前列腺素D2及其受体与哺乳动物生殖

前列腺素D2(PGD2)是前列腺素(PGs)家族成员之一,广泛分布于各种哺乳动物组织中,并发挥多种生理功能。PGD,可以促进睡眠、诱导过敏反应、抑制血小板凝集及松弛平滑肌等,并且在生殖系统中起重要作用。机体中存在生化和免疫功能截然不同的两类前列腺素D合成酶(PGDs)：脑型PGDS(L-PGDS)和生血型PGDS(hPGDS)。生殖系统中,L-PGDS主要存在于雄性生殖道,可能在睾丸发育、精子发生、精子成熟以及血一睾和血一附睾屏障等方面发挥重要作用。hPGDS在妊娠时期的子宫内膜和胚胎滋养层中表达,由其产生的PGD2可能通过DP和CRTH2两种受体来维持妊娠。此外,PGD2还可能与女性不孕以及精子在雌性生殖道内的运输等有关。     

创伤性脑损伤对大鼠海马骨架蛋白及学习记忆功能影响

创伤性脑损伤（traumatic brain injury,TBI）是极为常见的外伤性疾病,致死率和致残率很高。存活者伴随的空间认知功能障碍,给患者家庭和社会造成了极大的负担。目前,对TBI造成的空间记忆障碍缺乏系统研究。脑损伤后海马组织与记忆有关的分子以及组成神经元骨架的分子如何变化研究甚少。本研究采用Wistar大鼠为研究对象,并随机将其分为假手术（sham）组和创伤性脑损伤（TBI）组。TBI组再按致伤后时间长短分为6 h、12 h、24 h、72 h、15 d五个亚组。TBI组应用PinPointTM颅脑撞击器撞击而致伤,sham组不撞击。采用Morris水迷宫评价实验动物空间记忆能力;干湿重法测定脑含水量,评估脑水肿与海马水通道蛋白4（aquaporin-4,AQP-4）的相关性;海马神经元特异性核蛋白（neuron specific nuclear protein,NeuN）标记和免疫荧光检测评估TBI致大鼠神经元丢失情况;通过Western印迹检测TBI致海马骨架相关蛋白质和记忆相关蛋白质含量变化。本研究证实,与sham组相比,TBI组大鼠潜伏期明显增加［（61.98±12.82) s vs.(28.32±8.52) s,n=5,P<0.01,day 15］,探索时间明显缩短［（36.98±0.37) s vs. (73.68±5.09) s,n=5,P<0.01,day15］,表明脑创伤损害了动物的空间参考记忆能力和空间工作记忆能力。与sham组相比,TBI组大鼠海马AQP-4在蛋白质水平上的表达和脑含水量持续升高,15 d恢复正常;在12 h［（3.78±0.74),(83.78±0.35)%］和72 h［（3.49±0.85),(82.28±0.63)%］均形成两个波峰,n=5,P均<0.01,表明继发性脑损伤与持续脑水肿和海马AQP-4在蛋白质上的高表达有关。与sham组相比,NeuN标记和免疫荧光检测发现,TBI后24 h 致大鼠海马神经元丢失严重［（198.2±8.002) vs.(297.2±6.866) cells/mm2, n=5,P<0.01］,表明TBI动物的海马功能受损。与sham相比,TBI组海马神经元树突标志物微管结合蛋白2（microtubule associated proein 2,MAP2）和突触前终末特异性标记物突触素（synaptophysin,SYN）在蛋白质水平均伤后逐步降低（n=5,P均<0.01）,72 h［（0.55±0.05) vs.(1.27±0.08), (0.52±0.14) vs.(1.06±0.16), n=5,P均<0.01］降低最明显;TBI组形成神经元纤维缠结主要成分的过度磷酸化tau（ser404）,伤后逐步升高,72 h［（1.25±0.11)vs. (0.33±0.07), n=5,P<0.01］升高最明显。 MAP2、SYN和过度磷酸化的tau（ser404）检测指标的改变,表明脑损伤致神经元受损,神经元生长和损伤修复能力减弱,最终导致神经元骨架破环,TBI损害了动物的海马空间记忆能力。与sham组相比,TBI组大鼠海马环磷酸腺苷反应元件结合蛋白（cAMP response element binding protein,CREB）和磷酸化CREB ser133(phosphorylated CREB Ser133, pCREB Ser133)含量降低明显（n=5,P均<0.05）,表明脑损伤动物海马的存储记忆能力减弱;TBI组大鼠海马一般调控阻遏蛋白激酶2(general control nonderepressible 2 kinase,GCN2)蛋白质升高明显（n=5,P均<0.05）,表明脑损伤动物海马将新信息转化成长期记忆能力下降。本研究提示,创伤性脑损伤可使大鼠海马神经元骨架破坏,进而导致在学习记忆过程中起重要作用的分子蛋白质下调,抑制记忆储存的蛋白质（GCN2）上调,促使学习记忆功能障碍。     

创伤性脑损伤对大鼠海马骨架蛋白及学习记忆功能影响

创伤性脑损伤（traumatic brain injury,TBI）是极为常见的外伤性疾病,致死率和致残率很高。存活者伴随的空间认知功能障碍,给患者家庭和社会造成了极大的负担。目前,对TBI造成的空间记忆障碍缺乏系统研究。脑损伤后海马组织与记忆有关的分子以及组成神经元骨架的分子如何变化研究甚少。本研究采用Wistar大鼠为研究对象,并随机将其分为假手术（sham）组和创伤性脑损伤（TBI）组。TBI组再按致伤后时间长短分为6 h、12 h、24 h、72 h、15 d五个亚组。TBI组应用PinPointTM颅脑撞击器撞击而致伤,sham组不撞击。采用Morris水迷宫评价实验动物空间记忆能力;干湿重法测定脑含水量,评估脑水肿与海马水通道蛋白4（aquaporin-4,AQP-4）的相关性;海马神经元特异性核蛋白（neuron specific nuclear protein,NeuN）标记和免疫荧光检测评估TBI致大鼠神经元丢失情况;通过Western印迹检测TBI致海马骨架相关蛋白质和记忆相关蛋白质含量变化。本研究证实,与sham组相比,TBI组大鼠潜伏期明显增加［（61.98±12.82) s vs.(28.32±8.52) s,n=5,P<0.01,day 15］,探索时间明显缩短［（36.98±0.37) s vs. (73.68±5.09) s,n=5,P<0.01,day15］,表明脑创伤损害了动物的空间参考记忆能力和空间工作记忆能力。与sham组相比,TBI组大鼠海马AQP-4在蛋白质水平上的表达和脑含水量持续升高,15 d恢复正常;在12 h［（3.78±0.74),(83.78±0.35)%］和72 h［（3.49±0.85),(82.28±0.63)%］均形成两个波峰,n=5,P均<0.01,表明继发性脑损伤与持续脑水肿和海马AQP-4在蛋白质上的高表达有关。与sham组相比,NeuN标记和免疫荧光检测发现,TBI后24 h 致大鼠海马神经元丢失严重［（198.2±8.002) vs.(297.2±6.866) cells/mm2, n=5,P<0.01］,表明TBI动物的海马功能受损。与sham相比,TBI组海马神经元树突标志物微管结合蛋白2（microtubule associated proein 2,MAP2）和突触前终末特异性标记物突触素（synaptophysin,SYN）在蛋白质水平均伤后逐步降低（n=5,P均<0.01）,72 h［（0.55±0.05) vs.(1.27±0.08), (0.52±0.14) vs.(1.06±0.16), n=5,P均<0.01］降低最明显;TBI组形成神经元纤维缠结主要成分的过度磷酸化tau（ser404）,伤后逐步升高,72 h［（1.25±0.11)vs. (0.33±0.07), n=5,P<0.01］升高最明显。 MAP2、SYN和过度磷酸化的tau（ser404）检测指标的改变,表明脑损伤致神经元受损,神经元生长和损伤修复能力减弱,最终导致神经元骨架破环,TBI损害了动物的海马空间记忆能力。与sham组相比,TBI组大鼠海马环磷酸腺苷反应元件结合蛋白（cAMP response element binding protein,CREB）和磷酸化CREB ser133(phosphorylated CREB Ser133, pCREB Ser133)含量降低明显（n=5,P均<0.05）,表明脑损伤动物海马的存储记忆能力减弱;TBI组大鼠海马一般调控阻遏蛋白激酶2(general control nonderepressible 2 kinase,GCN2)蛋白质升高明显（n=5,P均<0.05）,表明脑损伤动物海马将新信息转化成长期记忆能力下降。本研究提示,创伤性脑损伤可使大鼠海马神经元骨架破坏,进而导致在学习记忆过程中起重要作用的分子蛋白质下调,抑制记忆储存的蛋白质（GCN2）上调,促使学习记忆功能障碍。     

PS-2基因的克隆及其在肝癌中的表达

利用荧光差异显示技术比较了正常肝、肝硬化和肝癌组织 m RNA的表达 ,1 4个有差异的条带通过 Northern blot分析表明其中 9个为阳性 .令人感兴趣的是一个～ 5 0 0 bp的 c DNA片段 ,它在正常肝和肝硬化中低表达 ,在肝癌组织中高表达 .通过测序 ,发现该片段与 PS- 2 ( presenilin- 2 )基因有 94 %的同源性 .PS- 2基因的突变与早发性阿尔茨海默氏症有关 ,但在肝癌发生中的作用未明 .也许 PS- 2基因的上调涉及到肝癌发生的分子机理     

Differential susceptibilities of serine/threonine phosphatases to oxidative and nitrosative stress

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are signal-transducing molecules that regulate the activities of a variety of proteins. In the present investigation, we have compared the effects of superoxide (O2-), nitric oxide (NO), and hydrogen peroxide (H2O2) on the activities of three highly homologous serine/threonine phosphatases, protein phosphatase type 1 (PP1), protein phosphatase type 2A (PP2A), and calcineurin (protein phosphatase type 2B). Although superoxide, generated from xanthine/xanthine oxidase or paraquat, and NO, generated from (+/-)-(E)-4-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide or sodium nitroprusside, potently inhibited the phosphatase activity of calcineurin in neuroblastoma cell lysates, they had relatively little effect on the activities of PP1 or PP2A. In contrast, H2O2 inhibited the activities of all three phosphatases in lysates but was not a potent inhibitor for any of the enzymes. Calcineurin inactivated by O2-, NO, and H2O2 could be partially reactivated by the reducing agent ascorbate or by the thiol-specific reagent dithiothreitol (DTT). Maximal reactivation was achieved by the addition of both reagents, which suggests that ROS and RNS inhibit calcineurin by oxidizing both a catalytic metal(s) and a critical thiol(s). Reactivation of H2O2-treated PP1 also required the combination of both ascorbate and DTT, whereas PP2A required only DTT for reactivation. These results suggest that, despite their highly homologous structures, calcineurin is the only major Ser/Thr phosphatase that is a sensitive target for inhibition by superoxide and nitric oxide and that none of the phosphatases are sensitive to inhibition by hydrogen peroxide.     

Fusion expression of DDR2 extracellular domain in insect cells and its purification and function characterization

Discoidin domain receptor 2 (DDR2) is a kind of protein tyrosine kinases associated with cell proliferation and tumor metastasis, and collagen, a ligand for DDR2, up-regulates matrix metalloproteinase 1 (MMP-1) and MMP-2 expression in extracellular matrix (ECM). To investigate the role of DDR2 in cartilage destruction in rheumatoid arthritis (RA), we expressed the extracellular domain (ECD) of DDR2 (without signal peptide and transmembrane domain, designated DR) in insect cells, purified and characterized DR, hoping to use it as a specific antagonist of DDR2. By using Bac-To-Bac Expression System with a His tag, we successfully obtained the recombinant bacularvirus containing DDR2 ECD, purified it and characterized its function. The soluble fraction of DR was about 12% of the total fused protein. After chromatographic purification, DR with 92% purity was obtained. Competitive inhibition assay demonstrated that DR blocked the binding between DDR2 and natural DDR2 receptors on NIH3T3 and synovial cells. Results of RT-PCR, Western blotting, and gelatinase zymography showed that DR was capable of inhibiting MMP-1 and MMP-2 secretion from NIH3T3 and RA synoviocytes stimulated by collagen II. For MMP-1, inhibition was displayed at the levels of mRNA and protein, whereas for MMP-2 it was at the level of protein. These findings suggested that the expressed DR inhibited the activity of natural DDR2 and relevant MMP-1 and MMP-2 expression in RA synoviocytes and NIH3T3 cells provoked by collagen II.     

Three single nucleotide polymorphisms leading to non-synonymous amino acid substitution in the human ribonuclease 2 and angiogenin genes exhibit markedly less genetic heterogeneity in six populations

Angiogenin and ribonuclease 2 (RNase 2) are members of the human RNase superfamily. Although three potential single nucleotide polymorphisms (SNPs) in these genes, which could give rise to an amino acid substitution in the protein, have been identified, relevant population data are not available, and accordingly they have not been applied to clinical-genetic analysis. For this purpose, a novel genotyping method for each SNP using the mismatched PCR-restriction fragment length polymorphism technique has been developed. Using this method, the genotype distribution of each SNP was investigated in six populations: Japanese (n = 167), Korean (n = 90), Mongolian (n = 92), Ovambos (n = 86), Turkish (n = 87), and German (n = 70). In all the populations, only one genotype was found in each SNP. Irrespective of differences in ethnic groups, the angiogenin and RNase 2 genes appear to exhibit markedly less genetic heterogeneity with regard to these SNPs.     

去泛素化酶JOSD2促进肝癌细胞的存活和转移

蛋白质泛素化是一种可逆的蛋白质翻译后修饰,在信号转导和蛋白质稳定性调控中发挥关键作用。去泛素化酶调控在许多种肿瘤中的作用机制尚不清楚。本文对63种去泛素化酶在肝细胞癌病人的生存和预后进行分析,发现去泛素化酶JOSD2(josephin domain containing 2)在肝细胞癌组织中表达显著高于癌旁(P<0.0001),且与总生存期相关(P<0.05)。JOSD2属于去泛素化酶MJD(machado josephin domain)亚家族成员,该家族其它成员与肝细胞癌发生无显著的相关性。对TCGA(The Cancer Genome Atlas)数据中JOSD2高表达样本和低表达样本的差异基因进行功能富集分析,显示JOSD2高表达样本中与细胞增殖相关通路显著富集(FDR<0.05)。在肝癌细胞系中过表达JOSD2,发现其能促进肝癌细胞的存活、迁移和侵袭(P<0.01)。综上所述,本文发现去泛素化酶JOSD2在肝细胞癌组织中高表达,高表达JOSD2的肝细胞癌病人总生存期显著降低(P=0.041),过表达JOSD2能促进肝癌细胞的存活和转移,提示JOSD2可能促进肝细胞癌的转移。     

Determination of the extraction kinetics for the quantification of polyhydroxyalkanoate monomers in mixed microbial systems

For the first time, a systematic approach was conducted to determine the key factors influencing the kinetics of hydroxyalkanote (HA) extraction in biological systems. Six mixed microbial systems where polyhydroxyalkanoate (PHA) is produced were evaluated. Experiments were carried out for full-scale and lab-scale activated sludge systems using different configurations (containing floccular or granular sludge), as well as specific PHA accumulating cultures that contain high or low intracellular PHA fractions. The overall reaction was limited by the kinetics of the PHA hydrolysis in floccular cultures, whereas in granular cultures, it was limited by the cell lysis step. The monomeric composition of the polymer also had an impact on the HA extraction rate: higher acid concentration and a longer digestion time should be employed when cells accumulate monomers with more substituents, such as hydroxy-2-methylbutyrate (H2MB) and hydroxy-2-methylvalerate (H2MV). This study optimised the method for HA extraction, which impacts the assessment of the quantity and quality of PHA biopolymers.     

TGR5和CDX2在胃黏膜肠化生及胃癌中的表达及意义

目的:探讨G蛋白偶联受体(G protein-coupled receptor,TGR5)和尾型同源盒2(Caudal type homeobox 2,CDX2)在胃黏膜肠化生(Intestinal Metaplasia,IM)及胃癌中的表达和意义。方法:采用免疫组织化学染色法检测TGR5和CDX2在57例慢性胃炎、85例IM、98例胃癌组织中的表达。比较各组间TGR5和CDX2的表达差异,并分析其与胃癌临床病理参数的关系及与胃癌患者预后的关系。利用Spearman秩相关检验分析TGR5和CDX2表达的相关性。结果:IM和胃癌组织中TGR5的高表达率分别为54.1%和58.2%,二者比较无显著差异(P0.05),但均显著高于慢性胃炎组织(P0.01)。TGR5高表达与胃癌患者TNM分期(III+IV期)(P=0.004)、淋巴结转移(P=0.046)及预后较差(P=0.006)相关。胃癌组织中CDX2的高表达率(30.6%)较IM组织(48.2%)显著降低(P0.05),但其均显著高于慢性胃炎组织(P0.01)。CDX2高表达与胃癌患者TNM分期(I+II期)(P=0.008)、无淋巴结转移(P=0.014)、预后较好(P=0.023)相关。TGR5和CDX2表达在慢性胃炎和IM中无相关性(P0.05),在胃癌中呈显著正相关(P=0.003)。结论:TGR5和CDX2在IM和胃癌组织中均显著上调,可能参与了IM和胃癌的发生发展。     

滇产回心草及回心康抗缺血心肌脂质过氧化作用及对前列环素／血栓素的影响

采用结扎大鼠冠脉造成急性心肌缺血模型,动态观测Ⅱ导联心电图ST段的变化,以S-T段上移为指标反映缺血程度,观察了滇产回心草及回心康对急性心肌缺血损伤的保护作用,同时检测血清SOD、MDA、PGI2和TXA2.结果表明,回心草及回心康均能显著减少S-T段上移,均以2 g/kg组为显著;其1 g/kg及2 g/kg均使心肌梗塞范围缩小(p＜0.05,p＜0.01);均使心肌缺血大鼠血清SOD显著提高(p＜0.05及p＜0.01);MDA显著降低(p＜0.05,p＜0.01).回心草及回心康还能提高大鼠血清PGI2水平,降低TXA2含量,以回心草2 g/kg及回心康2 g/kg为显著(p＜0.05),呈剂量依赖性.实验结果提示,回心草及回心康均具有抗心肌缺血及抗脂质过氧化作用,其提高PGI2/TXA2可能与其抗心肌缺血作用机制有关.     

综述:2型糖尿病与轻度认知障碍

阿尔茨海默病(Alzheimer's disease,AD)是一个连续的病理生理过程,包括轻度认知障碍前期(pre-MCI)、轻度认知障碍期(mild cognitive impairment,MCI)和痴呆期．AD临床期病程不可逆转,因此,pre-MCI和MCI的早期发现和干预就成为延缓和逆转AD发生的重要环节．大量研究表明,2型糖尿病(T2DM)胰岛素抵抗是导致MCI和AD的独立危险因素,T2DM与AD及AD前期认知功能障碍有密切关系．本文重点综述2型糖尿病与MCI及AD之间的相关性,探讨2型糖尿病治疗对AD的发生进行有效干预的可能性,为AD早期发现和临床治疗提供新线索．     

Preventive effects of ZPDC glycoprotein (24 kDa) on hepatotoxicity induced by mercury chloride in vitro and in vivo

Mercury is a potent environmental contaminant that exerts toxic effect on various vital organs in the human body. Recently, we isolated glycoprotein from Zanthoxylum piperitum DC (ZPDC), which has antioxidant and anticancer effects. In the present study, we determined the preventive effects of ZPDC glycoprotein on hepatic damage induced by mercury chloride (HgCl₂). We evaluated the activities of lactate dehydrogenase (LDH), alanine aminotransferase (ALT), antioxidant enzymes [superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx)], extracellular signal‐regulated kinase (ERK)1/2, p38 mitogen‐activated protein kinase (MAPK), cyclo‐oxygenase (COX‐2), inducible nitric oxide synthetase (iNOS), and activator protein (AP‐1) and the quantitative expressions of nuclear factor E2‐related factor (Nrf2), heme oxygenase (HO‐1), metallothionein (MT) and reduced glutathione (GSH) in mercury‐chloride‐exposed (50 μM and 10 mg/kg body weight) primary cultured hepatocytes and ICR mice, using biochemical assays, radioactivity and immunoblot analysis. The results demonstrated that ZPDC glycoprotein decreased the levels of LDH, ALT, HO‐1 and MT, whereas it increased the activities of hepatic antioxidant enzymes (SOD, CAT and GPx) and reduced GSH in mercury‐chloride‐exposed primary cultured hepatocytes. Also, it suppressed arachidonic acid release and expression of ERK, p38 MAPK, COX‐2, iNOS, AP‐1 and Nrf‐2 in primary cultured hepatocytes and ICR mice exposed to mercury chloride. Collectively, ZPDC glycoprotein may have potential applications to prevent hepatotoxicity induced by mercury chloride. Copyright © 2014 John Wiley & Sons, Ltd.     

Responses of water use efficiency of 9 plant species to light and CO2 and their modeling

Photosynthesis coupled with transpiration determines water use efficiency (WUE) at leaf level, and the responses of WUE controlled by gas exchanges through stomata to environment are the basis of carbon and water cycles in the ecosystem. In this paper, by using Li-6400 Portable Photosynthesis System (LI-COR), WUE at leaf level was analyzed under controlled photosynthetic photons flux density (PPFD) and CO₂ concentration conditions across 9 plant species including maize (Zea mays), sorghum (Sorghum vulgare), millet (Setaria italica), soybean (Glycine max), peanut (Arachis phyogaea), sweet potato (Ipomoea batatas), rice (Oryza sativa), Masson pine (Pinus massoniana) and Schima superba. We had developed a new model to estimate the water use efficiency in response to the combined effects of light and CO₂ concentration. Our measured data validated that this model could simulate the changes of water use efficiency very well under combined effect of light and CO₂ concentration. It could be used to estimate contribution of photosynthesis increase and transpiration decline on water use efficiency with the rising of CO₂ concentration. Great differences in water use efficiency occurred in these different plant species under various CO₂ concentration levels. Based on water use efficiency at regional scale, we concluded that plants should be separated into C₃ plants and C₄ plants, and furthermore, C₃ plants should be separated into herbaceous plants and woody plants. Our separation criteria would do a great favor in modeling the evapotranspiration of terrestrial ecosystem with carbon and water balance.     

NSAID-induced gut inflammation and vasoconstriction: Causes and potential reversal with beta-CGRP - A hypothesis

Traditional non-steroidal anti-inflammatory drugs, cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) inhibitors control inflammation. While these drugs are formulated to reduce one of the cardinal signs of inflammation by reducing prostaglandin levels at the site of inflammation, COX-1 inhibitors induce inflammation in the stomach as well as the small bowel. The COX-2 inhibitors, a large portion of the non-steroidal anti-inflammatory drug market, provide a gastro-intestinally safer class of drugs. However, COX-2 inhibitors induce vasoconstriction via actions in renal and cardiovascular tissues. Since COX-2 inhibitors also have anticancer potential, it is worthwhile to design drug formulations that will not cause hypertension or cardiovascular damage. An attempt has thus been made in this article to formulate a hypothesis to circumvent the COX inhibitors induced inflammation and vasoconstriction through COX independent activation of calcitonin gene-related peptide (CGRP), a potent vasodilator neuropeptide found throughout the vascular and sensory nervous system.     

检测PCV2、PPV、PRV疫苗株与野毒株的多重PCR方法

本文建立了一种同时检测猪圆环病毒2型（PCV2）、细小病毒（PPV）、及伪狂犬病毒（PRV）疫苗株与野毒株的多重PCR方法.根据GenBank上发表的PCV2、PPV和PRV gB、gE基因序列,针对各自保守区各设计一对特异性引物,用这四对引物对同一样品中的PCV2、PPV和PRV gB、gE进行检测,结果可同时扩增出269bp（PCV2）、581bp（PPV）、372bP（PRV gB）及147bp（PRV gE）四条特异性片段.对JEV、PRRSRV、大肠杆菌和双蒸水的PCR扩增结果均为阴性;敏感性测定结果表明,该多重PCR能检出10pg PCV2、PPV和PRV gB、gE检测敏感度分别为10^-6.2、10^-3.8、10^-5.8TCID50的模板.该方法的建立对临床上进行这三种疾病的鉴别诊断和混合感染的检测具有重要意义.     

米根霉乙醇脱氢酶突变株的筛选及其锌镁离子的调控研究

利用亚硝基胍(NTG)对米根霉As3.3461进行诱变,在含丙烯醇0.6%的YPD平板上筛选获得21株乙醇含量降低的突变株,其中突变株HBF-12乳酸产量最高。与出发菌株相比,突变株HBF-12的乙醇产量和乙醇脱氢酶(ADH)活力分别降低了73.6%和76%,乳酸产量和乳酸脱氢酶(LDH)活力分别提高了41.2%和19.6%。研究Zn2 与Mg2 对HBF-12中ADH与LDH活性的调控,结果显示Zn2 对ADH有强烈的激活作用,但抑制LDH活性;Mg2 则轻微抑制ADH活性,促使LDH活性增强。考察两种离子影响末端产物乙醇与乳酸形成的实验说明:培养基中Zn2 浓度与乳酸积累基本上呈负相关性,与乙醇积累呈正相关性,浓度降低有利于生物量积累;Mg2 浓度增加可以促进乳酸积累和生物量增加,对于乙醇积累无明显作用。发酵培养基中添加0.01%Zn2 、0.04%Mg2 ,突变株产酸可达96.21g/L。