Gene characterization and phylogenetic analysis of four mitochondrial genomes in Caenogastropoda

Caenogastropoda is a highly diverse group,containing~60%of all existing gastropods.Species in this subclass predominantly inhabit marine environments and have a high ecological and economic value.Owing to the increase in relevant phylogenetic studies,our understanding of between species relatedness in Caenogastropoda has improved.However,the biodiversity,taxonomic status,and phylogenetic relationships of this group remain unclear.In the present study,we performed next-generation sequencing of four complete mitochondrial genomes from three families(Buccinidae,Columbellidae,and Cypraeidae)and the four mitogenomes were classical circular structures,with a length of 16177 bp in Volutharpa ampullacea,16244 bp in Mitrella albuginosa,16926bp in Mauritia arabica asiatica and 15422 bp in Erronea errones.Base composition analysis indicated that whole sequences were biased toward A and T.Then compared them with 171 complete mitochondrial genomes of Caenogastropoda.The phylogenetic relationship of Caenogastropoda derived from Maximum Likelihood(ML)and Bayesian Inference(BI)trees constructed based on CDS sequences was consistent with the results of traditional morphological analysis,with all three families showing close relationships.This study supported Caenogastropoda at the molecular level as a separate clade of Mollusca.According to our divergence time estimations,Caenogastropoda was formed during the middle Triassic period(~247.2–237 Ma).Our novel mitochondrial genomes provide evidence for the speciation of Caenogastropoda in addition to elucidating the mitochondrial genomic evolution of this subclass.

肺腺癌相关组织学特征与PD-L1表达EGFR基因突变类型的关系

目的:探讨非小细胞肺癌(non-small cell lung cancer,NSCLC)中肺腺癌不同组织学亚型、气道播散、胸膜侵犯等预后相关因素与程序性死亡因子配体−1(programmed death factor ligand-1,PD-L1)蛋白的表达、表皮生长因子受体(epidermal growth factor receptor,EGFR)基因的突变类型的差异分析,为精准治疗提供依据。方法:收集2018年1月至2020年12月苏州大学附属第三医院病理确诊肺腺癌患者233例的临床病理资料,使用免疫组织化学染色方法观察肺癌组织内PD-L1表达,同时采用扩增阻滞突变系统(amplification refractory mutation system,ARMS)法对EGFR基因片段进行检测。结果:233例肺腺癌中PD-L1表达阳性38.2%(89/233),在男性、年龄≥65岁、低分化、肿瘤最大直径≥2 cm以及发生淋巴结转移、气道播散和脉管、胸膜侵犯患者中阳性率较高(P<0.05);EGFR突变阳性率70.8%(165/233),与患者性别显著相关(P<0.05);PD-L1表达和EGFR突变交叉阳性/交叉阴性与肿瘤的侵袭能力显著相关(P<0.05);PD-L1表达与贴壁结构、微乳头结构及实体型结构显著相关(均P<0.05),而EGFR基因突变状态与乳头结构、实体型结构相关(均P<0.05)。Pearson相关分析显示PD-L1比例与贴壁结构呈负相关(r=−0.252,P<0.001),与微乳头结构和实体型结构呈正相关(r=0.271,r=0.473,均P<0.001),与腺泡结构及乳头结构无相关性。PD-L1表达与EGFR中Exon19 Del突变有显著的相关性(P<0.001),研究发现无EGFR Exon19 Del突变的患者其PDL1表达较高。结论:肺腺癌患者PD-L1表达与肿瘤的组织学结构的比例构成、分化程度、气道播散及脉管、胸膜侵犯等预后较差因素显著相关,且PD-L1表达与EGFR Exon19 Del突变显著相关,无Exon19 Del突变患者将有可能成为PD-L1抑制剂免疫治疗的优势人群,从而为临床诊疗评判提供更为可靠的科学依据。

Interfacial Reinitiation of Free Radicals Enables the Regeneration of Broken Polymeric Hydrogel Actuators

Living organisms,from plants to animals,have inspired and guided the design and fabrication of polymeric hydrogels with biomimetic morphology,shape deformation,and actuation behavior.However,the existing polymeric hydrogels are fragile and vulnerable,which seriously hinders further application.Therefore,endowing hydrogels with a biomimetic self-growth property and regenerating the macroscopic shape of hydrogels after they suffer significant damage are highly desirable for the next generation of adaptive biomimetic hydrogels.Inspired by the tail regeneration of geckos,we herein report an efficient and universal strategy of interfacial diffusion polymerization(IDP),which can regenerate the polymeric layer at a solid–liquid interface,thereby growing new hydrogels on the existing hydrogel layers.Through changing the solvent viscosity and/or monomer type of the hydrogel precursor,diverse new hydrogels have been regenerated to endow the initial hydrogels with additional fluorescent functions and/or actuating properties.Due to the high efficiency and universality of IDP,an injured hydrogel actuator can be repaired,regenerated,and recovered to its initial condition,even after suffering severe damage such as cutting or piercing.We believe that the regeneration strategy of polymeric hydrogels will inspire the design of biomimetic materials and motivate the fabrication of the next generation of soft robots with adaptive and multifunctional properties.

N-acetyltransferase 10 promotes colon cancer progression by inhibiting ferroptosis through N4-acetylation and stabilization of ferroptosis suppressor protein 1 (FSP1) mRNA

Background:N-acetyltransferase 10(NAT10)is the only enzyme known tomediate the N4-acetylcytidine(ac4C)modification of mRNA and is crucial formRNA stability and translation efficiency.However,its role in cancer development and prognosis has not yet been explored.This study aimed to examine the possible role of NAT10 in colon cancer.Methods:The expression levels ofNAT10were evaluated by immunohistochemical analyses with a colon cancer tissue microarray,and its prognostic value in patients was further analyzed.Quantitative real-time polymerase chain reaction(qRT-PCR)and Western blotting were performed to analyze NAT10 expression in harvested colon cancer tissues and cell lines.Stable NAT10-knockdown and NAT10-overexpressing colon cancer cell lines were constructed using lentivirus.The biological functions of NAT10 in colon cancer cell lines were analyzed in vitro by Cell Counting Kit-8(CCK-8),wound healing,Transwell,cell cycle,and ferroptosis assays.Xenograft models were used to analyze the effect of NAT10 on the tumorigenesis and metastasis of colon cancer cells in vivo.Dot blotting,acetylated RNA immunoprecipitation-qPCR,and RNA stability analyses were performed to explore the mechanism by which NAT10 functions in colon cancer progression.Results:NAT10 was upregulated in colon cancer tissues and various colon cancer cell lines.This increased NAT10 expression was associated with shorter patient survival.Knockdown of NAT10 in two colon cancer cell lines(HT-29 and LoVo)impaired the proliferation,migration,invasion,tumor formation and metastasis of these cells,whereas overexpression of NAT10 promoted these abilities.Further analysis revealed that NAT10 exerted a strong effect on the mRNA stability and expression of ferroptosis suppressor protein 1(FSP1)in HT-29 and LoVo cells.In these cells,FSP1 mRNA was found to be modified by ac4C acetylation,and this epigenetic modification was associated with the inhibition of ferroptosis.Conclusions:Our study revealed that NAT10 plays a critical role in colon cancer development by affecting FSP1 mRNA stability and ferroptosis,suggesting that NAT10 could be a novel prognostic and therapeutic target in colon cancer.

Antifreezing and Stretchable Organohydrogels as Soft Actuators

Inspired by the freezing tolerance performances found in living creatures, an effect approach is presented to develop novelantifreezing polymeric organohydrogel actuators. Through construction of a bilayer hydrogel including a nonresponsivepolyacrylamide (PAAm) layer and a pH-responsive polyacrylic acid (PAA) layer in the presence of a mixed solvent of water andglycerol, organohydrogel actuators that could produce various shape deformations at subzero temperatures have been achieved,and the actuating speed could be tuned by adjusting the temperature and the ratio between glycerol and water. Moreover, aseries of application demonstrations including a weightlifting robot, artificial valve, and robotic arm have been displayed. Inaddition, by introducing the ionic compound KI into the glycerol-based organogel, flexible conductors that could perform stablesensing performance over a wide range of temperatures from -30℃ to 60℃ have been developed.

Simulating multiple urban land use changes by integrating transportation accessibility and a vector-based cellular automata:a case study on city of Toronto

The accessibility provided by the transportation system plays an essential role in driving urban growth and urban functional land use changes.Conventional studies on land use simulation usually simplified the accessibility as proximities and adopted the grid-based simulation strategy,leading to the insufficiencies of characterizing spatial geometry of land parcels and simulating subtle land use changes among urban functional types.To overcome these limita-tions,an Accessibility-interacted Vector-based Cellular Automata(A-VCA)model was proposed for the better simulation of realistic land use change among different urban functional types.The accessibility at both local and zonal scales derived from actual travel time data was considered as a key driver of fine-scale urban land use changes and was integrated into the vector-based CA simulation process.The proposed A-VCA model was tested through the simulation of urban land use changes in the City of Toronto,Canada,during 2012-2016.A vector-based CA without considering the driving factor of accessibility(VCA)and a popular grid-based CA model(Future Land Use Simulation,FLUS)were also implemented for compar-isons.The simulation results reveal that the proposed A-VCA model is capable of simulating fine-scale urban land use changes with satisfactory accuracy and good morphological feature(kappa=0.907,figure of merit=0.283,and cumulative producer’s accuracy=72.83%±1.535%).The comparison also shows significant outperformance of the A-VCA model against the VCA and FLUS models,suggesting the effectiveness of the accessibility-interactive mechanism and vector-based simulation strategy.The proposed model provides new tools for a better simula-tion of fine-scale land use changes and can be used in assisting the formulation of urban and transportation planning.