Evaluation of IFIT3 and ORM1 as Biomarkers for Discriminating Active Tuberculosis from Latent Infection

Objective Current commercially available immunological tests cannot be used for discriminating active tuberculosis(TB)from latent TB infection.To evaluate the value of biomarker candidates in the diagnosis of active TB,this study aimed to identify differentially expressed genes in peripheral blood mononuclear cells(PBMCs)between patients with active TB and individuals with latent TB infection by transcriptome sequencing.Methods The differentially expressed genes in unstimulated PBMCs and in Mycobacterium tuberculosis(Mtb)antigen-stimulated PBMCs from patients with active TB and individuals with latent TB infection were identified by transcriptome sequencing.Selected candidate genes were evaluated in cohorts consisting of 110 patients with TB,30 individuals with latent TB infections,and 50 healthy controls by quantitative real-time RT-PCR.Receiver operating characteristic(ROC)curve analysis was performed to calculate the diagnostic value of the biomarker candidates.Results Among the differentially expressed genes in PBMCs without Mtb antigen stimulation,interferon-induced protein with tetratricopeptide repeats 3(IFIT3)had the highest area under curve(AUC)value(0.918,95%CI:0.852-0.984,P<0.0001)in discriminating patients with active TB from individuals with latent TB infection,with a sensitivity of 91.86%and a specificity of 84.00%.In Mtb antigen-stimulated PBMCs,orosomucoid 1(ORM1)had a high AUC value(0.833,95%CI:0.752-0.915,P<0.0001),with a sensitivity of 81.94%and a specificity of 70.00%.Conclusion IFIT3 and ORM1 might be potential biomarkers for discriminating active TB from latent TB infection.

Mesenchymal-epithelial Transition Factor Regulates Monocyte Function during Mycobacterial Infection via Indoleamine 2,3-dioxygenase

Objective Mycobacterium tuberculosis(Mtb),the causative agent of tuberculosis(TB),causes an estimated 1.6 million human deaths annually,but the pathogenesis of TB remains unclear.Immunity plays a critical role in the onset and outcome of TB.This study aimed to uncover the roles of innate and adaptive immunity in TB.Methods The gene expression profiles generated by RNA sequencing from human peripheral blood mononuclear cells(PBMCs)stimulated with or without Mtb strain H37Rv antigens were analyzed.A total of 973 differentially expressed mRNAs were identified.Results The differentially expressed genes were enriched in innate immunity signaling functions.The mesenchymal-epithelial transition factor(MET)gene was significantly upregulated in CD14^(+)monocytes.A MET inhibitor improved the uptake of the BCG strain by monocytes and macrophages as well as inhibited the expression of indoleamine 2,3-dioxygenase(IDO).The expression of IDO was increased in PBMCs stimulated with Mtb antigens,and the IDO inhibitor promoted the expression of CD40,CD83,and CD86.Conclusion Our results might provide clues regarding the immunomodulatory mechanisms used by Mtb to evade the host defense system.

Investigation of amyloid deposition in uterine leiomyoma patients

Objects: To investigate the pathogenesis of amyloid presented in uterine leiomyoma. Methods: 36 uterine leiomyoma patients were recruited and divided into two groups according to Congo red staining results. 6 cases are Congo red staining-positive, and 30 cases Congo red staining-negative which represented amyloid positive and amyloid negative respectively. All patients’ serum total protein (TP), albumin (Alb) and prealbumin (PA) levels were measured as well as blood hemoglobin (Hb), cell counts of white blood cell (WBC), neutrophils (NEU) and lymphocyte (LYM). Glycogen in tissue was compared between amyloid accumulated and amyloid negative sections with periodic acid schiff staining (PAS) in leiomyoma patients. Results: All of blood Hb concentration, WBC, NEU and LYM have not been found significant differences between two groups. Also no obvious infiltration of inflammatory cells was observed in tissue with amyloid deposition in uterine leiomyoma patients. And levels of TP, Alb and prealbumin have not been found significant differences between two groups. The amyloid was negative in leiomyoma entity cells range by Congo red staining, while small blood vessels in myoma tissues were positively detected with high rate. Amyloid was found in normal tissue around myoma as well as in blood vessel of pseudo-capsule. Increased PAS-positive material induced by leiomyoma was not correlated with amyloid deposition. Conclusions: Metabolic changes in the setting of functional alterations of cell in local microenvironment with uterine leiomyoma, may be related to the amyloid deposition.

Mechanism of Ginkgo biloba L.leaf in the treatment of ischemic stroke based on network pharmacology,bioinformatics and molecular docking

Ginkgo biloba L.leaf(GBL)has been reported to protect against ischemic stroke(IS),one of the leading causes of death and longterm disability worldwide,while there is a lack of systematic study on the exact mechanism.Here,network pharmacology and bioinformatics were used to predict the active components,important targets,and potential mechanisms of GBL in the treatment of IS.Active compounds of GBL were screened based on drug-like index and oral bioavailability,key target genes were screened based on network pharmacology and gene chip,downstream pathways for the regulation of key target genes were predicted based on gene set enrichment analysis,and the interaction between key targets and active compounds was verified based on molecular docking.The results showed that GBL played a protective role in cerebral ischemia with mainly 14 active compounds,such as isoquercitrin,luteolin-4’-glucoside,beta-sitosterol,campesterol,diosmetin,ginkgolide B,ginkgolide C,ginkgolide J,ginkgolide M,isogoycyrol,laricitrin,luteolin,sesamin,and stigmasterol.Further studies revealed that GBL played important role in immunomodulation and inflammation inhibition after cerebral ischemia by acting on its peripheral targets ARG1 and MMP9 to regulate Toll-like receptor,Chemokine and Notch signaling pathway.Meanwhile,GBL played important role in reducing neuroinflammation and blood-brain barrier damage after cerebral ischemia by acting on its central targets,CCL2,PTGS2,IL6,IL1B and MMP9 to regulate the Cytokine-cytokine receptor interaction,Jak-STAT,and Toll-like receptor signaling pathway.Additionally,molecular docking verified that the active compounds mentioned above could bind to ARG1,MMP9,CCL2,PTGS2,IL6,and IL1B.The present study shows the multicomponent,multitarget and multichannel pharmacological effects of GBL on cerebral ischemia and provides a new strategy for the treatment of IS.

3D printed modular Bouligand dissipative structures with adjustable mechanical properties for gradient energy absorbing

Three-dimensional(3D)printing allows for the creation of complex,layered structures with precise micro and macro architectures that are not achievable through traditional methods.By designing 3D structures with geometric precision,it is possible to achieve selective regulation of mechanical properties,enabling efficient dissipation of mechanical energy.In this study,a series of modular samples inspired by the Bouligand structure were designed and produced using a direct ink writing system,along with a classical printable polydimethylsiloxane ink.By altering the angles of filaments in adjacent layers(from 30◦to 90◦)and the filament spacing during printing(from 0.8 mm to 2.4 mm),the mechanical properties of these modular samples can be adjusted.Compression mechanical testing revealed that the 3D printed modular Bouligand structures exhibit stress-strain responses that enable multiple adjustments of the elastic modulus from 0.06 MPa to over 0.8 MPa.The mechanical properties were adjusted more than 10 times in printed samples prepared using uniform materials.The gradient control mechanism of mechanical properties during this process was analyzed using finite element analysis.Finally,3D printed customized modular Bouligand structures can be assembled to create an array with Bouligand structures displaying various orientations and interlayer details tailored to specific requirements.By decomposing the original Bouligand structure and then assembling the modular samples into a specialized array,this research aims to provide parameters for achieving gradient energy absorption structures through modular 3D printing.

Preparation of Ligand Free Au NPs/PPV Composites with High Stability and Photo-electric Response

A novel kind of ligand free aurum nanoparticles（Au NPs）/poly（p-phenylene-vinylene）（PPV） composites was prepared via a simple approach. Although there were no ligands coating on the surface of the Au NPs, the Au NPs/PPV precursor composite exhibited excellent stability that no obvious variance was found as long as 6 months at -4 ℃ in aqueous and alcohol mixed solutions. This was attributed to the strong interaction between Au NPs and PPV precursor, which was further strengthened after heat transformation. Fourier transform infrared（FTIR） and Raman spectra showed the interaction between benzene ring in PPV and Au NPs led to the part transformation of the sp2 hybrid orbital into the sp3 one during the composite formation. As a result, the photoluminescence（PL） life time of PPV in the composite was longer than that of pure PPV. The Au NPs/PPV composite exhibited good photo-electric response, indicating their potential application in the area of the photoelectric conversion devices.

Highly efficient modulation of the electronic properties of organic semiconductors by surface doping with 2D molecular crystals

Doping is a critically important strategy to modulate the properties of organic semiconductors(OSCs) to improve their optoelectrical performances. Conventional bulk doping involves the incorporation of foreign molecular species(i.e., dopants) into the lattice of the host OSCs, and thus disrupts the packing of the host OSCs and induces structural defects, which tends to reduce the mobility and(or) the on/off ratio in organic field-effect transistors(OFETs). In this article, we report a highly efficient and highly controllable surface doping strategy utilizing 2D molecular crystals(2DMCs) as dopants to boost the mobility and to modulate the threshold voltage of OFETs. The amount of dopants, i.e., the thickness of the 2DMCs, is controlled at monolayer precision, enabling fine tuning of the electrical properties of the OSCs at unprecedented accuracy. As a result, a prominent increase of the average mobility from 1.31 to 4.71 cm2 V-1 s-1 and a substantial reduction of the threshold voltage from -18.5 to -1.8 V are observed. Meanwhile, high on/off ratios of up to 108 are retained.

Events as a means to foster knowledge-driven urban development:Experience from the new district development in Nanjing

Events can bring important impetus to urban development.In addition to hardware investments,such as infrastructure,events also have important potential in the development of knowledge cities.Nanjing is a typical city where China’s knowledge industry is rapidly growing.Since the end of the last century,Nanjing has been promoting new district development on the city’s periphery and has hosted a series of events,including the 10th National Games in 2005 and the 2nd Youth Olympic Games in 2014.In this process,the city government also hopes to explore the potential of the knowledge economy and is committed to providing a new direction for urban development.This work reviews the history of Nanjing’s knowledge city development from two different dimensions(land development and knowledge development)and summarises the related achievements and lessons in different periods.The authors aim to identify the diverse effects of events in urban social and economic development based on the analysis of the differences in governance structure between land development and knowledge development.This work contributes to the literature on events and provides insights into the potential uses of events as a mechanism for knowledge-driven urban development.

A Visual Analysis of Network Pharmacology Research Trends

Objective: To understand the current situation of network pharmacology, and to analyze external and internal characteristics of literature, is of great significance for the development of network pharmacology in the future and its application in the modernization of Chinese medicine.Methods: Bibliometrics were adapted to perform visual analysis on the research status of network pharmacology with Citespace and SPSS for windows 22.0 version(IBM, Armonk, New York, USA).Knowledge map was used to analyze the knowledge system in the field, to identify the research hotspots and dynamic frontiers, and to elaborate the research status and development trend of domestic network pharmacology.Results: The research on network pharmacology in China is at the stage of the formation and construction of basic theories.At present, we focuses on the solution of actual disease problems and basic theoretical research, while the application in the research field of traditional Chinese medicine is a new hot spot and trend in the future development.Conclusions: It is important to pay attention to the connection and communication among the knowledge groups, so that a systematic knowledge system can be formed in the field of network pharmacology in domestic as soon as possible.