SWI/SNF复合体基因突变促进NSCLC细胞在NSI小鼠体内肝转移的研究

背景与目的SWI/SNF复合体(switch/sucrose nonfermentable chromatin-remodeling complex,SWI/SNF)是一种重要的染色质重塑复合物,其亚基变异在多种肿瘤中存在,并与多种肿瘤细胞生物学特征相关。但其基因突变是否参与非小细胞肺癌(non-small cell lung cancer,NSCLC)肝转移过程尚不清楚。本研究拟探究SWI/SNF复合体基因突变对NSCLC肝转移的影响及潜在机制。方法我们使用全外显子组测序(whole-exome sequencing,WES)分析了NSCLC细胞H1299、H23和H460中SWI/SNF复合体基因突变。通过CRISPR/Cas9(clustered regularly interspaced short palindromic repeats)技术构建了ARID1A基因稳定敲除的H1299细胞株,建立了小鼠模型模拟NSCLC肝转移,观察不同基因突变对肝转移的影响。利用RNA-Seq和蛋白印迹分析差异基因的表达,并通过免疫组化技术(immunohistochemistry,IHC)检测了SWI/SNF复合体调控的靶分子在小鼠肝转移灶中的表达。结果WES分析确定了SWI/SNF复合体基因的突变情况。动物实验结果显示SWI/SNF复合体基因突变与免疫缺陷小鼠较高的肝转移率相关。转录组测序和蛋白印迹分析显示SWI/SNF复合体基因突变细胞中ALDH1A1和APOBEC3B表达上调,尤其是ARID1A蛋白缺失的H460和H1299 sgARID1A中ALDH1A1表达水平显著上升。IHC染色亦显示H460和H1299 sgARID1A细胞肝转移灶中ALDH1A1高表达。结论本研究强调了SWI/SNF复合体基因ARID1A和SMARCA4等突变在促进肺癌细胞肝转移中的关键作用。这些基因突变可能通过促进ALDH1A1与APOBEC3B高表达进而发挥肝特异性转移的作用,为深入探究肺癌肝转移分子机制提供了新线索。

Mitochondrial dysfunction in glaucomatous degeneration

Glaucoma is a kind of optic neuropathy mainly manifested in the permanent death of retinal ganglion cells(RGCs),atrophy of the optic nerve,and loss of visual ability.The main risk factors for glaucoma consist of the pathological elevation of intraocular pressure(IOP)and aging.Although the mechanism of glaucoma remains an open question,a theory related to mitochondrial dysfunction has been emerging in the last decade.Reactive oxygen species(ROS)from the mitochondrial respiratory chain are abnormally produced as a result of mitochondrial dysfunction.Oxidative stress takes place when the cellular antioxidant system fails to remove excessive ROS promptly.Meanwhile,more and more studies show that there are other common features of mitochondrial dysfunction in glaucoma,including damage of mitochondrial DNA(mt DNA),defective mitochondrial quality control,ATP reduction,and other cellular changes,which are worth summarizing and further exploring.The purpose of this review is to explore mitochondrial dysfunction in the mechanism of glaucomatous optic neuropathy.Based on the mechanism,the existing therapeutic options are summarized,including medications,gene therapy,and red-light therapy,which are promising to provide feasible neuroprotective ideas for the treatment of glaucoma.

Rehabilitation care of patients with neurogenic bladder after spinal cord injury:A literature review

This article reviews the research progress of rehabilitation treatment and nursing care of patients with neurogenic bladder after spinal cord injury,in order to provide reference for the rehabilitation treatment and nursing care of patients.We reviewed recent medical literature on patients with neurogenic bladder,focusing on neurogenic bladder caused by spinal cord injury.We analyzed 30 recent of publications in patients with neurogenic bladder after spinal cord injury,in addition to reviewing and evaluating the commonly used rehabilitation nursing methods for neurogenic bladder.Psychological counseling is a vital aspect which cannot be neglected in the process of neurogenic bladder rehabilitation.Hitherto,the commonly used drug and surgical treatments may have negatively impacted the mental health of patients in varying degrees.However,in clinical practice,applying intermittent catheterization in patients who have neurogenic bladder with spinal cord injury may help improve patients’life quality,mitigate psychological burden,and reduce negative emotions.

Study and application of crown feedback control in hot strip rolling

Crown feedback control is one part of the automatic shape control （ASC） system. On the basis of large simulation researches conducted, a linear crown feedback control model was put forward and applied in actual strip rolling. According to its successful op- eration in the ASP 1700 hot strip mill of Angang Group for one year and also from the statistical results of several crown measurements, it can be definitely said that this control model is highly effective and shows stable performance. The control effectiveness of different gauges of strips with the feedback control is found to increase by 10%-30% compared with that without feedback control.

Langerhans cell histiocytosis presenting as an isolated brain tumour:A case report

Langerhans cell histiocytosis(LCH)is a rare proliferative histiocyte disorder.It can affect any organ or system,especially the bone,skin,lung,and central nervous system(CNS).In the CNS,the hypothalamic-pituitary is predominantly affected,whereas the brain parenchyma is rarely affected.LCH occurring in the brain parenchyma can be easily confused with glioblastoma or brain metastases.Thus,multimodal imaging is useful for the differential diagnosis of these intracerebral lesions and detection of lesions in the other organs.CASE SUMMARY A 47-year-old man presented with a headache for one week and sudden syncope.Brain computed tomography(CT)and magnetic resonance imaging showed an irregularly shaped nodule with heterogeneous enhancement.On^(18)F-fluorodeoxyglucose(^(18)F-FDG)positron emission tomography/CT,a nodule with^(18)F-FDG uptake and multiple cysts in the upper lobes of both lungs were noted,which was also confirmed by high-resolution CT.Thus,the patient underwent surgical resection of the brain lesion for further examination.Postoperative pathology confirmed LCH.The patient received chemotherapy after surgery.No recurrence was observed in the brain at the 12-mo follow-up.CONCLUSION Multimodal imaging is useful for evaluating the systemic condition of LCH,developing treatment plans,and designing post-treatment strategies.

Spectroscopic and temperature sensing properties of Sm^(3+) in self-activated CsLu(WO_(4))_(2) phosphors

In this research,a series of Sm^(3+) doped CsLu(WO_(4))_(2) phosphors was prepared via high temperature solid phase technique to design new red phosphors and optical thermometric materials.Their structures,morphology,band gap and luminescence properties were characterized by X-ray diffraction,scanning electron microscopy,diffuse reflection and luminescence spectra,respectively.Under UV excitation,CsLu(WO_(4))_(2) gives rise to a blue broad emission band between 350 and 700 nm,which stems from the ^(3)T_(1u)→^(1)A_(1g) transition of WO_(6)^(6-) groups.When Sm^(3+) is introduced into CsLu(WO_(4))_(2),energy transfer between WO_(6)^(6-) groups and Sm^(3+) ions takes place in CsLu(WO_(4))_(2):Sm^(3+)phosphors,and color-tunable luminescence from blue to red is realized by controlling the Sm^(3+) doping concentration.The energy transfer efficiency between WO_(6)^(6-) groups and Sm^(3+) ons was analyzed,and the energy transfer mechanism was determined to be dipole-dipole interactions.According to the temperature-dependent luminescence spectra,WO_(6)^(6-)groups and Sm^(3+)ions exhibit large discrepancy in thermal quenching rates,and thus the temperature sensing properties of CsLu(WO_(4))_(2):Sm^(3+) in the temperature range of 283-403 K were analyzed.Based on the framework of fluorescence intensity ratio theory,the basic optical thermometry parameters including absolute and relative sensitivity of CsLu(WO_(4))_(2):Sm^(3+) we re calculated and the results show that it has great potential for application in optical thermometry.

Deep Learning and Its Applications in Biomedicine

Advances in biological and medical technologies have been providing us explosive vol- umes of biological and physiological data, such as medical images, electroencephalography, geno- mic and protein sequences. Learning from these data facilitates the understanding of human health and disease. Developed from artificial neural networks, deep learning-based algorithms show great promise in extracting features and learning patterns from complex data. The aim of this paper is to provide an overview of deep learning techniques and some of the state-of-the-art applications in the biomedical field. We first introduce the development of artificial neural network and deep learning. We then describe two main components of deep learning, i.e., deep learning architectures and model optimization. Subsequently, some examples are demonstrated for deep learning

Integrative Analyses of Lung Squamous Cell Carcinoma in Ten Chinese Patients with Transcriptome Sequencing

Few effective therapies have been developed for the treatment of lung squamous cell carcinoma （SQCC）, in part due to a lack of un- derstanding regarding the mechanisms underlying the initiation and development of this disease. Whole transcriptome sequencing not only provides insight into the expression of all transcribed genes, but offers an efficient approach for identifying genetic variations, including gene fusions, mutations and alternative splicing. In this study, we performed whole transcriptome sequencing of 10 patients with stage IIIA lung SQCC, and discovered a large number of single nucleotide variants （SNVs： mean of 12.2 SNVs/Mb）, with C〉T/G〉A and A〉G/T〉C transitions being the most frequently observed. Additionally, a total of 132 gene fusions were identified based upon TopHat alignments, 70.5% （93/132） of which occurred as a result of intra-chromosomal rearrangements. Based on the number of supporting reads for each fusion, we further validated 20 of the 26 top gene fusions by RT-PCR and Sanger sequencing. Taken together, these data provide an in-depth view of transcriptional alterations in lung SQCC patients, and may be useful for identification of new therapeutic targets.

Simultaneous and systematic analysis of cellular and viral gene expression during Enterovirus 71-induced host shutoff

Dear Editor, Enteroviruses, including poliovirus, enterovirus 71 (EV71), enterovirus 68, coxsackievirus A16, cause millions of infections every year. The infection can lead to serious human diseases and is a significant public health problem. Among them, EV71 is an emerging pathogen that causes severe hand, foot and mouth disease (HFMD) and neurological disease, especially in young children. Currently, there is no effective treatment to EV71-caused diseases, partially blaming to a lack of understanding EV71 replication mechanism (Solomon et al., 2010). As a member of Picornaviri-dae, EV71 infection induces a rapid induction of host shutoff, which is marked by the inhibition of cellular protein synthesis (Holland, 1963). In the meantime, viral protein synthesis takes over the cellular translational machinery. It is believed that the cellular protein synthesis shutoff benefits viral replication by relocating cellular resources and facilitating viral escape from host cell immune responses (Cao et al., 2017). Both transcription and translation inhibition have been suggested to contribute to the host protein synthesis shutoff during picornavirus infection (Holland, 1963;Belsham, 2009). However, the relative role of transcription and translation inhibition in virus-induced host shutoff is yet elusive.

Identification of novel loci influencing refractive error in East Asian populations using an extreme phenotype design

The global "myopia boom" has raised significant international concerns. Despite a higher myopia prevalence in Asia, previous large-scale genome-wide association studies(GWASs) were mostly based on European descendants. Here, we report a GWAS of spherical equivalent(SE) in 1852 Chinese Han individuals with extreme SE from Guangzhou(631 <-6.00 D and 574 > 0.00 D) and Wenzhou(593 <-6.00 D and54 >-1.75 D), followed by a replication study in two independent cohorts with totaling 3538 East Asian individuals. The discovery GWAS and meta-analysis identify three novel loci, which show genome-wide significant associations with SE, including 1 q25.2 FAM163 A, 10 p11.22 NRP1/PRAD3, and 10 p11.21 ANKRD30 A/MTRNR2 L7, together explaining 3.34% of SE variance. 10 p11.21 is successfully replicated.The allele frequencies of all three loci show significant differences between major continental groups(P < 0.001). The SE reducing(more myopic) allele of rs10913877(1 q25.2 FAM163 A) demonstrates the highest frequency in East Asians and much lower frequencies in Europeans and Africans(EAS = 0.60,EUR = 0.20, and AFR = 0.18). The gene-based analysis additionally identifies three novel genes associated with SE, including EI24, LHX5, and ARPP19. These results provide new insights into myopia pathogenesis and indicate the role of genetic heterogeneity in myopia epidemiology among different ethnicities.

MicroPhenoDB Associates Metagenomic Data with Pathogenic Microbes, Microbial Core Genes, and Human Disease Phenotypes

Microbes play important roles in human health and disease.The interaction between microbes and hosts is a reciprocal relationship,which remains largely under-explored.Current computational resources lack manually and consistently curated data to connect metagenomic data to pathogenic microbes,microbial core genes,and disease phenotypes.We developed the MicroPhenoDB database by manually curating and consistently integrating microbe-disease association data.MicroPhenoDB provides 5677 non-redundant associations between 1781 microbes and 542 human disease phenotypes across more than 22 human body sites.MicroPhenoDB also provides 696,934 relationships between 27,277 unique clade-specific core genes and 685 microbes.Disease phenotypes are classified and described using the Experimental Factor Ontology(EFO).A refined score model was developed to prioritize the associations based on evidential metrics.The sequence search option in MicroPhenoDB enables rapid identification of existing pathogenic microbes in samples without running the usual metagenomic data processing and assembly.MicroPhenoDB offers data browsing,searching,and visualization through user-friendly web interfaces and web service application programming interfaces.MicroPhenoDB is the first database platform to detail the relationships between pathogenic microbes,core genes,and disease phenotypes.It will accelerate metagenomic data analysis and assist studies in decoding microbes related to human diseases.MicroPhenoDB is available through http://www.liwzlab.cn/microphenodb and http://lilab2.sysu.edu.cn/microphenodb.