Artificial intelligence-based comprehensive analysis of immune-stemness-tumor budding profile to predict survival of patients with pancreatic adenocarcinoma

Objective:Pancreatic ductal adenocarcinoma(PDAC)is an aggressive malignancy.CD8^(+)T cells,cancer stem cells(CSCs),and tumor budding(TB)have been significantly correlated with the outcome of patients with PDAC,but the correlations have been independently reported.In addition,no integrated immune-CSC-TB profile for predicting survival in patients with PDAC has been established.Methods:Multiplexed immunofluorescence and artificial intelligence(AI)-based comprehensive analyses were used for quantification and spatial distribution analysis of CD8^(+)T cells,CD133^(+)CSCs,and TB.In vivo humanized patient-derived xenograft(PDX)models were established.Nomogram analysis,calibration curve,time-dependent receiver operating characteristic curve,and decision curve analyses were performed using R software.Results:The established‘anti-/pro-tumor’models showed that the CD8^(+)T cell/TB,CD8^(+)T cell/CD133^(+)CSC,TB-adjacent CD8^(+)T cell,and CD133^(+)CSC-adjacent CD8^(+)T cell indices were positively associated with survival of patients with PDAC.These findings were validated using PDX-transplanted humanized mouse models.An integrated nomogram-based immune-CSC-TB profile that included the CD8^(+)T cell/TB and CD8^(+)T cell/CD133^(+)CSC indices was established and shown to be superior to the tumor-nodemetastasis stage model in predicting survival of patients with PDAC.Conclusions:‘Anti-/pro-tumor’models and the spatial relationship among CD8^(+)T cells,CSCs,and TB within the tumor microenvironment were investigated.Novel strategies to predict the prognosis of patients with PDAC were established using AI-based comprehensive analysis and machine learning workflow.The nomogram-based immune-CSC-TB profile can provide accurate prognosis prediction for patients with PDAC.

The Hippo/YAP signaling pathway:the driver of cancer metastasis

Despite major improvements in cancer survival,metastasis is responsible for almost 90%of cancer-related mortality^(1,2).Nonetheless,the pathogenesis and molecular mechanisms of cancer metastasis remain poorly understood.

潮州音乐乐律研究评述——兼论潮乐乐律之源头

潮州音乐使用的乐律的测音研究目前已十分丰富,但都未从源头上揭示出这种乐律形成的学理。潮乐的乐律之源头实为明清以来广为流传的“均孔笛”为代表的均孔管类乐器,正是这种乐器及其演奏习惯对潮州音乐律制形成了决定性的影响。

Pancreatic adenocarcinoma and aging:understanding the menace for better management

Pancreatic ductal adenocarcinoma(PDAC)is the leading cause of cancer-related death worldwide.As PDAC is more common in older adults and the population is aging,the incidence of pancreatic adenocarcinoma is expected to increase in the coming years.As a result,the mechanism and clinical management of PDAC in the elderly population is receiving more attention.This review will discuss age-related morphological and pathological changes,clinical management,surgery and adjuvant therapies,and molecular changes in elderly PDAC patients.More research is needed to clarify molecular mechanisms and develop new prevention and treatment strategies for PDAC in elderly patients.

A Virulent PEDV Strain FJzz1 with Genomic Mutations and Deletions at the High Passage Level Was Attenuated in Piglets via Serial Passage In Vitro

Highly virulent porcine epidemic diarrhea virus(PEDV)strains re-emerged and circulated in China at the end of 2010,causing significant economic losses in the pork industry worldwide.To understand the genetic dynamics of PEDV during its passage in vitro,the PEDV G2 strain FJzzl was serially propagated in Vero cells for up to 200 passages.The susceptibility and adaptability of the FJzzl strain increased gradually as it was serially passaged in vitro.Sequence analysis revealed that amino acid(aa)changes were mainly concentrated in the S glycoprotein,which accounted for 72.22%-85.71%of all aa changes.A continuous aa deletion(^(55)I^(56)G^(57)E→^(55)K^(56)Δ^(57)Δ)occurred in the N-terminal domain of S1(Sl-NTD).To examine how the aa changes affected its virulence,FJzzl-F20 and FJzzl-F200 were selected to simultaneously evaluate their pathogenicity in suckling piglets.All the piglets in the FJzzl-F20-infected group showed typical diarrhea at 24 h postinfection,and the piglets died successively by 48 h postinfection.However,the clinical signs of the piglets in the FJzzl-F200-infected group were significantly weaker,and no deaths occurred.The FJzzl-F200-infected group also showed a lower level of fecal viral shedding and lower viral loads in the intestinal tissues,and no obvious histopathological lesions.TypeⅠandⅢinterferon were induced in the FJzzl-F200 infection group,together with pro-inflammatory cytokines,such as TNF-α,IL-1βand IL-8.These results indicate that the identified genetic changes may contribute to the attenuation of FJzzl strain,and the attenuated FJzzl-F200 may have the potential for developing PEDV live-attenuated vaccines.

酰基辅酶A和酰基肉碱的组学新方法揭示果蝇在不同发育阶段的脂肪酰代谢命运的链长依赖性差异

在生物体复杂的代谢途径中,脂酰辅酶A是一种非常重要的中间产物,准确快速地监测脂酰辅酶A的含量变化对生物学研究具有十分重要的意义.已有的脂酰辅酶A分析方法对仪器要求较高,导致方法普及性差,且目前尚无能够同时分析脂酰辅酶A和脂酰肉碱的组学方法.本文开发了一种全新的脂酰辅酶A和脂酰肉碱的组学方法:单针进样实现快速灵敏的组学轮廓分析.利用该方法对果蝇不同发育阶段及高脂饮食处理进行检测,获得了较完整的果蝇发育及不同饮食条件下的代谢图谱,并揭示了不同发育阶段下不同链长脂酰辅酶A的代谢差异.进一步通过标记十二烷酸和十六烷酸的代谢流实验,验证了果蝇蛹阶段更倾向于利用十六碳的脂酰辅酶A进行合成代谢.综上所述,该方法具有全面挖掘生物体深层次的脂肪酸代谢命运的潜力.