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.

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。

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。

基于形状文法的荆楚青铜酒具重构设计

对传统荆楚青铜酒具的造型研究,通过对其风格演变与器型、纹饰特征进行分析,结合当下对白酒酒具设计新的需求进行实践。运用文献研究法和形状文法对荆楚青铜酒具元素进行提取、转换,通过案例实践分析传统酒具造型运用于现代白酒酒具的设计路径。构建出荆楚传统青铜酒具的创新形态及推演设计过程,丰富现代白酒酒具设计的文化内涵,为同类产品设计研究提供过程参考。

白酒外包装设计中中国传统元素的运用分析

探讨白酒外包装设计中传统元素的应用对白酒品牌价值和艺术价值的影响。通过文献分析和实地调研,了解相关传统文化元素在白酒外包装的实际应用。研究结果显示,白酒包装设计中的传统元素可以赋予产品独特的视觉冲击力和文化情感。色彩能够传达出浓郁的民族特色和品牌特色氛围;运用书法能够展示品牌的文化内涵和审美价值。同时,中国传统元素在白酒外包装设计中的应用将产生巨大影响。这不仅表现在设计创新方面,而且可以最大化品牌价值和市场竞争力。

乌衣红曲黄酒年份特征挥发性物质指纹图谱分析

目的:建立乌衣红曲黄酒基酒挥发性成分指纹图谱,用于年份基酒酒龄的判别。方法:通过顶空固相微萃取-气相色谱联用质谱法(HS-SPME-GC-MS)分析不同陈酿时间的乌衣红曲黄酒中的挥发性成分,结合正交偏最小二乘法-判别分析(OPLS-DA)和Spearman相关性分析确定与年份相关的关键成分,用于构建年份基酒特征指纹图谱。结果:从不同年份的乌衣红曲黄酒中,共检出并定性挥发性成分122种,与陈酿时间显著相关的有20种(|r|>0.5),其中N-苯甲酰甘氨酸乙酯、6-庚烯酸乙酯、乙酸-2-乙基苯酯等8种与陈酿时间呈正相关关系,2-呋喃甲醇、辛酸、庚酸乙酯等12种与陈酿时间呈负相关关系。基于筛选的20种年份特征挥发性物质,构建了乌衣红曲黄酒基酒年份基酒指纹图谱。依据香气成分的OPLS-DA分析和指纹图谱数据信息将2~15年陈乌衣红曲基酒样品区分为青陈酒(2~4年)、中陈酒(5~9年)、老陈酒(10~15年)3个类别,并通过二次取样分析,验证所建图谱的可靠性。结论:GC-MS技术构建的挥发性成分指纹图谱可为乌衣红曲黄酒基酒品质评价及酒龄的识别提供基础数据。

红枣蒸馏酒原酒发酵工艺优化及品质分析

以干红枣为原料发酵制备红枣果酒,进而蒸馏获得红枣蒸馏酒,对红枣原酒发酵工艺进行优化及品质分析,探讨酒精度和甲醇含量在发酵阶段和蒸馏阶段随发酵温度、干酵母接种量及初始糖度的变化规律。结果表明,在单因素试验基础上,通过拟合方程得到最佳红枣原酒发酵工艺为发酵温度24℃、酵母接种量0.71 g/L、初始糖度22°Bx。在此优化条件下,甲醇含量为1.71 g/L,酒精度为12.51%vol。在蒸馏过程中,酒精度从66.2%vol逐渐下降直至为0,而甲醇含量从1.69 g/L增加至最大值5.05 g/L,随后迅速降低。采用拟合方程可描述蒸馏酒液收样体积与酒液中酒精度及甲醇对应的函数关系。红枣蒸馏酒酒体澄清透明,具有明显的枣香,独特的风格,感官评分为92分,甲醇含量为1.90 g/L,酒精度54.7%vol,酒精回收率73.0%。

膜浓缩液蒸发母液回灌填埋场对渗滤液水质及处理系统的影响研究

渗沥液是生活垃圾卫生填埋过程产生的二次污染物之一,但膜处理过程中会产生浓缩液。MVR蒸发是膜浓缩液的主要处理技术之一,但处理过程中会产生蒸发母液。研究探讨了蒸发母液回灌填埋堆体对渗滤液水质和设备腐蚀情况的影响。研究表明蒸发母液回灌会导致填埋堆体含水率升高,产生的渗滤液水质TDS和COD显著升高,进而导致DTRO进水TDS上升,产浓率和膜压力上升,盐分截留率下降,膜污染和设备腐蚀加剧。可见,蒸发母液回灌会对填埋场渗滤液产生和处置产生不利影响,应开发适宜的蒸发母液处理处置技术。

源于类芽胞杆菌的低聚糖脱支酶底物特异性及其应用研究

脱支酶是淀粉深加工产业的常用酶制剂,然而传统脱支酶难以完全满足淀粉糖绿色生产及副产物综合利用的需求,因此有必要挖掘适合的新型脱支酶。本研究筛选并构建来源于类芽胞杆菌STB16的低聚糖脱支酶基因(oga)的枯草芽孢杆菌表达系统,实现低聚糖脱支酶的异源表达,并探究重组酶的酶学性质和底物特异性。结果表明,枯草芽孢杆菌发酵上清液的酶活力可达162.33 U/mL,重组酶的最适反应温度50℃、最适反应pH值6.0,且专一地作用于底物中聚合度为1的分支的α-1,6-糖苷键。相比于其它类型的脱支酶(底物转化率低于检出限),重组低聚糖脱支酶对异麦芽糖、异麦芽三糖、潘糖等异麦芽低聚糖具有更彻底的水解能力,底物转化率达97.4%~100%,且产物为葡萄糖,因此更适合用于处理葡萄糖母液,可使一次母液、二次母液和色谱分离尾液中葡萄糖含量分别提升3.6%,12.7%和34.4%。相关研究结果可为新型脱支酶的开发和利用奠定理论基础,也为淀粉糖加工副产物的综合利用提供重要参考。

石蜡与氨基酸废母液粉配施对烟草重金属Cd吸附的阻控效应

烟草是强富集镉(Cd)的重要经济作物.为降低烟草对Cd的吸收,以矿区污染土壤(Cd含量为0.678 mg·kg^(−1))为种植基质,烟草专用肥(硝态氮)为对照,氨基酸母液粉为新型氮肥(氨基氮),并分别配施作为土壤微生物碳源的食品级石蜡,以期促进土壤微生物种群与数量的持续增加(石蜡降解速度缓慢),通过微生物的生化调控达到降低土壤有效态Cd含量,从而减少烟叶对镉的吸收.结果表明:(1)石蜡和氨基酸废母液粉配施(T4处理)显著(P<0.05)提高土壤微生物丰富度,ACE指数达到4464.47,Chao1指数达到3888.30,氨基酸废母液粉(T3处理)土壤微生物多样性最好,Shannon指数达到6.4066;(2)施加氨基酸废母液粉(T3、T4处理)可显著(P<0.05)提高土壤pH值,3个时期(烟叶旺长期、打顶期、成熟期)最大提高量分别为0.23、0.49和0.35;(3)石蜡和氨基酸废母液粉显著(P<0.05)降低土壤有效态Cd含量,3个时期较烟草专用肥组(T1处理)分别降低了14.8%—20.7%、18.6%—34.5%、20.5%—36.7%;(4)石蜡和氨基酸废母液粉显著(P<0.05)降低烟叶Cd含量,3个时期较烟草专用肥(T1处理)分别降低了0.6%—10.2%、8.2%—26.2%、13.8%—38.9%.因此,石蜡和氨基酸废母液粉配施能够有效提高土壤微生物丰富度和多样性,降低土壤有效态Cd含量,减少烟草对Cd的吸收.

酒中高级醇调控的研究进展

酒作为大众喜爱的饮品,人们对其需求量和品质的要求在不断提高。高级醇是酒中最主要的呈味物质之一,适量的高级醇可赋予酒体醇香的口感、增加酒体协调性,而高级醇含量过高或过低均会影响酒体的口感,当高级醇含量超过一定限度时还会对饮用者的身体健康造成损害。因此,调控酒中高级醇的含量及比例对有效提高酒体品质、促进酒产业健康发展具有重要意义。该文系统阐述酒中高级醇的形成机制,总结发酵工艺、酿酒酵母菌株以及菌株选育对高级醇的影响,旨在为酒工业化生产中高级醇精细化调控提供参考。

鱼粉压榨液中二十碳五烯酸和二十二碳六烯酸的富集及其甘油酯化

该文从鱼粉压榨液中富集二十碳五烯酸(eicosapentaenoic acid,EPA)和二十二碳六烯酸(docosahexaenoic acid,DHA),进而采用固定化酶CALB-A两步法催化合成甘油酯型鱼油。结果表明,经一级分子蒸馏富集的乙酯型鱼油中EPA+DHA含量为43.2%,回收率为87.04%;以固定化酶CALB-A催化该乙酯型鱼油和甘油反应合成甘油酯型鱼油,优化后的条件为,以甘油/乙酯物质的量比1∶4、2%加酶量(以底物总质量计)、底物浓度20%(质量分数)、反应温度50℃的条件在叔丁醇溶剂中反应6 h,回收的油相以3%加酶量(以底物总质量计)、反应温度50℃、真空条件下反应24 h,乙酯的转化率可以达到68.27%,甘油三酯(triacylglycerol,TAG)产率为62.51%;脂肪酸分析表明得到TAG中脂肪酸组成与原料一致。

再生木质素粒子增强纤维素透明膜的性能研究

本研究以硫酸盐制浆黑液为原料,通过钙离子螯合的方式提取粗制木质素,利用乙醇-水反溶剂法溶解再生以获得高纯度的木质素粒子。呈现细小均匀的颗粒形态并稳定悬浮在水中的再生木质素粒子能够与纤维素形成强氢键结合,并形成致密均匀的复合透明薄膜。木质素-纤维素复合膜(木质素添加量10%)的抗拉强度达105.77 MPa,相比于纯纤维素膜提高了27.6%;伸长率增幅67.6%。在光学方面,木质素-纤维素膜(木质素添加量5%)的可见光透过率可达87.9%。

响应面法优化零价铁活化过硫酸盐处理酱香型白酒废水

以贵州省仁怀市某白酒废水处理厂二沉池出水为研究对象,采用零价铁(Fe^(0))活化过硫酸盐(S_(2)O_(8)^(2-),PS)的高级氧化法对其深度处理,并进行工艺条件的优化。通过单因素实验考察了溶液初始pH、PS投加量、n(Fe^(0))∶n(PS)对白酒废水处理效果的影响,并采用响应面法进行优化验证。结果表明,过硫酸盐法可以有效地降低白酒废水的有机物浓度,优化工艺条件:溶液初始pH为4.08,PS投加量为理论投加量(1 mg/L COD完全氧化理论上需要12 mg/L PS)的1.39倍,n(Fe^(0))∶n(PS)=1.27。在此条件下,白酒废水的COD去除率达70.33%。

陈皮酵素对小鼠酒精性肝损伤及肠道菌群的调节作用

目的探讨陈皮酵素(Pericarpium citri reticulatae fermentation liquor,PF)对小鼠酒精性肝损伤和肠道的调节作用。方法将40只C57BL/6雄性小鼠随机分为正常组、模型组、阳性药物组[100mg/(kg·d)水飞蓟宾(silibinin,Sly)]和陈皮酵素组[500 mg/(kg·d)PF],每组10只,持续给药干预2周。通过分子生物学检测生物化学和病理学指标;16S rDNA高通量测序技术检测分析粪便微生物群。结果组织切片结果显示陈皮酵素可以显著改善酒精性肝损伤小鼠的肝脏和回肠组织损伤,减少酒精诱导的肝脏脂质积累。此外,陈皮酵素显著降低肝脏组织促炎因子[白细胞介素-1β(interleukin-1β,IL-1β)、白细胞介素-6(interleukin-6,IL-6)和肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)]的水平,缓解酒精引起的氧化应激。同时,陈皮酵素可修复酒精引起的肠道菌群紊乱,维持肠道菌群数量,修复肠道黏膜屏障损伤。结论陈皮酵素可改善酒精性肝损伤,其机制与抗氧化、抗炎和调节肠道菌群紊乱有关,值得推广应用与开发。