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Zoological Research 2015年第6期36卷 314-318页

作者： Min WANG amy f.t.arnsten Department of Neurobiology School of Medicine Yale University

Revealing how molecular mechanisms influence higher brain circuits in primates will be essential for understanding how genetic insults lead to increased risk of cognitive disorders. traditionally, modulatory influences on higher cortical circuits have been examined using lesion techniques, where a brain region is depleted of a particular transmitter to determine how its loss impacts cognitive function. for example, depletion of catecholamines or acetylcholine from the dorsolateral prefrontal cortex produces striking deficits in working memory abilities. More directed techniques have utilized direct infusions of drug into a specific cortical site to try to circumvent compensatory changes that are common following transmitter depletion. the effects of drug on neuronal firing patterns are often studied using iontophoresis, where a minute amount of drug is moved into the brain using a tiny electrical current, thus minimizing the fluid flow that generally disrupts neuronal recordings. All of these approaches can be compared to systemic drug administration, which remains a key arena for the development of effective therapeutics for human cognitive disorders. Most recently, viral techniques are being developed to be able to manipulate proteins for which there is no developed pharmacology, and to allow optogenetic manipulations in primate cortex. As the association cortices greatly expand in brain evolution, research in nonhuman primates is particularly important for understanding the modulatory regulation of our highest order cognitive operations.

关键词： Lesion Microinfusion Iontophoresis Viral manipulations Systemic administration

Contribution of NMDA receptors to dorsolateral prefrontal cortical networks in primates

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Neuroscience Bulletin 2015年第2期31卷 191-197页

作者： Min Wang amy f.t.arnsten Department of Neurobiology Yale Medical School

Cognitive disorders such as schizophrenia and Alzheimer＇s disease are associated with dysfunction of the highly evolved dorsolateral prefrontal cortex （dlPfC）, and with changes in glutamatergic N-methyI-D-aspartate receptors （NMDARs）. Recent research on the primate dlPfC discovered that the pyramidal cell circuits that generate the persistent firing underlying spatial working memory communicate through synapses on spines containing NMDARs with NR2B subunits （GluN2B） in the post-synaptic density. this contrasts with synapses in the hippocampus and primary visual cortex, where GluN2B receptors are both synaptic and extrasynaptic. Blockade of GluN2B in the dlPfC markedly reduces the persistent firing of the Delay cells needed for neuronal representations of visual space. Cholinergic stimulation of nicotinic （17 receptors within the glutamate synapse is necessary for NMDAR actions. In contrast, a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors have only subtle effects on the persistent firing of Delay cells, but contribute substantially to the firing of Cue and Response cells. Systemic administration of the NMDAR antagonist ketamine reduces the persistent firing of Delay cells, but increases the firing of some Response cells. the reduction in persistent firing produced by ketamine may explain why this drug can mimic or worsen the cognitive symptoms of schizophrenia. Similar actions in the medial PfC circuits representing the emotional aspects of pain may contribute to the rapid analgesic and anti-depressant actions of ketamine.

关键词： glutamate Alzheimer's disease schizophrenia depression ketamine

IMpower210:A phase Ⅲ study of second-line atezolizumab vs. docetaxel in East Asian patients with non-small cell lung cancer

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Chinese Journal of Cancer Research 2024年第2期36卷 103-113页

作者： Yi-Long Wu Shun Lu Gongyan Chen Jianxing He Jifeng feng Yiping Zhang Liyan Jiang Hongming Pan Jianhua Chang Jian fang amy Cai Lilian Bu Jane Shi Jinjing Xia Guangdong Lung Cancer Institute Guangdong Provincial Key Laboratory of Translational Medicine in Lung CancerGuangdong Provincial People's Hospital&Guangdong Academy of Medical SciencesSouthern Medical UniversityGuangzhou 510080China Shanghai Lung Cancer Center Shanghai Chest HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200025China Department of Respiration Harbin Cancer HospitalHarbin Medical UniversityHarbin 150081China Department of thoracic Oncology and Surgery the First Affliated Hospital of Guangzhou Medical UniversityGuangzhou 510120China Department of Medical Oncology Jiangsu Cancer HospitalNanjing 210009China Department of Medical Oncology Zhejiang Cancer HospitalHangzhou 330022China Department of Pulmonary Medicine Shanghai Chest HospitalShanghai Jiao Tong UniversityShanghai 200030China Department of Medical Oncology Sir Run Run Shaw HospitalZhejiang University School of MedicineHangzhou 310016China Department of Medical Oncology Shenzhen HospitalCancer Hospital of Chinese Academy of Medical SciencesShenzhen 518116China Department of thoracic Oncology Beijing Cancer HospitalBeijing 100142China Product Development Shanghai Roche Pharmaceutical LtdShanghai 201203China

Objective: IMpower210(NCt02813785) explored the efficacy and safety of single-agent atezolizumab *** as second-line treatment for advanced non-small cell lung cancer(NSCLC) in East Asian ***: Key eligibility criteria for this phase Ⅲ, open-label, randomized study included age ≥18 years;histologically documented advanced NSCLC per the Union for International Cancer Control/American Joint Committee on Cancer staging system(7th edition);Eastern Cooperative Oncology Group performance status of 0 or 1;and disease progression following platinum-based chemotherapy for advanced or metastatic NSCLC. Patients were randomized 2:1 to receive either atezolizumab(1,200 mg) or docetaxel(75 mg/m^(2)). the primary study endpoint was overall survival(OS) in the intention-to-treat(Itt) population with wild-type epidermal growth factor receptor expression(Itt EGfR-Wt) and in the overall Itt ***: Median OS in the Itt EGfR-Wt population(n=467) was 12.3 [95% confidence interval(95% CI),10.3-13.8] months in the atezolizumab arm(n=312) and 9.9(95% CI, 7.8-13.9) months in the docetaxel arm[n=155;stratified hazard ratio(HR), 0.82;95% CI, 0.66-1.03]. Median OS in the overall Itt population was 12.5(95% CI, 10.8-13.8) months with atezolizumab treatment and 11.1(95% CI, 8.4-14.2) months(n=377) with docetaxel treatment(n=188;stratified HR, 0.87;95% CI, 0.71-1.08). Grade 3/4 treatment-related adverse events(tRAEs) occurred in 18.4% of patients in the atezolizumab arm and 50.0% of patients in the docetaxel ***: IMpower210 did not meet its primary efficacy endpoint of OS in the Itt EGfR-Wt or overall Itt populations. Atezolizumab was comparatively more tolerable than docetaxel, with a lower incidence of grade3/4 tRAEs.

关键词： Atezolizumab East Asia non-small cell lung cancer programmed death-ligand 1 inhibitors monoclonal antibody

Hydraulic properties and drought response of a tropical bamboo (Cephalostachyum pergracile)

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Plant Diversity 2024年第3期46卷 406-415页

作者： Wanwalee Kongjarat Lu Han amy Ny Aina Aritsara Shu-Bin Zhang Gao-Juan Zhao Yong-Jiang Zhang Phisamai Maenpuen Ying-Mei Li Yi-Ke Zou Ming-Yi Li Xue-Nan Li Lian-Bin tao Ya-Jun Chen CAS Key Laboratory of tropical forest Ecology Xishuangbanna Tropical Botanical GardenChinese Academy of SciencesYunnan 666303China University of the Chinese Academy of Sciences Beijing 100049China t-StAR Core team Xishuangbanna Tropical Botanical GardenChinese Academy of SciencesYunnan 666303China School of Biology and Ecology University of MaineOronoMEUSA Climate Change Institute University of MaineOronoME 04469USA School of Biological and Chemical Science Pu’er UniversityXueyuan RoadYunnan 665000China Institute of Ecology and Geobotany School of Ecology and Environmental SciencesYunnan UniversityKunmingYunnan 650091China School of Ecology and Environment Southwest Forestry UniversityKunmingYunnan 650224China Yuanjiang Savanna Ecosystem Research Station Xishuangbanna Tropical Botanical GardenChinese Academy of SciencesYuanjiangYunnan 653300China

Bamboo plants are an essential component of tropical ecosystems,yet their vulnerability to climate extremes,such as drought,is poorly understood due to limited knowledge of their hydraulic *** pergracile,a commonly used tropical bamboo species,exhibited a substantially higher mortality rate than other co-occurring bamboos during a severe drought event in 2019,but the underlying mechanisms remain *** study investigated the leaf and stem hydraulic traits related to drought responses,including leaf-stem embolism resistance(P50leaf;P50stem) estimated using optical and X-ray microtomography methods,leaf pressure-volume and water-releasing ***,we investigated the seasonal water potentials,native embolism level(PLC) and xylem water source using stable *** found that *** exhibited strong resistance to embolism,showing low P50leaf,P50stem,and turgor loss point,despite its rapid leaf water ***,its leaves displayed greater resistance to embolism than its stem,suggesting a lack of effective hydraulic vulnerability segmentation(HVS) to protect the stem from excessive xylem *** the dry season,approximately 49% of the water was absorbed from the upper 20-cm-deep soil ***,significant diurnal variation in leaf water potentials and an increase in midday PLC from 5.87±2.33% in the wet season to 12.87±4.09%in the dry season were *** summary,this study demonstrated that the rapid leaf water loss,high reliance on surface water,and a lack of effective HVS in *** accelerated water depletion and increased xylem embolism even in the typical dry season,which may explain its high mortality rate during extreme drought events in 2019.

关键词： Climate change Drought Hydraulic safety Hydraulic vulnerability segmentation Stable isotope tree mortality

the HIf-1α/PLOD2 axis integrates extracellular matrix organization and cell metabolism leading to aberrant musculoskeletal repair

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Bone Research 2024年第2期12卷 289-301页

作者： Heeseog Kang amy L.Strong Yuxiao Sun Lei Guo Conan Juan Alec C.Bancroft Ji Hae Choi Chase A.Pagani Aysel A.fernandes Michael Woodard Juhoon Lee Sowmya Ramesh Aaron W.James David Hudson Kevin N.Dalby Lin Xu Robert J.tower Benjamin Levi Center for Organogenesis Regeneration and TraumaDepartment of SurgeryUniversity of Texas SouthwesternDallasTX 75390USA Section of Plastic Surgery Department of SurgeryUniversity of MichiganAnn ArborMI 48109USA Quantitative Biomedical Research Center Peter O’Donnell Jr.School of Public HealthUniversity of Texas SouthwesternDallasTX 75390USA Department of Orthopedics and Sports Medicine University of WashingtonSeattleWA 98195USA Division of Chemical Biology and Medicinal Chemistry College of PharmacyUniversity of Texas at AustinAustinTX 78712USA Department of Pathology Johns Hopkins UniversityBaltimoreMD 21218USA

While hypoxic signaling has been shown to play a role in many cellular processes,its role in metabolism-linked extracellular matrix(ECM)organization and downstream processes of cell fate after musculoskeletal injury remains to be ***(HO)is a debilitating condition where abnormal bone formation occurs within extra-skeletal *** andhypoxia-inducible factor 1α(HIf-1α)activation have been shown to promote ***,the underlying molecular mechanisms bywhich the HIf-1αpathway in mesenchymal progenitor cells(MPCs)contributes to pathologic bone formation remain to ***,we used a proven mouse injury-induced HO model to investigate the role of HIf-1αon aberrant cell ***-cell RNA sequencing(scRNA-seq)and spatial transcriptomics analyses of the HO site,we found that collagen ECM organizationis the most highly up-regulated biological process in *** mesenchymal cell-specific deletion of Hif1α(Hoxa11-CreER^(t2);Hif1a^(fl/fl))significantly mitigated HO in ***-seq analysis of these Hoxa11-CreER^(t2);Hif1a^(fl/fl)mice identified the PLOD2/LOXpathway for collagen cross-linking as downstream of the HIf-1αregulation of ***,our scRNA-seq data and mechanisticstudies further uncovered that glucose metabolism in MPCs is most highly impacted by HIf-1α*** a translational aspect,a pan-LOX inhibitor significantly decreased HO.A newly screened compound revealed that the inhibition of PLOD2 activity in MPCssignificantly decreased osteogenic differentiation and glycolytic *** suggests that the HIf-1α/PLOD2/LOX axis linked tometabolism regulates HO-forming MPC *** results suggest that the HIf-1α/PLOD2/LOX pathway represents a promisingstrategy to mitigate HO formation.

关键词： metabolism skeletal aberrant

Effects of L-arginine,guanidinoacetic acid and L-citrulline supplementation in reduced-protein diets on bone morphology and mineralization of laying hens

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Animal Nutrition 2023年第3期14卷 225-234页

作者： Hiep thi Dao amy f.Moss Emma J.Bradbury Robert A.Swick School of Environmental and Rural Science Faculty of ScienceAgricultureBusiness and LawUniversity of New EnglandArmidaleNew South Wales2351Australia faculty of Animal Science Vietnam National University of AgricultureTrau Quy TownGia Lam DistrictHanoi100000Vietnam Baiada Poultry Pty Limited Pendle HillNew South Wales2145Australia

the alterations in feed ingredients and the nutrient matrix to produce reduced-protein diets may affect bone morphology and mineralization in laying *** study was implemented to determine the effects of L-arginine(Arg),guanidinoacetic acid(GAA),and L-citrulline(Cit)supplementation to Argdeficient reduced-protein diets on bone morphology,strength,and mineralization status of laying *** housed Hy-Line Brown laying hens were evenly distributed to five dietary treatments with 25 replicates per treatment from 20 to 40 wk of *** consisted of a standard protein diet(17%crude protein,SP),a reduced-protein diet deficient in Arg(13%crude protein,RP),and RP supplemented with Arg(0.35%Arg,RP-Arg),GAA(0.46%GAA equivalent to 0.35%Arg,RP-GAA),or Cit(0.35%Cit equivalent to 0.35%Arg,RP-Cit)to reach the Arg level of SP *** fed the SP diet had similar bone weight,ash,length,width,Seedor index,breaking strength,and serum mineral concentration,but higher toe B level(Pto those fed the RP diet at wk *** fed the SP diet consumed more but also excreted more K and B compared to those fed the RP diet(Pfed the SP diet had lower Cu digestibility(P=0.01)and higher B retention(Pto those offered the RP *** of Arg,GAA,and Cit to the RP diet increased relative femur weight and length(Ptrulline supplementation also increased relative tibia and femur ash,and Zn digestibility(Ptation of GAA to the RP diet decreased serum Ca,P,and Mg levels,decreased tibia fe and Mg levels and toe Mg level,but increased Al,fe,Zn,and Mn digestibility(Pthe current findings demonstrated the capacity of laying hens to adapt to low mineral intake by increasing mineral ***,bone morphology and breaking strength,and serum mineral level in laying hens were not influenced by dietary CP *** Arg,GAA,or Cit supplementation were effective in improving bone morphology and

关键词： Ash Breaking strength femur Low protein Minerals Digestibility

Characterisation of undigested components throughout the gastrointestinal tract of broiler chickens fed either a wheat-or maizebased diet

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Animal Nutrition 2022年第1期8卷 153-159页

作者： Eunjoo Kim Natalie K.Morgan amy f.Moss Lily Li Peter Ader Mingan Choct School of Environmental and Rural Science University of New EnglandArmidaleNSW2351Australia BASf South East Asia038987Singapore BASf SE 68623LampertheimGermany

this study was to characterise the undigested nutrients present along the gastrointestinal tract of birds offered common wheat-or maize-based diets,with the goal of optimising utilisation of enzymes to enhance digestive ***-and maize-based diets were offered to 240 mixed-sex broilers(10 birds/pen;n=12)from 1 to 35 d *** of dry matter,starch,crude protein and nonstarch polysaccharides(NSP)were measured in the crop,gizzard,duodenum,jejunum,ileum,caeca and excreta at d 12 and 35 *** of nutrient levels in the excreta presented that more than 30%of nutrients provided in the feed was wasted,irrespective of wheat or maize diet *** average,92 g/kg crude protein,92 g/kg insoluble NSP and 14 g/kg oligosaccharides were not utilised by birds at d 12 *** quantity of water-insoluble NSP in the small intestine at d 12 was lower in birds offered the wheat-based diet compared to those fed the maize-based diet(Pth the reverse being true for water-soluble NSP(Ptein,79 g/kg insoluble NSP and 9 g/kg oligosaccharides remained in the excreta at 35 d of *** this time period,accumulation of feed in the gizzard was noted for birds offered both diets,but was more pronounced in those offered the maize-based diet(Pffered the maize-based diet demonstrated improved utilisation of oligosaccharides compared to those fed the wheat-based diet at both d 12 and 35(P=0.087 and P=0.047,respectively).Protein utilisation in the jejunum and ileum was greater in birds offered the wheat-based diet compared to those fed the maize-based diet(P=0.004 and Ptively).thus,while both diets supported standard growth performance of birds,the degree and flow of nutrient disappearance along the gastrointestinal tract was influenced by cereal type and bird age.

关键词： Broiler chicken Nutrient digestibility Undigested dietary component

Non-starch polysaccharide-degrading enzymes may improve performance when included in wheat- but not maize-based diets fed to broiler chickens under subclinical necrotic enteritis challenge

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Animal Nutrition 2022年第3期10卷 54-67页

作者： Eunjoo Kim amy f.Moss Natalie K.Morgan Kosar Gharib-Naseri Peter Ader Mingan Choct School of Environmental and Rural Science University of New EnglandArmidaleNSW 2351Australia BASf SE 68623LampertheimGermany

the present study investigated whether supplementing fibre-degrading enzymes can ameliorate the severity of subclinical necrotic enteritis(NE)in broiler chickens offered wheat-or maize-based diets.A total of 1,544 mixed-sex broiler chickens were assigned to 16 experimental treatments as a 2×2×4 factorial arrangement of *** factors were the following:NE challenge,yes or no;diet type,wheat-or maize-based;and enzyme supplementation,control(no enzyme),family 10 xylanase(XYN10),family 11 xylanase(XYN11)or b-mannanase(MAN).Each treatment was replicated 6 times,with 16 birds per replicate pen.A three-way challenge×diet type×enzyme interaction occurred for body weight at 21 d of age(P=0.025)and overall feed conversion ratio(P=0.001).In the non-challenged birds fed the wheat-based diet,supplementing MAN increased d 21 body weight compared to the *** challenged birds fed the maize-based diet,supplemental XYN11 impeded body weight and overall fCR compared to the *** offered the maize-based diet presented heavier relative gizzard weights at both 16 and 21 d of age(Pty(P=0.046)compared to those fed the wheatbased *** supplementation reduced ileal and jejunal digesta viscosity at 16 d of age only in birds fed the wheat-based diet(Pta viscosity in birds fed the maizebased diet,and MAN reduced it in birds fed the wheat-based diet at 21 d of age(P=0.030).Supplementing XYN11 improved ileal soluble non-starch polysaccharides(NSP)digestibility in birds fed the wheat-based diet compared to non-supplemented birds(Pfed the wheat-based diet displayed a higher abundance of Bifidobacterium,Lactobacillus and Enterobacteriaceae and butyric acid in the caeca at 16 d of age compared to birds fed the maize-based diet(Ptal XYN11 exacerbated the negative impact of NE on growth performance in birds fed the maizebased *** wheat-based diets with

关键词： Broiler chicken Carbohydrase Mannanase Necrotic enteritis Prebiotic oligosaccharides Xylanase

Ileal profile of non-starch polysaccharides and oligosaccharides in response to exogenous enzymes in broiler chickens offered wheat-or maize-based diets under subclinical necrotic enteritis challenge

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Animal Nutrition 2022年第3期10卷 207-215页

the present study evaluated the impacts of fibre-degrading enzymes on the profiles of non-starch polysaccharides(NSP)and oligosaccharides(OS)in the ileum of broiler chickens offered wheat-or maize-based diets under subclinical necrotic enteritis(NE)challenge.A 224 factorial arrangement of treatments was *** were the following:NE challenge,no or yes;diet type,wheat-or maizebased;and supplemental enzymes,control(no enzyme),family 10 xylanase(XYN10),family 11 xylanase(XYN11)or b-mannanase(MAN).Birds in the challenged group were inoculated with Eimeria on d 9 and Clostridium perfringens on d 14 and 15.A 3-way interaction(P=0.047)occurred on overall(d 0 to 16)weight *** NE was present,all the supplemental enzymes increased weight gain in birds fed the wheat-based diet;whereas in those fed the maize-based diet supplemental XYN10 and XYN11 decreased weight *** NE was absent,birds fed the wheat-based diet supplemented with XYN10 or MAN presented increased weight gain compared to non-supplemented birds,but no improvements with enzyme addition were observed in birds fed the maize-based diet.A 3-way interaction(P=0.002)was observed on insoluble NSP level in the *** NE was absent,all the supplemental enzymes reduced the ileal level of insoluble NSP,regardless of diet *** the challenged birds,supplementing XYN10 and MAN reduced insoluble NSP level in the ileum,but only in birds fed the wheat-based *** soluble NSP level was reduced by supplemental XYN11 and MAN,but only in birds fed the wheatbased diet,resulting in a 2-way diet typeenzyme interaction(Pt in birds offered the wheat-based diet supplemented with ***,supplementation of NSP-degrading enzymes to the wheat-based diet enhanced bird performance regardless of NE challenge,with XYN11 significantly increasing oligosaccharide ***,enzyme addition did not improve growth performance in birds fed maize-based diet

关键词： Broiler chicken Non-starch polysaccharide Subclinical necrotic enteritis Oligosaccharide

Protease supplementation reduced the heat increment of feed and improved energy and nitrogen partitioning in broilers fed maize-based diets with supplemental phytase and xylanase

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Animal Nutrition 2022年第3期10卷 19-25页

作者： Klint W.McCafferty Mingan Choct Sosthene Musigwa Natalie K.Morgan Aaron J.Cowieson amy f.Moss USDA-ARS Poultry Research Unit School of Environmental and Rural SciencesMississippi State39762United States University of New England ArmidaleNSW2351Australia DSM Nutritional Products Kaiseraugst4303Switzerland

An experiment was conducted to explore the effects of digestible amino acid(dAA)concentrations and supplemental protease on live performance and energy partitioning in *** 308 male broilers(n?288)were distributed into 24 floor pens and offered 1 of 4 dietary treatments with 6 replicates from 1 to 35 d of *** treatments consisted of a 2×2 factorial arrangement with dAA concentrations(standard and reduced[34 g/kg below standard])and supplemental protease(without or with)as the main *** 1,15,28,and 35 d of age,feed and broilerswereweighed to determine live ***20 to 23 d of age,a total of 32 birds(2 birds/chamber,4 replicates)were placed in closed-calorimeter chambers to determine respiratory exchange(heat production,HP),apparent metabolisable energy(AME),retained energy(RE),and net energy(NE).from 29 to 35 d of age,supplemental protease in the reduced-dAA diet decreased broiler feed conversion ratio(fCR)by 5.6 points,whereas protease supplementation in the standard-dAA diet increased fCR by 5.8 *** indirect calorimetry assay revealed that supplemental protease decreased(Pthe heat increment of feed(HIf)by 0.22 MJ/***,from 20 to 23 d of age,broilers offered the reduced-dAA diet with supplemental protease had a higher daily body weight gain(BWG)(t10.4%),N intake(t7.1%),and N retention(t8.2%)than those offered the standard-dAA with supplemental *** offered the reduced-dAA without supplemental protease exhibited a 3.6%higher AME-to-crude protein(CP)ratio than those offered other *** supplementation in the standard-and reduced-dAA diets resulted in 2.7%and 5.6%lower AME intake-to-N retention ratios,respectively,compared with the unsupplemented ***-dAA increased(Ptake(t4.8%),RE(t9.8%),NE intake(t5.8%),NE intake-to-CP ratio(t3.0%),and RE fat-to-RE ratio(t8.6%).Protease supplementation increased(Ptory quotient(t1.2%)and N retention-to-N intake ratio(t2.2%),

关键词： Exogenous enzyme Mono-component protease Net energy Amino acid