SOX2-dependent expression of dihydroorotate dehydrogenase regulates oral squamous cell carcinoma cell proliferation

Oral squamous cell carcinoma(OSCC)become a heavy burden of public health,with approximately 300000 newly diagnosed cases and 145000 deaths worldwide per year.Nucleotide metabolism fuel DNA replication and RNA synthesis,which is indispensable for cell proliferation.But how tumor cells orchestrate nucleotide metabolic enzymes to support their rapid growth is largely unknown.Here we show that expression of pyrimidine metabolic enzyme dihydroorotate dehydrogenase(DHODH)is upregulated in OSCC tissues,compared to non-cancerous adjacent tissues.Enhanced expression of DHODH is correlated with a shortened patient survival time.Inhibition of DHODH by either shRNA or selective inhibitors impairs proliferation of OSCC cells and growth of tumor xenograft.Further,loss of functional DHODH imped de novo pyrimidine synthesis,and disrupt mitochondrial respiration probably through destabilizing the MICOS complex.Mechanistic study shows that transcriptional factor SOX2 plays an important role in the upregulation of DHODH in OSCC.Our findings add to the knowledge of how cancer cells co-opt nucleotide metabolism to support their rapid growth,and thereby highlight DHODH as a potential prognostic and therapeutic target for OSCC treatment.

水痘的预防与监控措施分析

目的研究水痘患儿实施预防与监控的临床价值。方法纳入本院(2017年4月-2018年4月)门诊接收的水痘患儿(n=84)作为研究对象,以随机表抽签法为基准,分为实验组(n=42,实施针对性预防)、对照组(n=42,实施常规疾病预防),对84例患儿临床症状消失时间、并发症发生率、生活质量评估。结果临床症状消失时间:实验组临床症状消失时间低于对照组(P<0.05)。并发症发生率:实验组并发症发生率低于对照组(P<0.05)。生活质量:实验组生活质量高于对照组(P<0.05)。结论水痘患儿实施预防与监控的临床价值显著,既可缩短临床症状消失时间,又可降低并发症发生率,值得借鉴。

RIOX1-demethylated cGAS regulates ionizing radiation-elicited DNA repair

Exposure to radiation causes DNA damage;hence, continuous surveillance and timely DNA repair are important for genome stability. Epigenetic modifications alter the chromatin architecture, thereby affecting the efficiency of DNA repair. However, how epigenetic modifiers coordinate with the DNA repair machinery to modulate cellular radiosensitivity is relatively unknown. Here, we report that loss of the demethylase ribosomal oxygenase 1(RIOX1) restores cell proliferation and reduces cell death after exposure to ionizing radiation. Furthermore, RIOX1 depletion enhances homologous recombination(HR) repair but not nonhomologous endjoining(NHEJ) repair in irradiated bone marrow cells and oral mucosal epithelial cells. Mechanistic study demonstrates that RIOX1 removes monomethylation at K491 of cyclic GMP-AMP synthase(c GAS) to release c GAS from its interaction with the methyl-lysine reader protein SAGA complex-associated factor 29(SGF29), which subsequently enables c GAS to interact with poly(ADP-ribosyl)ated poly(ADP-ribose) polymerase 1(PARP1) at DNA break sites, thereby blocking PARP1-mediated recruitment of Timeless. High expression of RIOX1 maintains c GAS K491 me at a low level, which impedes HR repair and reduces cellular tolerance to ionizing radiation. This study highlights a novel RIOX1-dependent mechanism involved in the non-immune function of c GAS that is essential for the regulation of ionizing radiation-elicited HR repair.

Data mining-based study on sub-mentally healthy state among residents in eight provinces and cities in China

OBJECTIVE: To apply data mining methods to research on the state of sub-mental health among residents in eight provinces and cities in China and to mine latent knowledge about many conditions through data mining and analysis of data on 3970 sub-mentally healthy individuals selected from 13385 relevant question naires.METHODS: The strategic tree algorithm was used to identify the main mani festations of the state of sub-mental health. The backpropogation artificial neural network was used to analyze the main mani festations of sub-healthy mental states of three different degrees. A sub-mental health evaluation model was then established to achieve predictive evaluationresults.RESULTS: Using classifications from the Scale of Chinese Sub-healthy State, the main manifestations of sub-mental health selected using the strate gictree were F1101(Do you lack peace of mind?),F1102(Are you easily nervous when something comes up?), and F1002(Do you often sigh?). The relative intensity of manifestations of sub-mental health was highest for F1101, followed by F1102,and then F1002. Through study of the neural network, better differentiation could be made between moderate and severe and between mild and severe states of sub-mental health. The differentiation between mild and moderate sub-mental health states was less apparent. Additionally, the sub-mental health state evaluation model, which could be used to predict states of sub-mental health of different individuals, was established using F1101, F1102, F1002, and the mental self-assessment totals core.CONCLUSION: The main manifestations of the state of sub-mental health can be discovered using data mining methods to research and analyze the latent laws and knowledge hidden in research evidence on the state of sub-mental health. The state of sub-mental health of different individuals can be rapidly predicted using the model established here.This can provide a basis for assessment and intervention for sub-mental health. It can also replace the relatively outdated approaches to research on sub-health in the technical era of information and digitization by combining the study of states of sub-mental health with information techniques and by further quantifying the relevant information.

Viral metagenomics reveals diverse viruses in the fecal samples of children with diarrhea

Diarrhea is the third leading cause of death in developing countries in children under the age of five.About half a million children die of diarrhea every year,most of which in developing countries.Viruses are the main pathogen of diarrhea.In China,the fecal virome of children with diarrhea has been rarely studied.Using an unbiased viral metagenomics approach,we analyzed the fecal virome in children with diarrhea.Many DNA or RNA viruses associated with diarrhea identified in those fecal samples were mainly from six families of Adenoviridae,Astroviridae,Caliciviridae,Parvoviridae,Picornaviridae,and Reoviridae.Among them,the family of Caliciviridae accounts for the largest proportion of 78.42%,following with Adenoviridae(8.94%)and Picornaviridae(8.36%).In addition to those diarrhea-related viruses that have already been confirmed to cause human diarrhea,the viruses not associated with diarrhea were also identified including anellovirus and picobirnavirus.This study increased our understanding of diarrheic children fecal virome and provided valuable information for the prevention and treatment of viral diarrhea in this area.

Dependence of interface energetics and kinetics on catalyst loading in a photoelectrochemical system

Solar hydrogen production by the photoelectrochemical method promises a means to store solar energy.While it is generally understood that the process is highly sensitive to the nature of the interface between the semiconductor and the electrolyte,a detailed understanding of this interface is still missing.For instance,few prior studies have established a clear relationship between the interface energetics and the catalyst loading amount.Here we aim to study this relationship on a prototypical Si-based photoelectrochemical system.Two types of interfaces were examined,one with GaN nanowires as a protection layer and one without.It was found that when GaN was present,higher Pt loading (> 0.1 μg/cm2) led to not only better water reduction (and,hence,hydrogen evolution) kinetics but also more favorable interface energetics for greater photovoltages.In the absence of the protection layer,by stark contrast,increased Pt loading exhibited no measurable influence on the interface energetics,and the main difference was observed only in the hydrogen evolution kinetics.The study sheds new light on the importance of interface engineering for further improvement of photoelectrochemical systems,especially concerning the role of catalysts and protection layers.