Single-Cell RNA Sequencing Reveals Potential for Endothelial-to-Mesenchymal Transition in Tetralogy of Fallot

Background:Tetralogy of Fallot(TOF)is a very common cyanotic congenital heart disease.Endothelial-to-mesenchymal transition(EndoMT)is recognized as a physiological mechanism involved in embryonic heart development and endothelial formation.However,there is still a gap in the reports related to the mechanism of EndoMT development in TOF.Methods:First,transcriptomic data of single cell nuclei of TOF and Donor were obtained based on the Gene Expression Omnibus(GEO)database,and the data were normalized and clus-tered by dimensionality reduction using the Seurat package.Subsequently,differentially expressed genes(DEGs)between TOF and Donor were screened using the“FindMarkers”function,and the gene sets of interest were enriched.Finally,to characterize the dynamics of EndoMT occurrence in TOF,we performed pseudotime cell tra-jectory inference as well as utilized SCENIC analysis to probe the gene regulatory networks(GRNs)dominated by transcription factors(TFs)in endothelial cells.Results:We identified a total of six cell clusters based on single-cell nuclear transcriptome data from TOF and Donor.We found that 611 genes with up-regulated expression within TOF showed conversion to mesenchyme.By subdividing endothelial cell subtypes,endothelial cells 2 were shown to be involved in cell adhesion,migration and extracellular matrix processes.Pseudo-time and SCENIC analyses showed that endothelial cell 2 has EndoMT potential.In addition,ERG and TEAD1 are TFs that play key reg-ulatory roles in this subtype,and both of their target genes are also highly expressed in TOF.This demonstrates that ERG and TEAD1 effectively promote the EndoMT process.Conclusion:Our study reveals the molecular mechanisms underlying the development of EndoMT in TOF,which demonstrates that manipulating the endothelial-to-mesenchymal transition may offer unprecedented therapeutic potential for the treatment of TOF.

Controlled preparation of P-doped g-C3N4 nanosheets for efficient photocatalytic hydrogen production

Hydrogen production by photolysis of water by sunlight is an environmentally-friendly preparation technology for renewable energy.Graphitic carbon nitride(g-C3N4),despite with obvious catalytic effect,is still unsatisfactory for hydrogen production.In this work,phosphorus element is incorporated to tune g-C3N4's property through calcinating the mixture of g-C3N4 and Na H2PO2,sacrificial agent and co-catalyst also been supplied to help efficient photocatalytic hydrogen production.Phosphorus(P)doped g-C3N4 samples(PCN-S)were prepared,and their catalytic properties were studied.X-ray diffraction(XRD),X-ray photoelectron spectroscopy(XPS),scanning electron microscopy(SEM)and ultraviolet diffuse reflection(UV-DRS)were used to study their structures and morphologies.The results show that the reaction rate of PCN-S is 318μmol·h^-1·g^-1,which is 2.98 times as high as pure carbon nitride nanosheets(CN)can do.Our study paves a new avenue,which is simple,environment-friendly and sustainable,to synthesize highly efficient P doping g-C3N4 nanosheets for solar energy conversion.

树突状细胞联合CIK细胞应用于晚期恶性实体瘤治疗的临床疗效观察(英文)

Objective: The aim of this study was to observe the therapeutic effect of cytokine induced killer (CIK) cells in combination with dendritic cells (DCs) on advanced solid carcinoma patients. Methods: Isolated peripheral blood mononuclear cells (PBMCs) from 110 advanced solid tumor patients. Added granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor-α (TNF-α) and interleukin-4 (IL-4) to adherent cells to induce DCs, and sensitized DCs with antigens of autologous tumor cells or extrinsic tumor cell lines. Cultured suspending cells with interferon-γ (IFN-γ), interleukin-2 (IL-2) and CD3 monoclonal antibody (CD3 McAb) to prepare CIK cells, then co-cultured with DCs. After analyzing the phenotype and checking tumor markers and immune function, the autologous CIK cells and DCs were transfused into the cancer patients. Results: Forty-two patients with measurable nidus, 2 achieved complete remission (CR), 9 partial remission (PR) and 15 stable disease (SD), while 37 patients with immeasurable nidus, 25 had efficient response. The tumor markers and immune function both improved significantly compared with those before treatment. Conclusion: DCs and CIK cells combinational treatment is safe and effective on advanced solid carcinoma and provide a new and efficacious immunity therapeutic methods for the cancer patients.

Three-dimensional oxygen-doped porous graphene:Sodium chloridetemplate preparation,structural characterization and supercapacitor performances

Supercapacitor is a new type of energy storage device,which has the advantages of high-power property and long cycle life.In this study,three-dimensional graphene(3 D-GN)with oxygen doping and porous structure was prepared from graphene oxide(GO)by an inexpensive sodium chloride(NaCl)template,as a promising electrode material for the supercapacitor.The structure,morphology,specific surface area,pore size,of the sample were characterized by XRD,SEM,TEM and BET techniques.The electrochemical performances of the sample were tested by CV and CDC techniques.The 3 D-GE product is a threedimensional nano material with hierarchical porous structures,its specific surface area is much larger than that of routine stacked graphene(GN),and it contains a large number of mesoporous and macropores,a small amount of micropores.The capacitance characteristics of the 3 D-GN electrode material are excellent,showing high specific capacitance(173.5 F·g^(-1)at 1 A·g^(-1)),good rate performance(109.2 F·g^(-1)at 8 A·g^(-1))and long cycle life(88%capacitance retention after 10,000 cycles at 8 A·g^(-1))

Multi-valent mRNA vaccines against monkeypox enveloped or mature viron surface antigens demonstrate robust immune response and neutralizing activity

Monkeypox was declared a global health emergency by the World Health Organization,and as of March 2023,86,000 confirmed cases and 111 deaths across 110 countries have been reported.Its causal agent,monkeypox virus(MPV)belongs to a large family of double-stranded DNA viruses,Orthopoxviridae,that also includes vaccinia virus(VACV)and others.MPV produces two distinct forms of viral particles during its replication cycles:the enveloped viron(EV)that is released via exocytosis,and the mature viron(MV)that is discharged through lysis of host cells.This study was designed to develop multi-valent m RNA vaccines against monkeypox EV and MV surface proteins,and examine their efficacy and mechanism of action.Four m RNA vaccines were produced with different combinations of surface proteins from EV(A35R and B6R),MV(A29L,E8L,H3L and M1R),or EV and MV,and were administered in Balb/c mice to assess their immunogenicity potentials.A dynamic immune response was observed as soon as seven days after initial immunization,while a strong Ig G response to all immunogens was detected with ELISA after two vaccinations.The higher number of immunogens contributed to a more robust total Ig G response and correlating neutralizing activity against VACV,indicating the additive potential of each immunogen in generating immune response and nullifying VACV infection.Further,the m RNA vaccines elicited an antigen-specific CD4^(+)T cell response that is biased towards Th1.The m RNA vaccines with different combinations of EVand MV surface antigens protected a mouse model from a lethal dose VACV challenge,with the EV and MV antigens-combined vaccine offering the strongest protection.These findings provide insight into the protective mechanism of multi-valent m RNAvaccines against MPV,and also the foundation for further development of effective and safe m RNA vaccines for enhanced protection against monkeypox virus outbreak.