[1] Lock S. What is AI chatbot phenomenon ChatGPT and could it replace humans[N]. The Guardian, 2022, 5.
[2] Van N R, Perkel J M. AI and science:What 1,600 researchers think[J]. Nature, 2023, 621(7980):672-675.
[3] Thorp H H. ChatGPT is fun, but not an author[J]. American Association for the Advancement of Science, 2023,379(6630):313.
[4] Savage N. Drug discovery companies are customizing ChatGPT:Here's how[J]. Nature Biotechnology, 2023, 41:585-586.
[5] Wang F, Feng X, Kong R, et al. Generating new protein sequences by using dense network and attention mechanism[J]. Mathematical Biosciences and Engineering,2023, 20(2):4178-4197.
[6] Watson J L, Juergens D, Bennett N R, et al. De novo design of protein structure and function with RFdiffusion[J].Nature, 2023, 620(7976):1089-1100.
[7] Torres S V, Leung P J Y, Venkatesh P, et al. De novo design of high-affinity binders of bioactive helical peptides[J]. Nature, 2023, 12, doi:s41586-023-06953-1.
[8] Kim H Y, Lampertico P, Nam J Y, et al. An artificial intelligence model to predict hepatocellular carcinoma risk in Korean and Caucasian patients with chronic hepatitis B[J]. Journal of Hepatology, 2022, 76(2):311-318.
[9] Martinino A, Aloulou M, Chatterjee S, et al. Artificial intelligence in the diagnosis of hepatocellular carcinoma:A systematic review[J]. Journal of Clinical Medicine, 2022,11(21):6368.
[10] Nauck M A, Quast D R, Wefers J, et al. GLP-1 receptor agonists in the treatment of type 2 diabetes-state-ofthe-art[J]. Molecular Metabolism, 2021, 46:101102.
[11] Alexopoulos A S, Buse J B. Initial injectable therapy in type 2 diabetes:Key considerations when choosing between glucagon-like peptide 1 receptor agonists and insulin[J]. Metabolism, 2019, 98:104-111.
[12] Davies M J, Aroda V R, Collins S, et al. Management of hyperglycaemia in type 2 diabetes, 2022. A consensus report by the American Diabetes Association(ADA)and the European Associ ation for the Study of Diabetes(EASD)[J]. Diabetologia, 2022, 65(12):1925-1966.
[13] Ussher J R, Drucker D J. Glucagon-like peptide 1 receptor agonists:Cardiovascular benefits and mechanisms of action[J]. Nature Reviews Cardiology, 2023, 20(7):463-474.
[14] Arastu N, Cummins O, Uribe W, et al. Efficacy of subcutaneous semaglutide compared to placebo for weight lo ss in obese, non-diabetic adults:A systematic review&meta-analysis[J]. International Journal of Clinical Pharmacy, 2022, 44(4):852-859.
[15] Rubino D, Abrahamsson N, Davies M, et al. Effect of continued weekly subcutaneous semaglutide vs placebo on weight loss maintenance in adults with overweight or obesity:The step 4 randomized clinical trial[J]. JAMA,2021, 325(14):1414-1425.
[16] Tushuizen M E, Diamant M, Heine R J. Postprandial dysmetabolism and cardiovascular disease in type 2 diabetes[J]. Postgraduate Medical Journal, 2005, 81(951):1-6.
[17] Yin Y, Zhou X E, Hou L, et al. An intrinsic agonist mechanism for activation of glucagon-like peptide-1 receptor by its extracellular domain[J]. Cell Discovery,2016, 2:16042.
[18] Ghosh P, Fontanella R A, Scisciola L, et al. Targeting redox imbalance in neurodegeneration:Characterizing the role of GLP-1 receptor agonists[J]. Theranostics, 2023,13(14):4872-4884.
[19] Dalle S, Ravier M A, Bertrand G. Emerging roles for β-arrestin-1 in the control of the pancreatic β-cell function and mass:New therapeutic strategies and consequences for drug screening[J]. Cell Signal, 2011, 23(3):522-528.
[20] Gros R, You X, Baggio L L, et al. Cardiac function in mice lacking the glucagon-like peptide-1 receptor[J].Endocrinology, 2003, 144(6):2242-2252.
[21] Goedert M. Alzheimer's and Parkinson's diseases:The prion concept in relation to assembled Aβ, tau, and α-synuclein[J]. Science, 2015, 349(6248):601.
[22] Stefanoska K, Gajwani M, Tan A R P, et al. Alzheimer's disease:Ablating single master site abolishes tau hyperphosphorylation[J]. Science Advances, 2022, 8(27):eabl-8809.
[23] Zhang W, Xiao D, Mao Q, et al. Role of neuroinflammation in neurodegeneration development[J]. Signal Transduction and Targeted Therapy, 2023, 8(1):267.
[24] Jucker M, Walker L C. Alzheimer's disease:From immunotherapy to immunoprevention[J]. Cell, 2023, 186(20):4260-4270.
[25] Jucker M, Walker L C. Propagation and spread of pathogenic protein assemblies in neurodegenerative diseases[J]. Nature Neuroscience, 2018, 21(10):1341-1349.
[26] Hur J Y, Frost G R, Wu X, et al. The innate immunity protein IFITM3 modulates γ-secretase in Alzheimer's disease[J]. Nature, 2020, 586(7831):735-740.
[27] Mahley R W, Huang Y. Apolipoprotein E sets the stage:Response to injury triggers neuropathology[J]. Neuron,2012, 76(5):871-885.
[28] Yoshiyama Y, Higuchi M, Zhang B, et al. Synapse loss and microglial activation precede tangles in a P301S tauopathy mouse model[J]. Neuron, 2007, 53(3):337-351.
[29] Nisbet R M, Polanco J C, Ittner L M, et al. Tau aggregation and its interplay with amyloid-β[J]. Acta Neuropathologica, 2014, 129(2):207-220.
[30] Maphis N, Xu G, Kokiko-cochran O N, et al. Reactive microglia drive tau pathology and contribute to the spreading of pathological tau in the brain[J]. Brain,2015, 138(6):1738-1755.
[31] Venegas C, Heneka M T. Danger-associated molecular patterns in Alzheimer's disease[J]. Journal of Leukocyte Biology, 2017, 101(1):87-98.
[32] Onyango I G, Jauregui G V,ČARNáM, et al. Neuroinflammation in Alzheimer's disease[J]. Biomedicines,2021, 9(5):524.
[33] Couzin-Frankel J, Hand E, Langin K, et al. Runners-Up[J]. Science, 2023, 382(6676):1228-1233.
[34] Cummings J, Osse A M L, Cammann D, et al. Anti-amyloid monoclonal antibodies for the treatment of Alzheimer's disease[J]. BioDrugs, 2024, 38:5-22.
[35] Golde T E, Levey A I. Immunotherapies for Alzheimer's disease[J]. Science, 2023, 382(6676):1242-1244.
[36] Teunissen C E, Verberk I M W, Thijssen E H, et al.Blood-based biomarkers for Alzheimer's disease:Towards clinical implementation[J]. The Lancet Neurology,2022, 21(1):66-77.
[37] Chen Y, Hong Z, Wang J, et al. Circuit-specific gene therapy reverses core symptoms in a primate Parkinson's disease model[J]. Cell, 2023, 186(24):5394-410.e18.
[38] Przedborski S. The two-century journey of Parkinson disease research[J]. Nature Reviews Neuroscience, 2017, 18(4):251-259.
[39] Gao C, Jiang J, Tan Y, et al. Microglia in neurodegenerative diseases:Mechanism and potential therapeutic targets[J]. Signal Transduction and Targeted Therapy,2023, 8(1):359.
[40] Duffy M F, Collier T J, Patterson J R, et al. Lewy bodylike alpha-synuclein inclusions trigger reactive microgliosis prior to nigral degeneration[J]. Journal of Neuroinflammation, 2018, 15(1):129.
[41] Chatzi C, Brade T, Duester G. Retinoic acid functions as a key GABAergic differentiation signal in the basal ganglia[J]. PLoS Biology, 2011, 9(4):e1000609.
[42] Blum D, Torch S, Lambeng N, et al. Molecular pathways involved in the neurotoxicity of 6-OHDA, dopamine and MPTP:Contribution to the apoptotic theory in Parkinson's disease[J]. Progress in Neurobiology, 2001, 65(2):135-172.
[43] Poewe W, Seppi K, Tanner C M, et al. Parkinson disease[J]. Nature Reviews Disease Primers, 2017, 3:17013.
[44] Kikuchi T, Morizane A, Doi D, et al. Human iPS cellderived dopaminergic neurons function in a primate Parkinson's disease model[J]. Nature, 2017, 548(7669):592-596.
[45] Maimaitili M, Chen M, Febbraro F, et al. Enhanced production of mesencephalic dopaminergic neurons from lineage-restricted human undifferentiated stem cells[J]. Nature Communications, 2023, 14(1):7871.
[46] Park S, Park C W, Eom J H, et al. Preclinical and doseranging assessment of hESC-derived dopaminergic progenitors for a clinical trial on Parkinson's disease[J].Cell Stem Cell, 2024, 31(1):25-38.e8.
[47] Arnold C, Webster P. 11 clinical trials that will shape medicine in 2024[J]. Nature Medicine, 2023, 29(12):2964-2968.
[48] Malhi G S, Mann J J. Depression[J]. The Lancet, 2018,392(10161):2299-2312.
[49] Santomauro D F, Mantilla H A M, Shadid J, et al. Global prevalence and burden of depressive and anxiety disorders in 204 countries and territories in 2020 due to the COVID-19 pandemic[J]. The Lancet, 2021, 398(10312):1700-1712.
[50] Holingue C. Mental disorders around the world:Facts and figures from the WHO world mental health surveys[J]. American Journal of Psychiatry, 2018, 175(9):911-912.
[51] Vos T, Barber R M, Bell B, et al. Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990-2013:A systematic analysis for the Global Burden of Disease Study 2013[J]. The Lancet, 2015, 386(9995):743-800.
[52] Marx W, Penninx B W J H, Solmi M, et al. Major depressive disorder[J]. Nature Reviews Disease Primers,2023, 9(1):44.
[53] Kuehner C. Why is depression more common among women than among men?[J]. The Lancet Psychiatry,2017, 4(2):146-158.
[54] Yuan M, Yang B, Rothschild G, et al. Epigenetic regulation in major depression and other stress-related disorders:Molecular mechanisms, clinical relevance and therapeutic potential[J]. Signal Transduction and Targeted Therapy, 2023, 8(1):309.
[55] Chesney E, Goodwin G M, Fazel S. Risks of all-cause and suicide mortality in mental disorders:A meta-review[J]. World Psychiatry, 2014, 13(2):153-160.
[56] Whooley M A, Wong J M. Depression and cardiovascular disorders[J]. Annual Review of Clinical Psychology,2013, 9(1):327-354.
[57] Howard D M, Adams M J, Clarke T K, et al. Genomewide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions[J]. Nature Neuroscience, 2019, 22(3):343-352.
[58] Guo B, Zhang M, Hao W, et al. Neuroinflammation mechanisms of neuromodulation therapies for anxiety and depression[J]. Translational Psychiatry, 2023, 13(1):5.
[59] Knowland D, Lim B K. Circuit-based frameworks of depressive behaviors:The role of reward circuitry and beyond[J]. Pharmacology Biochemistry and Behavior, 2018,174:42-52.
[60] Fries G R, SaldanaA V A, Finnstein J, et al. Molecular pathways of major depressive disorder converge on the synapse[J]. Molecular Psychiatry, 2022, 28(1):284-297.
[61] Burke H M, Davis M C, Otte C, et al. Depression and cortisol responses to psychological stress:A meta-analysis[J]. Psychoneuroendocrinology, 2005, 30(9):846-856.
[62] Osimo E F, Pillinger T, Rodriguez I M, et al. Inflammatory markers in depression:A meta-analysis of mean differences and variability in 5,166 patients and 5,083 controls[J]. Brain, Behavior, and Immunity, 2020, 87:901-909.
[63] Cryan J F, O'riordan K J, Cowan C S M, et al. The microbiota-gut-brain axis[J]. Physiological Reviews, 2019,99(4):1877-2013.
[64] Li K, Zhou T, Liao L, et al. β CaMKII in lateral habenula mediates core symptoms of depression[J]. Science,2013, 341(6149):1016-1020.
[65] Cui Y, Yang Y, Ni Z, et al. Astroglial Kir4.1 in the lateral habenula drives neuronal bursts in depression[J]. Nature, 2018, 554(7692):323-327.
[66] Yang Y, Cui Y, Sang K, et al. Ketamine blocks bursting in the lateral habenula to rapidly relieve depression[J].Nature, 2018, 554(7692):317-322.
[67] Ma S, Chen M, Jiang Y, et al. Sustained antidepressant effect of ketamine through NMDAR trapping in the LHb[J]. Nature, 2023, 622(7984):802-809.
[68] Willner P, Scheel-Krüger J, Belzung C. The neurobiology of depression and antidepressant action[J]. Neurosci ence&Biobehavioral Reviews, 2013, 37(10):2331-2371.
[69] Malhi G S, Bassett D, Boyce P, et al. Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for mood disorders[J]. Australian and New Zealand Journal of Psychiatry, 2015, 49(12):1087-1206.
[70] Marwaha S, Palmer E, Suppes T, et al. Novel and emerging treatments for major depression[J]. Lancet, 2023, 401(10371):141-153.
[71] Papp M, Cubala W J, Swiecicki L, et al. Perspectives for therapy of treatment-resistant depression[J]. British Journal of Pharmacology, 2022, 179(17):4181-4200.
[72] Espinoza R T, Kellner C H. Electroconvulsive therapy[J]. The New England Journal of Medicine, 2022, 386(7):667-672.
[73] Runia N, Mol G J J, Hillenius T, et al. Effects of deep brain stimulation on cognitive functioning in treatmentresistant depression:A systematic review and meta-analysis[J]. Molecular Psychiatry, 2023, 9, doi:10.1038/s41380-023-02262-1.
[74] Anand A, Mathew S J, Sanacora G, et al. Ketamine versus ECT for nonpsychotic treatment-resistant major depression[J]. The New England Journal of Medicine,2023, 388(25):2315-2325.
[75] Zanos P, Moaddel R, Morris P J, et al. Ketamine and ketamine metabolite pharmacology:Insights into therapeutic mechanisms[J]. Pharmacological Reviews, 2018,70(3):621-660.
[76] Qian T, Wang H, Wang P, et al. A genetically encoded sensor measures temporal oxytocin release from different neuronal compartments[J]. Nature Biotechnology, 2023,41(7):1-14.
[77] Wang H, Qian T, Zhao Y, et al. A tool kit of highly selective and sensitive genetically encoded neuropeptide sensors[J]. Science, 2023, 382(6672):eabq8173.
[78] Mueller I, Zimmerman P A, Reeder J C. Plasmodium malariae and plasmodium ovale-the'bashful'malaria parasites[J]. Trends in Parasitology, 2007, 23(6):278-283.
[79] Yam X Y, Preiser P R. Host immune evasion strategies of malaria blood stage parasite[J]. Molecular BioSystems,2017, 13(12):2498-2508.
[80] Cowman A F, Berry D, Baum J. The cellular and molecular basis for malaria parasite invasion of the human red blood cell[J]. Journal of cell Biology, 2012, 198(6):961-971.
[81] Beeson J G, Kurtovic L, Valim C, et al. The RTS,S malaria vaccine:Current impact and foundation for the future[J]. Science Translational Medicine, 2022, 14(671):eabo6646.
[82] Rts S. Efficacy and safety of RTS, S/AS01 malaria vaccine with or without a booster dose in infants and children in Africa:Final results of a phase 3, individually randomised, controlled trial[J]. Lancet, 2015, 386(9988):31-45.
[83] Datoo M S, Natama H M, SoméA, et al. Efficacy and immunogenicity of R21/Matrix-M vaccine against clinical malaria after 2 years'follow-up in children in Burkina Faso:A phase 1/2b randomised controlled trial[J].The Lancet Infectious Diseases, 2022, 22(12):1728-1736.
[84] Alimonti J B, Ball T B, Fowke K R. Mechanisms of CD4+T lymphocyte cell death in human immunodeficiency virus infection and AIDS[J]. Journal of General Virology, 2003, 84(7):1649-1661.
[85] Sepkowitz K A. AIDS—the first 20 years[J]. New England Journal of Medicine, 2001, 344(23):1764-1772.
[86] Holmes C B, Losina E, Walensky R P, et al. Review of human immunodeficiency virus type 1-related opportunistic infections in sub-Saharan Africa[J]. Clinical Infectious Diseases, 2003, 36(5):652-662.
[87] Vogel M, Schwarze-Zander C, Wasmuth J C, et al. The treatment of patients with HIV[J]. DeutschesÄrzteblatt International, 2010, 107(28/29):507.
[88] Butler E T, Chamberlin M. Bacteriophage SP6-specific RNA polymerase. I. Isolation and characterization of the enzyme[J]. Journal of Biological Chemistry, 1982, 257(10):5772-5778.
[89] Krieg P A, Melton D. Functional messenger RNAs are produced by SP6 in vitro transcription of cloned cDNAs[J]. Nucleic Acids Research, 1984, 12(18):7057-7070.
[90] Dunn J J, Studier F W, Gottesman M. Complete nucleotide sequence of bacteriophage T7 DNA and the locations of T7 genetic elements[J]. Journal of Molecular Biology, 1983, 166(4):477-535.
[91] Studier F W, Moffatt B A. Use of bacteriophage T7 RNA polymerase to direct selective high-level expression of cloned genes[J]. Journal of Molecular Biology, 1986, 189(1):113-130.
[92] KarikóK, Ni H, Capodici J, et al. mRNA is an endogenous ligand for Toll-like receptor 3[J]. Journal of Biological Chemistry, 2004, 279(13):12542-12550.
[93] KarikóK, Buckstein M, Ni H, et al. Suppression of RNA recognition by toll-like receptors:The impact of nucleoside modification and the evolutionary origin of RNA[J]. Immunity, 2005, 23(2):165-175.
[94] Nobel Committee for Physiology or Medicine 2023[N/OL].[2023-12-12]. https://www.nobelprize.org/about/the-nobel-committee-for-physiology-or-medicine/.
[95] Svitkin Y V, Cheng Y M, Chakraborty T, et al. N1-methyl-pseudouridine in mRNA enhances translation through eIF2α-dependent and independent mechanisms by increasing ribosome density[J]. Nucleic Acids Research,2017, 45(10):6023-6036.
[96] Hikabe O, Hamazaki N, Nagamatsu G, et al. Reconstitution in vitro of the entire cycle of the mouse female germ line[J]. Nature, 2016, 539(7628):299-303.
[97] Hamazaki N, Kyogoku H, Araki H, et al. Reconstitution of the oocyte transcriptional network with transcription factors[J]. Nature, 2021, 589(7841):264-269.
[98] Yoshino T, Suzuki T, Nagamatsu G, et al. Generation of ovarian follicles from mouse pluripotent stem cells[J].Science, 2021, 373(6552):eabe0237.
[99] Murakami K, Hamazaki N, Hamada N, et al. Generation of functional oocytes from male mice in vitro[J]. Nature,2023, 615(7954):900-906.
[100] Method of the Year 2023:Methods for modeling development[J]. Nature Methods, 2023, 20(12):1831-1832.
[101] Rossant J, Tam P P L. Opportunities and challenges with stem cell-based embryo models[J]. Stem Cell Reports, 2021, 16(5):1031-1038.
[102] Rossant J, Tam P P L. New insights into early human development:Lessons for stem cell derivation and differentiation[J]. Cell Stem Cell, 2017, 20(1):18-28.
[103] Liu X, Tan J P, Schröder J, et al. Modelling human blastocysts by reprogramming fibroblasts into iBlastoids[J]. Nature, 2021, 591(7851):627-632.
[104] Abel A, Sozen B. Shifting early embryology paradigms:Applications of stem cell-based embryo models in bioengineering[J]. Current Opinion in Genetics&Development, 2023, 81:102069.
[105] Yu L, Wei Y, Duan J, et al. Blastocyst-like structures generated from human pluripotent stem cells[J]. Nature,2021, 591(7851):620-626.
[106] Amadei G, Handford C E, Qiu C, et al. Embryo model completes gastrulation to neurulation and organogenesis[J]. Nature, 2022, 610(7930):143-153.
[107] Lau K Y C, Rubinstein H, Gantner C W, et al. Mouse embryo model derived exclusively from embryonic stem cells undergoes neurulation and heart development[J].Cell Stem Cell, 2022, 29(10):1445-1458.
[108] Eisenstein M. Seven technologies to watch in 2023[J].Nature, 2023, 613(7945):794-797.
[109] Weatherbee B A T, Gantner C W, Iwamoto-Stohl L K,et al. Pluripotent stem cell-derived model of the postimplantation human embryo[J]. Nature, 2023, 622(7983):584-593.
[110] Oldak B, Wildschutz E, Bondarenko V, et al. Complete human day 14 post-implantation embryo models from naive ES cells[J]. Nature, 2023, 622(7983):562-573.
[111] De G N, De P L, Munsie M.'Ceci n'est pas un embryon?'The ethics of human embryo model research[J].Nature Methods, 2023, 20(12):1863-1867.
[112] Pasricha S R, Darkesmith H. Hemoglobinopathies in the fetal position[J]. New England Journal of Medicine,2018, 379(17):1675-1677.
[113] Bauer D E, Orkin S H. Hemoglobin switching's surprise:The versatile transcription factor BCL11A is a master repressor of fetal hemoglobin[J]. Current Opinion in Genetics&Development, 2015, 33:62-70.
[114] Bak R O, Dever D P, Porteus M H. CRISPR/Cas9 genome editing in human hematopoietic stem cells[J]. Nature Protocols, 2018, 13(2):358-376.
[115] Frangoul H, Ho T W, Corbacioglu S. CRISPR-Cas9gene editing for sickle cell disease and β-thalassemia[J]. The New England Journal of Medicine, 2021, 384(23):252-260.
[116] Gibson B A, Doolittle L K, Schneider M W G, et al. Organization of chromatin by intrinsic and regulated phase separation[J]. Cell, 2019, 179(2):470-484.
[117] Murray D T, Kato M, Lin Y, et al. Structure of FUS rotein fibrils and its relevance to self-assembly and phase separation of low-complexity domains[J]. Cell,2017, 171(3):615-627.
[118] Mehta S, Zhang J. Liquid-liquid phase separation drives cellular function and dysfunction in cancer[J].Nature Reviews Cancer, 2022, 22(4):239-252.
[119] Ding M, Xu W, Pei G, et al. Long way up:Rethink diseases in light of phase separation and phase transition[J]. Protein Cell, 2023, doi:org/10.1093/procel/pwad057.
[120] Li P, BanjadeE S, Cheng H C, et al. Phase transitions in the assembly of multivalent signalling proteins[J].Nature, 2012, 483(7389):336-340.
[121] Zhao P, Han W, Shu Y, et al. Liquid-liquid phase separation drug aggregate:Merit for oral delivery of amorphous solid dispersions[J]. Journal of Controlled Release, 2023, 353:42-50.