1.Ku70 Functions as an RNA Helicase to Regulate miR-124 Maturation and Neuronal Cell Differentiation
Ai-Xue HUANG ; Rui-Ting LI ; Yue-Chao ZHAO ; Jie LI ; Hui LI ; Xue-Feng DING ; Lin WANG ; Can XIAO ; Xue-Mei LIU ; Cheng-Feng QIN ; Ning-Sheng SHAO
Progress in Biochemistry and Biophysics 2024;51(6):1418-1433
ObjectiveHuman Ku70 protein mainly involves the non-homologous end joining (NHEJ) repair of double-stranded DNA breaks (DSB) through its DNA-binding properties, and it is recently reported having an RNA-binding ability. This paper is to explore whether Ku70 has RNA helicase activity and affects miRNA maturation. MethodsRNAs bound to Ku protein were analyzed by RNA immunoprecipitation sequencing (RIP-seq) and bioinfomatic anaylsis. The expression relationship between Ku protein and miRNAs was verified by Western blot (WB) and quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) assays. Binding ability of Ku protein to the RNAs was tested by biolayer interferometry (BLI) assay. RNA helicase activity of Ku protein was identified with EMSA assay. The effect of Ku70 regulated miR-124 on neuronal differentiation was performed by morphology analysis, WB and immunofluorescence assays with or without Zika virus (ZIKV) infection. ResultsWe revealed that the Ku70 protein had RNA helicase activity and affected miRNA maturation. Deficiency of Ku70 led to the up-regulation of a large number of mature miRNAs, especially neuronal specific miRNAs like miR-124. The knockdown of Ku70 promoted neuronal differentiation in human neural progenitor cells (hNPCs) and SH-SY5Y cells by boosting miR-124 maturation. Importantly, ZIKV infection reduced the expression of Ku70 whereas increased expression of miR-124 in hNPCs, and led to morphologically neuronal differentiation. ConclusionOur study revealed a novel function of Ku70 as an RNA helicase and regulating miRNA maturation. The reduced expression of Ku70 with ZIKV infection increased the expression of miR-124 and led to the premature differentiation of embryonic neural progenitor cells, which might be one of the causes of microcephaly.
2.Research status of quercetin-mediated MAPK signaling pathway in prevention and treatment of osteoporosis
Ke-Xin YUAN ; Xing-Wen XIE ; Ding-Peng LI ; Yi-Sheng JING ; Wei-Wei HUANG ; Xue-Tao WANG ; Hao-Dong YANG ; Wen YAN ; Yong-Wu MA
The Chinese Journal of Clinical Pharmacology 2024;40(9):1375-1379
Quercetin can mediate the activation of mitogen-activated protein kinase(MAPK)signaling pathways to prevent osteoporosis(OP).This paper comprehensively discusses the interrelationship between MAPK and osteoporosis-related cells based on the latest domestic and international research.Additionally,it elucidates the research progress of quercetin in mediating the MAPK signaling pathway for OP prevention.The aim is to provide an effective foundation for the clinical prevention and treatment of OP and the in-depth development of quercetin.
3.Raman Spectroscopy Combined with Partial Least Squares for Quantitative Analysis of Two Kinds of Microplastics in Water Samples
Jian-Ming DING ; Xin WANG ; Rong-Ling ZHANG ; Li-Yuan ZHOU ; Tian-Long ZHANG ; Hong-Sheng TANG ; Hua LI
Chinese Journal of Analytical Chemistry 2024;52(10):1581-1590
Microplastics(MPs)are emerging contaminants in aquatic environments characterized by their polar structure,small particle size(Typically less than 5 mm),large surface area,good stability,and resistance to biodegradation.They pose adverse effects on the normal physiological activities of aquatic organisms and can accumulate in biota,including humans.Therefore,there is an urgent need for rapid and accurate quantitative analysis of MPs in water environments.In this study,Raman spectroscopy combined with partial least squares(PLS)was employed for rapid and accurate quantitative analysis of polyethylene(PE)and polystyrene(PS)MPs in real water samples.Initially,33 simulated water samples containing different concentrations of MPs were prepared,and their Raman spectra were collected.Six spectral preprocessing methods(Normalization,multiplicative scatter correction,standard normal variate transformation,first derivative,second derivative,and wavelet transform)were investigated for their impact on the predictive performance of PLS calibration models.Subsequently,three variable selection methods including synergy interval partial least squares(SiPLS),variable importance in projection(VIP)and mutual information(MI)were employed to optimize the input variables of the PLS calibration model.The predictive capability of the PLS calibration model was evaluated and validated using leave-one-out cross-validation.Under the optimal conditions of spectral preprocessing,variable selection,input variables and latent variables,the wavelet transform-partial least squares(WT-PLS)calibration model based on distilled water was established,and the contents of PE and PS in real water samples were predicted with prediction correlation coefficients(R2p)of 0.9540 and 0.8472 for PE and PS,respectively,and prediction errors(Errorp)of 0.0690 and 0.1126,respectively.Furthermore,a mixed sample MI-PLS calibration model was developed,demonstrating the best predictive performance in real water samples(With R2p values of 0.9776 and 0.9755 for PE and PS,respectively,and Errorp values of 0.0360 and 0.0392,respectively).This method provided a novel approach and new methodology for quantitative analysis of MPs and other organic pollutants in real water samples.
4.Laser Ablation Inductively Coupled Plasma Mass Spectrometry Analysis of Multilayer Thin Film Thickness of PbS Quantum Dot Photovoltaic Devices
Ding-Wen ZHANG ; Hui-Lai LI ; Fan LI ; Wei GUO ; Lan-Lan JIN ; Sheng-Hong HU
Chinese Journal of Analytical Chemistry 2024;52(10):1609-1618
Accurate determination of the thickness of multi-layered nanofilm materials is of great importance to advance the development of thin film deposition technology and ensure the quality assurance of photovoltaic materials.Laser ablation inductively coupled plasma mass spectrometry(LA-ICP-MS)has been successfully employed for depth profiling of thin film materials,such as metal coatings.However,the accuracy of interface discrimination and thin layer thickness measurement is limited by the mixing effects of elemental signals.In this work,a high-depth resolution method for measuring the thin film thickness of lead sulfide(PbS)colloidal quantum dot(CQD)photovoltaic devices by LA-ICP-MS was introduced.The influence of different laser parameters on the mixing effects of element signals during the ablation process was compared,and the results showed that the laser ablation behavior of multi-layered nanofilm materials were improved and the mixing of element signals were reduced by optimizing parameters such as laser energy density and spot diameter.Meanwhile,a self-developed aerosol rapid wash-out small volume tubular ablation cell was used to effectively improve the aerosol transport efficiency,and the wash-out time of aerosol was(1.60±0.6)s.Compared with commercial cylindrical ablation cells,the depth profile of multi-layer thin film samples was clearer.The depth profile of the interlayer interface showed a significant melting phenomenon during the ablation of the PbS CQD layer,leading to severe mixing of elemental signals at the PbS/ZnO layer interface.Under the conditions such as 2.5 J/cm2 laser energy,32 μm spot diameter,and 1 Hz repetition rate,the average ablation rates of Au,PbS and ZnO layers in PbS CQD photovoltaic devices were(60±2)nm/pulse,(69±5)nm/pulse,and(22±2)nm/pulse,with depth resolution of(26±2)nm,(213±11)nm,and(68±6)nm,respectively.The thickness of PbS CQD photovoltaic device films from the same batch was determined,and the test results exhibited good consistency with scanning electron microscope(SEM)measurement values,with a relative deviation of less than 6%.This method could accurately determine the thickness of nanoscale multilayer thin film samples,which was crucial for improving the performance of photovoltaic devices and controlling product quality.
5.Optimization of batch dispensing parameters for dispensing robots
Hai-Wen DING ; Tong TONG ; Li-Li DU ; Sheng LIU
Chinese Medical Equipment Journal 2024;45(2):35-40
Objective To optimize the batch dispensing parameters of dispensing robots to ensure the standardization and homogenization of finished infusion.Methods Five parameters for intelligent dispensing robots were optimized with orthogonal test including push and pull times,standing time,needle rotation speed,solvent volume and pulling angle,with the insoluble particles as the evaluation index.Four finished infusion solutions including pantoprazole sodium solution,esomeprazole sodium solution,omeprazole sodium solution and eplazole sodium solution prepared at room temperature for 0,2,4,6 and 8 h were compared in terms of appearance,pH,osmolality and number of insoluble particles;the amounts of drug residue in empty syringe bottles and the efficiency of batch dispensing of the four finished infusion solutions using dispensing robot and manual operation were observed.Results After optimization the batch dispensing parameters of the robot were set as 2 times(push and pull times),5 s(standing time),low speed(needle rotation speed),6 mL(solvent volume)and 90°(pulling angle).After 8 h of dispensing at room temperature,the eplazole sodium solution became light yellow and clarified,and the number of insoluble particles went beyond the prescribed value in Chinese Pharmacopoeia 2020;the remained three solutions were colorless and clarified at 0,2,4,6 and 8 h,and the number of insoluble particles complied with the requirements of Chinese Pharmacopoeia 2020;there were no significant changes in pH and osmolality at 0,2,4,6 and 8 h.The robot had less drug residue than manual operation,and the efficiency of two robots operated by one person was higher than that of one person manually or one robot by one person,and all the differences were statistically significant(P<0.05).Conclusion The batch dispensing parameters optimized with orthogonal test contributes to the standardization and homogeneity of the finished solutions with decreased drug residue while increased batch dispensing efficiency.[Chinese Medical Equipment Journal,2024,45(2):35-40]
6.Design,numerical simulation and experimental study of novel oxygenator
Ming-Hao YUE ; Shi-Yao ZHANG ; Ji-Nian LI ; Hui-Chao LIU ; Zi-Hua SU ; Ya-Wei WANG ; Zeng-Sheng CHEN ; Shi-Hang LIN ; Jin-Yu LI ; Ya-Ke CHENG ; Yong-Fei HU ; Cun-Ding JIA ; Ming-Zhou XU
Chinese Medical Equipment Journal 2024;45(3):23-28
Objective To design a novel oxygenator to solve the existing problems of extracorporeal membrane oxygenation(ECMO)machine in high transmembrane pressure difference,low efficiency of blood oxygen exchange and susceptibility to thrombosis.Methods The main body of the oxygenator vascular access flow field was gifted with a flat cylindrical shape.The topology of the vascular access was modeled in three dimensions,and the whole flow field was cut into a blood inlet section,an inlet buffer,a heat exchange zone,a blood oxygen exchange zone,an outlet buffer and a blood outlet section.The oxygenator was compared with Quadrox oxygenator by means of ANSYS FLUENT-based simulation and prototype experiments.Results Simulation calculations showed the oxygenator designed was comparable to the clinically used ones in general,and gained advantages in transmembrane pressure difference,blood oxygen exchange and flow uniformity.Experimental results indicated that the oxygenator behaved better than Quadrox oxygenator in transmembrane pressure difference and blood oxygen exchange.Conclusion The oxygenator has advantages in transmem-brane pressure difference,temperature change,blood oxygen ex-change and low probability of thrombosis.[Chinese Medical Equipment Journal,2024,45(3):23-28]
7.Multicenter study on distinguishing long bone osteosarcoma from Ewing sarcoma based on CT image histogram and texture feature analysis
Jianwei LI ; Jingzhen HE ; Jiuming JIANG ; Sheng DING ; Libin XU ; Sijie HU ; Chengyi JIANG ; Li ZHANG ; Meng LI
Chinese Journal of Postgraduates of Medicine 2024;47(10):875-880
Objective:To explore the application value of histogram and texture feature analysis based on CT images in distinguishing long bone osteosarcoma (OS) from Ewing sarcoma (ES).Methods:A retrospective collection of 25 patients with long bone osteosarcoma and 25 patients with Ewing sarcoma confirmed by surgery and pathology in National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Qilu Hospital of Shandong University and Nanjing Drum Tower Hospital, Nanjing University Medical School, from March 2018 to May 2023 was conducted. All patients were randomly divided into a training set (21 cases of OS and 19 cases of ES) and a validation set (4 cases of OS and 6 cases of ES) in an 8∶2 ratio. The region of interest (ROI) on CT images to extract texture feature parameters was manually sketched. Random forest and least absolute shrinkage and selection operator (LASSO) algorithm were used for feature screening. Logistic regression (LR), random forest (RF), support vector machine (SVM) and K-nearest neighbor (KNN) classifiers were used to establish models respectively. Receiver operating characteristic (ROC)curve was drawn and area under the curve (AUC) was calculated to evaluate the diagnostic efficiency of the four models.Results:A total of 100 texture parameters were extracted from CT images, and 8 feature parameters (maximum 3D diameter, 10th percentile, kurtosis, maximum pixel intensity value, inverse normalization, grayscale level variance, long range high grayscale emphasis, and low grayscale area emphasis) were obtained through screening. Four classifiers were used to establish models, and the AUC values of the four models (LR, RF, SVM, KNN) in the validation group were 0.92, 0.79, 0.83, and 0.73, respectively. LR and SVM classifier algorithm trains models had high diagnostic efficiency, with an accuracy of 90%, sensitivity of 83%, specificity of 100%, and AUC of 92% for the LR classifier validation set; the accuracy of SVM classifier validation set was 80%, sensitivity was 67%, specificity was 100%, and AUC was 83%.Conclusions:LR and SVM models have high value in distinguishing OS and ES.
8.Roles of intestinal mucosa,intestinal immunity and microbiota in entero-genic Candida albicans infection
Hui-Ting CHEN ; Jia-Sheng LI ; Zhi-Chang XU ; Ding-Mei QIN ; Yi ZHANG ; Rui-Rui WANG
Chinese Journal of Infection Control 2024;23(5):631-637
Enterogenic Candida albicans(C.albicans)infection refers to the translocation of intestinal colonized C.albicans under certain conditions,breaking through the intestinal tract,causing tissue infection or even invasive C.albicans infection.As the first contact point of Candida,the intestinal mucosa is the first line defending coloni-zation or invasion of C.albicans,often inhibiting infection by physical barrier and activating host immunity.As an-other defense mechanism,the intestinal microbiota jointly resists the invasive infection of C.albican through regula-ting pH,secreting antimicrobial peptides,and competing for adhesion points.This review summarizes the roles of three key factors,namely intestinal mucosa,intestinal immunity and microbiota,in enterogenic C.albicans infec-tion,providing new ideas for scientific research on invasive candidiasis caused by intestinal colonization.
9.Prevalence of psoriatic arthritis in Chinese population with psoriasis: A multicenter study conducted by experienced rheumatologists.
Hua ZHANG ; Miao CHEN ; Ran CUI ; Xia LI ; Kexiang YAN ; Lihong CHEN ; Zhenghua ZHANG ; Ning YU ; Xinling BI ; Hui DENG ; Yangfeng DING ; Qiong HUANG ; Sheng-Ming DAI
Chinese Medical Journal 2023;136(12):1439-1447
BACKGROUND:
Reports on the prevalence of psoriatic arthritis (PsA) among Chinese patients with psoriasis are very limited. This study, conducted by rheumatologists, estimated the prevalence of PsA in a large number of Chinese patients with psoriasis.
METHODS:
Consecutive patients with a confirmed diagnosis of psoriasis attending nine dermatology clinics in five hospitals were recruited. All psoriasis patients were asked to complete a questionnaire comprising 16 questions to identify possible cases of PsA. All patients with one or more positive answers to the questionnaire were evaluated by two experienced rheumatologists.
RESULTS:
A total of 2434 psoriasis patients, including 1561 males and 873 females, were enrolled. Both the questionnaire and rheumatologists' examinations were completed in the dermatology clinics. The results identified 252 patients with PsA, comprising 168 males and 84 females. The overall prevalence of PsA among psoriasis patients was 10.4% (95% confidence interval [95% CI], 9.1%-11.7%). By sex, the prevalence was 10.8% (95% CI, 9.2%-12.5%) for males and 9.6% (95% CI, 7.7%-11.9%) for females and there was no significant sex difference in the prevalence of PsA (P = 0.38). Of the 252 PsA patients, 125 (49.6%, 95% CI, 41.3%-59.1%) were newly diagnosed by rheumatologists. Consequently, the prevalence of undiagnosed PsA among psoriasis patients was 5.2% (95% CI, 4.4%-6.2%).
CONCLUSION
The prevalence of PsA in the Chinese population with psoriasis is about 10.4%, which is almost double that of previous reports in the Chinese population, but lower than that in Caucasians.
Humans
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Female
;
Male
;
Arthritis, Psoriatic/epidemiology*
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Rheumatologists
;
Prevalence
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East Asian People
;
Psoriasis/epidemiology*
10.An injectable signal-amplifying device elicits a specific immune response against malignant glioblastoma.
Qiujun QIU ; Sunhui CHEN ; Huining HE ; Jixiang CHEN ; Xinyi DING ; Dongdong WANG ; Jiangang YANG ; Pengcheng GUO ; Yang LI ; Jisu KIM ; Jianyong SHENG ; Chao GAO ; Bo YIN ; Shihao ZHENG ; Jianxin WANG
Acta Pharmaceutica Sinica B 2023;13(12):5091-5106
Despite exciting achievements with some malignancies, immunotherapy for hypoimmunogenic cancers, especially glioblastoma (GBM), remains a formidable clinical challenge. Poor immunogenicity and deficient immune infiltrates are two major limitations to an effective cancer-specific immune response. Herein, we propose that an injectable signal-amplifying nanocomposite/hydrogel system consisting of granulocyte-macrophage colony-stimulating factor and imiquimod-loaded antigen-capturing nanoparticles can simultaneously amplify the chemotactic signal of antigen-presenting cells and the "danger" signal of GBM. We demonstrated the feasibility of this strategy in two scenarios of GBM. In the first scenario, we showed that this simultaneous amplification system, in conjunction with local chemotherapy, enhanced both the immunogenicity and immune infiltrates in a recurrent GBM model; thus, ultimately making a cold GBM hot and suppressing postoperative relapse. Encouraged by excellent efficacy, we further exploited this signal-amplifying system to improve the efficiency of vaccine lysate in the treatment of refractory multiple GBM, a disease with limited clinical treatment options. In general, this biomaterial-based immune signal amplification system represents a unique approach to restore GBM-specific immunity and may provide a beneficial preliminary treatment for other clinically refractory malignancies.

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