dye wastewater indicated that the COD, color and TOC of actual wastewater were decreased by 62.23%, 50.12% and 41.26% in 3 h, respectively, and the ratio of BODs/COD was increased from 0.19 to 0.30.

Mechanism study of electrochemical oxidation in the terylene diaphragm cell.

By using a self-made carbon/polytetrafluoroethylene (C/PTFE) O2-fed as cathode and Ti/IrO2/RuO2 as anode, the effects of electrochemical oxidation of phenol and the coal-gas wastewater containing phenol were studied. The terylene diaphragm which kept pH >12 in cathodic compartment and pH < 1 in the anodic compartment was selected in the experiment in comparison with the other types of diaphragm. Furthermore, hydroxyl radical (HO*) was determined in the cathodic compartment of the diaphragm cell by electron spin resonance spectrum (ESR) and the fluorescence spectra. Compared with pH, the accumulated H2O2 and the COD removal of the no-diaphragm cell, the mechanism of electrochemical oxidation in the terylene diaphragm cell was supposed. The degradation of phenol was supposed to be cooperative oxidation by direct or indirect electrochemical oxidation at the anode and H2O2, HO* produced by oxygen reduction at the cathode. The mineralization of phenol in the diaphragm cell was better than that in the no-diaphragm cell. When the coal-gas wastewater was treated by the electrolysis system with terylene diaphragm, the average removal efficiency of the volatile phenol and COD were 100% and 79.6%, respectively.

Microcalorimetric study on host-guest complexation of naphtho-15-crown-5 with four ions of alkaline earth metal.

Thermodynamic parameters of complexation of naphto-15-crown-5 with four alkaline earth ions in aqueous media was determined using titration microcalorimetry at 298.15 K. The stability of the complexes, thermal effect and entropy effect of the complexation is discussed on the basis of the guest ions structure and the solvent effect. The stability constants tendency to vary with ion radius was interpreted. Complex of naphtha-15-crown-5 with calcium ion is very stable due to the synergism of static electric interaction and size selectivity between the host and the guest.

[Simultaneous Analysis of 18 Glucocorticoids in Surface Water].

A method of ultra-performance liquid chomatography tandam mass spectrometry(UPLC-MS/MS) combined with solid-phase extraction (SPE) has been developed for simultaneous analysis of 18 glucocorticoids in surface water. The analytes were first enriched and purified through a HLB cartridge, and eluted with acetonitrile/ethyl acetate (1:1, V/V), then detected by UPLC-MS/MS. The detection used gradient elution process with methanol and 0. 1% formic acid/water (V/V) as the mobile phase to achieve baseline separations of these 18 analytes. The linear range was 1. 0-1 000 µg.L-1. The method detection limits (MDLs) were 0. 10-1. 0 ng.L-1 except for cortisone acetate and cortisol acetate(10 ng.L-1) with overall mean recoveries of 65% - 108% in surface water. Application of this method for 5 surface waters from Beijing area showed that 8 glucocorticoids were detected with the concentration range of 0. 20-476 ng.L-1. Triamcinolone, triamcinolone acetonide, cortisol acetate and clobetasol propionate were detected for the first time in surface water samples, suggesting that this method is efficient for real sample analysis.

Catalysts for decomposing ozone tail gas.

The preparation of immobilizing-catalysts for decomposing ozone by using dipping method was studied. XRD, XPS and TEM were used to characterize the catalysts. The three kinds of catalysts were selected preferentially, and their catalytic activities were investigated. The results showed that the catalyst with activated carbon dipping acetate (active components are Mn:Cu = 3:2, active component proportion in catalyst is 15%, calcination temperature is 200 degrees C) has the best catalytic activity for ozone decomposing. One gram of catalyst can decompose 17.6 g ozone at initial ozone concentration of 2.5 g/m3 and the residence time in reactor of 0.1 s. The experimental results also indicated that humidity of reaction system had negative effect on catalytic activity.

UV-catalytic treatment of spent caustic from ethene plant with hydrogen peroxide and ozone oxidation.

The performance of UV/H2O2, UV/O3 and UV/H2O2/O3 oxidation systems for treating spent caustic from an ethylene plant was investigated. In UV/H2O2 system, with the increase of H2O2 dosage, removal efficiencies of COD and the ratio of biochemical oxygen demand (BOD) to chemical oxygen demand (COD) of the effluent were increased and a better performance was obtained than the H2O2 system alone. In UV/H2O2 system, removal efficiency of COD reach 68% under the optimum condition, and BOD/COD ratio was significantly increased from 0.22 to 0.52. In UV/O3 system, with the increase of O3 dosage, removal efficiency of COD and BOD/COD ratio were increased, and a better performance was obtained than the O3 system alone. Under the optimum condition, removal efficiency of COD was 54%, and BOD/COD ratio was significantly increased from 0.22 to 0.48. In UV/H2O2/O3 system, COD removal efficiency was found to be 22.0% higher than UV/O3 system.

[Preparation of red mud loaded Co catalysts: optimization using response surface methodology (RSM) and activity evaluation].

The removal efficiency of catalytic ozonation of bezafibrate (BZF) by red mud loaded Co catalysts (Co/RM) was used as the index value in statistical experimental designs. The most important factors influencing BZF degradation (P < 0.05) in water were dipping mass of cobalt and calcination temperature. Under the conditions of 4.14% of dipping mass of cobalt and 389 degrees C of calcination temperature, the BZF removal efficiency was 71.29% as calculated by predictive value and a maximum removal efficiency of 70.74% was actually achieved. The experiment data was very close to the predictive value and the deviation was 1% (< 5%). The results indicated that the response surface methodology and mathematical model was reliable for experimental design. By comparing the differences of BZF degradation in RM and Co/RM processes, it was observed that Co/RM exhibited the greater catalytic activity. Furthermore, the surface structure and composition properties of the two catalysts were evaluated by N2 adsorption, XRD and UV-Vis analysis. It was found that the specific surface area and total pore volume had the same variation trend, RM < Co/RM, which was consistent with the trend of catalytic ozonation. It was also found that Co3O4, the active component formed on the surface of RM by the addition of cobalt into red mud, enhanced the catalytic activity. Moreover, the dissolved metal concentration in the solution for catalytic ozonation of BZF degradation by RM or Co/RM was determined by ICP-OES. The results showed that for both catalysts there was no leaching of catalytic active components into the solution, which could suggest that the two catalysts were safe and could have certain application prospect.

Formation and characteristics of aqueous two-phase systems formed by a cationic surfactant and a series of ionic liquids.

Aqueous two-phase systems (ATPS) were obtained in the aqueous mixtures of a cationic surfactant and a series of ionic liquids (ILs). The effects of IL structure, temperature and additives on the phase separation were systematically investigated. The microstructures of some ATPS were observed by freeze-fracture replication technique. Lyotropic liquid crystal was found in the bottom phase besides micelles under different conditions. Remarkably, both IL structure and additives profoundly affected the formation and properties of the ATPSs. The phase separation can be attributed to the existence of different aggregates and the cation-π interactions of the cationic surfactant with the ILs, which has a significant role in the formation of ATPS. The extraction capacity of the studied ATPS was also evaluated through their application in the extraction of two biosubstances. The results indicate that the ILs with BF4(-) as anion show much better extraction efficiencies than the corresponding ILs with Br(-) as anion do under the same conditions. l-Tryptophan was mainly distributed into the NPTAB-rich phase, while methylene blue and capsochrome were mainly in the IL-rich phase.