Study on the spatial and temporal evolutionary characteristics of ozone concentration and the impact of human activities in China in 2019

Ozone(O_(3))pollution has a profound impact on human health,vegetation development,and the ecological environment,making it a critical focus of global academic research.In recent years,O_(3)pollution in China has been on a steady rise,with ozone emerging as the sole conventional pollutant to consistently increase in concentration without any decline.This study conducted a quantitative analysis of O_(3)concentrations across 367 Chinese cities in 2019,examining spatial autocorrelation and local clustering of O_(3)levels,and investigated the diverse relationships between human activity factors and O_(3)concentration.The seasonal fluctuation of O_(3)exhibited the“M-type”pattern,with peak concentrations in winter and the lowest levels in summer.The center of O_(3)pollution migrated southeastward,with the area of highest concentration progressively shifting south along the eastern coast.Moreover,O_(3)concentration showed a strong positive correlation with population density,road freight volume,and industrial emissions,suggesting that human activities,vehicle emissions,and industrial operations are significant contributors to O_(3)production.The results provide comprehensive information on the characteristics,causes,and occurrence mechanism of O_(3)in Chinese cities that can be utilized by global government departments to formulate strategies to prevent and control O_(3)pollution.

帕金森病相关蛋白Parkin:癌症中一个不同寻常的角色

Parkin基因的突变可引起家族性帕金森病。越来越多的证据表明,Parkin也可作为肿瘤抑制因子来发挥功能。Parkin是一种E3泛素连接酶,在与肿瘤发生相关的各种细胞过程中起到重要的作用,包括细胞周期、细胞增殖、凋亡、转移、线粒体自噬和代谢重编程。在此,我们对Parkin在癌症中的作用和机制进行综述。

The effect of lens parameters on the development of the primary angle-closure glaucoma

Objective ：To investigate the role the lens dimensions played on the pathogenesis of primary angle-closure glaucoma. Methods：38 eyes of 20 patients with primary angle-closure glaucoma （PACG） and 35 eyes of 22 normal individuals without ocular abnormalities were examined. The anatomical parameters of the lens and other structures of the anterior segment were calculated using B ultrasound, computer image processing and ultrasound biomicroscopy （UBM）. The parameters were compared between the patients and normal subjects. Correlation analysis was used to determine the relationship between the radii of curvature of the anterior lens surface （RCALS） and the other parameters of the anterior segment. Results：Compared with the normal eyes, the eyes of PACG had thicker lens, steeper curvature of anterior lens surface, decreased depth of the anterior chamber, narrower chamber angle, and more anterior position of the ciliary bodies and lens. All these differences were significant（P 〈 0.05 or P 〈 0.01）. In the PACG group, the RCALS had significantly negative correlation with the central and peripheral lens thickness （P 〈 0.01 and P 〈 0.05 respectively）, and had positive correlation with relative lens position, anterior chamber depth（ACD）, angle-open distance at 500 um（AOD500）, trabecular iris angle （TIA） and trabecular ciliary processes distance（TCPD, P 〈 0.05 or P 〈 0.01 ）. Conclusion：The occurrence of PACG is relevant to the abnormal anatomical structures of the anterior segment. Among all factors, the lens parameters play an important role in the pathogenesis. Increased lens thickness, relative more anterior position of lens, especially steepened curvature of anterior lens surface are predisposing factors of the pathologic phenomenon in PACG including pupillary blockage, shallow anterior chamber, secondary closure of chamber angle and elevation of intraocular pressure.

Gain-of-function mutant p53 in cancer progression and therapy

p53 is a key tumor suppressor,and loss of p53 function is frequently a prerequisite for cancer development.The p53 gene is the most frequently mutated gene in human cancers;p53 mutations occur in>50%of all human cancers and in almost every type of human cancers.Most of p53 mutations in cancers are missense mutations,which produce the full-length mutant p53(mutp53)protein with only one amino acid difference from wild-type p53 protein.In addition to loss of the tumor-suppressive function of wild-type p53,many mutp53 proteins acquire new oncogenic activities independently of wild-type p53 to promote cancer progression,termed gain-of-function(GOF).Mutp53 protein often accumulates to very high levels in cancer cells,which is critical for its GOF.Given the high mutation frequency of the p53 gene and the GOF activities of mutp53 in cancer,therapies targeting mutp53 have attracted great interest.Further understanding the mechanisms underlying mutp53 protein accumulation and GOF will help develop effective therapies treating human cancers containing mutp53.In this review,we summarize the recent advances in the studies on mutp53 regulation and GOF as well as therapies targeting mutp53 in human cancers.

Tumor suppressor p53 and metabolism

p53 plays a key role in tumor suppression. The tumor suppressive function of p53 has long been attributed to its ability to induce apoptosis, cell cycle arrest, and senescence in cells. However, recent studies suggest that other functions of p53 also contribute to its role as a tumor suppressor, such as its function in metabolic regulation. p53 regulates various metabolic pathways to maintain the metabolic homeostasis of cells and adapt cells to stress. In addition, recent studies have also shown that gain-offunction (GOF) mutant p53 proteins drive metabolic reprogramming in cancer cells, contributing to cancer progression. Further understanding of p53 and its GOF mutants in metabolism will provide new opportunities for cancer therapy.

Hot deformation characterization of as-homogenized Al-Cu-Li X2A66 alloy through processing maps and microstructural evolution

Uniaxial compression tests were carried out on an Al-Cu-Li alloy at a temperature range of 300–500℃ and a strain rate range of 0.001–10 s^-1. Four representative instability maps based on Gegel, AlexanderMalas(A-M), Kumar-Prasad(K-P) and Murty-Rao(M-R) criteria were constructed. Through formula deduction and microstructural observation, it can be concluded that M-R criterion is more accurate than K-P criterion, and the first two criteria are better than Gegel and A-M criteria. From a power dissipation map and a M-R instability map, the optimized processing parameters are 480–500℃/0.001–0.1 s^-1 and 420–480℃/0.1-1 s^-1. The corresponding microstructural analysis shows that dynamic recovery and partial dynamic recrystallization are main dynamic softening mechanisms. Transmission electron microscopy observation indicated that a large number of primary coarse T1(Al2 Cu Li) particles precipitated in the homogenized specimen. After deformation at 500℃, most of the primary T1 particles dissolved back into the matrix, and secondary fine T1 particles precipitated at deformation-induced dislocations, high angle grain boundaries and other dispersed particles.

Tumor suppressor p53 cross-talks with TRIM family proteins

p53 is a key tumor suppressor.As a transcription factor,p53 accumulates in cells in response to various stress signals and selectively transcribes its target genes to regulate a wide variety of cellular stress responses to exert its function in tumor suppression.In addition to tumor suppression,p53 is also involved in many other physiological and pathological processes,e.g.anti-infection,immune response,development,reproduction,neurodegeneration and aging.To maintain its proper function,p53 is under tight and delicate regulation through different mechanisms,particularly the posttranslational modifications.The tripartite motif(TRIM)family proteins are a large group of proteins characterized by the RING,B-Box and coiled-coil(RBCC)domains at the N-terminus.TRIM proteins play important roles in regulation of many fundamental biological processes,including cell proliferation and death,DNA repair,transcription,and immune response.Alterations of TRIM proteins have been linked to many diseases including cancer,infectious diseases,developmental disorders,and neurodegenera-tion.Interestingly,recent studies have revealed that many TRIM proteins are involved in the regulation of p53,and at the same time,many TRIM proteins are also regulated by p53.Here,we review the cross-talk between p53 and TRIM proteins,and its impact upon cellular biological processes as well as cancer and other diseases.

Tumor suppressor p53 meets microRNAs

Tumor suppressor p53 plays a central role in tumor prevention.As a transcription factor,p53 mainly exerts its function through transcription regulation of its target genes to initiate various cellular responses.To maintain its proper function,p53 is tightly regulated by a wide variety of regulators in cells.Thus,p53,its regulators and regulated genes form a complex p53 network which is composed of hundreds of genes and their products.microRNAs(miRNAs)are a class of endogenously expressed,small non-coding RNA molecules which play a key role in regulation of gene expression at the post-transcriptional level.Recent studies have demonstrated that miRNAs interact with p53 and its network at multiple levels.p53 regulates the transcription expression and the maturation of a group of miRNAs.On the other hand,miRNAs can regulate the activity and function of p53 through direct repression of p53 or its regulators in cells.These findings have demonstrated that miRNAs are important components in the p53 network,and also added another layer of complexity to the p53 network.

EC330, a small-molecule compound, is a potential novel inhibitor of LIF signaling

Dear Editor,LIF,a multi-functional cytokine,is frequently overexpressed in many human cancers,including breast,colorectal,and pancreatic cancers(Liu et al.,2013;Li et al.,2014;Yu et al.,2014;Pascual-Garcia et al.,2019;Shi et al.,2019;Wang et al.,2019).LIF overexpression is frequently associated with poor prognosis in human cancers(Liu et al.,2013;Li et al.,2014;Yu et al.,2014).LIF functions through binding to LIF receptor complex composed of LIF receptor(LIF-R)and glycoprotein gp130(Taga and Kishimoto,1997;Heinrich et al.,2003;Watanabe et al.,2006).LIF overexpression induces activation of several oncogenic signaling pathways in a cell/tissue type-specific manner,including STAT3,PI3K/AKT,and mTOR,which in turn promotes proliferation,metastasis,and therapeutic resistance of cancer cells(Liu et al.,2013;Li et al.,2014;Yu et al.,2014;Shi et al.,2019).Recent studies have suggested that LIF is a potential important target for cancer therapy,especially for cancers with LIF overexpression.LIF neutralization antibodies(LIF neu Abs)have been reported to block LIF signaling and largely abolish the promoting effect of LIF on cancer progression(Li et al.,2014;Yue et al.,2016;Shi et al.,2019).

Tumor suppressor p53:new functions of an old protein

p53 was discovered 30 years ago.Extensive studies have been done on p53 since then,which makes p53 one of the most extensively studied genes.p53 has long been recognized as a key tumor suppressor.Cell cycle arrest,apoptosis and senescence have been traditionally recognized as the main functions of p53 in tumor suppression.Recently,some novel functions of p53 have been identified,including the regulation of energy metabolism,antioxidant defense,and microRNA expression and maturation,which all contribute to the role of p53 in tumor suppression.Furthermore,the contribution of p53 to normal biologic processes(e.g.reproduction and aging)and some other aspects of diseases(e.g.neurodegenerative diseases)is only now being appreciated.Here we will review recent advances in the study of some new functions of p53.

Parkinson’s disease-associated protein Parkin: an unusual player in cancer

The mutation of the Parkin gene is a cause of familial Parkinson’s disease.A growing body of evidence suggests that Parkin also functions as a tumor suppressor.Parkin is an ubiquitin E3 ligase,and plays important roles in a variety of cellular processes implicated in tumorigenesis,including cell cycle,cell proliferation,apoptosis,metastasis,mitophagy and metabolic reprogramming.Here we review the role and mechanism of Parkin in cancer.

The role of p53 in reproduction,an unexpected function for a tumor suppressor

At the beginning of the 21st century,the role of p53 as a tumor suppressor was well established;however,the function of p53 other than tumor suppression,especially its function under physiological conditions,was poorly understood.Here,we revisited the journey of a multidisciplinary team of researchers that revealed an unexpected and important function of p53 in regulating maternal reproduction at that time.This finding of p53 in maternal reproduction helped us gain important insights about the p53 protein and expanded our understanding of p53 protein functions in addition to its tumor suppressive function.This fin ding also provided a possible clue to explain the observed evolutionary selection on some alleles ofthe p53 pathway.