[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.

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.

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.

[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.

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.

[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.

[Influence of reaction time of urea hydrolysis-based co-precipitation on the structure of ZnAl layered double hydroxides and the phosphate adsorption].

A series of ZnAl layered double hydroxides (LDHs) were prepared by urea hydrolysis-based homogeneous co-precipitation for studying their structure and phosphate adsorption capacities. The results show that all the samples exhibited a typical layered structure as the reaction time extended from 12 h to 96 h, whereas Zn/Al molar ratio in the ZnAls decreased from 2.06 to 0.70 and the specific surface area markedly increased to be 7.6-fold higher than that of ZnAl-12. Phosphate adsorption capacity of the ZnAl was in general increased gradually with the reaction time extension, which can be attributed to the surface area rising as well as the increased positive charge of LDHs layer caused by a higher proportion of Al. This reveals that physicochemical adsorption on LDHs surface would have played an important role during the phosphate adsorption. With a reaction time of 24 h, a high amount of exchangeable interlayer anions was observed, giving rise to a highest phosphate uptake of 34.1 mg x g(-1) by the ZnAl-24. It indicates the ion exchange was another major pathway for the phosphate removal. For all the ZnAls with different reaction times, the phosphate adsorption isotherms fit well with Langmuir-type equations; the adsorption kinetics followed pseudo-second-order models.

[Influence of nitrate on the simultaneous methanogenesis and denitrification reaction of anaerobic biofilm and granular sludge].

The aims of this study are to further investigate the impact mechanism of nitrate on the simultaneous methanogenesis and denitrification (SMD) process of anaerobic biofilm, and to extend the application of the biofilm process in the treatment of high nitrogen and COD concentration organic wastewater. The SMD reactions were successfully carried out in a hybrid anaerobic biofilm and sludge reactor (HABSR) and an up-flow anaerobic sludge blanket (UASB), and the influence of nitrate on the performance of simultaneous carbon and nitrogen removal in biofilm and granular sludge were investigated using batch tests. The results showed that the nitrate concentration could obviously affect the carbon and nitrogen removal in both biofilm and granular sludge, and the increase of nitrate concentration had more serious impact on the granular sludge, and the biofilm presented higher COD and nitrogen removal efficiency and stronger resistance to toxic materials than the granular sludge. As the nitrate concentration was increased from 75 to 600 mg x L(-1), the COD removal rates were reduced from 273.26 to 0.1 mg x (h x g)(-1) in granular sludge and reduced from 95 to 1.7 mg x (h x g)(-1) in biofilm. At the same time, the denitrification rate of biofilm and granular sludge were increased form 21.43 and 22.31 mg x (h x g)(-1) to 83.72 and 61.06 mg x (h x g)(-1), respectively. The biofilm recovered the COD degradation rate more quickly and easily than the granular sludge, and the maximum COD removal rate reached 712.44 mg x (h x g)(-1). The nitrite accumulation was observed to be the major cause that affected the simultaneous carbon and nitrogen removal of biofilm and granular sludge. It's found that the maximum nitrite accumulation in biofilm was only one tenth of that of the granular sludge at the same nitrate concentration. The HABSR was proved to be an important alternative for SMD reaction employed in the treatment of high nitrogen and COD concentration organic wastewater.

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.

Atmospheric concentrations, sources and gas-particle partitioning of PAHs in Beijing after the 29th Olympic Games.

A comprehensive sampling campaign was carried out to study atmospheric concentration of polycyclic aromatic hydrocarbons (PAHs) in Beijing and to evaluate the effectiveness of source control strategies in reducing PAHs pollution after the 29th Olympic Games. The sub-cooled liquid vapor pressure (logP(L)(o))-based model and octanol-air partition coefficient (K(oa))-based model were applied based on each seasonal dateset. Regression analysis among log K(P), logP(L)(o) and log K(oa) exhibited high significant correlations for four seasons. Source factors were identified by principle component analysis and contributions were further estimated by multiple linear regression. Pyrogenic sources and coke oven emission were identified as major sources for both the non-heating and heating seasons. As compared with literatures, the mean PAH concentrations before and after the 29th Olympic Games were reduced by more than 60%, indicating that the source control measures were effective for reducing PAHs pollution in Beijing.

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.

Dechlorane plus in multimedia in northeastern Chinese urban region.

Dechlorane plus (DP) was quantified by gas chromatography/mass spectrometry (GC/MS) in soil and ambient air (collected from Harbin City, a typical northeastern Chinese urban region), water and sediment samples (collected in the segment within Harbin of Songhua River, located in northeast of China). The average concentrations of DP in sediment and soil samples were 123.6 pg g⁻¹ dry weight (dw), and 11.3 pg g⁻¹ dw, respectively. However, the concentration of DP in water was below the method detection limit (MDL). The inter-media comparison between water and sediment suggested that the sediment may be a receptor for DP. For air samples, two methods were used for collecting air in order to compare, active air sampling (AAS) and passive air sampling (PAS). The average concentrations of DP were 0.4 pg m⁻³ and 6.9 pg m⁻³ for AAS and PAS samples, respectively. Discrepancies of deployment period and different calculated method for DP concentration may help to explain the remarkable difference between PAS and AAS. Overall, DP in all matrices in Harbin City showed lower concentrations than that in the Great Lakes region. The anti-DP isomer was consistently greater than that of the syn-DP isomer in all matrices. The average fractional abundance of the syn-DP isomer (f(syn)) was smaller than the technical DP composition (f(syn)=0.35) according to other studies in the Great Lakes region. As we know, this study is the first attempt to comprehensively study DP concentrations in four different matrices (water, ambient air, sediment and soil) in China.

[Electrochemical degradation of 4-chlorophenol using a Pd/MWNTs catalytic electrode].

Nitric acid in various volume fraction (8%, 15%, 20%, and 68%) was used on the multi-wall carbon nanotubes (MWNTs) pre-treatment and then the formaldehyde reduction method was utilized for the preparation the Pd/MWNTs catalysts which were fully characterized by Boehm titration method, X-ray diffraction (XRD), infrared spectroscopy, scanning electron microscopy (SEM), and cyclic voltammetry(CV) techniques. The electrochemical degradation of 4-chlorophenol was investigated in a diaphragm electrolysis system using the Pd/MWNTs gas-diffusion cathode. The results indicated that the active organic function groups increased on the surface of the carbon nanotube pre-treated by using 68% nitric acid. Pd particles with an average size of 9.2 nm were highly dispersed in the carbon nanotube with an amorphous structure. Additionally, the Pd/MWNTs catalyst in Pd/MWNTs gas-diffusion electrode system accelerated the two-electron reduction of O2 to hydrogen peroxide (H2O2) when feeding air. The Pd/MWNTs gas-diffusion cathode can not only reductively dechlorinate 4-chlorophenols by feeding hydrogen gas, but also accelerate the two-electron reduction of O2 to H2O2 by feeding air. Therefore, the removal efficiency and the average removal efficiency of 4-chlorophenol in terms of total organic carbon (TOC) reached about 86.9% and 71.6% after 140 min electrolysis, respectively.

Degradation mechanism of diethyl phthalate with electrogenerated hydroxyl radical on a Pd/C gas-diffusion electrode.

Using a self-made Pd/C gas-diffusion electrode as the cathode and a Ti/IrO(2)/RuO(2) anode, the degradation of diethyl phthalate (DEP) has been investigated in an undivided electrolysis device by electrochemical oxidation processes. Hydroxyl radical (HO) was determined in the reaction mixture by the electron spin resonance spectrum (ESR). The result indicated that the Pd/C catalyst in Pd/C gas-diffusion electrode system accelerated the two-electron reduction of fed O(2) to H(2)O(2), which is in favor of producing HO. Additionally, the percentage removal of DEP and COD reached about 80.9 and 40.2% after 9h electrolysis, respectively. It suggested that most of DEP were oxidized to intermediates using the Pd/C gas-diffusion electrode. Furthermore, the ratio of BOD(5)/COD of resulted solutions was three times larger than the initial ones. Hence, the electrochemical oxidation enhanced the biodegradation character of the DEP solution. Finally, main aromatic intermediates (e.g., monoethyl phthalate (MEP) and phthalic acid (PA)) and main aliphatic carboxylic intermediates (e.g., formic, mesoxalic, oxalic, malonic, succinic, maleic, dodecanoic, and hexadecanoic acids) were identified by GC-MS. Moreover, a reaction scheme involving all these intermediates was proposed.

[Rapid startup and nitrogen removal characteristic of anaerobic ammonium oxidation reactor in packed bed biofilm reactor with suspended carrier].

Packed bed biofilm reactor with suspended carrier was used to cultivate ANAMMOX bacteria with sludge inoculums from WWTP secondary settler. The startup of ANAMMOX reactor was comparatively studied using high nitrogen loading method and low nitrogen loading method with aerobically biofilmed on the carrier, and the nitrogen removal characteristic was further investigated. The results showed that the reactor could be started up successfully within 90 days using low nitrogen loading method, the removal efficiencies of ammonium and nitrite were nearly 100% and the TN removal efficiencywas over 75% , however, the high nitrogen loading method was proved unsuccessfully for startup of ANAMMOX reactor probably because of the inhibition effect of high concentration of ammonium and nitrite. The pH value of effluent was slightly higher than the influent and the pH value can be used as an indicator for the process of ANAMMOX reaction. The packed bed ANAMMOX reactor with suspended carrier showed good characteristics of high nitrogen loading and high removal efficiency, 100% of removal efficiency could be achieved when the influent ammonium and nitrite concentration was lower than 800 mg/L.

Seasonal variations of sources of polycyclic aromatic hydrocarbons (PAHs) to a northeastern urban city, China.

Understanding the seasonal variations of sources of polycyclic aromatic hydrocarbons (PAHs) in air in urban region is important to the effective control of air pollution in the region. Based on a year round dataset (from August 2008 to July 2009), the sources of atmospheric PAHs in Harbin, a typical Chinese northeastern urban city, were analyzed by principal component analysis (PCA) and positive matrix factorization (PMF). The average total (gas plus particulate) PAH concentration varied from 6.3 ng m(-3) to 340 ng m(-3) with a mean of 100+/-94 ng m(-3), with higher concentrations in heating season than those in non-heating season. PCA and PMF identified similar source factors to atmospheric PAHs with obvious seasonal variation. The results obtained by PMF method indicated that the main sources were coal-fired boiler (39%), diesel engine (34%) and coal average (22%) in heating season and traffic emissions (59%), ground evaporation (18%) and coal average (17%) in non-heating season. Excellent correlation coefficients between predicted and measured concentrations of PAHs indicated that PMF was a useful model for source apportionment of PAHs in atmosphere.

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.

Treatment of antibiotic fermentation wastewater by combined polyferric sulfate coagulation, Fenton and sedimentation process.

Attempts were made in this study to examine the combined polyferric sulfate (PFS) coagulation, Fenton and sedimentation process for treatment of non-degradable antibiotic fermentation wastewater. The experimental results indicated that 66.6% of color and 72.4% of chemical oxygen demand (COD) were removed under the optimum conditions of PFS dosage 200mg/L and pH 4.0. In addition, optimal parameters of Fenton process were determined to be 150 mg/L of H(2)O(2) dosage, 120 mg/L of FeSO(4) and 1h of reaction time. When Fenton treated effluent was controlled at pH 7.0, the pollutants could be further removed by sedimentation process. The overall color, COD and suspended solids (SS) removal reached 97.3%, 96.9% and 86.7% under selected conditions, respectively. Thus this study might offer an effective way for wastewater treatment of antibiotics manufacturer and pharmaceutical industry.

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.