Amino acids and mammary gland development:nutritional implications for milk production and neonatal growth

Milk is synthesized by mammary epithelial cells of lactating mammals. The synthetic capacity of the mammary gland depends largely on the number and efficiency of functional mammary epithelial cells. Structural development of the mammary gland occurs during fetal growth, prepubertal and post-pubertal periods, pregnancy, and lactation under the control of various hormones （particularly estrogen, growth hormone, insulin-like growth factor-I, progesterone, placental lactogen, and prolactin） in a species- and stage-dependent manner. Milk is essential for the growth, development, and health of neonates. Amino acids （AA）, present in both free and peptide-bound forms, are the most abundant organic nutrients in the milk of farm animals. Uptake of AA from the arterial blood of the lactating dam is the ultimate source of proteins （primarily 13-casein and a-lactalbumin） and bioactive nitrogenous metabolites in milk. Results of recent studies indicate extensive catabolism of branched-chain AA （leucine, isoleucine and valine） and arginine to synthesize glutamate, glutamine, alanine, aspartate, asparagine, proline, and polyamines. The formation of polypeptides from AA is regulated not only by hormones （e.g., prolactin, insulin and glucocorticoids） and the rate of blood flow across the lactating mammary gland, but also by concentrations of AA, lipids, glucose, vitamins and minerals in the maternal plasma, as well as the activation of the mechanistic （mammalian） target rapamycin signaling by certain AA （e.g., arginine, branched-chain AA, and glutamine）. Knowledge of AA utilization （including metabolism） by mammary epithelial cells will enhance our fundamental understanding of lactation biology and has important implications for improving the efficiency of livestock production worldwide.

Protein hydrolysates in animal nutrition：Industrial production, bioactive peptides,and functional significance

Recent years have witnessed growing interest in the role of peptides in animal nutrition. Chemical, enzymatic, or microbial hydrolysis of proteins in animal by-products or plant-source feedstuffs before feeding is an attractive means of generating high-quality small or large peptides that have both nutritional and physiological or regulatory functions in livestock, poultry and fish. These peptides may also be formed from ingested proteins in the gastrointestinal tract, but the types of resultant peptides can vary greatly with the physiological conditions of the animals and the composition of the diets. In the small intestine, large peptides are hydrolyzed to small peptides,which are absorbed into enterocytes faster than free amino acids（AAs） to provide a more balanced pattern of AAs in the blood circulation. Some peptides of plant or animal sources also have antimicrobial, antioxidant,antihypertensive, and immunomodulatory activities. Those peptides which confer biological functions beyond their nutritional value are called bioactive peptides. They are usually 2–20 AA residues in length but may consist of 〉20AA residues. Inclusion of some（e.g. 2–8%） animal-protein hydrolysates（e.g., porcine intestine, porcine mucosa,salmon viscera, or poultry tissue hydrolysates） or soybean protein hydrolysates in practical corn-and soybean mealbased diets can ensure desirable rates of growth performance and feed efficiency in weanling pigs, young calves,post-hatching poultry, and fish. Thus, protein hydrolysates hold promise in optimizing the nutrition of domestic and companion animals, as well as their health（particularly gut health） and well-being.

氨基酸和乳腺发育对母畜产奶量和新生幼畜生长的营养意义(续)

2哺乳期乳腺中的氨基酸代谢蛋白质可以调节整个机体体内平衡的代谢途径,而氨基酸是构成蛋白质的基础材料[70]。在哺乳期,动物需要大量的氨基酸,通过乳腺组织来合成乳汁[79]。对于在营养上的必需氨基酸来说,支链氨基酸(Branched-Chain AA,BCAA)近年来已经获得了人们极大的关注[67-69]。例如,母猪乳腺摄入的支链氨基酸在数量上远多于乳汁中的这些氨基酸的含量,而谷氨酰胺的情况则相反[69,79-80]。人们已经证实,在泌乳的乳腺组织中支链氨基酸进行着大量的分解代谢,以便为其他氨基酸(如谷氨酸和谷氨酰胺)的生物合成提供氨基[69],而谷氨酸和谷氨酰胺是新生幼畜生长和消化道成熟所必需的营养素[67]。最新的研究证明,支链氨基酸在调节乳腺代谢中有着重要的作用。例如,亮氨酸通过激活TOR细胞信号通路可以促进蛋白质在牛乳腺上皮细胞(Mammary Epithelial Cells,MEC)中的合成[70]。

氨基酸和乳腺发育对母畜产奶量和新生幼畜生长的营养意义(续完)

5重要的乳蛋白所有重要的乳蛋白（血清白蛋白和免疫球蛋白除外）均是由氨基酸合成并由乳腺上皮细胞（Mammary Epithelial Cell,MEC）分泌的。合成蛋白质所需的氨基酸或从血液中摄取,或在MEC中利用众多前体物质合成[67]。乳蛋白由酪蛋白（α-S1、α-S2、β和κ）和乳清蛋白（α-乳白蛋白、β-乳球蛋白、乳铁蛋白、γ-球蛋白和血清白蛋白）组成。

氨基酸和乳腺发育对母畜产奶量和新生幼畜生长的营养意义(续)

4乳腺上皮细胞（Mammary Epithelial Cells,MEC）合成乳汁 分析乳汁的组成成分不仅可以揭示乳汁中的常量和微量营养物质的含量,而且还能揭示乳汁含有的各种保护性因子,如抗菌脂质和蛋白质.大部分保护性因子并不是由乳腺自身专门产生的,相反它们直接来自母体的血液,并被转运到乳汁中.乳蛋白质包括酪蛋白、乳白蛋白、骨桥蛋白、松弛肽以及能结合铁离子以阻止微生物生长的乳铁蛋白、能水解细菌细胞壁的溶菌酶、

氨基酸和乳腺发育对母畜产奶量和新生幼畜生长的营养意义

乳汁是哺乳动物在哺乳期由乳腺上皮细胞合成的物质。乳腺合成乳汁的能力在很大程度上取决于功能性乳腺上皮细胞的数量和效率。在各种激素(特别是雌激素、生长激素、胰岛素样生长因子-1、黄体酮、胎盘催乳素和催乳素等)的控制下,乳腺结构在胎儿生长期、青春期前期和青春期后期、怀孕期和哺乳期以物种依赖性和阶段依赖性的方式不断发育。乳汁对新生幼畜的生长、发育和健康来说至关重要。氨基酸是家畜乳汁中最为丰富的有机营养物,它以游离态和肽结合态的形式存在。哺乳母畜动脉血液中的氨基酸是乳汁中蛋白质(主要是β-酪蛋白和α-乳清蛋白)和生物活性氮代谢产生的最终来源。最新的研究结果指出,支链氨基酸(亮氨酸、异亮氨酸和缬氨酸)和精氨酸会大量分解代谢以合成谷氨酸、谷氨酰胺、丙氨酸、天冬氨酸、天冬酰胺、脯氨酸和多胺。氨基酸形成多肽不仅受激素(如催乳素、胰岛素和糖皮质激素)和流经哺乳期乳腺的血流速度的调控,还受母体血浆中氨基酸、脂肪、葡萄糖、维生素和矿物质浓度以及由某些氨基酸(如精氨酸、支链氨基酸和谷氨酰胺)机械性(哺乳动物)靶向雷帕霉素通路的活化程度的影响。掌握乳腺上皮细胞利用氨基酸(包括代谢)的相关知识将会加强我们对泌乳生物学的全面了解,并且对提高全球畜牧生产效率具有重要的意义。

Autophagy and tight junction proteins in the intestine and intestinal diseases

The intestinal epithelium(IE) forms an indispensible barrier and interface between the intestinal interstitium and the luminal environment. The IE regulates water, ion and nutrient transport while providing a barrier against toxins, pathogens(bacteria, fungi and virus) and antigens. The apical intercellular tight junctions(TJ) are responsible for the paracellular barrier function and regulate transepithelial flux of ions and solutes between adjacent cells. Increased intestinal permeability caused by defects in the IE TJ barrier is considered an important pathogenic factor for the development of intestinal inflammation, diarrhea and malnutrition in humans and animals. In fact, defects in the IE TJ barrier allow increased antigenic penetration, resulting in an amplified inflammatory response in inflammatory bowel disease(IBD), necrotizing enterocolitis and ischemia-reperfusion injury. Conversely, the beneficial enhancement of the intestinal TJ barrier has been shown to resolve intestinal inflammation and apoptosis in both animal models of IBD and human IBD. Autophagy(self-eating mechanism) is an intracellular lysosome-dependent degradation and recycling pathway essential for cell survival and homeostasis.Dysregulated autophagy has been shown to be directly associated with many pathological processes,including IBD. Importantly, the crosstalk between IE TJ and autophagy has been revealed recently. We showed that autophagy enhanced IE TJ barrier function by increasing transepithelial resistance and reducing the paracellular permeability of small solutes and ions, which is, in part, by targeting claudin-2,a cation-selective, pore-forming, transmembrane TJ protein, for lysosome(autophagy)-mediated degradation. Interestingly, previous studies have shown that the inflamed intestinal mucosa in patients with active IBD has increased claudin-2 expression. In addition, inflammatory cytokines(for example,tumor necrosis factor-α, interleukin-6, interleukin-13, and interleukin-17) whose levels are increased in IBD patients cause an increase in claudin-2 expression and a claudin-2-dependent increase in TJ permeability. Thus, the role of claudin-2 in intestinal pathological processes has been attributed, in part, to the increase of intestinal TJ permeability. Claudin-2 represents a new therapeutic target in treating IBD,diarrhea and malnutrition in animals and humans.

Dietary modulation of endogenous host defense peptide synthesis as an alternative approach to in-feed antibiotics

Traditionally, antibiotics are included in animal feed at subtherapeutic levels for growth promotion and disease prevention.However, recent links between in-feed antibiotics and a rise in antibiotic-resistant pathogens have led to a ban of all antibiotics in livestock production by the European Union in January 2006 and a removal of medically important antibiotics in animal feeds in the United States in January 2017.An urgent need arises for antibiotic alternatives capable of maintaining animal health and productivity without triggering antimicrobial resistance.Host defense peptides(HDP) are a critical component of the animal innate immune system with direct antimicrobial and immunomodulatory activities.While in-feed supplementation of recombinant or synthetic HDP appears to be effective in maintaining animal performance and alleviating clinical symptoms in the context of disease, dietary modulation of the synthesis of endogenous host defense peptides has emerged as a cost-effective,antibiotic-alternative approach to disease control and prevention.Several different classes of smallmolecule compounds have been found capable of promoting HDP synthesis.Among the most efficacious compounds are butyrate and vitamin D.Moreover, butyrate and vitamin D synergize with each other in enhancing HDP synthesis.This review will focus on the regulation of HDP synthesis by butyrate and vitamin D in humans, chickens, pigs, and cattle and argue for potential application of HDP-inducing compounds in antibiotic-free livestock production.

Safety Design for the China Space Station

The safety of a space station under normal and abnormal conditions can be ensured only by comprehensively identifying various hazards of the space station during its whole mission cycle and formulating control measures against each hazard.This paper describes the safety design process of the China Space Station,as well as detailed safety design measures for general hazards,fault hazards,dangerous events,and critical missions,so as to achieve safety goals as far as possible under the circumstances of limited resources and transportation capacity of the space station.The key work of safety design includes identification of hazard sources and dangerous events,formulation of safety control measures,and design of safety safeguard measures.Identification of hazards and hazardous events is based on both defined content in design schemes and previous on-orbit flight experience of manned spacecraft.The formulated safety control measures are based on analyzing each hazard to determine key links of safety control and formulate corresponding control measures for effective hazard control under minimum resource cost.In the case of a serious failure,the space station can remain safe within a certain time by its autonomous hazard disposal.