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.

Improved Algorithm for Efficient Extraction of Relaxation Parameter Values from Wideband Permittivity of Baijiu

The complex permittivity of baijiu varies with frequency,and dielectric spectroscopy has been used to evaluate the quality.To simplify the analysis and reduce the number of the parameters,a dielectric relaxation model is often used to fit the permittivity data.However,existing fitting methods such as the least squares and particle swarm optimization methods are often computationally complex and require preset initial values.Therefore,a simpler calculation method of the relaxation parameters considering the geometric characteristics of the permittivity spectrum is proposed.It is based on the relationship between the Cole-Cole relaxation parameters and the Cole-Cole diagram,which is fitted by a geometric method.First,the concepts of the Cole-Cole parameters and the diagram are introduced,and then the process of obtaining the parameters from the complex permittivity measurement data is explained.Taking baijiu with 56%alcohol by volume(ABV)as an example,the fitting is better than the least squares method and similar to the particle swarm optimization.This method is then used for the parameter fitting of baijiu with ABV of 42-52%,and the average error is less than 1%,demonstrating its wider applicability.Finally,a prediction model is used for baijiu with 53%ABV,and the error is only 1.51%.Hence,the method can be applied to the measurement of ABV of baijiu.

Characterization and comparison of the aroma-active compounds on different grades of sesame-flavor Baijiu by headspace solid-phase microextraction and gas chromatography-olfactometry-mass spectrometry

This study investigated the aroma-active compounds and compared the differences of three different grades of sesame-flavor Baijiu by headspace solid-phase microextraction(HS-SPME)coupled with gas chromatography-olfactometry-mass spectrometry(GC-O-MS).A total of 54 aroma-active compounds were detected.Principal component analysis showed that JZ1,JZ2,and JZ3 were well separated from each other.JZ1 as the premium-grade Baijiu had the highest aroma intensities,concentrations.According to aroma intensities and concentrations,dimethyl trisulfide,butanoic acid,phenylacetaldehyde,2-furylmethanethiol,ethyl hexanoate,2,6-dimethylpyrazine,etc.could be potentially applied as volatile makers to distinguish the three different grades of sesame-flavor Baijiu as their significant difference(P<0.05)in three Baijiu samples.Roasted aroma had the significant difference(P<0.05)in three sample base on aroma profiles.Meanwhile,2-furylmethanethiol,2,6-dimethylpyrazine were related to the roasted aroma,they may be had a significant contribution to the differences of three different grades of sesame-flavor Baijiu.This study has provided a comprehensive understanding of the differences of three different grades of sesame-flavor Baijiu.

Characterization of terpenoids and norisoprenoids from base and retail Qingke Baijiu by GC×GC-TOFMS and multivariate statistical analysis

Qingke(highland barley)Baijiu is a special Chinese Baijiu which is mainly produced from Qinghai-Tibet Plateau.Since the pine board is used as the bottom of the fermentation pit,we deduced that the terpenoids and norisoprenoids in pine board might be introduced into Qingke Baijiu.Thus,the terpenoids and norisoprenoids in Qingke Baijiu were investigated by headspace solid phase microextraction(HS-SPME)combined with comprehensive two-dimensional gas chromatography coupled to time-of-flight mass spectrometry(GC×GC-TOFMS).The results showed thatγ-terpinene(0.70-530.72μg/L),α-phellandrene(0.34-256.66μg/L),longicyclene(0-38.55μg/L),α-pinene(1.21-35.54μg/L)and limonene(0.93-23.69μg/L)were the top 5 terpenoids/norisoprenoids in Qingke Baijiu.Pulegone was detected and reported for the first time in Baijiu,and the concentrations in Qingke Baijiu were 0.78μg/L(fresh)and 3.90μg/L(7 years old).According to the principal component analysis(PCA)plot,young,aged,and retail Qingke Baijiu could be differentiated clearly.Fold change(FC)and t-tests analysis indicated thatβ-pinene,γ-terpinene,andα-selinene were the most different terpenoids/norisoprenoids between young and aged Qingke Baijiu,and longifolene was the most different terpenoids/norisoprenoids between base and retail Qingke Baijiu.The terpenoids and norisoprenoids,such as(E)-β-ionone,isoborneol andβ-cyclocitral,could be potential markers indicating the ageing process of Qingke Baijiu.

Wine,beer and Chinese Baijiu in relation to cardiovascular health:the impact of moderate drinking

Excessive alcohol consumption(≥15 drinks per week)causes chronic diseases and multiple other health conditions.Nevertheless,alcohol beverages have been used as a vital medicine ingredient in various cultures since ancient times.A wealth of epidemiological and experimental research has shown that light-moderate alcohol consumption,regardless of beverage type,is associated with reducing cardiovascular incidence and mortality rate.Due to the disparities in raw materials,fermentation techniques,production environment,etc.,alcoholic beverages tend to possess different non-ethanol component profiles,thus resulting in varying degrees of health effects.Furthermore,bioactive compounds in alcohol are continuously discovered as well as the mechanisms underlying their cardioprotective contributions at a molecular level.This article elucidates the epidemiology of moderate alcohol consumption and various cardiovascular conditions,along with the limitations and controversies of current studies.In addition,protective effects and putative mechanisms of both ethanol and non-ethanol components of wine,beer,and Chinese Baijiu,the three most representative alcoholic beverages worldwide,are to be evaluated within the context of a rational drinking pattern.

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.

价键原子指数用于酱香型习酒香气成分保留性质研究

酱香型习酒是一种风味极其独特的酱香型白酒,具有风味醇厚、幽雅细腻和回味悠长的香气,香气成分繁多而复杂.为探究酱香型白酒的主要挥发性物质的组成及香气风味成分的差异,研究建构酱香型习酒香气成分保留指数的定量结构-保留相关性模型,根据酱香型习酒香气成分分子中原子的空间与电性结构,基于拓扑理论,提出了一种新的结构参数-价键原子指数~mA.另计算了酱香型习酒香气成分的电拓扑状态指数(Em),优化筛选了指数中的~0A、E_(1)、E_(2)、E_(14),将4种结构参数作为神经网络三层结构的输入节点数,色谱保留指数作为三层结构的输出节点数,网络结构采用4-12-1方式.建立的预测香气成分保留指数模型的相关系数达到0.9965,计算得到的酱香型习酒香气成分保留指数RI预测值的平均相对误差为1.41%.结果表明,酱香型习酒挥发性香气成分的保留指数,与价键原子指数和电拓扑状态指数之间具有很好的非线性关系,非氢原子结构及—CH_(3)、>CH_(2)、—O—等基团,是影响酱香型习酒香气成分保留指数的主要因素.

白酒酿造微生物酯化酶的研究进展

酯化酶是一类具有催化酯类物质合成活性的酶类。广义上的酯化酶被广泛应用于食品,化工,医药、军工及环保等领域中。白酒酿造微生物酯酶在白酒发酵生香过程中具有重要作用,其代谢产生的乙酸乙酯、乳酸乙酯、丁酸乙酯和己酸乙酯等酯类物质是中国白酒最为重要的风味物质。因此,深入研究中国白酒酿酒微生物酯化酶,对提高白酒优质品率、提升酿酒原料利用率具有重要意义。从微生物酯化酶的来源、特性、分子进化以及在白酒酿造中的应用进行了综述,旨在为中国白酒微生物资源的深入研究和发掘提供一定的思路。

白酒中风味成分的检测分析技术研究进展

白酒历史悠久,是中国的国酒。白酒中的风味成分虽然含量较低,但其类别、组成及比例对产品口感、风味及香气极为重要。近年来,对风味成分的研究已成为白酒领域的热点,本文综述了白酒风味成分检测分析方面的研究进展,介绍了风味成分检测前处理技术与分析方法,总结了各大香型白酒中的风味挖掘及分析的最新成果,探讨了研究中存在的局限与不足,并展望了未来技术发展的方向和趋势。

酒瓶挂珠和材质分析及其对白酒中钠浓度的影响分析

本研究分析了挂珠和不同材质酒瓶的玻璃成分、表面和接触角,在此基础上,用其贮存不同档次的白酒,对货架期的白酒定期进行钠(Na)浓度检测,分析其变化规律。结果表明:选取的酒瓶玻璃主要成分SiO_(2)含量为82~83mol%,密度为2.50~2.52g/cm^(3),质地均匀;存储过程中,挂珠现象对白酒中Na浓度变化几乎无影响;初探表明接触角大的酒瓶长时间存储白酒可能会引起白酒中Na浓度增加。研究结果可为相关企业把控产品质量和白酒储藏提供重要参考。

从元代“汗酒”看中国蒸馏酒起源

元代的蒸馏酒虽有“汗酒”“烧酒”“重酿酒”等汉语名称,但一度流行的“阿剌吉酒”等音译名称,使得中国蒸馏酒起源成为颇具争议的国际性学术问题。本文在系统梳理史籍所载“汗酒”及其制备用具的基础上,结合考古发现的相关资料,通过“汗酒”名称和蒸馏器具渊源的探析,认为“汗酒”之名理应源自历史典故“汗出如浆”,而制备“汗酒”的酒铛实乃釜、甑等多件套甗式蒸馏器。尤其“酒铛”与古代蒸馏器实物的相互对应,有助于重新审视中国蒸馏酒、蒸馏器的起源及演化历程。

浓香双曲酿造工艺与酒醅微生物群落演替规律的研究

本研究按照浓香型白酒工艺特点,利用不锈钢发酵容器,以混合均匀后的浓香产酒大曲和浓香生香大曲作为糖化发酵剂,粉碎高粱为原料,采用清蒸混入、续糟发酵的生产方式,形成浓香双曲酿造工艺。通过常规理化分析技术和Illumina MiSeq高通量测序技术对双曲酿造工艺酒醅的理化指标和微生物菌群进行测定和分析,以进一步探究其发酵机理。结果表明,整个发酵过程中理化指标的变化具有较明显的规律性,酒精度前期迅速增加,后期趋于平缓,并在第9 d时达到最大值。发酵过程中共检测出317个属,其中真菌225个、细菌92个,酒醅中主要优势真菌属有2种,伊萨酵母属(Issatchenkia)在发酵过程中占绝对优势;主要优势细菌属有3种,发酵前期乳酸菌属(Lactobacillus)占绝对优势,发酵后期unclassified-Lactobacillales占绝对优势。酒醅发酵过程中微生物群落结构的变化与理化因子有显著关系,对真菌而言,还原糖含量与双足囊菌属(Dipodascus)、嗜热子真菌属(Thermomyces)的相对丰度呈极显著正相关;对细菌而言,淀粉和还原糖的含量与葡萄球菌属(Staphylococcus)相对丰度呈显著正相关,水分含量和酒精度与unclassified-Lactobacillales相对丰度呈显著正相关。酒醅发酵过程中温度、酒精度和酸度推动了微生物群落结构的演替。

不同发酵期浓香型青稞酒糟醅理化指标及基酒香气组分差异

基于前期优化的浓香型青稞酒发酵工艺,探究不同发酵期(40 d,50 d和60 d)对浓香型青稞酒糟醅理化指标和基酒挥发性香气组分的影响。结果表明,不同发酵期浓香型青稞酒出窖糟醅的水分、酸度、还原糖和淀粉差异显著(p<0.05)。随着发酵期的增加,出窖糟醅的水分增加,还原糖、酸度和淀粉呈现下降趋势。延长发酵期有利于延长微生物分解代谢,提高淀粉的利用率,提升出酒率。不同发酵期青稞酒的挥发性香气组分含量差异较大。随着发酵期增加,挥发性香气组分的种类及总含量呈现增加趋势。酸类、醇类和酯类为主要的挥发性香气组分,酸类和醇类组分的含量呈现先增加后下降的趋势,可能与醇酸酯化合成酯类有关,与酯类组分的含量增加趋势相一致。长发酵期有利于提高青稞酒中酯类组分的含量,进而增加青稞酒的香气浓郁度和丰富度。

贵州仁怀生物多样性及其环境背景

通过对仁怀市自然环境、遗传资源多样性、物种多样性、生态系统多样性、景观与土地利用开展全面、深入、系统地调查,结果发现仁怀市自然地理环境较为特殊,区内共记录野生生物物种5515种,其中植物2590种,动物1262种,微生物1663种,包括贵州省新记录科1个、新记录属9个、新记录种116个。仁怀市分布有国家重点保护野生植物21种,国家重点保护野生动物26种。本研究首次全面摸清了仁怀市生物多样性本底资源现状,并尝试系统地从无机环境、微生物和生物多样性方面阐释酱香白酒生产条件的特殊性,对仁怀市生物多样性保护和利用、酱香白酒产业的可持续发展具有一定的指导意义。

锆基非晶合金电解质等离子体抛光工艺及废液处理

电解质等离子体抛光技术在非晶合金结构件的应用仍处于探索阶段,而且会产生含较高浓度的重金属和氟离子废液。为了提高锆基非晶合金结构件的表面质量以满足其使役性能,研究抛光时间、工作电压、硫酸铵浓度、初始温度、工件入水深度、阳极挂具材料等电解质等离子体抛光工艺参数对锆基非晶合金表面粗糙度、晶化情况的影响,并利用正交试验进行参数组合优化,对比不同参数对于表面粗糙度的影响显著程度。最后针对抛光后废液污染的问题,探究并配套合适的废液处理方案。结果表明:影响抛光后材料表面质量因素的显著程度为抛光时间>工作电压>初始温度>硫酸铵浓度,最优抛光工艺参数组合为抛光时间8 min,工作电压220 V,初始温度88℃,硫酸铵浓度为5%,此时表面粗糙度为0.103μm。经化学混凝沉淀法和离子交换树脂法组合工艺处理后,出水废液中的重金属和氟离子浓度均能达国家电镀污染物排放标准。研究成果可为电解质等离子体抛光在锆基非晶合金的实际生产提供工艺指导,有助于推广锆基非晶合金结构件的产业化应用,促进锆基非晶合金的大规模工业生产。

手绘插画在青春白酒包装设计中的应用研究

开发年轻消费群体市场已经成为新时期很多大型酒企的战略目标。青春白酒是树立品牌年轻化的重要策略,而插画艺术的视觉语言鲜明、艺术形态新颖,与青春白酒类品牌结合,有利于活力的体现和情感的传递,也更能有效与市场上的同类产品产生差异,形成自己的风格。文章以现代造型观念和插画表现形式进行白酒包装的创新,以年轻一代的审美导向作为主要参考,设计出具有新的视角语言、新的艺术形态的青春类白酒包装。遵循此方向,探讨如何丰富和发展手绘插画形式的青春白酒的包装设计,具有较高的研究意义和应用价值。

三种不同过滤方式对特香型白酒质量的影响研究

从白酒的气相色谱成分、离子色谱成分、感官评定等方面研究分析活性炭吸附过滤、冷冻过滤、聚能量膜过滤对特香型白酒的影响。结果表明:活性炭吸附过滤对酒体骨架成分及风味影响较大、净化能力较强,适用于过滤风味欠佳的酒体;冷冻过滤对酒体骨架成分及风味影响较小,适用于过滤风味一般的酒体;聚能量膜过滤对酒体骨架成分及风味基本无影响、滤后酒体的自然微黄颜色及风味可以最大程度地得以保留,适用于过滤风味较好的酒体。