AbMole小課堂丨MHY1485：作為mTOR激活劑和自噬抑制劑，在干細(xì)胞、腫瘤和多種動(dòng)物模型中的研究應(yīng)用mTOR作為細(xì)胞內(nèi)關(guān)鍵的信號(hào)傳導(dǎo)樞紐，參與調(diào)控細(xì)胞的多種生理過程。MHY1485（AbMole，M9050）因能高效激活mTOR信號(hào)通路，被廣泛用于多個(gè)研究領(lǐng)域中。此外，MHY1485還表現(xiàn)出高效的自噬抑制活性，為探索細(xì)胞代謝平衡、應(yīng)激反應(yīng)等機(jī)制提供了重要工具。一、MHY1485的作用機(jī)理mTOR（哺乳動(dòng)物雷帕霉素靶蛋白）是細(xì)胞中一個(gè)關(guān)鍵的激酶，mTOR整合細(xì)胞內(nèi)外的營(yíng)養(yǎng)、能量、生長(zhǎng)因子等信號(hào)，調(diào)控包括蛋白質(zhì)合成、代謝、細(xì)胞生長(zhǎng)增殖在內(nèi)的許多重要生命過程。mTOR一般以復(fù)合物的形式發(fā)揮功能，在哺乳動(dòng)物細(xì)胞內(nèi)主要有兩種mTOR蛋白，即mTORC1和mTORC2。MHY1485（AbMole，M9050）主要作用于mTORC1，并對(duì)mTORC1表現(xiàn)出較強(qiáng)的激動(dòng)活性ADDINEN.CITE<EndNote><Cite><Author>Zhu</Author><Year>2018</Year><RecNum>827</RecNum><DisplayText><styleface="superscript">[1]</style></DisplayText><record><rec-number>827</rec-number><foreign-keys><keyapp="EN"db-id="f2td9w00a22awteprfrp9vaup9d9zwa9tdfr"timestamp="1755676679">827</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Zhu,Lin</author><author>Hao,Jun</author><author>Cheng,Meijuan</author><author>Zhang,Cuihong</author><author>Huo,Chunxiu</author><author>Liu,Yaping</author><author>Du,Wei</author><author>Zhang,Xianghong</author></authors></contributors><titles><title>Hyperglycemia-inducedBcl-2/Bax-mediatedapoptosisofSchwanncellsviamTORC1/S6K1inhibitionindiabeticperipheralneuropathy</title><secondary-title>ExperimentalCellResearch</secondary-title></titles><periodical><full-title>ExpCellRes</full-title><abbr-1>Experimentalcellresearch</abbr-1></periodical><pages>186-195</pages><volume>367</volume><number>2</number><keywords><keyword>Diabeticperipheralneuropathy</keyword><keyword>Schwanncell</keyword><keyword>Apoptosis</keyword><keyword>mTORC1</keyword><keyword>S6K1</keyword><keyword>Bcl-2</keyword><keyword>Bax</keyword></keywords><dates><year>2018</year><pub-dates><date>2018/06/15/</date></pub-dates></dates><isbn>0014-4827</isbn><urls><related-urls><url>/science/article/pii/S0014482718301848</url></related-urls></urls><electronic-resource-num>/10.1016/j.yexcr.2018.03.034</electronic-resource-num></record></Cite></EndNote>[1]。研究表明，MHY1485能夠顯著增加mTOR在Ser2448位點(diǎn)的磷酸化水平，并上調(diào)其下游靶蛋白4E-BP1的磷酸化ADDINEN.CITEADDINEN.CITE.DATA[2]。MHY1485還是一種被廣泛使用的自噬抑制劑。在細(xì)胞的自噬過程中，自噬體需與溶酶體融合形成自噬-溶酶體，才能降解其所包裹的物質(zhì)。MHY1485能夠抑制這一融合過程，使自噬體無法與溶酶體正常結(jié)合。另外一方面，由MHY1485激活的mTORC1也會(huì)抑制其下游自噬相關(guān)蛋白的活性，如抑制ULK1（UNC-51樣激酶1）復(fù)合體的活性，從而阻礙自噬的起始過程ADDINEN.CITE<EndNote><Cite><Author>Kim</Author><Year>2015</Year><RecNum>828</RecNum><DisplayText><styleface="superscript">[3]</style></DisplayText><record><rec-number>828</rec-number><foreign-keys><keyapp="EN"db-id="f2td9w00a22awteprfrp9vaup9d9zwa9tdfr"timestamp="1755677035">828</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Kim,Y.C.</author><author>Guan,K.L.</author></authors></contributors><titles><title>mTOR:apharmacologictargetforautophagyregulation</title><secondary-title>JClinInvest</secondary-title><alt-title>TheJournalofclinicalinvestigation</alt-title></titles><periodical><full-title>JClinInvest</full-title><abbr-1>TheJournalofclinicalinvestigation</abbr-1></periodical><alt-periodical><full-title>JClinInvest</full-title><abbr-1>TheJournalofclinicalinvestigation</abbr-1></alt-periodical><pages>25-32</pages><volume>125</volume><number>1</number><edition>2015/02/06</edition><keywords><keyword>Animals</keyword><keyword>Autophagy/*drugeffects</keyword><keyword>Humans</keyword><keyword>Metformin/pharmacology</keyword><keyword>Sirolimus/*pharmacology</keyword><keyword>TORSerine-ThreonineKinases/*antagonists&inhibitors/physiology</keyword></keywords><dates><year>2015</year><pub-dates><date>Jan</date></pub-dates></dates><isbn>0021-9738(Print) 0021-9738</isbn><accession-num>25654547</accession-num><urls></urls><custom2>PMC4382265</custom2><electronic-resource-num>10.1172/jci73939</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[3]。MHY1485的科研應(yīng)用MHY1485在干細(xì)胞和類器官研究的應(yīng)用在體外細(xì)胞實(shí)驗(yàn)中，MHY1485（AbMole，M9050）被用于探索mTOR通路對(duì)細(xì)胞增殖、分化及代謝的影響。例如MHY1485（1-10μM）在成肌細(xì)胞模型中可通過激活mTORC1促進(jìn)肌管形成，上調(diào)肌細(xì)胞分化相關(guān)基因（如MyoD、MyoG）的表達(dá)，揭示mTORC1在肌細(xì)胞發(fā)育中的正向調(diào)控作用ADDINEN.CITE<EndNote><Cite><Author>Cook</Author><Year>2024</Year><RecNum>829</RecNum><DisplayText><styleface="superscript">[4]</style></DisplayText><record><rec-number>829</rec-number><foreign-keys><keyapp="EN"db-id="f2td9w00a22awteprfrp9vaup9d9zwa9tdfr"timestamp="1755677761">829</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Cook,NorahE.</author><author>McGovern,MaceyR.</author><author>Zaman,Toheed</author><author>Lundin,PamelaM.</author><author>Vaughan,RogerA.</author></authors></contributors><titles><title>EffectofmTORCAgonismviaMHY1485withandwithoutRapamycinonC2C12MyotubeMetabolism</title></titles><pages>6819</pages><volume>25</volume><number>13</number><dates><year>2024</year></dates><isbn>1422-0067</isbn><accession-num>doi:10.3390/ijms25136819</accession-num><urls><related-urls><url>/1422-0067/25/13/6819</url></related-urls></urls></record></Cite></EndNote>[4]。在腦類器官的培養(yǎng)中，短期的MHY1485（1-5μM）處理可促進(jìn)細(xì)胞的增殖并誘導(dǎo)細(xì)胞分化，長(zhǎng)期處理則有助于腦類器官的成型，提示mTOR通路的調(diào)節(jié)對(duì)于神經(jīng)干細(xì)胞的分化和腦類器官的培養(yǎng)至關(guān)重要ADDINEN.CITEADDINEN.CITE.DATA[5]。MHY1485還可用于腸道類器官的培養(yǎng)，例如MHY1485能夠增加SLC7A5基因敲除小鼠腸道類器官中pS6的水平，使其與野生型小鼠腸道類器官相似，這表明MHY1485可以通過激活mTORC1信號(hào)通路，調(diào)節(jié)腸道類器官的生長(zhǎng)和發(fā)育ADDINEN.CITE<EndNote><Cite><Author>Bao</Author><Year>2024</Year><RecNum>831</RecNum><DisplayText><styleface="superscript">[6]</style></DisplayText><record><rec-number>831</rec-number><foreign-keys><keyapp="EN"db-id="f2td9w00a22awteprfrp9vaup9d9zwa9tdfr"timestamp="1755679237">831</key><keyapp="ENWeb"db-id="">0</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Bao,Lingyu</author><author>Fu,Liezhen</author><author>Su,Yijun</author><author>Chen,Zuojia</author><author>Peng,Zhaoyi</author><author>Sun,Lulu</author><author>Gonzalez,FrankJ.</author><author>Wu,Chuan</author><author>Zhang,Hongen</author><author>Shi,Bingyin</author><author>Shi,Yun-Bo</author></authors></contributors><titles><title>AminoacidtransporterSLC7A5regulatescellproliferationandsecretarycelldifferentiationanddistributioninthemouseintestine</title><secondary-title>InternationalJournalofBiologicalSciences</secondary-title></titles><periodical><full-title>IntJBiolSci</full-title><abbr-1>Internationaljournalofbiologicalsciences</abbr-1></periodical><pages>2187-2201</pages><volume>20</volume><number>6</number><section>2187</section><dates><year>2024</year></dates><isbn>1449-2288</isbn><urls></urls><electronic-resource-num>10.7150/ijbs.94297</electronic-resource-num></record></Cite></EndNote>[6]。圖SEQ圖\*ARABIC1.MHY1485用于腦類器官的長(zhǎng)期培養(yǎng)ADDINEN.CITEADDINEN.CITE.DATA[5]MHY1485調(diào)節(jié)細(xì)胞代謝mTOR通路的核心功能之一是調(diào)節(jié)細(xì)胞的代謝。MHY1485（AbMole，M9050）作為mTOR的激動(dòng)劑，在多種組織和細(xì)胞的代謝調(diào)節(jié)中有著重要的研究應(yīng)用。例如研究人員使用MHY1485（2μM）處理3T3-L1脂肪細(xì)胞，發(fā)現(xiàn)MHY1485影響了細(xì)胞的脂質(zhì)代謝ADDINEN.CITE<EndNote><Cite><Author>Liu</Author><Year>2020</Year><RecNum>832</RecNum><DisplayText><styleface="superscript">[7]</style></DisplayText><record><rec-number>832</rec-number><foreign-keys><keyapp="EN"db-id="f2td9w00a22awteprfrp9vaup9d9zwa9tdfr"timestamp="1755680286">832</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Liu,Z.</author><author>Liao,W.</author><author>Yin,X.</author><author>Zheng,X.</author><author>Li,Q.</author><author>Zhang,H.</author><author>Zheng,L.</author><author>Feng,X.</author></authors></contributors><auth-address>DepartmentofNutrition,SchoolofPublicHealth,SunYat-senUniversity,Guangzhou,China. GuangdongProvincialKeyLaboratoryofFood,NutritionandHealth,Guangzhou,China.</auth-address><titles><title>Resveratrol-inducedbrownfat-likephenotypein3T3-L1adipocytespartlyviamTORpathway</title><secondary-title>FoodNutrRes</secondary-title><alt-title>Food&nutritionresearch</alt-title></titles><periodical><full-title>FoodNutrRes</full-title><abbr-1>Food&nutritionresearch</abbr-1></periodical><alt-periodical><full-title>FoodNutrRes</full-title><abbr-1>Food&nutritionresearch</abbr-1></alt-periodical><volume>64</volume><edition>2020/02/13</edition><keywords><keyword>3T3-L1adipocytes</keyword><keyword>Browning</keyword><keyword>mTOR</keyword><keyword>resveratrol</keyword><keyword>NaturalScienceFoundationofGuangdongProvince,China(No.2014A030313097).</keyword></keywords><dates><year>2020</year></dates><isbn>1654-661X(Print) 1654-661x</isbn><accession-num>32047421</accession-num><urls></urls><custom2>PMC6983979</custom2><electronic-resource-num>10.29219/fnr.v64.3656</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[7]。此外，MHY1485還可增強(qiáng)腫瘤細(xì)胞的葡萄糖攝取和乳酸生成，說明MHY1485還可調(diào)節(jié)腫瘤細(xì)胞的能量代謝ADDINEN.CITEADDINEN.CITE.DATA[8]。在另一項(xiàng)研究中，實(shí)驗(yàn)人員使用MHY1485（10μM）處理C2C12肌管細(xì)胞，以評(píng)估m(xù)TORC1激活對(duì)細(xì)胞代謝和胰島素敏感性的影響ADDINEN.CITEADDINEN.CITE.DATA[9]。MHY1485用于細(xì)胞自噬的研究MHY1485（AbMole，M9050）還對(duì)細(xì)胞自噬表現(xiàn)出抑制效應(yīng)。在一項(xiàng)研究中，使用HepG2細(xì)胞系構(gòu)建了阿霉素（DOX）耐受的細(xì)胞模型。實(shí)驗(yàn)結(jié)果顯示，MHY1485能夠顯著抑制自噬相關(guān)蛋白LC3A的表達(dá)，并影響ULK1的磷酸化水平，從而抑制自噬，進(jìn)而增強(qiáng)細(xì)胞對(duì)阿霉素的敏感性ADDINEN.CITEADDINEN.CITE.DATA[10]。在對(duì)血管性癡呆大鼠模型的研究中，實(shí)驗(yàn)人員通過永久結(jié)扎雙側(cè)頸總動(dòng)脈建立該模型，隨后使用了Rapamycin（雷帕霉素）和MHY1485來研究PI3K/AKT/mTOR軸對(duì)線粒體自噬的影響。結(jié)果顯示，雷帕霉素處理的大鼠認(rèn)知功能得到改善，神經(jīng)元損傷和線粒體功能障礙顯著減輕；而MHY1485的加入則逆轉(zhuǎn)了雷帕霉素對(duì)凋亡的抑制，以及雷帕霉素對(duì)線粒體自噬的激活A(yù)DDINEN.CITEADDINEN.CITE.DATA[11]。MHY1485在動(dòng)物模型中的應(yīng)用MHY1485（AbMole，M9050）作為一種mTOR激活劑，在多種動(dòng)物模型中展現(xiàn)了其在不同生理過程中的重要作用。例如有文獻(xiàn)探究了MHY1485對(duì)小鼠卵巢卵泡發(fā)育的影響，研究中使用了CD-1和B6D2F1品系的小鼠，發(fā)現(xiàn)MHY1485處理后卵巢組織中mTOR信號(hào)通路蛋白的磷酸化水平增加，卵泡發(fā)育得到促進(jìn)ADDINEN.CITEADDINEN.CITE.DATA[12]。在非酒精性脂肪性肝炎（NASH）大鼠模型中，研究發(fā)現(xiàn)姜黃素（Curcumin）通過調(diào)節(jié)mTORC1-TFEB通路恢復(fù)脂滴自噬，減少脂質(zhì)積累，而mTORC1激活劑MHY1485部分消除了這種效應(yīng)，表明姜黃素在上述模型中的活性可能與mTORC1信號(hào)通路有關(guān)ADDINEN.CITEADDINEN.CITE.DATA[13]。范例詳解ChemicalEngineeringJournal488(2024)151071鄭州大學(xué)附屬第三醫(yī)院的科研人員在該文章中研究了新型納米鉑（Nano-Pt）在骨肉瘤中的作用及機(jī)制，通過細(xì)胞實(shí)驗(yàn)（MG-63、U2-OS、143B三種骨肉瘤細(xì)胞系）和動(dòng)物模型驗(yàn)證其效果。發(fā)現(xiàn)Nano-Pt可進(jìn)入骨肉瘤細(xì)胞，顯著抑制細(xì)胞增殖、遷移和克隆形成，促進(jìn)凋亡，且對(duì)正常細(xì)胞毒性較低；在裸鼠異種移植模型中，能抑制腫瘤生長(zhǎng)，且對(duì)心、肝、脾、肺、腎等正常組織損傷較小。Nano-Pt還能通過誘導(dǎo)自噬增強(qiáng)抗腫瘤效果。由AbMole提供的MHY1485（AbMole，M9050）作為mTOR激動(dòng)劑，被用于驗(yàn)證Nano-Pt通過抑制PI3K/AKT/mTOR通路誘導(dǎo)自噬的機(jī)制。實(shí)驗(yàn)人員通過檢測(cè)自噬相關(guān)蛋白（如LC3-B、P62）、凋亡相關(guān)蛋白（如BAX、Caspase-3）的表達(dá)及凋亡流式細(xì)胞術(shù)結(jié)果，證實(shí)MHY1485可逆轉(zhuǎn)Nano-Pt對(duì)PI3K/AKT/mTOR通路的抑制作用，從而減弱Nano-Pt誘導(dǎo)的自噬和凋亡，反向驗(yàn)證了Nano-Pt通過抑制上述通路發(fā)揮作用。圖SEQ圖\*ARABIC2.MHY1485抑制骨肉瘤細(xì)胞自噬ADDINEN.CITE<EndNote><Cite><Author>Wang</Author><Year>2024</Year><RecNum>839</RecNum><DisplayText><styleface="superscript">[14]</style></DisplayText><record><rec-number>839</rec-number><foreign-keys><keyapp="EN"db-id="f2td9w00a22awteprfrp9vaup9d9zwa9tdfr"timestamp="1755740728">839</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Wang,Jialin</author><author>Yue,Haodi</author><author>Huang,Xin</author><author>Zhang,Mengjun</author></authors></contributors><titles><title>Novelnano-platinuminducesautophagythroughdualpathwaysinthetreatmentofosteosarcomaincelllineswithdifferentP53expressionpatterns</title><secondary-title>ChemicalEngineeringJournal</secondary-title></titles><periodical><full-title>ChemicalEngineeringJournal</full-title></periodical><pages>151071</pages><volume>488</volume><keywords><keyword>Osteosarcoma</keyword><keyword>Nanomedicine</keyword><keyword>Autophagyregulatorypathway</keyword><keyword>PI3K/AKT/mTORpathway</keyword><keyword>P53/mTORpathway</keyword></keywords><dates><year>2024</year><pub-dates><date>2024/05/15/</date></pub-dates></dates><isbn>1385-8947</isbn><urls><related-urls><url>/science/article/pii/S1385894724025580</url></related-urls></urls><electronic-resource-num>/10.1016/j.cej.2024.151071</electronic-resource-num></record></Cite></EndNote>[14]Internationalimmunopharmacology142(2024)113196遼寧中醫(yī)藥大學(xué)、北部戰(zhàn)區(qū)總醫(yī)院的科研團(tuán)隊(duì)在上述論文中探討了紅景天苷（Salidroside，Sal）對(duì)2型糖尿病（T2DM）小鼠心房顫動(dòng)（AF）的影響及機(jī)制。結(jié)果發(fā)現(xiàn)T2DM小鼠出現(xiàn)心房電生理學(xué)重構(gòu)和結(jié)構(gòu)變化，并且AF易感性顯著升高，同時(shí)心房中mTOR-STAT3-MCP-1信號(hào)通路激活，炎癥標(biāo)志物增加，單核細(xì)胞/巨噬細(xì)胞浸潤(rùn)增多。Sal可以劑量依賴性方式改善T2DM小鼠的心功能，減輕心房結(jié)構(gòu)和電重構(gòu)，減少心房炎癥；其通過下調(diào)mTOR-STAT3-MCP-1通路活性，降低心房單核細(xì)胞/巨噬細(xì)胞浸潤(rùn)，從而降低AF的易感性。來自AbMole的MHY1485（AbMole，M9050）作為mTOR激動(dòng)劑用于證實(shí)Salidroside的作用依賴于對(duì)mTOR通路的抑制ADDINEN.CITE<EndNote><Cite><Author>Ren</Author><Year>2024</Year><RecNum>840</RecNum><DisplayText><styleface="superscript">[15]</style></DisplayText><record><rec-number>840</rec-number><foreign-keys><keyapp="EN"db-id="f2td9w00a22awteprfrp9vaup9d9zwa9tdfr"timestamp="1755741270">840</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Ren,Wenpu</author><author>Huang,Yuting</author><author>Meng,Shan</author><author>Cao,Zijun</author><author>Qin,Nana</author><author>Zhao,Jikai</author><author>Huang,Tao</author><author>Guo,Xiaodong</author><author>Chen,Xin</author><author>Zhou,Zijun</author><author>Zhu,Yan</author><author>Yu,Liming</author><author>Wang,Huishan</author></authors></contributors><titles><title>SalidrosidetreatmentdecreasesthesusceptibilityofatrialfibrillationindiabeticmicebyreducingmTOR-STAT3-MCP-1signalingandatrialinflammation</title><secondary-title>InternationalImmunopharmacology</secondary-title></titles><periodical><full-title>IntImmunopharmacol</full-title><abbr-1>Internationalimmunopharmacology</abbr-1></periodical><pages>113196</pages><volume>142</volume><keywords><keyword>Atrialfibrillation</keyword><keyword>Salidroside</keyword><keyword>mTOR</keyword><keyword>Type2diabetesmellitus</keyword><keyword>MCP-1</keyword></keywords><dates><year>2024</year><pub-dates><date>2024/12/05/</date></pub-dates></dates><isbn>1567-5769</isbn><urls><related-urls><url>/science/article/pii/S1567576924017181</url></related-urls></urls><electronic-resource-num>/10.1016/imp.2024.113196</electronic-resource-num></record></Cite></EndNote>[15]。圖SEQ圖\*ARABIC3.EffectsofMHY1485onmTOR-STAT3signaling,chemokine/cytokineproductionaswellasremodelingmarkersADDINEN.CITE<EndNote><Cite><Author>Ren</Author><Year>2024</Year><RecNum>840</RecNum><DisplayText><styleface="superscript">[15]</style></DisplayText><record><rec-number>840</rec-number><foreign-keys><keyapp="EN"db-id="f2td9w00a22awteprfrp9vaup9d9zwa9tdfr"timestamp="1755741270">840</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Ren,Wenpu</author><author>Huang,Yuting</author><author>Meng,Shan</author><author>Cao,Zijun</author><author>Qin,Nana</author><author>Zhao,Jikai</author><author>Huang,Tao</author><author>Guo,Xiaodong</author><author>Chen,Xin</author><author>Zhou,Zijun</author><author>Zhu,Yan</author><author>Yu,Liming</author><author>Wang,Huishan</author></authors></contributors><titles><title>SalidrosidetreatmentdecreasesthesusceptibilityofatrialfibrillationindiabeticmicebyreducingmTOR-STAT3-MCP-1signalingandatrialinflammation</title><secondary-title>InternationalImmunopharmacology</secondary-title></titles><periodical><full-title>IntImmunopharmacol</full-title><abbr-1>Internationalimmunopharmacology</abbr-1></periodical><pages>113196</pages><volume>142</volume><keywords><keyword>Atrialfibrillation</keyword><keyword>Salidroside</keyword><keyword>mTOR</keyword><keyword>Type2diabetesmellitus</keyword><keyword>MCP-1</keyword></keywords><dates><year>2024</year><pub-dates><date>2024/12/05/</date></pub-dates></dates><isbn>1567-5769</isbn><urls><related-urls><url>/science/article/pii/S1567576924017181</url></related-urls></urls><electronic-resource-num>/10.1016/imp.2024.113196</electronic-resource-num></record></Cite></EndNote>[15].參考文獻(xiàn)及鳴謝ADDINEN.REFLIST[1]LinZhu,JunHao,MeijuanCheng,etal.,Hyperglycemia-inducedBcl-2/Bax-mediatedapoptosisofSchwanncellsviamTORC1/S6K1inhibitionindiabeticperipheralneuropathy,Experimentalcellresearch367(2)(2018)186-195.[2]Y.J.Choi,Y.J.Park,J.Y.Park,etal.,InhibitoryeffectofmTORactivatorMHY1485onautophagy:suppressionoflysosomalfusion,PloSone7(8)(2012)e43418.[3]Y.C.Kim,K.L.Guan,mTOR:apharmacologictargetforautophagyregulation,TheJournalofclinicalinvestigation125(1)(2015)25-32.[4]NorahE.Cook,MaceyR.McGovern,ToheedZaman,etal.,EffectofmTORCAgonismviaMHY1485withandwithoutRapamycinonC2C12MyotubeMetabolism,25(13)(2024)6819.[5]S.B.Park,B.Lim,K.Y.Kim,etal.,LongandShort-TermEffectofmTORRegulationonCerebralOrganoidGrowthandDifferentiations,Tissueengineeringandregenerativemedicine21(1)(2024)159-169.[6]LingyuBao,LiezhenFu,YijunSu,etal.,AminoacidtransporterSLC7A5regulatescellproliferationandsecretarycelldifferentiationanddistributioninthemouseintestine,Internationaljournalofbiologicalsciences20(6)(2024)2187-2201.[7]Z.Liu,W.Liao,X.Yin,etal.,Re