ExosomalmicroRNA let-7c-5p enhances cell malignant characteristics by inhibiting TAGLN in oral cancer

Background:Oral cancer,a malignancy that is prevalent worldwide,is often diagnosed at an advanced stage.MicroRNAs(miRNAs)in circulating exosomes have emerged as promising cancer biomarkers.The role of miRNA let-7c-5p in oral cancer remains underexplored,and its potential involvement in tumorigenesis warrants comprehensive investigation.Methods:Serum samples from 30 patients with oral cancer and 20 healthy controls were used to isolate exosomes and quantify their RNA content.Isolation of the exosomes was confirmed through transmission electron microscopy.Quantitative PCR was used to assess the miRNA profiles.The effects of let-7c-5p and TAGLN overexpression on oral cancer cell viability,migration,and invasion were analyzed via CCK-8 and Transwell assays.Moreover,we conducted mRNA sequencing of exosomal RNA from exosomes overexpressing let-7c-5p to delineate the gene expression profile and identify potential let-7c-5p target genes.Results:let-7c-5p was upregulated in serumderived exosomes of patients with oral cancer.Overexpression of let-7c-5p in the TCA8113 and CAL-27 cell lines enhanced their proliferative,migratory,and invasive capacities,and overexpression of let-7c-5p cell-derived exosomes promoted oral cancer cell invasiveness.Exosomal mRNA sequencing revealed 2,551 differentially expressed genes between control cell-derived exosomes and overexpressed let-7c-5p cell-derived exosomes.We further identified TAGLN as a direct target of let-7c-5p,which has been implicated in modulating the oncogenic potential of oral cancer cells.Overexpression of TAGLN reverses the promoting role of let-7c-5p on oral cancer cells.Conclusion:Our findings highlight the role of exosomal let-7c-5p in enhancing oral cancer cell aggressiveness by downregulating TAGLN expression,highlighting its potential as a diagnostic and therapeutic strategy.

Accelerating net-zero carbon emissions by electrochemical reduction of carbon dioxide

Electroreduction of CO_(2)shows great potential for global CO_(2)utilization and uptake when collaborated with renewable electricity.Recent advances have been achieved in fundamental understanding and electrocatalyst development for CO_(2)electroreduction.We think this research area has progressed to the stage where significant efforts can focus on translating the obtained knowledge to the development of largescale electrolyzers,which have the potential to accelerate the transition of the current energy system into a sustainable and zero-carbon emission energy structure.In this perspective paper,we first critically evaluate the advancement of vapor-feed devices that use CO_(2)as reactants,from the point of view of industry applications.Then,by carefully comparing their performance to the state-of-the-art water electrolyzers which are well-established technology providing realistic performance targets,we looped back and discussed the remaining challenges including electrode catalysts,reaction conditions,mass transporting,membrane,device durability,operation mode,and so on.Finally,we provide perspectives on the challenges and suggest opportunities for generating fundamental knowledge and achieving technological progress toward the development of practical CO_(2)electrolyzers for the goal of building lowcarbon or/and net carbon-free economies.

Research on neck dissection for oral squamous-cell carcinoma:a bibliometric analysis

Neck dissection for oral squamous-cell carcinoma(OSCC)is a clinically controversial issue and has therefore been the subject of abundant research.However,no one has performed a bibliometric study on this topic to date.The aim of this study was to assess the development of research on neck dissection for OSCC in terms of the historical evolution,current hotspots and future directions,particularly including research trends and frontiers from 2010 to 2019.Literature records related to research on neck dissection for OSCC were retrieved from the Web of Science Core Collection(WoSCC).CiteSpace was used as a tool to perform a bibliometric analysis of this topic.The survey included 2096 papers.“Otorhinolaryngology”was the most popular research area.The most active institutions and countries were Memorial Sloan Kettering Cancer Center and the USA,respectively.Shah J.P.was the most cited author.Among the six identified“core journals”,Head&Neck ranked first.The top three trending keywords were‘invasion’,‘upper aerodigestive’and‘negative neck’.‘D’Cruz AK(2015)’was the most cited and the strongest burst reference in the last decade.The study evaluated the effect on survival of elective versus therapeutic neck dissection in patients with lateralized early-stage OSCC.The depth of invasion and the management of N0 OSCC were research frontiers in this field.The present study provides a comprehensive bibliometric analysis of research on neck dissection for OSCC,which will assist investigators in exploring potential research directions.

Activation of NLRP3 Inflammasome via Drp1 Overexpression in Kupffer Cells Aggravates Ischemia-reperfusion Injury in Hepatic Steatosis

Background and Aims:Donors with fatty livers are considered to address the shortage of livers for transplantation,but those livers are particularly sensitive to ischemia-reperfusion injury(IRI),and an increased incidence of graft failure is observed.Kupffer cells account for 20–35%of liver nonparenchymal cells,and have been shown to participate in the process of IRI and inflammatory reactions of hepatic steatosis.NOD-like receptor thermal protein domain-associated protein 3(NLRP3)is an intracellular sensor activated by Kupffer cells to promote generation and participates in IRI.Dynamics-associated protein 1(Drp1)is one of the main proteins regulating mitochondrial division and exacerbates IRI by affecting mitochondrial dynamics.The mechanism of interaction of Kupffer cells with Drp1 and NLRP3 to aggravate IRI has not been clarified.Methods:A mouse model of hepatic steatosis was established by feeding the mice with a high-fat diet.In vitro experiments were performed using AML12 normal mouse liver cells and RAW264.7 mononuclear macrophage cells cultured in medium with palmitate and oleic acid.Western blotting and immunohistochemical(IHC)staining were used to detect the expression of NLRPP3 and Drp1 in IRI in the control and high-fat diet groups.The expression of F4/80+cells during IRI in hepatic steatosis was verified by IHC staining,and the role of NLRPP3 and Drp1 in Kupffer-cell mediated IRI was investigated by targeting Drp-1 inhibition.Results:Drp1 and NLRP3 expression was increased during IRI in hepatic steatosis,and the expression of Drp1 and NLRP3 were decreased after the elimination of Kupffer cells.That indicated Kupffer cells were involved in the process of IRI in hepatic steatosis through the action of Drp1 and NLRP3.After Drp1 inhibition,liver function was restored and NLRP3 expression level was reduced.Conclusions:Kupffer cells aggravated IRI in hepatic steatosis via NLRP3 and Drp1.Drp1 inhibitors might be useful as specific therapeutics to alleviate IRI in hepatic steatosis and may have promise in case of liver donor shortage.

Transplantation of Mesenchymal Stem Cells Attenuates Acute Liver Failure in Mice via an Interleukin-4-dependent Switch to the M2 Macrophage Anti-inflammatory Phenotype

Background and Aims:Transplantation of mesenchymal stem cells(MSCs)derived from bone marrow(BM)is an alternative treatment of acute liver failure(ALF)mainly be-cause of the resulting anti-inflammatory activity.It is not known how MSCs regulate local immune responses and liver regeneration.This study explored the effects of MSCs on hepatic macrophages and the Wnt signaling pathway in ALF.Methods:MSCs were isolated from BM aspirates of C57BL/6J mice,and transplanted in mice with ALF induced by D-galactosamine(D-Gal).The proliferation of hepato-cytes was assayed by immunohistochemical(IHC)staining of Ki-67 and proliferating cell nuclear antigen(PCNA).The levels of key proteins in the Wnt signaling pathway were assayed by western blotting and cytokines were determined enzyme-linked immunosorbent assays(ELISAs).A mac-rophage polarization assay characterized the M1/M2 ratio.The potential role of interleukin-4(IL-4)in the biological ac-tivity of MSCs was determined by silencing of IL-4.Results:Transplantation of allogeneic MSCs significantly attenuated D-Gal-induced hepatic inflammation and promoted liver re-generation.MSC transplantation significantly promoted a phenotypic switch from proinflamatory M1 macrophages to anti-inflammatory M2 macrophages,leading to significant Wnt-3a induction and activation of the Wnt signaling path-way in mice with D-Gal-induced ALF.Of the paracrine fac-tors secreted by MSCs(G-CSF,IL-6,IL-1 beta,IL-4,and IL-17A),IL-4 was specifically induced following transplantation in the ALF model mice.The silencing of IL-4 significantly ab-rogated the phenotypic switch to M2 macrophages and the protective effects of MSCs in both the ALF model mice and a co-culture model in an IL-4 dependent manner.Conclu-sions:In vivo and in vitro studies showed that MSCs ame-liorated ALF through an IL-4-dependent macrophage switch toward the M2 anti-inflammatory phenotype.The findings may have clinical implications in that overexpression of IL-4 may enhance the therapeutic effects of allogeneic MSC transplantation in the treatment of ALF.

Photo-driven water splitting photoelectrochemical cells by tandem organic dye sensitized solar cells with I-/I3- as redox mediator

Dye-sensitized photoelectrochemical tandem cells have shown the promise for light driven hydrogen production from water owing to the low cost,wide absorption spectra in the visible region and ease to process of their constitutive photoelectrode materials.However,most photo-driven water splitting photoelectrochemical cells driven by organic dye sensitized solar cells exhibit unsatisfactory hydrogen evolution rate,primarily attributed to their poor light capturing ability and low photocurrent performance.Here we present the construction of a tandem system consisting of an organic blue-colored S5 sensitizer-based dyesensitized photoelectrochemical cell(DSPEC) wired in series with three spectral-complemental dyes BTA-2,APP-3 and APP-1 sensitizers-based dye-sensitized solar cell(DSC),respectively.The two spectral-complemental chromophores were used in DSC and DSPEC to ensure that the full solar spectrum could be absorbed as much as possible.The results showed that the photocurrent of tandem device was closely related to the open-circuit voltage(Voc) of sensitized DSC,in which the tandem configuration consisting of S5 based DSPEC and BTA-2 based DSC gave the best photocurrent.On this basis,tandem device with the only light energy and no external applied electrical bias was further constructed of BTA-2 based 2-junction DSC and S5 based DSPEC and obtained a photocurrent of 500 μA cm-2 for hydrogen generation.Furthermore,I-/I3-was used as a redox couple between dye regeneration and O2 production on the surface of Pt-IrO2/WO3.The strategy opens up the application of pure organic dyes in DSC/DSPEC tandem device.