1、微生物介导的硫元素循环研究及技术开发

2、机器学习辅助的生物催化剂开发

3、平台化学品的生物制造

4、有机固废资源化处理技术

   

081703-生物化工

代谢工程，微生物技术

   

博士

2011年，博士毕业后留所工作。

1、大肠杆菌基因工程菌及其构建方法和在生产丙酮酸中的应用。授权号CN104946576A

2、一种高产丙酮酸的大肠杆菌基因工程菌及其构建方法和应用。授权号CN106167772B

[1] 杨茂华, 邢建民, 穆廷桢, 苗得露. 一种高耐受有机硫的嗜盐硫碱杆菌及其培养方法和在生物脱硫中的应用. CN: [[[CN111690575A]]], [[["2020-09-22"]]].

[2] 杨茂华, 邢建民, 穆廷桢, 苗得露. 一种高产单质硫的嗜盐嗜碱性微氧硫微螺菌及其在生物脱硫中的应用. CN: CN111676169B, 2021-11-12.

[3] 杨茂华, 邢建民, 苗得露, 穆廷桢. 一种可实现菌群分区的生物脱硫活性颗粒及其制备方法和应用. CN: CN111760443B, 2021-09-14.

[4] 穆廷桢, 刑建民, 杨茂华, 苗得露, 赵胥浩. 一种生物脱硫混合菌系及其应用. CN: CN112899193A, 2021-06-04.

[5] 穆廷桢, 邢建民, 杨茂华, 苗得露, 赵胥浩. 一种含硫气体脱硫装置系统及方法. CN: CN112892202A, 2021-06-04.

[6] 杨茂华, 邢建民, 穆廷桢. 一种木质纤维素酶解体系中多酶组分吸附行为的分析方法及其应用. CN: CN112342268A, 2021-02-09.

[7] 杨茂华, 邢建民, 穆廷桢, 苗得露. 一种嗜盐嗜碱性硫氧化复合菌剂及其制备方法和在生物脱硫中的应用. CN: CN111996134A, 2020-11-27.

[8] 杨茂华, 邢建民, 穆廷桢, 苗得露. 一种嗜盐嗜碱性硫微螺菌及其培养方法和在生物脱硫中的应用. CN: CN111676176A, 2020-09-18.

[9] 邢建民, 穆廷桢, 杨茂华, 苗得露. 一种生物脱硫系统. CN: CN209722067U, 2019-12-03.

[10] 穆廷桢, 邢建民, 杨茂华, 苗得露. 一种嗜盐嗜碱生物脱硫处理工艺及处理装置. CN: CN110240961A, 2019-09-17.

[11] 邢建民, 穆廷桢, 杨茂华, 苗得露. 一种生物脱硫系统和生物燃气脱硫方法. CN: CN106975342A, 2017-07-25.

[12] 邢建民, 穆廷桢, 杨茂华, 郝学密. 一种重组质粒及其制备方法和应用. CN: CN106834332A, 2017-06-13.

[13] 杨茂华, 邢建民, 穆廷桢, 钟伟, 吴丹. 一种用于发酵生产丙酮酸的培养基及其应用. CN: CN106434431A, 2017-02-22.

[14] 杨茂华, 王钦宏, 邢建民, 穆廷桢, 钟伟. 一种高产丙酮酸的大肠杆菌基因工程菌及其构建方法和应用. CN: CN106167772A, 2016-11-30.

[15] 邢建民, 田江南, 杨茂华, 穆廷桢, 钟伟. 一种用于芬顿反应的负载型固体催化剂及其制备方法. CN: CN106040244A, 2016-10-26.

[16] 邢建民, 刘谊兰, 杨茂华, 王钦宏, 马延和. 一种微生物基因改造方法、用于生产高级脂肪醇、高级脂肪烃的基因工程菌及其应用. CN: CN105462905A, 2016-04-06.

[17] 杨茂华, 邢建民, 刘谊兰, 白冰. 大肠杆菌基因工程菌及其构建方法和在生产丙酮酸中的应用. CN: CN104946576A, 2015-09-30.

[18] 邢建民, 郭岩, 杨茂华, 宋子煜. 一株具有异养硝化好氧反硝化功能的盐田盐单胞菌及其应用. CN: CN103805529A, 2014-05-21.

[19] 邢建民, 杨茂华, 刘谊兰, 王彩霞, 闫道江. 一种由木质纤维素制备碳微球的方法. CN: CN103588190A, 2014-02-19.

[20] 邢建民, 刘谊兰, 杨茂华. 用于生产己二酸的重组质粒、基因工程菌、其制备方法及用途. CN: CN103484490A, 2014-01-01.

1 Maohua Yang et al. Switch on a more efficient pyruvate synthesis pathway based on transcriptome analysis and metabolic evolution. Journal of Bioscience and Bioengineering，2017, 124,523-527.

2 Maohua Yang et al. Analysis of gluconate metabolism for pyruvate production in engineered Escherichia coli based on genome -wide transcriptomes. Letters in Applied Microbiology，2017,65,165-172

3 Maohua Yang et al. Improvement of Pyruvate Production Based on Regulation of Intracellular Redox State in Engineered Escherichia coli. Biotechnology and Bioprocess Engineering，2017, 22: 376-381 

[1] 穆廷桢, 杨茂华, 邢建民. 有机硫对生物脱硫过程的抑制机理及其研究进展. 生物工程学报. 2021, 37(2): 461-472, http://lib.cqvip.com/Qikan/Article/Detail?id=7104000433.
[2] 刘志霞, 杨茂华, 穆廷桢, 刘金龙, 邢建民. 表面活性剂对嗜盐嗜碱硫碱弧菌D301生成及利用硫颗粒的影响. 微生物学通报. 2021, 48(2): 362-372, http://lib.cqvip.com/Qikan/Article/Detail?id=7104321971.
[3] 杨茂华, 穆廷桢, 苗得露, 刘金龙, 张翔, 邢建民. 盐碱湖硫循环及嗜盐嗜碱硫功能菌研究进展. 应用与环境生物学报. 2021, 27(3): 786-799, [4] Mu, Tingzhen, Yang, Maohua, Xing, Jianmin. Performance and characteristic of a haloalkaliphilic bio-desulfurizing system using Thioalkalivibrio verustus D301 for efficient removal of H2S. BIOCHEMICAL ENGINEERING JOURNAL[J]. 2021, 165: http://dx.doi.org/10.1016/j.bej.2020.107812.
[5] Chen, Zheng, Yang, Gama, Hao, Xuemi, Samak, Nadia A, Jia, Yunpu, Peh, Sumit, Mu, Tingzhen, Yang, Maohua, Xing, Jianmin. Recent advances in microbial capture of hydrogen sulfide from sour gas via sulfur-oxidizing bacteria. ENGINEERING IN LIFE SCIENCESnull. 2021, 21(10): 693-708, http://dx.doi.org/10.1002/elsc.202100006.
[6] Zhong, Wei, Yang, Maohua, Hao, Xuemi, Sharshar, Moustafa Mohamed, Wang, Qinhong, Xing, Jianmin. Improvement of D-lactic acid production at low pH through expressing acid-resistant gene IoGAS1 in engineered Saccharomyces cerevisiae. JOURNAL OF CHEMICAL TECHNOLOGY AND BIOTECHNOLOGY[J]. 2021, 96(3): 732-742, https://www.webofscience.com/wos/woscc/full-record/WOS:000583406600001.
[7] 李向园, 杨茂华, 穆廷桢, 刘金龙, 赵国群, 邢建民. 一株嗜盐嗜碱硫氧化菌的筛选、鉴定及硫氧化特性. 微生物学通报[J]. 2020, 47(8): 2372-2381, http://lib.cqvip.com/Qikan/Article/Detail?id=7102689427.
[8] Samak, Nadia A, Jia, Yunpu, Sharshar, Moustafa M, Mu, Tingzhen, Yang, Maohua, Peh, Sumit, Xing, Jianmin. Recent advances in biocatalysts engineering for polyethylene terephthalate plastic waste green recycling. ENVIRONMENT INTERNATIONALnull. 2020, 145: http://dx.doi.org/10.1016/j.envint.2020.106144.
[9] Mu, Tingzhen, Yang, Maohua, Xing, Jianmin. Deep and high-efficiency removal of sulfate through a coupling system with sulfate-reducing and sulfur-oxidizing capacity under haloalkaliphilic condition. BIOPROCESS AND BIOSYSTEMS ENGINEERING[J]. 2020, 43(6): 1009-1015, https://www.webofscience.com/wos/woscc/full-record/WOS:000515623400001.
[10] Olajuyin, Ayobami Matthew, Yang, Maohua, Mu, Tingzhen, Sharshar, Moustafa Mohamed, Xing, Jianmin. Succinate Production with Metabolically Engineered Escherichia coli Using Elephant Grass Stalk (Pennisetum purpureum) Hydrolysate as Carbon Source. WASTE AND BIOMASS VALORIZATION[J]. 2020, 11(5): 1717-1725, https://www.webofscience.com/wos/woscc/full-record/WOS:000523383800008.
[11] Sharshar, Moustafa Mohamed, Samak, Nadia Abdrabou, Ambreen, Sadaf, Hao, Xuemi, Mu, Tingzhen, Maarouf, Mohamed, Zheng, Chen, Gao, Yibo, Liu, Zhixia, Jia, Yunpu, Li, Xiangyuan, Zhong, Wei, Peh, Sumit, Yang, Maohua, Xing, Jianmin. Improving confirmed nanometric sulfur bioproduction using engineered Thioalkalivibrio versutus. BIORESOURCE TECHNOLOGY[J]. 2020, 317: http://dx.doi.org/10.1016/j.biortech.2020.124018.
[12] Ayobami Matthew Olajuyin, Maohua Yang, Anders Thygesen, Jiangnan Tian, Tingzhen Mu, Jianmin Xing. Effective production of succinic acid from coconut water (Cocos nucifera) by metabolically engineered Escherichia coli with overexpression of Bacillus subtilis pyruvate carboxylase. Biotechnology Reports. 2019, 24: http://dx.doi.org/10.1016/j.btre.2019.e00378.
[13] Sharshar, Moustafa Mohamed, Samak, Nadia Abdrabo, Hao, Xuemi, Mu, Tingzhen, Zhong, Wei, Yang, Maohua, Peh, Sumit, Ambreen, Sadaf, Xing, Jianmin. Enhanced growth-driven stepwise inducible expression system development in haloalkaliphilic desulfurizing Thioalkalivibrio versutus. BIORESOURCE TECHNOLOGY[J]. 2019, 288: 121486-, http://dx.doi.org/10.1016/j.biortech.2019.121486.
[14] Mu, Tingzhen, Xing, Jianmin, Yang, Maohua. Sulfate reduction by a haloalkaliphilic bench-scale sulfate-reducing bioreactor and its bacterial communities at different depths. BIOCHEMICAL ENGINEERING JOURNAL[J]. 2019, 147: 100-109, http://dx.doi.org/10.1016/j.bej.2019.04.008.
[15] Tian, Jiangnan, Yang, Maohua, Mu, Tingzhen, Sharshar, Moustafa Mohamed, Ayobami, Matthew Olajuyin, Xing, Jianmin. Efficient rhodamine B degradation using electro-fenton process with PbO2-coated titanium as the anode. ENVIRONMENTAL PROGRESS & SUSTAINABLE ENERGY[J]. 2019, 38(1): 189-197, http://ir.ipe.ac.cn/handle/122111/27752.
[16] Zhong, Wei, Yang, Maohua, Mu, Tingzhen, Wu, Fan, Hao, Xuemi, Chen, Ruonan, Sharshar, Moustafa Mohamed, Thygesen, Anders, Wang, Qinhong, Xing, Jianmin. Systematically redesigning and optimizing the expression of (D)-lactate dehydrogenase efficiently produces high-optical-purity (D)-lactic acid in Saccharomyces cerevisiae. BIOCHEMICAL ENGINEERING JOURNAL[J]. 2019, 144: 217-226, http://ir.ipe.ac.cn/handle/122111/28239.
[17] Olajuyin, Ayobami Matthew, Yang, Maohua, Mu, Tingzhen, Tian, Jiangnan, Thygesen, Anders, Adesanoye, Omolola Abidemi, Adaramoye, Oluwatosin Adekunle, Song, Andong, Xing, Jianmin. Enhanced production of succinic acid from methanol-organosolv pretreated Strophanthus preussii by recombinant Escherichia coli. BIOPROCESS AND BIOSYSTEMS ENGINEERING[J]. 2018, 41(10): 1497-1508, https://www.webofscience.com/wos/woscc/full-record/WOS:000443552900009.
[18] Tian, Jiangnan, Sharshar, Moustafa Mohamed, Yang, Maohua, Mu, Tingzhen, Xing, Jianmin. Degradation of Rhodamine B at Neutral pH Using Modified Sponge Iron as a Heterogeneous Electro-Fenton Catalyst. ENVIRONMENTAL PROGRESS & SUSTAINABLE ENERGY[J]. 2018, 37(3): 989-995, http://dx.doi.org/10.1002/ep.12760.
[19] Mu, Tingzhen, Zhao, Jixiang, Guan, Yueping, Tian, Jiangnan, Yang, Maohua, Guo, Chen, Xing, Jianmin. Desulfurization with Thialkalivibrio versutus immobilized on magnetic nanoparticles modified with 3-aminopropyltriethoxysilane. BIOTECHNOLOGY LETTERS[J]. 2017, 39(6): 865-871, http://ir.ipe.ac.cn/handle/122111/22657.
[20] Mu, Tingzhen, Yang, Maohua, Zhao, Jixiang, Sharshar, Moustafa Mohammed, Tian, Jiangnan, Xing, Jianmin. Improvement of desulfurizing activity of haloalkaliphilic Thialkalivibrio versutus SOB306 with the expression of Vitreoscilla hemoglobin gene. BIOTECHNOLOGY LETTERS[J]. 2017, 39(3): 447-452, http://ir.ipe.ac.cn/handle/122111/21953.
[21] Mu, Tingzhen, Zhou, Jiemin, Yang, Maohua, Xing, Jianmin. Complete genome sequence of Thialkalivibrio versutus D301 isolated from Soda Lake in northern China, a typical strain with great ability to oxidize sulfide. JOURNAL OF BIOTECHNOLOGY[J]. 2016, 227(JUNE): 21-22, http://dx.doi.org/10.1016/j.jbiotec.2016.04.019.
[22] Tian, Jiangnan, Olajuyin, Ayobami Matthew, Mu, Tingzhen, Yang, Maohua, Xing, Jianmin. Efficient degradation of rhodamine B using modified graphite felt gas diffusion electrode by electro-Fenton process. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH[J]. 2016, 23(12): 11574-11583, http://ir.ipe.ac.cn/handle/122111/20961.
[23] Tian, Jiangnan, Zhao, Jixiang, Olajuyin, Ayobami Matthew, Sharshar, Moustafa Mohamed, Mu, Tingzhen, Yang, Maohua, Xing, Jianmin. Effective degradation of rhodamine B by electro-Fenton process, using ferromagnetic nanoparticles loaded on modified graphite felt electrode as reusable catalyst: in neutral pH condition and without external aeration. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH[J]. 2016, 23(15): 15471-15482, http://dx.doi.org/10.1007/s11356-016-6721-2.
[24] Olajuyin, Ayobami Matthew, Yang, Maohua, Liu, Yilan, Mu, Tingzhen, Tian, Jiangnan, Adaramoye, Oluwatosin Adekunle, Xing, Jianmin. Efficient production of succinic acid from Palmaria palmata hydrolysate by metabolically engineered Escherichia coli. BIORESOURCE TECHNOLOGY[J]. 2016, 214: 653-659, http://dx.doi.org/10.1016/j.biortech.2016.04.117.
[25] Bai, Bing, Zhou, Jiemin, Yang, Maohua, Liu, Yilan, Xu, Xiaohui, Xing, Jianmin. Efficient production of succinic acid from macroalgae hydrolysate by metabolically engineered Escherichia coli. BIORESOURCE TECHNOLOGY[J]. 2015, 185: 56-61, http://dx.doi.org/10.1016/j.biortech.2015.02.081.
[26] 白冰, 杨茂华, 刘谊兰, 邢建民. 基于能量代谢优化的丁二酸生物合成强化. 中国科学:化学[J]. 2015, 45(5): 564-570, http://ir.ipe.ac.cn/handle/122111/20044.
[27] Yang, Maohua, Xing, Jianmin, Liu, Yuyang, Liu, Yilan, Mu, Tingzhen, Zhou, Jiemin. Formation and Characterization of Pseudo-Lignin Microspheres during High-pressure Water Pretreatment. BIORESOURCES[J]. 2015, 10(4): 8474-8486, http://www.irgrid.ac.cn/handle/1471x/1047815.
[28] Wang, Caixia, Ming, Wei, Yan, Daojiang, Zhang, Congcong, Yang, Maohua, Liu, Yilan, Zhang, Yu, Guo, Baohua, Wan, Yinhua, Xing, Jianmin. Novel membrane-based biotechnological alternative process for succinic acid production and chemical synthesis of bio-based poly (butylene succinate). BIORESOURCE TECHNOLOGY[J]. 2014, 156(1): 6-13, http://dx.doi.org/10.1016/j.biortech.2013.12.043.
[29] Yan, Daojiang, Wang, Caixia, Zhou, Jiemin, Liu, Yilan, Yang, Maohua, Xing, Jianmin. Construction of reductive pathway in Saccharomyces cerevisiae for effective succinic acid fermentation at low pH value. BIORESOURCE TECHNOLOGY[J]. 2014, 156(1): 232-239, http://dx.doi.org/10.1016/j.biortech.2014.01.053.
[30] Zhou, JieMin, Song, ZiYu, Yan, DaoJiang, Liu, YiLan, Yang, MaoHua, Cao, HongBin, Xing, JianMin. Performance of a haloalkaliphilic bioreactor and bacterial community shifts under different COD/SO42- ratios and hydraulic retention times. JOURNAL OF HAZARDOUS MATERIALS[J]. 2014, 274(1): 53-62, http://dx.doi.org/10.1016/j.jhazmat.2014.03.061.
[31] Liu, Yilan, Chen, Ting, Yang, Maohua, Wang, Caixia, Huo, Weiyan, Yan, Daojiang, Chen, Jinjin, Zhou, Jiemin, Xing, Jianmin. Analysis of mixtures of fatty acids and fatty alcohols in fermentation broth. JOURNAL OF CHROMATOGRAPHY A[J]. 2014, 1323(3): 66-72, http://dx.doi.org/10.1016/j.chroma.2013.10.094.
[32] Zhou, Wei, Yang, Maohua, Wang, Caixia, Liu, Jianfei, Xing, Jianmin. Changes in plant cell-wall structure of corn stover due to hot compressed water pretreatment and enhanced enzymatic hydrolysis. WORLD JOURNAL OF MICROBIOLOGY & BIOTECHNOLOGY[J]. 2014, 30(8): 2325-2333, http://www.irgrid.ac.cn/handle/1471x/857849.
[33] Zhou, JieMin, Song, ZiYu, Yan, DaoJiang, Liu, YiLan, Yang, MaoHua, Cao, HongBin, Xing, JianMin. Performance of a haloalkaliphilic bioreactor under different NO3-/SO42- ratios. BIORESOURCE TECHNOLOGY[J]. 2014, 153(1): 216-222, http://www.irgrid.ac.cn/handle/1471x/837061.
[34] 郭岩, 周雪媚, 杨茂华, 李玉光, 杨德慧, 周威, 邢建民. 高效嗜碱好氧反硝化细菌的筛选及其脱硝特性. 过程工程学报[J]. 2013, 13(4): 687-692, http://www.irgrid.ac.cn/handle/1471x/856723.
[35] 闫道江, 王彩霞, 周杰民, 刘谊兰, 杨茂华, 邢建民. 酿酒酵母产苹果酸的还原TCA路径构建及发酵调控. 生物工程学报[J]. 2013, 29(10): 1484-1493, http://www.irgrid.ac.cn/handle/1471x/857401.
[36] Wang, Caixia, Thygesen, Anders, Liu, Yilan, Li, Qiang, Yang, Maohua, Dang, Dan, Wang, Ze, Wan, Yinhua, Lin, Weigang, Xing, Jianmin. Bio-oil based biorefinery strategy for the production of succinic acid. BIOTECHNOLOGY FOR BIOFUELS[J]. 2013, 6(6): 74-74, http://ir.ipe.ac.cn/handle/122111/13714.
[37] Song, Ziyu, Zhou, Xuemei, Li, Yuguang, Yang, Maohua, Xing, Jianmin. Bio-desulfurization and denitrification by anaerobicanoxic process for the treatment of wastewater from flue gas washing. WATER SCIENCE AND TECHNOLOGY[J]. 2013, 67(9): 2042-2049, http://ir.ipe.ac.cn/handle/122111/13337.
[38] Liu Jianfei, Cao Yan, Yang Maohua, Li Huiquan, Xing Jianmin. Saccharification of the Pretreated Corn Stover by Microwave Assisted DMSO/AmimCl Co-solvents. ACTA CHIMICA SINICA[J]. 2012, 70(18): 1950-1956, http://www.irgrid.ac.cn/handle/1471x/725132.
[39] Liu Jianfei, Cao Yan, Yang Maohua, Li Huiquan, Xing Jianmin. Saccharification of the Pretreated Corn Stover by Microwave Assisted DMSO/AmimCl Co-solvents. ACTA CHIMICA SINICA[J]. 2012, 70(18): 1950-1956, http://dx.doi.org/10.6023/A12050221.
[40] Wang, Dan, Li, Qiang, Yang, Maohua, Zhang, Yunjian, Su, Zhiguo, Xing, Jianmin. Efficient production of succinic acid from corn stalk hydrolysates by a recombinant Escherichia coli with ptsG mutation. PROCESS BIOCHEMISTRY[J]. 2011, 46(1): 365-371, http://dx.doi.org/10.1016/j.procbio.2010.09.012.
[41] Yang, Maohua, Zhang, Aimin, Liu, Binbin, Li, Wangliang, Xing, Jianmin. Improvement of cellulose conversion caused by the protection of Tween-80 on the adsorbed cellulase. BIOCHEMICAL ENGINEERING JOURNAL[J]. 2011, 56(3): 125-129, http://dx.doi.org/10.1016/j.bej.2011.04.009.
[42] 杨茂华. 木质纤维素高效酶解过程研究. 2011, 139-, http://www.irgrid.ac.cn/handle/1471x/713626.
[43] Li, Qiang, Li, Wangliang, Wang, Dan, Liu, Binbin, Tang, Huang, Yang, Maohua, Liu, Qingfen, Xing, Jianmin, Su, Zhiguo. pH Neutralization while Succinic Acid Adsorption onto Anion-Exchange Resins. APPLIED BIOCHEMISTRY AND BIOTECHNOLOGY[J]. 2010, 160(2): 438-445, http://www.irgrid.ac.cn/handle/1471x/778897.
[44] Yang, Maohua, Li, Wangliang, Liu, Binbin, Li, Qiang, Xing, Jianmin. High-concentration sugars production from corn stover based on combined pretreatments and fed-batch process. BIORESOURCE TECHNOLOGY[J]. 2010, 101(13): 4884-4888, http://dx.doi.org/10.1016/j.biortech.2009.12.013.
[45] Li, Qiang, Wang, Dan, Wu, Yong, Yang, Maohua, Li, Wangliang, Xing, Jianmin, Su, Zhiguo. Kinetic evaluation of products inhibition to succinic acid producers Escherichia coli NZN111, AFP111, BL21, and Actinobacillus succinogenes 130Z(T). JOURNAL OF MICROBIOLOGY[J]. 2010, 48(3): 290-296, http://www.irgrid.ac.cn/handle/1471x/740244.
[46] Liu, Binbin, Yang, Maohua, Qi, Benkun, Chen, Xiangrong, Su, Zhiguo, Wan, Yinhua. Optimizing L-(+)-lactic acid production by thermophile Lactobacillus plantarum As 1 3 using alternative nitrogen sources with response surface method. BIOCHEMICAL ENGINEERING JOURNAL[J]. 2010, 52(2-3): 212-219, http://dx.doi.org/10.1016/j.bej.2010.08.013.

   

（ 1 ） 发酵-分离耦合生产聚合级丁二酸及PBS合成, 主持, 部委级, 2013-01--2015-12
（ 2 ） 甘蔗渣组分高效分离及定向转化, 主持, 国家级, 2014-01--2016-12
（ 3 ） 生物质液体燃料的高温生物炼制, 参与, 国家级, 2012-01--2015-12
（ 4 ） 硫碱弧菌（Thialkalivibrio versutus）D301氨基谷胱甘肽介导的聚硫化物跨膜转运机制及其调控硫代谢功能研 究, 主持, 国家级, 2019-01--2022-12