A drug-loaded flexible substrate improves the performance of conformal cortical electrodes

Cortical electrodes are a powerful tool for the stimulation and/or recording of electrical activity in the nervous system.However,the inevitable wound caused by surgical implantation of electrodes presents bacterial infection and inflammatory reaction risks associated with foreign body exposure.Moreover,inflammation of the wound area can dramatically worsen in response to bacterial infection.These consequences can not only lead to the failure of cortical electrode implantation but also threaten the lives of patients.Herein,we prepared a hydrogel made of bacterial cellulose(BC),a flexible substrate for cortical electrodes,and further loaded antibiotic tetracycline(TC)and the anti-inflammatory drug dexamethasone(DEX)onto it.The encapsulated drugs can be released from the BC hydrogel and effectively inhibit the growth of Gram-negative and Gram-positive bacteria.Next,therapeutic cortical electrodes were developed by integrating the drug-loaded BC hydrogel and nine-channel serpentine arrays;these were used to record electrocorticography(ECoG)signals in a rat model.Due to the controlled release of TC and DEX from the BC hydrogel substrate,therapeutic cortical electrodes can alleviate or prevent symptoms associated with the bacterial infection and inflammation of brain tissue.This approach facilitates the development of drug delivery electrodes for resolving complications caused by implantable electrodes.

Panoramic comparison between NK cells in healthy and cancerous liver through single-cell RNA sequencing

Objective:NK cells play crucial roles in the immune defense mechanisms against viral infections and transformed cells.However,the developmental progression,transcriptomic landscape,and functional subtypes of liver NK cells are not well defined.Hepatocellular carcinoma(HCC)accounts for approximately 80%of primary liver cancer worldwide,yet the biological characteristics of NK cells in the HCC environment are unclear.Therefore,we aimed to determine these cells’roles in tumorigenesis and prognosis.Methods:We compared the single-cell RNA sequencing profiles of NK cells purified from blood(n=1),healthy liver tissues(n=3),HCC tumor tissues(n=4),and peritumor liver tissues(n=1)to identify NK cell subsets.Furthermore,we performed bioinformatics analysis by using The Cancer Genome Atlas(TCGA)data to identify prognostic biomarkers simultaneously overexpressed in the blood and tumor tissues of patients with HCC.Results:Transcriptomic analysis revealed 5 NK cell subsets(L1-NK-CD56bright,L2-NK-CD56dim,L3-NK-HLA,L4-LrNK-FCGR3A,and L5-LrNK-XCL1)in the healthy liver tissues.However,the transitional L3 subset and the CXCR6+CD16+L4 subset with strong anti-tumor activity were absent in the HCC and peritumor liver tissues.Furthermore,4 common prognosis-associated genes(RHOB,TALDO1,HLA-DPA1,and TKT)were significantly overexpressed in the paired tumor tissue and blood.Conclusions:Our study revealed 5 specific subsets of NK cells in healthy human liver tissues.However,only 3 of the 5 NK cell subsets were present in HCC and peritumor tissues.The cytotoxic NK cell subsets were absent in HCC tissues.Furthermore,we identified 4 potential non-invasive prognostic biomarkers in patients with HCC.

Enhanced photocatalytic performance of Bi_(2)O_(2)CO_(3)/Bi_(4)O_(5)Br_(2)/reduced graphene oxide Z-schemehe terojunction via a one-pot room-temperature synthesis

Bi_(2)O_(2)CO_(3)(BOC)/Bi_(4)O_5Br_(2)(BOB)/reduced graphene oxide(rGO)Z-scheme heterojunction with promising photocatalytic properties was synthesized via a facile one-pot room-temperature method.Ultra-thin nanosheets of BOC and BOB were grown in situ on r GO.The formed 2D/2D direct Z-scheme heterojunction of BOC/BOB with oxygen vacancies(OVs)effectively leads to lower negative electron reduction potential of BOB as well as higher positive hole oxidation potential of BOC,showing improved reduction/oxidation ability.Particularly,rGO is an acceptor of the electrons from the conduction band of BOC.Its dual roles significantly improve the transfer performance of photo-induced charge carriers and accelerate their separation.With layered nanosheet structure,rich OVs,high specific surface area,and increased utilization efficiency of visible light,the multiple synergistic effects of BOC/BOB/rGO can achieve effective generation and separation of the electron-holes,thereby generating more·O_(2)^(-)and h^(+).The photocatalytic reduction efficiency of CO_(2)to CO(12.91μmol/(g·hr))is three times higher than that of BOC(4.18μmol/(g·hr)).Moreover,it also achieved almost 100%removal of Rhodamine B and cyanobacterial cells within 2 hours.

Influence of immunosuppressive drugs on natural killer cells in therapeutic drug exposure in liver transplantation

Background:Natural killer(NK)cells are enriched in the liver and are the main regulators in liver transplantation regarding rejection or tolerance,viral infection,or tumor recurrence.Immunosuppression consists of a triple drug standard regimen comprising tacrolimus(TAC)and corticosteroids(CS)with either mycophenolate mofetil(MMF)or sirolimus(SIR)/everolimus(EVE).The aim of this study was to evaluate the impact of trough levels of these regimens under clinical conditions and exposure on human NK-cell activity and function in order to better understand the antiviral and anti-tumor effects of mammalian target of rapamycin inhibitor(mTORI).Methods:Peripheral blood mononuclear cells(PBMCs)were collected from liver transplant recipients and healthy controls.Number and phenotypes of NK cells in vivo were analyzed by flow cytometry.In this study we simulated the immunosuppressive microenvironment in vitro.PBMCs were cultured at the clinically effective plasma concentration of drugs for 3 d to detect the effect of immunosuppressants on NK cells.Drug type and concentration:single drug[EVE,5 ng/mL;SIR,5 ng/mL;TAC,5 ng/mL;cyclosporine A(CSA),125 ng/mL;MMF,15μg/mL;CS,0.5μg/mL]and combined immunosuppressants(Group 1:TAC,5 ng/mL+MMF,15μg/mL+CS,0.5μg/mL;Group 2:TAC,5 ng/mL+SIR,5 ng/mL+CS,0.5μg/mL;Group 3:TAC,5 ng/mL+EVE,5 ng/mL+CS,0.5μg/mL).In addition,NK cells were sorted from PBMCs and treated under the above conditions to detect NK cell killing function and RNA transcription characteristics.Results:CS significantly impaired the cytolytic activity of NK cells,followed by MMF and SIR/EVE.CS and TAC/CSA significantly decreased the secretion of IFN-γand CD107a.NK cell function in liver transplant recipients was most pronouncedly inhibited by a triple immunosuppressive regimen,with CS playing the most prominent role compared with the other drugs.The MMF-containing regimen demonstrated a significant increase in the expression of suppressive genes,especially of the Siglec7/9 family.The SIR group had stronger NK cell activity compared with that of the MMF group,although liver transplantation patients have lower NK cell activity and function.Conclusions:Despite an overall comparable immunosuppressive efficiency in terms of prevention of acute rejection,a mTORIs-including regimen might be considered as having less impact on NK cell function.