Integration of network pharmacology and bone marrow mesenchymal stem cells experimental research to reveal the molecular mechanisms for Hai Honghua medicinal liquor against osteoporosis

Background:Hai Honghua medicinal liquor(HHML)formula has been used in clinical practice for a long time,mainly for the treatment of freshly closed fractures,to promote osteogenesis,to increase bone mass,and thus to promote fracture healing.However,the underlying mechanisms of HHML in the treatment of osteoporosis(OP)are still unclear.Methods:Firstly,Traditional Chinese Medicines Systems Pharmacology Database and Analysis Platform and The Encyclopedia of Traditional Chinese Medicine were used to screen the targets of the active compounds of HHML.At the same time,OP targets were identified through GeneCards,Online Mendelian Inheritance in Man,DisGeNET,Therapeutic Target Database,Comparative Toxicogenomics Database and Human Phenotype Ontology databases.Next,protein-protein interaction and pathway networks were constructed for compound-disease common targets,and core targets and compounds were screened for molecular docking.Furthermore,rat bone marrow mesenchymal stem cells were extracted as model cells,and the osteogenic effects of HHML were verified via in vitro experiments.Results:Total of 343 common targets of HHML-OP and the top 10 target proteins in the protein-protein interaction network are TP53,AKT1,STAT3,HSP90AA1,ESR1,TNF,IL6,MAPK1,MAPK3 and MAPK8.Enrichment analysis yielded that the key molecular pathway was the PI3K/Akt signaling pathway.Molecular docking analysis showed that baicalein,erysodienone and naringenin docked with the target proteins AKT1,STAT3 and TP53,respectively,with low binding energy and high affinity.In addition,In vitro experiments demonstrated that HHML promoted the proliferation of bone marrow mesenchymal stem cells;compared with the control group,HHML-treated cells showed enhanced alkaline phosphatase staining,promoted the expression of OCN,RUNX2,BSP,and COL1 mRNAs as well as the expression of PI3K and AKT phosphorylated proteins.Secondly,the expression of target proteins revealed that HHML promoted the phosphorylation of STAT3 protein and inhibited the expression of P53.Conclusions:Our study investigated that HHML treatment with OP promotes bone formation possibly through activation of the PI3K/Akt signaling pathway and may involve STAT3 and TP53 target interactions.

The mechanistic study on Wa medicine Niang-Mu-Liang medicinal liquor mitigating diabetes mellitus erectile dysfunction in rats by inhibiting ferroptosis

Background:This study aims to investigate the therapeutic effect of Wa medicine Niang-Mu-Liang medicinal liquor(NML)on rats with diabetes mellitus erectile dysfunction(DMED)and its impact on the ferroptosis signaling pathway.Methods:Thirty Sprague-Dawley rats were randomly divided into three groups:Control,DMED,and NML.After establishing the DMED model,treatments were administered for 8 weeks.After the administration,apomorphine hydrochloride tests were conducted to measure the mass and organ index of testes and epididymides,sperm concentration and viability in each group.Penile corpus cavernosum tissues were stained with hematoxylin and eosin.Nitric oxide and cyclic guanosine monophosphate levels in the penile corpus cavernosum tissues were determined using biochemical kits and enzyme-linked immunosorbent assay,while the expression of proteins related to the ferroptosis signaling pathway was measured by Western blot.Results:Compared to the DMED group,the DMED rats treated with NML showed significantly increased erection frequency,testicular and epididymal mass and index,sperm count and viability,along with noticeable improvement in the pathological morphology of penile corpus cavernosum.The content of nitric oxide and cyclic guanosine monophosphate,and the expression of ferritin heavy chain,ferritin light chain,and glutathione peroxidase 4 proteins in penile corpus cavernosum tissue were elevated,while the expression of transferrin and STEAP3 proteins was reduced.Conclusion:NML can improve erectile function in DMED rats by inhibiting the ferroptosis signaling pathway.

Research of the molecular mechanism of Hai Honghua medicinal liquor in the treatment of fracture based on network pharmacology combined with molecular docking

Background:Hai Honghua medicinal liquor(HHML),a famous hospital formula composed of 19 traditional Chinese medicines,has been successfully applied in treating soft tissue injury,fresh closed fracture,limb dysfunction after fracture healing,shoulder,neck and leg pain,knee joint pain and other clinical multiple diseases for 30 years in clinical.However,research on the material basis of HHML for the treatment of fracture healing-related disorders is still in a gap.Therefore,it is particularly important to explore the active ingredients,core targets and potential pharmacological mechanisms of HHML to promote fracture healing.Methods:We screened the core active components of each traditional Chinese medicine in formula and its action targets through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and Encyclopedia of Traditional Chinese Medicine database.The fracture related targets were retrieved from several different public databases,including GeneCards,Online Mendelian Inheritance in Man,DisGeNET and Therapeutic Target Database.Bioinformatics analysis to obtain key bioactive components,underlying targets and signaling pathways,containing the Venn diagram of the intersection with components and diseases gene targets,protein–protein interaction,as well as the Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes analysis,and finally molecular docking.Results:A total of 249 bioactive ingredients of HHML and 325 HHML-fracture-related targets were screened.The network analysis revealed that quercetin,luteolin,kaempferol,Licochalcone A,naringenin and 8-Isopentenyl-kaempferol may be potential candidate agents.Multiple targets are involved including TP53,MAPK3,STAT3,AKT1,MAPK1,HSP90AA1,ESR1 and PIK3CA may be closely linked targets.PI3K-AKT signaling pathway may play a significant role of HHML in treatment of fracture.What’s more,molecular docking suggested that 8-isopentenyl kaempferol,glycyrrhiza chalcone A,and naringenin bound to AKT1,PIK3CA,and ESR1,respectively,exhibiting lower energy and more stable characteristics.Conclusions:The findings indicate the potential active ingredients,target proteins and molecular mechanisms of HHML for the treatment of fractures to provide the exact idea for the next research on the mechanism of action of HHML formula for fracture treatment.

Characterization of Formacell Lignin Derived from Black Liquor as a Potential Green Additive for Advanced Biocomposites

Black liquor is obtained as a by-product of the pulping process,which is used to convert biomass into pulp by removing lignin,hemicelluloses and other extractives from wood to free cellulose fibers.Lignin represents a major constituent in black liquor,with quantities varying from 20%to 30%,of which a very low share is used for manufacturing value-added products,while the rest is mainly burned for energy purposes,thus underestimating its great potential as a raw material.Therefore,it is essential to establish new isolation and extraction methods to increase lignin valorization in the development of bio-based chemicals.The aim of this research work was to determine the effect of KOH or ethanol concentration as an isolation agent on lignin yields and the chemical characteristics of lignin isolated from formacell black liquor of oil palm empty fruit bunch(OPEFB).Isolation of lignin was carried out using KOH with various concentrations ranging from 5%to 15%(w/v).Ethanol was also used to precipitate lignin from black liquor at concentrations varying from 5%to 30%(v/v).The results obtained showed that the addition of KOH solution at 12.5%and 15%concentrations resulted in better lignin yield and chemical properties of lignin,i.e.,pH values of 3.86 and 4.27,lignin yield of 12.78%and 14.95%,methoxyl content of 11.33%and 10.13%,and lignin equivalent weights of 476.25 and 427.03,respectively.Due to its phenolic structure and rich functional groups that are favorable for modifications,lignin has the potential to be used as a green additive in the development of advanced biocomposite products in various applications to replace current fossil fuel-based material,ranging from fillers,fire retardants,formaldehyde scavengers,carbon fibers,aerogels,and wood adhesives.

Effects of Rice Straw Steam-explosion Spent Liquor on the Growth of Cabbage Seedlings

The direct use of spent liquor from pulping and papermaking engineering,which is abundant in active organic matter,can avoid resource wastage and environmental pollution.In this study,the effects of soaking solution and filtrate from steam-exploded rice straw on seed germination and the early development of cabbage were investigated.The results have shown that soaking solution and filtrate stimulated early cabbage growth at low concentrations.Optimal germination potential and the rate of soaking solution-treated cabbage seeds increased by 8%and 5%,respectively;meanwhile,that of the filtrate-treated cabbage seeds increased by 11%and 5%,respectively.Promotion of root growth by steam-exploded rice straw spent liquor was expressed in lateral root multiplication.The fresh weight of cabbage seedlings treated with the soaking solution/filtrate increased by more than 50%and the dry weight over 20%.Comparatively,the stimulation of filtrate on seed germination and early development of cabbage is superior to that of the soaking solution.Steam-exploded rice straw spent liquor is rich in bioactive lignin and oligosaccharides,which makes it a promising biostimulant for promoting crop growth.

Chinese Yibin Liquor Culture Goes Global

Chinese national culture is extensive and profound,and liquor culture is an important part of it.As an important part of Chinese liquor culture,Yibin liquor culture in Sichuan Province not only has the weight of Chinese traditional culture,but also has the new characteristics of Sichuan liquor industry under the new normal.Chinese culture of moderation,loyalty and Chinese culture can be found in Yibin liquor brand.Nowadays,Yibin liquor,the capital of liquor,is popular in five continents for its rich aroma and long Chinese culture.It is of great significance to promote the dissemination of“Sichuan liquor”culture that enhances the multilingual communication of“Sichuan liquor”culture and strengthens traditional culture education to increase consumers’recognition of Chinese liquor culture.

A win-win technique of stabilizing sand dune and purifying paper mill black-liquor

The principle and technique were reported here to produce lignin-based sand stabilizing material （LSSM） using extracted lignin from black liquor of straw paper mills. Field tests using LSSM to stabilize and green sand dunes were started in 2002. The field experiment was carded out in August 2005 when the newly formed plant community was 3 years old. The results from the comprehensive field experiment demonstrated that unlike polyvinyl acetate or foamed asphalt commonly used for dune stabilization, LSSM was plant- friendly material and could be used in combination with seeding and planting of desert species. With the help of LSSM, the desert species （i.e., Agriophyllum squarrosum （L.） Moq. and Artemisia desertorum Spreng. etc.） could be used to form community in 2-3 yeas and to stabilize sand dune effectively. The newly formed community was sustainable under an extremely dry climate condition. The organic matter and total nitrogen in the soil increased significantly as the community were formed, while the change in P and K contents in the soil was negligible.

Treatment of black liquor from the papermaking industry by acidification and reuse

Two different kinds of black liquor from the papermaking industry were treated by acidification and reuse. The experimental parameters and conditions were discussed in detail. The experimental results indicated that the treatment process mentioned in this article is an effective process for the treatment of black liquor from the papermaking industry. By the treatment, the solid materials in black liquor are transferred into two by products and the other components are reused or evaporated. Thus, no wastewater except some condensation water would be discharged in pulping process and the problem of pollution of black liquor would be effectively solved.

Comparison of Algorithms for an Electronic Nose in Identifying Liquors

When the electronic nose is used to identify different varieties of distilled liquors, the pattern recognition algorithm is chosen on the basis of the experience, which lacks the guiding principle. In this research, the different brands of distilled spirits were identified using the pattern recognition algorithms （principal component analysis and the artificial neural network）. The recognition rates of different algorithms were compared. The recognition rate of the Back Propagation Neural Network （BPNN） is the highest. Owing to the slow convergence speed of the BPNN, it tends easily to get into a local minimum. A chaotic BPNN was tried in order to overcome the disadvantage of the BPNN. The convergence speed of the chaotic BPNN is 75.5 times faster than that of the BPNN.

Effect of Maotai liquor on the liver: an experimental study

BACKGROUND: Epidemiology investigation showed that no worker drunk Maotai liquor for nearly 30 years died of hepatic diseases, and no obvious hepatic fibrosis and cirrho- sis were found in 99 workers who had drunk Maotai liquor for a long period by epidemiology investigation and needle biopsy. The same finding was detected in rats that were drunk by Maotai liquor continued for 56 days. This study was to investigate the effects of Maotai liquor on the liver and its mechanism of preventing hepatic fibrosis. METHODS: After ingestion of Maotai for 56 consecutive days, male SD rats were killed for detecting the levels of metallothionein and malondialdehyde (MDA) in liver tis- sues. Rat hepatic stellate cells (HSCs) and human HSCs were cultured in vitro to observe the effect of Maotai on HSCs proliferation and collagen synthesis. After ingestion of Maotai for 14 consecutive weeks, the livers of male SD rats were harvested for pathohistological examination. RESULTS: The level of metallothionein in the liver of Mao- tai-induced rats increased by 22 folds, whereas the levels of hepatic lipid peroxide and MDA was decreased significantly ( P <0.05) in Maotai-induced animals suffering from CCl4. Maotai demonstrated obvious inhibitory effect on prolifera- tion of HSCs and the inhibition was concentration-depen- dent. Gene expression and protein secretion of collagens could also be inhibited by Maotai. In alcoholic group, typi- cal liver cirrhosis was observed. In Maotai group, however, though fatty degeneration of hepatocytes and mild fibrosis of the interstitium were observed, no obvious hepatic fibro- sis and cirrhosis were found. CONCLUSION: It might be an important mechanism of interfering the progress of hepatic fibrosis that Maotai in- creases the level of metallothionein in the liver and inhibits the activation of HSCs and the synthesis of collagen pro- teins.

Combined effect of US/PFS on the black liquor of making paper

The reed pulping black liquor is used as a sample. Researches of (1) combined effect of ultrasound(US)/polyferric sulphate(PFS)/hydrogen peroxide(H 2O 2); (2) effects of the horn tip areas; (3) effect of dose of PFS were carried. Extrapolation of these experiments indicated treatment results are possibly related to complex chemical compositions in the reed pulping black liquor.

Application of Two-Dimensional Correlation UV-Vis Spectroscopy in Chinese Liquor Moutai Discrimination

Chinese liquor Moutai is the “National alcoholic drink” in China and plays a very important role of social activities in Chinese people’s life. In pursuit of high profits, some illegal counterfeit Moutai liquors have begun to appear in the market. Therefore, it is an urgent need for new techniques to discriminate the genuine and counterfeit Moutai liquor. In this work, the conventional Ultraviolet-Visible (UV-Vis) spectroscopy and two-dimensional correlation UV-Vis spectroscopy are applied to obtain the UV-Vis characteristic of Moutai liquor and counterfeit one, respectively. The experimental results reveal that the conventional UV-Vis spectra of the genuine and counterfeit Moutai liquor are similar. However, the two-dimensional correlation UV-Vis spectra of them are different and this method would be applied to differentiate the counterfeit Moutai liquor from the genuine Moutai liquor. Compared with conventional methods, this novel method has the advantages of easy operation, simple instrumentation and direct recognition, which make it a potential tool in the fields of food safety.

Hydraulic and carbonizing actions of sulfuric acid to straw pulp and paper black liquor

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Isolation of Hemicellulose from Wood Chips via Extraction with Kraft Green Liquor

The present paper covers the extraction of hemicelluloses from woods, i.e., Eucalyptus Globulus, white fir and Douglas fir via green liquor pretreatment and alkali post-treatment with sodium hydroxide. The effects of such extraction conditions as extraction time, temperature on the yields of hemicellulose and the degree of deliginification were investigated. Sugar analyses using Dionex indicate that xylose, glucose and mannose are the main sugar types present in the hemicellulose from Eucalyptus. Other sugar components such as arabinose and galactose were also found in Dogulas fir hemicellulose. The highest yield of hemicellulose was 8.4% for Eucalyptus extracted with green liquor at 130 ℃ for 3.5 h. Further sodium hydroxide extraction for 5 h gave a hemicellulose yield of about 20%. The use of green liquor for the extraction of wood hemicellulose is believed to be the first attempt.

Growth properties of mixed liquor suspended solids in SMBR for pharmaceutical wastewater treatment

This paper presents the performance results of a 366-day pilot-scale submerged membrane bioreactor (SMBR) for treating high-strength pharmaceutical wastewater. The study focuses on the growth properties of mixed liquor suspended solids (MLSS) in SMBR operated at high volumetric loading rates. The influences of MLSS on COD removal,sludge yield,oxygen utilization rates and sludge viscosity are studied. Results show that the bioreactor can be operated at higher volumetric loading rate with a low sludge yield. VSS/SS and observed sludge yield coefficient (Yo) present a decreasing trend with the decrease of hydraulic retention time (HRT) . Sludge oxygen utilization rate decreases with the increase of mixed liquor volatile suspended solids (MLVSS) . A mathematical model between sludge viscosity and MLSS is developed.

Near-Infrared Spectroscopy Combined with Partial Least Squares Discriminant Analysis Applied to Identification of Liquor Brands

The identification of liquor brands is very important for food safety. Most of the fake liquors are usually made into the products with the same flavor and alcohol content as regular brand, so the identification for the liquor brands with the same flavor and the same alcohol content is essential. However, it is also difficult because the components of such liquor samples are very similar. Near-infrared (NIR) spectroscopy combined with partial least squares discriminant analysis (PLS-DA) was applied to identification of liquor brands with the same flavor and alcohol content. A total of 160 samples of Luzhou Laojiao liquor and 200 samples of non-Luzhou Laojiao liquor with the same flavor and alcohol content were used for identification. Samples of each type were randomly divided into the modeling and validation sets. The modeling samples were further divided into calibration and prediction sets using the Kennard-Stone algorithm to achieve uniformity and representativeness. In the modeling and validation processes based on PLS-DA method, the recognition rates of samples achieved 99.1% and 98.7%, respectively. The results show high prediction performance for the identification of liquor brands, and were obviously better than those obtained from the principal component linear discriminant analysis method. NIR spectroscopy combined with the PLS-DA method provides a quick and effective means of the discriminant analysis of liquor brands, and is also a promising tool for large-scale inspection of liquor food safety.

Acid precipitation coupled electrodialysis to improve separation of chloride and organics in pulping crystallization mother liquor

Inefficient separation of inorganic salts and organic matters in crystallization mother liquor is still a problem to industrial wa stewater treatment since the high salinity significantly impedes organic pollutant degradation by oxidation or incineration.In the study,acidification combined electrodialysis(ED)was attempted to effectively separate Cl-ions from organics in concentrate pulping wastewater.Membrane’s rejection rate to total organic carbon(TOC)was 85%at wastewater intrinsic pH=9.8 and enhanced to 93%by acidifying it to pH=2 in ED process.Negative-charged alkaline organic compounds(mainly lignin)could be liberated from their sodium salt forms and coagulated in acidification pretreatment.Neutralization of the organic substances also made their electro-migration less effective under electric driving force and in particular improved separation efficiency of chloride and organics.After acid-ED coupled treatment(pH=2 and J=40 mA·cm-2)[TOC]remarkably reduced from 1.315 g·L-1 to 0.048 g·L-1 and[Cl-]accumulated to 130 g·L-1 in concentrate solution.Recovery rate of NaCl was 89%and the power consumption was 0.38 kW·h·kg-1 NaCl.Irreversible fouling was not caused as electric resistance of membrane pile maintained stably.In conclusion,acidic-ED is a practical option to treat salinity organic wastewater when current techniques including thermal evaporation and pressure-driven membrane se paration present limitations.

Rapid qualitative and quantitative analysis of strong aroma base liquor based on SPME-MS combined with chemometrics

To objectively classify and evaluate the strong aroma base liquors(SABLs)of different grades,solid-phase microextraction-mass spectrometry(SPME-MS)combined with chemometrics were used.Results showed that SPME-MS combined with a back-propagation artificial neural network(BPANN)method yielded almost the same recognition performance compared to linear discriminant analysis(LDA)in distinguishing different grades of SABL,with 84%recognition rate for the test set.Partial least squares(PLS),successive projection algorithm partial least squares(SPA-PLS)model,and competitive adaptive reweighed samplingpartial least squares(CARS-PLS)were established for the prediction of the four esters in the SABL.CARS-PLS model showed a greater advantage in the quantitative analysis of ethyl acetate,ethyl butyrate,ethyl caproate,and ethyl lactate.These results corroborated the hypothesis that SPME-MS combined with chemometrics can effectively achieve an accurate determination of different grades of SABL and prediction performance of esters.

Discriminant Analysis of Liquor Brands Based on Moving-Window Waveband Screening Using Near-Infrared Spectroscopy

Partial least squares discriminant analysis (PLS-DA) with integrated moving-window (MW) waveband screening was applied to the discriminant analysis of liquor brands with near-infrared (NIR) spectroscopy. Luzhou Laojiao, a popular liquor with strong fragrant flavor, was used as the identified liquor brand (160 samples, negative, 52 vol alcoholicity). Liquors of 10 other brands with strong fragrant flavor were used as the interferential brands (200 samples, positive, 52 vol alcoholicity). The Kennard-Stone algorithm was used for the division of modeling samples to achieve uniformity and representativeness. Based on the MW-PLS-DA, a simplified optimal model set with 157 wavebands was further proposed. This set contained five types of wavebands corresponding to the NIR absorption bands of water, ethanol, and other micronutrients (i.e., acids, aldehydes, phenols, and aromatic compounds) in liquor for practical choice. Using five selected simple models with 4775 - 4239, 7804 - 6569, 6264 - 5844, 9435 - 7896, and 12066 - 10373 cm-1, the validation recognition rates were obtained as 99.3% or higher. Results show good prediction performance and low model complexity, and also provided a valuable reference for designing small dedicated instruments. The proposed method is a promising tool for large-scale inspection of liquor food safety.

Preparation of Liquor Flavoring from Yellow Water Based on Water Absorbent Resin

[Objective] This study was conducted to extract the scarce natural liquor flavorings desired by many liquor factories from yellow water. [Method] Strong water absorbent resin was used to absorb moisture from the yellow water in order to concentrate it into dense yellow water at first, followed by azcotropic dis- tillation of the previously concentrated yellow water, and then, catalytic esterification was performed to the remaining liquid after the distillation. [ Results] The 7. 066 7 fractions of concentrated yellow water with 56.7% ethanol could be obtained after the treatment of 100 fractions of yellow water with strong water absorbent resin. Azeotrope of 0.432 8 fraction of natural acetaldehyde, 0. 269 4 fraction of ethyl formate and methyl alcohol, 0. 975 0 fraction of ethyl acetate and methyl alco- hol could be obtained after the azeotropic distillation per 100 fractions of concentrated yellow water. After the addition of CaC12, O. 220 7 fraction of ethyl formate and 0. 514 2 fraction of ethyl acetate could be obtained after distillation of the azeotrope. Finally, 92. 094 8 fractions of esterification liquid with 38 kinds of flavor- ing compound could be obtained after catalytic esterification of 100 fractions of concentrated yellow water, and the content of ethyl acetate, ethyl propionate, ethyl- butyrate, ethyl valerate, ethyl lactate and ethyl bexanoate were as much as 142.9, 22.2, 54.2, 3.3,75.4 and 158.9 g/L, respectively. [ Conclusion] Top-grade Luzhou-flavor liquor could be made by mixing 6.5 fractions of common liquor with acetaldehyde, ethyl formate, ethyl acetate and esterification liquid which were ob- tained from 1 fraction of yellow water. Therefore, the yellow water has a great recycling value, and it tells us that the technique of extracting liquor flavorings from yellow water has tremendous market value.