Neuroprotective effect of heat shock protein 70 Inhibition of Tau protein expression

BACKGROUND： Previous studies have shown that heat shock protein 70 （HSP70） has neuroprotective effects by decreasing phosphorylation of Tau protein, thereby reducing the expression of Tau protein and proper aggregation. OBJECTIVE： To observe and verify expressional changes of HSP70 and Tau in retinal ganglion cells following stretch injury to the right optic nerve in rats, and to determine the effect of heat stress pretreatment on HSP70 and Tau protein expressions. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Laboratory of Neurology Research Institute of the First Affiliated Hospital of Chongqing Medical University from March to June 2006. MATERIALS： Instant SABC immunohistochemistry kit, as well as mouse anti-HSP70 and rabbit anti-Tau polyclonal antibodies, were purchased from Wuhan Boster Bioengineering Limited, China. METHODS： A total of 57 male, Wistar rats were randomly assigned to 4 groups： control （n = 3）; 150-180 g stretch force was induced in the right optic nerves in stretch-only group （n = 18） to establish optic nerve stretch injury model; heat stress was applied to 18 animals in heat-stress treatment group; 18 rats in the heat-stress pretreatment plus stretch group were subjected to identical stretch injury as stretch-only group after 24-hour heat-stress pretreatment. According to sacrifice time, the groups were assigned to 6 subgroups at different time points of 4, 8, and 16 hours, and 1,3, and 5 days, with 3 rats in each subgroup. No treatment was performed in the control group except anesthesia. MAIN OUTCOME MEASURES： Morphological changes of optic nerves and retinal ganglion cells following stretch injury were observed by light microscopy following hematoxylin-eosin staining. HSP70 and Tau protein expression levels were observed in retinal ganglial cells from each group using im munohistochemistry. RESULTS： （1） Compared with the control group, morphological axonal and retinal ganglial cell changes, as well as a decreased number of retinal ganglial cells, were identified in the stretch-only group （P 〈 0.01）. Pathological damage in optical nerve and retinal ganglial cells were not remarkable in the heat-stress pretreatment plus stretch group, with no statistical difference in the number of retinal ganglial cells compared with the control group （P 〉 0.05）. （2） Compared with the control group significantly increased HSP70 expression in retinal ganglial cells occurred in the stretch-only, heat-stress treatment, and heat-stress pretreatment plus stretch groups （P 〈 0.05 or P 〈 0.01 ）. The peak of HSP70 expression was earlier in the heat-stress pretreatment plus stretch group compared with the stretch-only and heat-stress treatment groups, and was expressed over a longer period of time compared with the heat-stress treatment group. Compared with the control group, Tau expression in the retinal ganglial cells rapidly increased 4-16 hours following stretch injury in the stretch-only group （P 〈 0.05 or P 〈 0.01）, and obviously decreased in the heat-stress pretreatment plus stretch group （P 〈 0.05 or P 〈 0.01 ）. CONCLUSION： Tau expression increased following stretch injury, with an earlier expression peak than HSP70, which indicated that stretch injury-induced HSP70 expression was not strong or quick enough to sufficiently protect the nerve. A much more enhanced HSP70 expression, with an earlier peak and longer expression period, was observed in rats subjected to stretch injury following heat stress, which demonstrated that HSP70 exhibited neuroprotective functions by reducing abnormal aggregation of Tau.

Prognostic model for prostate cancer based on glycolysis-related genes and non-negative matrix factorization analysis

Background:Establishing an appropriate prognostic model for PCa is essential for its effective treatment.Glycolysis is a vital energy-harvesting mechanism for tumors.Developing a prognostic model for PCa based on glycolysis-related genes is novel and has great potential.Methods:First,gene expression and clinical data of PCa patients were downloaded from The Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO),and glycolysis-related genes were obtained from the Molecular Signatures Database(MSigDB).Gene enrichment analysis was performed to verify that glycolysis functions were enriched in the genes we obtained,which were used in nonnegative matrix factorization(NMF)to identify clusters.The correlation between clusters and clinical features was discussed,and the differentially expressed genes(DEGs)between the two clusters were investigated.Based on the DEGs,we investigated the biological differences between clusters,including immune cell infiltration,mutation,tumor immune dysfunction and exclusion,immune function,and checkpoint genes.To establish the prognostic model,the genes were filtered based on univariable Cox regression,LASSO,and multivariable Cox regression.Kaplan–Meier analysis and receiver operating characteristic analysis validated the prognostic value of the model.A nomogram of the risk score calculated by the prognostic model and clinical characteristics was constructed to quantitatively estimate the survival probability for PCa patients in the clinical setting.Result:The genes obtained from MSigDB were enriched in glycolysis functions.Two clusters were identified by NMF analysis based on 272 glycolysis-related genes,and a prognostic model based on DEGs between the two clusters was finally established.The prognostic model consisted of LAMPS,SPRN,ATOH1,TANC1,ETV1,TDRD1,KLK14,MESP2,POSTN,CRIP2,NAT1,AKR7A3,PODXL,CARTPT,and PCDHGB2.All sample,training,and test cohorts from The Cancer Genome Atlas(TCGA)and the external validation cohort from GEO showed significant differences between the high-risk and low-risk groups.The area under the ROC curve showed great performance of this prognostic model.Conclusion:A prognostic model based on glycolysis-related genes was established,with great performance and potential significance to the clinical application.

Nano-imaging agents for brain diseases: Environmentally responsive imaging and therapy

Precise imaging is essential for the accurate diagnosis and surgical guidance of brain diseases but it is challenging due to the difficulties in crossing the blood-brain barrier(BBB),the difficulties in disease lesion targeting,and the limited contrast in the brain environment.Nano-imaging agents were characterized by functionalized modifications,high contrast,small size,and high biocompatibility,thus providing advantages in BBB crossing,brain targeting,imaging resolution,and real-time monitoring,holding great potential in brain disease imaging.Specific characteristics in brain environment and brain diseases(e.g.,marker proteins on the BBB,the pathogenic proteins in the neurodegenerative diseases or brain tumors,and the tumor and inflammatory microenvironment)provide opportunities for the functionalized nano-imaging agents to improve BBB crossing and disease targeting.Moreover,the versatile nano-imaging agents are endowed with therapeutic agents to facilitate the theranostics of brain diseases.Here,we summarized the common materials and imaging techniques of nano-imaging agents and their imaging treatment applications.We discussed their BBB penetration,environmental response for disease targeting,and therapeutic effects.We also provided insights on the advantages,challenges,and application of nano-imaging agents in detecting and treating brain diseases such as neurodegenerative diseases,brain tumors,stroke,and traumatic brain injury.These discussions will help develop nano-imaging agents-based theranostic platforms for the precise diagnosis and treatment of brain diseases.

广东省医学会泌尿外科疑难病例多学科会诊(第12期)——输尿管癌的综合治疗

广东省医学会泌尿外科学分会疑难病例多学科联合诊疗(multidisciplinary treatment,MDT)在林天歆主任委员倡导下举办已成功举办了十一期。会议从多学科、多角度详细剖析每一个泌尿系疑难病例,结合MDT各学科疾病诊治新进展对病例中存在的疑难和争议问题展开高质量、多维度的讨论。进而在为每一例疑难病例提供最佳治疗方案的同时也为参会医师了解泌尿外科领域前沿诊治理念和技术提供了平台。该项学术活动必将进一步提高和开拓我省泌尿外科青年和基层医师的诊治水平和个人视野,助力我省泌尿外科整体诊疗水平高质量发展!

Adsorption of herring sperm DNA onto pine sawdust biochar:Thermodynamics and site energy distribution

Environmental deoxyribonucleic acid(eDNA),which includes antibiotic resistance genes,is ubiquitous in the environment.The interactions between eDNA and biochar,a promising material widely used in soil amendment and water treatment,greatly affect the environmental behavior of eDNA.Hitherto few experimental evidences are available yet,especially on the information of thermodynamics and energy distribution to explains the interactions between biochar and eDNA.This study investigated the adsorption of herring sperm DNA(hsDNA)on pine sawdust biochar,with a specific emphasis on the adsorption thermodynamics and site energy distribution.The adsorption of hsDNA on biochar was enhanced by an increase in the pyrolysis and adsorption temperatures.The higher surface area,strongerπ−πinteraction,and weaker electrostatic repulsion between hsDNA and biochars prepared at high pyrolysis temperatures facilitated the adsorption of hsDNA.The thermodynamics indicated that the adsorption of hsDNA on biochar was spontaneous and endothermic.Therefore,higher temperature was beneficial for the adsorption of hsDNA on biochar;this was well explained by the increase in E*and F(E*)with the adsorption temperature.These results are useful for evaluating the migration and transformation of eDNA in the presence of biochar.

scPlant:A versatile framework for single-cell transcriptomic data analysis in plants

Single-cell transcriptomics has been fully embraced in plant biological research and is revolutionizing our understanding of plant growth,development,and responses to external stimuli.However,single-cell tran-scriptomic data analysis in plants is not trivial,given that there is currently no end-to-end solution and that integration of various bioinformatics tools involves a large number of required dependencies.Here,we pre-sent scPlant,a versatile framework for exploring plant single-cell atlases with minimuminput data provided by users.The scPlant pipeline is implemented with numerous functions for diverse analytical tasks,ranging from basic data processing to advanced demands such as cell-type annotation and deconvolution,trajec-tory inference,cross-species data integration,and cell-type-specific gene regulatory network construc-tion.In addition,a variety of visualization tools are bundled in a built-in Shiny application,enabling explo-ration of single-cell transcriptomic data on the fly.

Nanomaterials for visualized tumor surgical navigation and postoperative recurrence inhibition

Preoperative localization of the tumor sites and intraoperative real-time monitoring are essential for precise surgery but are meanwhile challenging due to the lack of high-resolution,easy-to-operate,and fast visualization techniques.On the other hand,tumor recurrence and metastasis after surgery greatly reduce the survival rate of patients.Intervening tumor recurrence during surgery is a future direction of tumor treatment.Nanomaterials with external condition responsiveness(light,ultrasound,and magnetic field)can accurately assist intraoperative detection and surgical resection due to their functions such as tumor cell targeting,fluorescence imaging,and real time monitoring,providing a more accurate,shorter duration,and visualization method of surgical resection.Moreover,nanomaterials are versatile and can easily be tailored for application in different tumors.Locally filled or systemically circulating nanomaterials with slow drug release and residual tumor cell-targeting ability have promising applications in inhibiting tumor recurrence.Here,we review surgical navigation and postoperative recurrence interventional nanomaterials and their landscape in guiding tumor treatment.We summarize the classification and characteristics of these nanomaterials and discuss their application in the surgical navigation and recurrence inhibition of different tumors.We also provide an outlook on the challenges and future development of nanomaterials for visualized tumor surgical navigation and postoperative recurrence inhibition.

花卉品鉴与雅俗之辨——日本内阁文库藏明万历刻本《花品》考论

日本内阁文库收藏明万历刻本《花品》,为天壤间仅见之本,鲜为世人所知。该书之体例与内容颇具特色,在古代花卉类著作中独树一帜。该书在前人花卉著述的基础上,以拟人化的花卉品格为主要标准,对各种花卉进行了前所未有的全面细致的分品,反映了作者独特的花卉品第观念与明代花卉鉴赏文化所达到的新高度,其崇雅抑俗的倾向切合了晚明雅文化发展的时代特征,在中国古代花卉文化史上占有重要地位。书中还包含对于花卉品种和栽培技术的详细记载,在花卉史、园艺史方面亦具研究价值。

Systematic annotation of conservation states provides insights into regulatory regions in rice

Plant genomes contain a large fraction of noncoding sequences.The discovery and annotation of conserved noncoding sequences(CNSs)in plants is an ongoing challenge.Here we report the application of comparative genomics to systematically identify CNSs in 50 well-annotated Gramineae genomes using rice(Oryza sativa)as the reference.We conduct multiple-way whole-genome alignments to the rice genome.The rice genome is annotated as 20 conservation states(CSs)at single-nucleotide resolution using a multivariate hidden Markov model(Cons HMM)based on the multiple-genome alignments.Different states show distinct enrichments for various genomic features,and the conservation scores of CSs are highly correlated with the level of associated chromatin accessibility.We find that at least 33.5%of the rice genome is highly under selection,with more than 70%of the sequence lying outside of coding regions.A catalog of 855,366 regulatory CNSs is generated,and they significantly overlapped with putative active regulatory elements such as promoters,enhancers,and transcription factor binding sites.Collectively,our study provides a resource for elucidating functional noncoding regions of the rice genome and an evolutionary aspect of regulatory sequences in higher plants.