Antibody-based PD-IIPD-L1 blockade therapies have taken center stage in immunotherapies for cancer, with multiple clinical successes. PD-1 signaling plays pivotal roles in tumor-driven T-cell dysfunction. In contrast ...Antibody-based PD-IIPD-L1 blockade therapies have taken center stage in immunotherapies for cancer, with multiple clinical successes. PD-1 signaling plays pivotal roles in tumor-driven T-cell dysfunction. In contrast to prior approaches to generate or boost tumor-specific T-cell responses, antibody-based PD-1/PD-L1 blockade targets tumor-induced T-cell defects and restores pre- existing T-cell function to modulate antitumor immunity. in this review, the fundamental knowledge on the expression regulations and inhibitory functions of PD-1 and the present understanding of antibody-based PD-1/ PD-L1 blockade therapies are briefly summarized. We then focus on the recent breakthrough work concerning the structural basis of the PD-IIPD-Ls interaction and how therapeutic antibodies, pembrolizumab targeting PD-1 and avelumab targeting PD-L1, compete with the binding of PD-1/PD-L1 to interrupt the PD-1/PD-L1 interaction. We believe that this structural informationwill benefit the design and improvement of therapeutic antibodies targeting PD-1 signaling.展开更多
Dear Editor,Blockade of PD-1/PD-L1 signaling pathway by monoclonal antibodies(MAbs)to release the anti-tumor activity of pre-existing tumor specific T cell immunity has initiated a new era for tumor immunotherapy.Admi...Dear Editor,Blockade of PD-1/PD-L1 signaling pathway by monoclonal antibodies(MAbs)to release the anti-tumor activity of pre-existing tumor specific T cell immunity has initiated a new era for tumor immunotherapy.Administration of anti-PD-1 MAbs(nivolumab and pembrolizumab)in either monotherapy or in combination with anti-CTLA-4 MAbs or traditional chemother-apy has achieved a tumor regression rate of 30%-50%in dealing with melanoma,non-small cell lung cancer,etc.(Larkin et al.,2015).展开更多
Transcriptional coactivators regulate the rate of gene expression in the nucleus.Nuclear receptor coactivator 6(NCOA6),a coactivator,has been implicated in embryonic development,metabolism,and cancer pathogenesis,but ...Transcriptional coactivators regulate the rate of gene expression in the nucleus.Nuclear receptor coactivator 6(NCOA6),a coactivator,has been implicated in embryonic development,metabolism,and cancer pathogenesis,but its role in innate immunity and inflammatory diseases remains unclear.Here,we demonstrated that NCOA6 was expressed in monocytes and macrophages and that its level was increased under proinflammatory conditions.Unexpectedly,nuclear NCOA6 was found to translocate to the cytoplasm in activated monocytes and then become incorporated into the inflammasome with NLRP3 and ASC,forming cytoplasmic specks.Mechanistically,NCOA6 associated with the ATP hydrolysis motifs in the NACHT domain of NLRP3,promoting the oligomerization of NLRP3 and ASC and thereby instigating the production of IL-1βand active caspase-1.Of note,Ncoa6 deficiency markedly inhibited NLRP3 hyperactivation caused by the Nlrp3^(R258W) gain-of-function mutation in macrophages.Genetic ablation of Ncoa6 substantially attenuated the severity of two NLRP3-dependent diseases,folic-induced acute tubular necrosis and crystal-induced arthritis,in mice.Consistent with these findings,NCOA6 was highly expressed in macrophages derived from gout patients,and NCOA6-positive macrophages were significantly enriched in gout macrophages according to the transcriptome profiling results.Conclusively,NCOA6 is a critical regulator of NLRP3 inflammasome activation and is therefore a promising target for NLRP3-dependent diseases,including gout.展开更多
Neuromodulation by ultrasound has recently received attention due to its noninvasive stimulation capability for treating brain diseases.Although there have been several studies related to ultrasonic neuromodulation,th...Neuromodulation by ultrasound has recently received attention due to its noninvasive stimulation capability for treating brain diseases.Although there have been several studies related to ultrasonic neuromodulation,these studies have suffered from poor spatial resolution of the ultrasound and low repeatability with a fixed condition caused by conventional and commercialized ultrasound transducers.In addition,the underlying physics and mechanisms of ultrasonic neuromodulation are still unknown.To determine these mechanisms and accurately modulate neural circuits,researchers must have a precisely controllable ultrasound transducer to conduct experiments at the cellular level.Herein,we introduce a new MEMS ultrasound stimulation system for modulating neurons or brain slices with high spatial resolution.The piezoelectric micromachined ultrasonic transducers(pMUTs)with small membranes(submm membranes)generate enough power to stimulate neurons and enable precise modulation of neural circuits.We designed the ultrasound transducer as an array structure to enable localized modulation in the target region.In addition,we integrated a cell culture chamber with the system to make it compatible with conventional cell-based experiments,such as in vitro cell cultures and brain slices.In this work,we successfully demonstrated the functionality of the system by showing that the number of responding cells is proportional to the acoustic intensity of the applied ultrasound.We also demonstrated localized stimulation capability with high spatial resolution by conducting experiments in which cocultured cells responded only around a working transducer.展开更多
Developing fluorescence probes with multiple responses has vital significance but remains challenging.Herein,for the first time,we present a mitochondrial DNA(mtDNA)-triggered pH response signalamplified fluorescent p...Developing fluorescence probes with multiple responses has vital significance but remains challenging.Herein,for the first time,we present a mitochondrial DNA(mtDNA)-triggered pH response signalamplified fluorescent probe(QCY-DBT)for multiple cell detection.The probe exhibited a large stokes shift(229 nm),excellent DNA selectivity over RNA,and ultrasensitivity of detection limit(DL;74.0 ng/mL).Thus,QCY-DBT was successfully applied to analyze multiple human peripheral blood cells and visualize mtDNA in healthy and apoptotic cells.In the tumor acidic environment(pH 6.0–7.0),the absorbance of QCY-DBT at 436 nm increased,and the fluorescence signal(665 nm)was amplified by mtDNA,which enabled the direct observation of tumor cells.Our study provides help in designing smart probes with multiple responses for efficient abnormal cell detection.展开更多
Biodegradable metals as electrodes, interconnectors, and device conductors are essential components in the emergence of transient electronics, either for passive implants or active electronic devices, especially in th...Biodegradable metals as electrodes, interconnectors, and device conductors are essential components in the emergence of transient electronics, either for passive implants or active electronic devices, especially in the fields of biomedical electronics. Magnesium and its alloys are strong candidates for biodegradable and implantable conducting materials because of their high conductivity and biocompatibility, in addition to their well-understood dissolution behavior. One critical drawback of Mg and its alloys is their considerably high dissolution rates originating from their low anodic potential, which disturbs the compatibility to biomedical applications. Herein, we introduce a single-phase thin film of a Mg-Zn binary alloy formed by sputtering, which enhances the corrosion resistance of the device electrode, and verify its applicability in biodegradable electronics. The formation of a homogeneous solid solution of single-phase Mg-3Zn was confirmed through X-ray diffraction and transmission electron microscopy. In addition, the dissolution behavior and chemistry was also investigated in various biological fluids by considering the effect of different ion species. Micro-tensile tests showed that the Mg-3Zn alloy electrode exhibited an enhanced yield strain and elongation in relation to a pure Mg electrode. Cell viability test revealed the high biocompatibility rate of the Mg-3Zn binary alloy thin film. Finally, the fabrication of a wireless heater demonstrated the integrability of biodegradable electrodes and highlighted the ability to prolong the lifecycle of thermotherapy-relevant electronics by enhancing the dissolution resistance of the Mg alloy.展开更多
Objective and Impact Statement:We describe an electroenzymatic mediator(EM)sensor based on an electroenzymatic assembly peak separation strategy,which can efficiently realize the simultaneous detection of 3 typical ca...Objective and Impact Statement:We describe an electroenzymatic mediator(EM)sensor based on an electroenzymatic assembly peak separation strategy,which can efficiently realize the simultaneous detection of 3 typical cardiovascular disease(CVD)metabolites in 5μl of plasma under one test.This work has substantial implications toward improving the efficiency of chronic CVD assessment.Introduction:Monitoring CVD of metabolites is strongly associated with disease risk.Independent and time-consuming detection in hospitals is unfavorable for chronic CVD management.Methods:The EM was flexibly designed by the cross-linking of electron mediators and enzymes,and 3 EM layers with different characteristics were assembled on one electrode.Electrons were transferred under tunable potential;3 metabolites were quantitatively detected by 3 peak currents that correlated with metabolite concentrations.Results:In this study,the EM sensor showed high sensitivity for the simultaneous detection of 3 metabolites with a lower limit of 0.01 mM.The linear correlation between the sensor and clinical was greater than 0.980 for 242 patients,and the consistency of risk assessment was 94.6%.Conclusion:Metabolites could be expanded by the EM,and the sensor could be a promising candidate as a home healthcare tool for CVD risk assessment.展开更多
Abstinence from prolonged psychostimulant use prompts stimulant withdrawal syndrome.Molecular adaptations within the dorsal striatum have been considered the main hallmark of stimulant abstinence. Here we explored str...Abstinence from prolonged psychostimulant use prompts stimulant withdrawal syndrome.Molecular adaptations within the dorsal striatum have been considered the main hallmark of stimulant abstinence. Here we explored striatal miRNA-target interaction and its impact on circulating miRNA marker as well as behavioral dysfunctions in methamphetamine(MA) abstinence. We conducted miRNA sequencing and profiling in the nonhuman primate model of MA abstinence, followed by miRNA qPCR,LC-MS/MS proteomics, immunoassays, and behavior tests in mice. In nonhuman primates, MA abstinence triggered a lasting upregulation of miR-137 in the dorsal striatum but a simultaneous downregulation of circulating miR-137. In mice, aberrant increase in striatal miR-137-dependent inhibition of SYNCRIP essentially mediated the MA abstinence-induced reduction of circulating miR-137. Pathway modeling through experimental deduction illustrated that the MA abstinence-mediated downregulation of circulating miR-137 was caused by reduction of SYNCRIP-dependent miRNA sorting into the exosomes in the dorsal striatum. Furthermore, diminished SYNCRIP in the dorsal striatum was necessary for MA abstinence-induced behavioral bias towards egocentric spatial learning. Taken together, our data revealed circulating miR-137 as a potential blood-based marker that could reflect MA abstinence-dependent changes in striatal miR-137/SYNCRIP axis, and striatal SYNCRIP as a potential therapeutic target for striatum-associated cognitive dysfunction by MA withdrawal syndrome.展开更多
Novel advances in the field of brain imaging have enabled the unprecedented clinical application of various imaging modalities to facilitate disease diagnosis and treatment. Electrical impedance tomography(EIT) is a f...Novel advances in the field of brain imaging have enabled the unprecedented clinical application of various imaging modalities to facilitate disease diagnosis and treatment. Electrical impedance tomography(EIT) is a functional imaging technique that measures the transfer impedances between electrodes on the body surface to estimate the spatial distribution of electrical properties of tissues. EIT offers many advantages over other neuroimaging technologies,which has led to its potential clinical use. This qualitative review provides an overview of the basic principles,algorithms, and system composition of EIT. Recent advances in the field of EIT are discussed in the context of epilepsy,stroke, brain injuries and edema, and other brain diseases. Further, we summarize factors limiting the development of brain EIT and highlight prospects for the field. In epilepsy imaging, there have been advances in EIT imaging depth,from cortical to subcortical regions. In stroke research, a bedside EIT stroke monitoring system has been developed for clinical practice, and data support the role of EIT in multi-modal imaging for diagnosing stroke. Additionally, EIT has been applied to monitor the changes in brain water content associated with cerebral edema, enabling the early identification of brain edema and the evaluation of mannitol dehydration. However, anatomically realistic geometry,inhomogeneity, cranium completeness, anisotropy and skull type, etc., must be considered to improve the accuracy of EIT modeling. Thus, the further establishment of EIT as a mature and routine diagnostic technique will necessitate the accumulation of more supporting evidence.展开更多
Circulating tumor cells(CTCs)have tremendous potential to indicate disease progression and monitor therapeutic response using minimally invasive approaches.Considering the limitations of affinity strategies based on t...Circulating tumor cells(CTCs)have tremendous potential to indicate disease progression and monitor therapeutic response using minimally invasive approaches.Considering the limitations of affinity strategies based on their cost,effectiveness,and simplicity,size-based enrichment methods that involve low-cost,label-free,and relatively simple protocols have been further promoted.Nevertheless,the key challenges of these methods are clogging issues and cell aggregation,which reduce the recovery rates and purity.Inspired by the natural phenomenon that the airflow around a windmill is disturbed,in this study,a windmill-like hole array on the SU-8 membrane was designed to perturb the fluid such that cells in a fluid would be able to self-mix and that the pressure acting on cells or the membrane would be dispersed to allow a greater velocity.In addition,based on the advantages of fluid coatings,a lipid coating was used to modify the membrane surface to prevent cell aggregation and clogging of the holes.Under the optimal conditions,recovery rates of 93%and 90%were found for A549 and HeLa cells in a clinical simulation test of our platform with a CTC concentration of 20-100 cells per milliliter of blood.The white blood cell(WBC)depletion rate was 98.7%(n=15),and the CTC detection limit was less than 10 cells per milliliter of blood(n=6).Moreover,compared with conventional membrane filtration,the advantages of the proposed device for the rapid(2 mL/min)and efficient enrichment of CTCs without clogging were shown both experimentally and theoretically.Due to its advantages in the efficient,rapid,uniform,and clog-free enrichment of CTCs,our platform offers great potential for metastatic detection and therapy analyses.展开更多
Cardiovascular diseases cause huge socio-economic burden worldwide.Although a mammalian myocardium has its own limited healing capability,scaffold materials capable of releasing stem cell recruiting/engrafting factors...Cardiovascular diseases cause huge socio-economic burden worldwide.Although a mammalian myocardium has its own limited healing capability,scaffold materials capable of releasing stem cell recruiting/engrafting factors may facilitate the regeneration of the infarcted myocardium.The aim of this research was to develop cardiac patches capable of simultaneously eluting substance P(SP)and insulin-like growth factor-1C(IGF-1C)peptide.Polycaprolactone/collagen type 1-based patches with or without SP and IGF-1C peptide were fabricated by co-electrospinning,which exhibited nanofibrous morphology.SP and IGF-1C/SP patches recruited significantly higher numbers of bone marrow-mesenchymal stem cells than that of the negative control and patch-only groups in vitro.The developed patches were transplanted in an infarcted myocardium for up to 14 days.Mice underwent left anterior descending artery ligation and received one of the following treatments:(i)sham,(ii)saline,(iii)patch-only,(iv)IGF-1C patch,(v)SP patch and(vi)IGF-1C/SP patch.SP and IGF-1C/SP patch-treated groups exhibited better heart function and attenuated adverse cardiac remodeling than that of the saline,patch-only and individual peptide containing cardiac patches.SP patch and IGF-1C/SP patch-treated groups also showed higher numbers of CD31-positive vessels and isolectin B4-positive capillaries than that of other groups.IGF-1C/SP-treated group also showed thicker left ventricular wall in comparison to the saline and patch-only groups.Moreover,IGF-1C/SP patches recruited significantly higher numbers of CD29-positive cells and showed less numbers of Tunel-positive cells compared with the other groups.These data suggest that SP and IGF-1C peptides may act synergistically for in situ tissue repair.展开更多
Dear Editor,The Ras superfamily of GTPases are conserved in eukary?otes from yeast to humans,and play essential roles in the regulation of a variety of key cellular processes,including cell differentiation and prolife...Dear Editor,The Ras superfamily of GTPases are conserved in eukary?otes from yeast to humans,and play essential roles in the regulation of a variety of key cellular processes,including cell differentiation and proliferation,membrane trafficking,nuclear import and export,cytoskeletal remodeling and mitogenic signaling(Karnoub and Weinberg,2008).Notably,numerous studies have shown that many members of the Ras-related small GTPases are involved in diverse aspects of tumorigenesis and tumor progress!on(Chen et al.,2014;Liu et al.,2017).展开更多
In this paper,we prepared the nanoparticle drug carrier system between nanoparticles chitosan and Epigallocatechin-3 O-gallate(EGCG)for breast cancer cell inhibiting application.For this drug carrier system,chitosan a...In this paper,we prepared the nanoparticle drug carrier system between nanoparticles chitosan and Epigallocatechin-3 O-gallate(EGCG)for breast cancer cell inhibiting application.For this drug carrier system,chitosan acts as a carrier and EGOG as a drug.Which were systematically characterized and thoroughly evaluated in terms of their inhibition rate and biocompatibility.We also did a cell scratch test and the result indicated that the chitosan EGCG nanoparticles have inhibitory effect on the growth of breast cancer cells.The inhibition rate could reach up to 21.91%.This work revealed that the modification of nanopartidles paved a way for specific biomedical applications.展开更多
This paper aims to evaluate the individual and joint toxicities of cadmium sulfate （CdSO4） and α-naphthoflavone （ANF） in zebrafish embryos. As a result, CdSO4 caused both lethal and sub-lethal effects, such as 24...This paper aims to evaluate the individual and joint toxicities of cadmium sulfate （CdSO4） and α-naphthoflavone （ANF） in zebrafish embryos. As a result, CdSO4 caused both lethal and sub-lethal effects, such as 24 h post-fertilization （hpf） death and 72 hpf delayed hatching. However, ANF only caused sub-lethal effects, including 48 hpf cardiac edema and 72 hpf delayed hatching. Taking 24 hpf death and 48 hpf cardiac edema as endpoints, the toxicities of CdSO4 and ANF were significantly enhanced by each other. Consistently, both CdSO4 and ANF caused significant oxidative stress, including decreases in the reduced glutathione （GSH） level, inhibition of superoxide dis- mutase （SOD） activity, as well as increases in malondialdehyde （MDA） content in zebrafish embryos, but these mixtures produced much more significant alterations on the biomarkers. Co-treatment of CdSO4 and ANF significantly down-regulated the mRNA level of multidrug resistance-associated protein （mrp） 1 and cytochrome P450 （cyp） la, which constituted the protective mechanisms for zebraflsh embryos to chemical toxins. In conclusion, co-treatment of CdSO4 and ANF exhibited a much more severe damage in zebraflsh embryos than individual treatment. Meanwhile, production of oxidative stress and altered expression of mrpl and cypla could be important components of such joint toxicity.展开更多
In this work,novel antibacterial cellulose diacetate/poly(ethylenimine)/hyaluronic acid(CDA/PEI/HA)composite three-dimension(3D)scaffolds were prepared through electrospinning and post-processing.Firstly,CDA/PEI 2D co...In this work,novel antibacterial cellulose diacetate/poly(ethylenimine)/hyaluronic acid(CDA/PEI/HA)composite three-dimension(3D)scaffolds were prepared through electrospinning and post-processing.Firstly,CDA/PEI 2D composite nanofiber membranes were prepared by electrospinning,and then the CDA/PEI/HA 3D composite scaffolds were fabricated by post-processing and freeze-drying of CDA/PEI membranes.In particular,HA was added to improve the biocompatibility of composite scaffolds.Compared with CDA/PEI scaffolds,CDA/PEI/HA composite scaffolds showed higher water absorbing rate,higher water retention rate and higher mechanical strength.Moreover,CDA/PEI/HA composite scaffolds with abundant positive charge were benefit for improving antibacterial activity.CDA/PEI/HA scaffolds with biology function of HA were benefit for improving hemocompatibility and cell proliferation of CDA/PEI scaffolds.In summary,antibacterial CDA/PEI/HA scaffolds could protect wound from bacterial infection,improve cellular behavior and accelerate wound healing.Thus,CDA/PEI/HA scaffolds could be potential application for wound dressing.展开更多
Infectious of hepatitis C viruses(HCVs)lead to hepatic fibrosis,cirrhosis even hepatoma.Developing rapid and sensitive diagnostic method for HCV is of great importance.Based on the host-and-guest interaction between c...Infectious of hepatitis C viruses(HCVs)lead to hepatic fibrosis,cirrhosis even hepatoma.Developing rapid and sensitive diagnostic method for HCV is of great importance.Based on the host-and-guest interaction between cucurbit[7]uril(CB[7])and methylene blue(MB),a CB[7]-graphene nano-composite(CB[7]-N3-GO)is raised for the electrochemical detection of HCV DNA.The method is able to linearly detect the HCV nucleic acid in the range of 0.2—10 nmol/L with detection limit as low as 160.4 pmol/L.The proposed detection strategy is able to discriminate the lb and 6k subtypes of HCV and has a prospective potential in the blood screen for HCV in clinical diagnosis.展开更多
Tumor necrosis factor-alpha(TNF-α) is a type of critical pro-inflammatory cytokines,which participates in numerous cellular signal pathways and is regarded as a critical protein biomarker for inflammatory based disea...Tumor necrosis factor-alpha(TNF-α) is a type of critical pro-inflammatory cytokines,which participates in numerous cellular signal pathways and is regarded as a critical protein biomarker for inflammatory based diseases.In this contribution,we have developed a strategy to fabricate multiple DNA star trigon structures with fluorescence signals from four hairpin probes which are detonated by a single molecule of TNF-α.This process causes significant enhancement of fluorescence and a sensitive and selective biosensor for TNF-α assay is constructed.This method is able to achieve the limit of detection(LOD) at 5 pg/mL(0.285 pM).Moreover,some other advantages such as fast response,high selectivity and convenient operation promise the potential use of this method for TNF-α measurement in point of care testing application.Upon further development,this strategy can also be converted to detect other analytes such as small molecules,nucleic acids and other proteins.展开更多
An ultrasensitive electrochemical aptasensor is presented for prostate specific antigen(PSA) detection. DNA tetrahedronaptamer is designed, which not only facilitates the molecular self-assembly events,but also improv...An ultrasensitive electrochemical aptasensor is presented for prostate specific antigen(PSA) detection. DNA tetrahedronaptamer is designed, which not only facilitates the molecular self-assembly events,but also improves the recognition efficiency between PSA and aptamer sequence on the electrode interface. The DNA conformation on top of DNA tetrahedron changes accordingly, which can be further digested by Exonuclease T(Exo T), a type of single-strand specific nuclease. Electrochemical species are removed synchronously and the initial PSA level can thus be determined. A linear range from 0.5 pg mL^(-1) to50 ng mL^(-1) is achieved with the limit of detection(LOD) as low as 0.15 pg mL^(-1). Moreover, this proposed method is highly selective and is successfully applied to determine PSA in human serum samples.展开更多
Background Chronic obstructive pulmonary disease(COPD)is a severe public health problem.Cigarette smoke(CS)is a risk factor for COPD and lung cancer.The underlying molecular mechanisms of CS-induced malignant transfor...Background Chronic obstructive pulmonary disease(COPD)is a severe public health problem.Cigarette smoke(CS)is a risk factor for COPD and lung cancer.The underlying molecular mechanisms of CS-induced malignant transformation of bronchial epithelial cells remain unclear.In this study,we describe a lung-on-a-chip to explore the possible mechanistic link between cigarette smoke extract(CSE)-associated COPD and lung cancer.Methods An in vitro lung-on-a-chip model was used to simulate pulmonary epithelial cells and vascular endothelial cells with CSE.The levels of IL-6 and TNF-αwere tested as indicators of inflammation using an enzyme-linked immune sorbent assay.Apical junction complex mRNA expression was detected with qRT-PCR as the index of epithelial-to-mesenchymal transition(EMT).The effects of CSE on the phosphorylation of signal transduction and transcriptional activator 3(STAT3)were detected by Western blotting.Flow cytometry was performed to investigate the effects of this proto-oncogene on cell cycle distribution.Results Inflammation caused by CSE was achieved in a lung-on-a-chip model with a mimetic movement.CSE exposure induced the degradation of intercellular connections and triggered the EMT process.CSE exposure also activated the phosphorylation of proto-oncogene STAT3,while these effects were inhibited with HJC0152.Conclusions CSE exposure in the lung-on-a-chip model caused activation of STAT3 in epithelial cells and endothelial cells.HJC0152,an inhibitor of activated STAT3,could be a potential treatment for CS-associated COPD and lung cancer.展开更多
Light has been sought and explored by human since ancient times.As the most important form of light,fluorescence is significant to applications in bioimaging and optoelectronic devices.However,fluorescence quenching p...Light has been sought and explored by human since ancient times.As the most important form of light,fluorescence is significant to applications in bioimaging and optoelectronic devices.However,fluorescence quenching problem constitutes a serious bottleneck in materials creation.Inspired from the core–shell structure in nature,we report an effective strategy to overcome this long-standing problem by utilizing a molecular core–shell structure.With an emissive core and multifunctional shell fragments,these compounds show aggregation-induced delayed fluorescence(AIDF)properties by restricting singlet oxygen(^(1)O_(2))generation and suppressing the triplet–triplet annihilation(TTA).Protected by the functional shell,the aggregation-induced emission luminogens(AIEgens)exhibit strong emission with high photoluminescent quantum yield and exciton utilization.Furthermore,because the shell materials can form exciplex with electron-transport materials,the fully solution-processed organic light-emitting diodes(OLEDs)based on these core–shell materials show low turnon voltages,excellent device performance with current efficiency of 61.4 cd A–1 and power efficiency of 42.8 lm W–1,which is a record-breaking efficiency based on all-solution processed organic multilayer systems among the AIE-OLEDs so far.This simple visualization strategy based on molecular core–shell structure provides a promising platform for AIEgens used in the fully wet-processed optoelectronic field.展开更多
基金This work was supported by the National Basic Research Program （973 Program） （Nos. 2013CB531502 and 2014CB542503）, the National Natural Science Foundation of China （Grant Nos. 31390432 and 31500722）, Grand S＆T project of China Health and Family Planning Commission （2013ZX10004608-002 and 2016ZX10004201-009）, the Strategic Priority Research Program of the Chinese Academy of Sciences （CAS XDB08020100）. GFG is supported partly as a leading principal investigator of the NSFC Innovative Research Group （81321063）.
文摘Antibody-based PD-IIPD-L1 blockade therapies have taken center stage in immunotherapies for cancer, with multiple clinical successes. PD-1 signaling plays pivotal roles in tumor-driven T-cell dysfunction. In contrast to prior approaches to generate or boost tumor-specific T-cell responses, antibody-based PD-1/PD-L1 blockade targets tumor-induced T-cell defects and restores pre- existing T-cell function to modulate antitumor immunity. in this review, the fundamental knowledge on the expression regulations and inhibitory functions of PD-1 and the present understanding of antibody-based PD-1/ PD-L1 blockade therapies are briefly summarized. We then focus on the recent breakthrough work concerning the structural basis of the PD-IIPD-Ls interaction and how therapeutic antibodies, pembrolizumab targeting PD-1 and avelumab targeting PD-L1, compete with the binding of PD-1/PD-L1 to interrupt the PD-1/PD-L1 interaction. We believe that this structural informationwill benefit the design and improvement of therapeutic antibodies targeting PD-1 signaling.
基金This work was supported by the National Natural Science Founda-tion of China(Grant Nos.31390432 and 31500722)the National Basic Research Program(973 Program)(NO.2013CB531502)+1 种基金We also thank Yuanyuan Chen and Zhenwel Yang from Institute of Biophysics,Chinese Academy of Sciences for their technical support in the SPR assayG.F.G.is a leading prinoiple Investigator of NSFC Innovative Research Group(Grant No.81621091).
文摘Dear Editor,Blockade of PD-1/PD-L1 signaling pathway by monoclonal antibodies(MAbs)to release the anti-tumor activity of pre-existing tumor specific T cell immunity has initiated a new era for tumor immunotherapy.Administration of anti-PD-1 MAbs(nivolumab and pembrolizumab)in either monotherapy or in combination with anti-CTLA-4 MAbs or traditional chemother-apy has achieved a tumor regression rate of 30%-50%in dealing with melanoma,non-small cell lung cancer,etc.(Larkin et al.,2015).
基金supported by grants from the National Research Foundation of Korea(NRF)funded by the Ministry of Science and ICT(2015R1A3A2032927 and 2021R1A2C1008130).
文摘Transcriptional coactivators regulate the rate of gene expression in the nucleus.Nuclear receptor coactivator 6(NCOA6),a coactivator,has been implicated in embryonic development,metabolism,and cancer pathogenesis,but its role in innate immunity and inflammatory diseases remains unclear.Here,we demonstrated that NCOA6 was expressed in monocytes and macrophages and that its level was increased under proinflammatory conditions.Unexpectedly,nuclear NCOA6 was found to translocate to the cytoplasm in activated monocytes and then become incorporated into the inflammasome with NLRP3 and ASC,forming cytoplasmic specks.Mechanistically,NCOA6 associated with the ATP hydrolysis motifs in the NACHT domain of NLRP3,promoting the oligomerization of NLRP3 and ASC and thereby instigating the production of IL-1βand active caspase-1.Of note,Ncoa6 deficiency markedly inhibited NLRP3 hyperactivation caused by the Nlrp3^(R258W) gain-of-function mutation in macrophages.Genetic ablation of Ncoa6 substantially attenuated the severity of two NLRP3-dependent diseases,folic-induced acute tubular necrosis and crystal-induced arthritis,in mice.Consistent with these findings,NCOA6 was highly expressed in macrophages derived from gout patients,and NCOA6-positive macrophages were significantly enriched in gout macrophages according to the transcriptome profiling results.Conclusively,NCOA6 is a critical regulator of NLRP3 inflammasome activation and is therefore a promising target for NLRP3-dependent diseases,including gout.
基金This work was supported by the Brain Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Science and ICT(NRF-2017M3C7A1028854)Bio&Medical Technology Development Program of the National Research Foundation(NRF)funded by the Ministry of Science&ICT(NRF-2017M3A9B3061319)This work was also supported by the KIST Institutional Program(2E29200).
文摘Neuromodulation by ultrasound has recently received attention due to its noninvasive stimulation capability for treating brain diseases.Although there have been several studies related to ultrasonic neuromodulation,these studies have suffered from poor spatial resolution of the ultrasound and low repeatability with a fixed condition caused by conventional and commercialized ultrasound transducers.In addition,the underlying physics and mechanisms of ultrasonic neuromodulation are still unknown.To determine these mechanisms and accurately modulate neural circuits,researchers must have a precisely controllable ultrasound transducer to conduct experiments at the cellular level.Herein,we introduce a new MEMS ultrasound stimulation system for modulating neurons or brain slices with high spatial resolution.The piezoelectric micromachined ultrasonic transducers(pMUTs)with small membranes(submm membranes)generate enough power to stimulate neurons and enable precise modulation of neural circuits.We designed the ultrasound transducer as an array structure to enable localized modulation in the target region.In addition,we integrated a cell culture chamber with the system to make it compatible with conventional cell-based experiments,such as in vitro cell cultures and brain slices.In this work,we successfully demonstrated the functionality of the system by showing that the number of responding cells is proportional to the acoustic intensity of the applied ultrasound.We also demonstrated localized stimulation capability with high spatial resolution by conducting experiments in which cocultured cells responded only around a working transducer.
基金financially supported by the National Key Research and Development Plan(No.2018AAA0100301)National Science Foundation of China(No.21925802)+1 种基金Research Funds for the Central Universities(No.DUT22LAB601)the Basic Research Project of Free Exploration(No.2021Szvup019)。
文摘Developing fluorescence probes with multiple responses has vital significance but remains challenging.Herein,for the first time,we present a mitochondrial DNA(mtDNA)-triggered pH response signalamplified fluorescent probe(QCY-DBT)for multiple cell detection.The probe exhibited a large stokes shift(229 nm),excellent DNA selectivity over RNA,and ultrasensitivity of detection limit(DL;74.0 ng/mL).Thus,QCY-DBT was successfully applied to analyze multiple human peripheral blood cells and visualize mtDNA in healthy and apoptotic cells.In the tumor acidic environment(pH 6.0–7.0),the absorbance of QCY-DBT at 436 nm increased,and the fluorescence signal(665 nm)was amplified by mtDNA,which enabled the direct observation of tumor cells.Our study provides help in designing smart probes with multiple responses for efficient abnormal cell detection.
基金supported by the Renewable Energy Technology Development (Develop technology to enhance reliability and durability for parts of hydrogen storage tank system) (2022303004020B) grant funded by the Korea Energy Technology Evaluation Planning (KETEP)the Ministry of Science and ICT (Development Project for Emerging Research Instruments Technology),(Project Number: (2022)ERIC)06_1Commercialization Promotion Agency for R&D Outcomes (COMPA)。
文摘Biodegradable metals as electrodes, interconnectors, and device conductors are essential components in the emergence of transient electronics, either for passive implants or active electronic devices, especially in the fields of biomedical electronics. Magnesium and its alloys are strong candidates for biodegradable and implantable conducting materials because of their high conductivity and biocompatibility, in addition to their well-understood dissolution behavior. One critical drawback of Mg and its alloys is their considerably high dissolution rates originating from their low anodic potential, which disturbs the compatibility to biomedical applications. Herein, we introduce a single-phase thin film of a Mg-Zn binary alloy formed by sputtering, which enhances the corrosion resistance of the device electrode, and verify its applicability in biodegradable electronics. The formation of a homogeneous solid solution of single-phase Mg-3Zn was confirmed through X-ray diffraction and transmission electron microscopy. In addition, the dissolution behavior and chemistry was also investigated in various biological fluids by considering the effect of different ion species. Micro-tensile tests showed that the Mg-3Zn alloy electrode exhibited an enhanced yield strain and elongation in relation to a pure Mg electrode. Cell viability test revealed the high biocompatibility rate of the Mg-3Zn binary alloy thin film. Finally, the fabrication of a wireless heater demonstrated the integrability of biodegradable electrodes and highlighted the ability to prolong the lifecycle of thermotherapy-relevant electronics by enhancing the dissolution resistance of the Mg alloy.
基金This work was supported by the National Key R&D Program of China(2021YFB3201202)the National Natural Science Foundation of China(nos.22005331,52275581,and 82372142)+3 种基金the Key Research and Development Program of Jiang su Province(nos.BE2022739,BE2020768,and SBE2022780090)the Youth Innovation Promotion Association of CAS(nos.2019322 and Y2022088)the Instrument Developing Project of the Chinese Academy of Sciences(nos.YJKYYQ20200046 and ZDKYYQ20210004)the Science and Technology Development Program of Suzhou(no.SJC2021019).
文摘Objective and Impact Statement:We describe an electroenzymatic mediator(EM)sensor based on an electroenzymatic assembly peak separation strategy,which can efficiently realize the simultaneous detection of 3 typical cardiovascular disease(CVD)metabolites in 5μl of plasma under one test.This work has substantial implications toward improving the efficiency of chronic CVD assessment.Introduction:Monitoring CVD of metabolites is strongly associated with disease risk.Independent and time-consuming detection in hospitals is unfavorable for chronic CVD management.Methods:The EM was flexibly designed by the cross-linking of electron mediators and enzymes,and 3 EM layers with different characteristics were assembled on one electrode.Electrons were transferred under tunable potential;3 metabolites were quantitatively detected by 3 peak currents that correlated with metabolite concentrations.Results:In this study,the EM sensor showed high sensitivity for the simultaneous detection of 3 metabolites with a lower limit of 0.01 mM.The linear correlation between the sensor and clinical was greater than 0.980 for 242 patients,and the consistency of risk assessment was 94.6%.Conclusion:Metabolites could be expanded by the EM,and the sensor could be a promising candidate as a home healthcare tool for CVD risk assessment.
基金funded by Korea Institute of Science and Technology Intramural Funding (2E26640,2E30952Republic of Korea)+7 种基金National Research Council of Science & Technology (NST) grant by Korean government (MSIP) (CRC-15-04-KISTRepublic of Korea)Center for Women In Science,Engineering,and Technology (WISET) grant by Korean government (WISET2020-525Republic of Korea)National Research Foundation of Korea (2017R1A2B2003993,2020R1A2C2004610Republic of Korea)UST Young Scientist Research Program through Korea University of Science and Technology (UST) (2017YS03Republic of Korea)。
文摘Abstinence from prolonged psychostimulant use prompts stimulant withdrawal syndrome.Molecular adaptations within the dorsal striatum have been considered the main hallmark of stimulant abstinence. Here we explored striatal miRNA-target interaction and its impact on circulating miRNA marker as well as behavioral dysfunctions in methamphetamine(MA) abstinence. We conducted miRNA sequencing and profiling in the nonhuman primate model of MA abstinence, followed by miRNA qPCR,LC-MS/MS proteomics, immunoassays, and behavior tests in mice. In nonhuman primates, MA abstinence triggered a lasting upregulation of miR-137 in the dorsal striatum but a simultaneous downregulation of circulating miR-137. In mice, aberrant increase in striatal miR-137-dependent inhibition of SYNCRIP essentially mediated the MA abstinence-induced reduction of circulating miR-137. Pathway modeling through experimental deduction illustrated that the MA abstinence-mediated downregulation of circulating miR-137 was caused by reduction of SYNCRIP-dependent miRNA sorting into the exosomes in the dorsal striatum. Furthermore, diminished SYNCRIP in the dorsal striatum was necessary for MA abstinence-induced behavioral bias towards egocentric spatial learning. Taken together, our data revealed circulating miR-137 as a potential blood-based marker that could reflect MA abstinence-dependent changes in striatal miR-137/SYNCRIP axis, and striatal SYNCRIP as a potential therapeutic target for striatum-associated cognitive dysfunction by MA withdrawal syndrome.
基金supported by the National Natural Science Foundation of China (81773353)Jilin Scientific and Technological Development Program (20200404148YY, 20200601005JC, 20210101317JC)+2 种基金Jilin Province Special Projec t of Medical and Health Talents (JLSCZD2019-032)the Research Funding Program of Norman Bethune Biomedical Engineering Center (BQEGCZX2019025)National College Students Innovation and Entrepreneurship Training Program (CN)(202010183691)。
文摘Novel advances in the field of brain imaging have enabled the unprecedented clinical application of various imaging modalities to facilitate disease diagnosis and treatment. Electrical impedance tomography(EIT) is a functional imaging technique that measures the transfer impedances between electrodes on the body surface to estimate the spatial distribution of electrical properties of tissues. EIT offers many advantages over other neuroimaging technologies,which has led to its potential clinical use. This qualitative review provides an overview of the basic principles,algorithms, and system composition of EIT. Recent advances in the field of EIT are discussed in the context of epilepsy,stroke, brain injuries and edema, and other brain diseases. Further, we summarize factors limiting the development of brain EIT and highlight prospects for the field. In epilepsy imaging, there have been advances in EIT imaging depth,from cortical to subcortical regions. In stroke research, a bedside EIT stroke monitoring system has been developed for clinical practice, and data support the role of EIT in multi-modal imaging for diagnosing stroke. Additionally, EIT has been applied to monitor the changes in brain water content associated with cerebral edema, enabling the early identification of brain edema and the evaluation of mannitol dehydration. However, anatomically realistic geometry,inhomogeneity, cranium completeness, anisotropy and skull type, etc., must be considered to improve the accuracy of EIT modeling. Thus, the further establishment of EIT as a mature and routine diagnostic technique will necessitate the accumulation of more supporting evidence.
基金This work was supported by the National Key R&D Program of China(No.2021YFC2500401)the National Natural Science Foundation of China(No.61874133,No.61901469,No.22005331)+4 种基金the Key Research and Development Program of Jiangsu Province(No.BE2018080,No.BE2019684,No.BE2020768)the Jihua Laboratory Foundation(No.X190181TD190)the Youth Innovation Promotion Association of CAS(No.2019322,No.2018360,No.Y201856)the Instrument Developing Project of the Chinese Academy of Sciences(No.YJKYYQ20190057,No.YJKYYQ20200046,No.ZDKYYQ20210004)the Science and Technology Development Program of Suzhou(No.SYG201907).
文摘Circulating tumor cells(CTCs)have tremendous potential to indicate disease progression and monitor therapeutic response using minimally invasive approaches.Considering the limitations of affinity strategies based on their cost,effectiveness,and simplicity,size-based enrichment methods that involve low-cost,label-free,and relatively simple protocols have been further promoted.Nevertheless,the key challenges of these methods are clogging issues and cell aggregation,which reduce the recovery rates and purity.Inspired by the natural phenomenon that the airflow around a windmill is disturbed,in this study,a windmill-like hole array on the SU-8 membrane was designed to perturb the fluid such that cells in a fluid would be able to self-mix and that the pressure acting on cells or the membrane would be dispersed to allow a greater velocity.In addition,based on the advantages of fluid coatings,a lipid coating was used to modify the membrane surface to prevent cell aggregation and clogging of the holes.Under the optimal conditions,recovery rates of 93%and 90%were found for A549 and HeLa cells in a clinical simulation test of our platform with a CTC concentration of 20-100 cells per milliliter of blood.The white blood cell(WBC)depletion rate was 98.7%(n=15),and the CTC detection limit was less than 10 cells per milliliter of blood(n=6).Moreover,compared with conventional membrane filtration,the advantages of the proposed device for the rapid(2 mL/min)and efficient enrichment of CTCs without clogging were shown both experimentally and theoretically.Due to its advantages in the efficient,rapid,uniform,and clog-free enrichment of CTCs,our platform offers great potential for metastatic detection and therapy analyses.
基金supported by the KIST Institutional Program and by the KUKIST Graduate School of Converging Science and Technology Program.Project supported by the National Science Foundation for Young Scientists of China(Grant No.81701839)The Youth Foundation of Tianjin Medical University(Grant No.2015KYZQ14).
文摘Cardiovascular diseases cause huge socio-economic burden worldwide.Although a mammalian myocardium has its own limited healing capability,scaffold materials capable of releasing stem cell recruiting/engrafting factors may facilitate the regeneration of the infarcted myocardium.The aim of this research was to develop cardiac patches capable of simultaneously eluting substance P(SP)and insulin-like growth factor-1C(IGF-1C)peptide.Polycaprolactone/collagen type 1-based patches with or without SP and IGF-1C peptide were fabricated by co-electrospinning,which exhibited nanofibrous morphology.SP and IGF-1C/SP patches recruited significantly higher numbers of bone marrow-mesenchymal stem cells than that of the negative control and patch-only groups in vitro.The developed patches were transplanted in an infarcted myocardium for up to 14 days.Mice underwent left anterior descending artery ligation and received one of the following treatments:(i)sham,(ii)saline,(iii)patch-only,(iv)IGF-1C patch,(v)SP patch and(vi)IGF-1C/SP patch.SP and IGF-1C/SP patch-treated groups exhibited better heart function and attenuated adverse cardiac remodeling than that of the saline,patch-only and individual peptide containing cardiac patches.SP patch and IGF-1C/SP patch-treated groups also showed higher numbers of CD31-positive vessels and isolectin B4-positive capillaries than that of other groups.IGF-1C/SP-treated group also showed thicker left ventricular wall in comparison to the saline and patch-only groups.Moreover,IGF-1C/SP patches recruited significantly higher numbers of CD29-positive cells and showed less numbers of Tunel-positive cells compared with the other groups.These data suggest that SP and IGF-1C peptides may act synergistically for in situ tissue repair.
文摘Dear Editor,The Ras superfamily of GTPases are conserved in eukary?otes from yeast to humans,and play essential roles in the regulation of a variety of key cellular processes,including cell differentiation and proliferation,membrane trafficking,nuclear import and export,cytoskeletal remodeling and mitogenic signaling(Karnoub and Weinberg,2008).Notably,numerous studies have shown that many members of the Ras-related small GTPases are involved in diverse aspects of tumorigenesis and tumor progress!on(Chen et al.,2014;Liu et al.,2017).
基金the support of the National Natural Science Foundation of China(NSFC Nos.61722508 and 11305020)Nanophotonics and Biophotonics Key Laboratory of Jilin Province,P.R.China(20140622009JC)and(14GH005).
文摘In this paper,we prepared the nanoparticle drug carrier system between nanoparticles chitosan and Epigallocatechin-3 O-gallate(EGCG)for breast cancer cell inhibiting application.For this drug carrier system,chitosan acts as a carrier and EGOG as a drug.Which were systematically characterized and thoroughly evaluated in terms of their inhibition rate and biocompatibility.We also did a cell scratch test and the result indicated that the chitosan EGCG nanoparticles have inhibitory effect on the growth of breast cancer cells.The inhibition rate could reach up to 21.91%.This work revealed that the modification of nanopartidles paved a way for specific biomedical applications.
基金Project supported by the National Natural Science Foundation of China （No. 21307154）
文摘This paper aims to evaluate the individual and joint toxicities of cadmium sulfate （CdSO4） and α-naphthoflavone （ANF） in zebrafish embryos. As a result, CdSO4 caused both lethal and sub-lethal effects, such as 24 h post-fertilization （hpf） death and 72 hpf delayed hatching. However, ANF only caused sub-lethal effects, including 48 hpf cardiac edema and 72 hpf delayed hatching. Taking 24 hpf death and 48 hpf cardiac edema as endpoints, the toxicities of CdSO4 and ANF were significantly enhanced by each other. Consistently, both CdSO4 and ANF caused significant oxidative stress, including decreases in the reduced glutathione （GSH） level, inhibition of superoxide dis- mutase （SOD） activity, as well as increases in malondialdehyde （MDA） content in zebrafish embryos, but these mixtures produced much more significant alterations on the biomarkers. Co-treatment of CdSO4 and ANF significantly down-regulated the mRNA level of multidrug resistance-associated protein （mrp） 1 and cytochrome P450 （cyp） la, which constituted the protective mechanisms for zebraflsh embryos to chemical toxins. In conclusion, co-treatment of CdSO4 and ANF exhibited a much more severe damage in zebraflsh embryos than individual treatment. Meanwhile, production of oxidative stress and altered expression of mrpl and cypla could be important components of such joint toxicity.
基金financially supported by the National Key Research and Development Program(No.2016YFC1100703)。
文摘In this work,novel antibacterial cellulose diacetate/poly(ethylenimine)/hyaluronic acid(CDA/PEI/HA)composite three-dimension(3D)scaffolds were prepared through electrospinning and post-processing.Firstly,CDA/PEI 2D composite nanofiber membranes were prepared by electrospinning,and then the CDA/PEI/HA 3D composite scaffolds were fabricated by post-processing and freeze-drying of CDA/PEI membranes.In particular,HA was added to improve the biocompatibility of composite scaffolds.Compared with CDA/PEI scaffolds,CDA/PEI/HA composite scaffolds showed higher water absorbing rate,higher water retention rate and higher mechanical strength.Moreover,CDA/PEI/HA composite scaffolds with abundant positive charge were benefit for improving antibacterial activity.CDA/PEI/HA scaffolds with biology function of HA were benefit for improving hemocompatibility and cell proliferation of CDA/PEI scaffolds.In summary,antibacterial CDA/PEI/HA scaffolds could protect wound from bacterial infection,improve cellular behavior and accelerate wound healing.Thus,CDA/PEI/HA scaffolds could be potential application for wound dressing.
基金Supported by the National Key R&D Program of China(No.2017YFC0108505)the Youth Innovation Promotion Association of China(No.2015261)+2 种基金the National Natural Science Foundation of China(No.31500805)the“333 High-level Talents Training Project of Jiangsu Province”,Chinathe Science and Technology Program of Suzhou,China(No.SYG201508).
文摘Infectious of hepatitis C viruses(HCVs)lead to hepatic fibrosis,cirrhosis even hepatoma.Developing rapid and sensitive diagnostic method for HCV is of great importance.Based on the host-and-guest interaction between cucurbit[7]uril(CB[7])and methylene blue(MB),a CB[7]-graphene nano-composite(CB[7]-N3-GO)is raised for the electrochemical detection of HCV DNA.The method is able to linearly detect the HCV nucleic acid in the range of 0.2—10 nmol/L with detection limit as low as 160.4 pmol/L.The proposed detection strategy is able to discriminate the lb and 6k subtypes of HCV and has a prospective potential in the blood screen for HCV in clinical diagnosis.
基金supported by the National Key Instrument Developing Project of China(ZDYZ2013-1)the National Natural Science Foundation of China(31400847)the Natural Science Foundation of Jiangsu Province of China(BK20141204)
文摘Tumor necrosis factor-alpha(TNF-α) is a type of critical pro-inflammatory cytokines,which participates in numerous cellular signal pathways and is regarded as a critical protein biomarker for inflammatory based diseases.In this contribution,we have developed a strategy to fabricate multiple DNA star trigon structures with fluorescence signals from four hairpin probes which are detonated by a single molecule of TNF-α.This process causes significant enhancement of fluorescence and a sensitive and selective biosensor for TNF-α assay is constructed.This method is able to achieve the limit of detection(LOD) at 5 pg/mL(0.285 pM).Moreover,some other advantages such as fast response,high selectivity and convenient operation promise the potential use of this method for TNF-α measurement in point of care testing application.Upon further development,this strategy can also be converted to detect other analytes such as small molecules,nucleic acids and other proteins.
基金supported by the National Natural Science Foundation of China(81771929)China Postdoctoral Science Foundation(2017M611911)
文摘An ultrasensitive electrochemical aptasensor is presented for prostate specific antigen(PSA) detection. DNA tetrahedronaptamer is designed, which not only facilitates the molecular self-assembly events,but also improves the recognition efficiency between PSA and aptamer sequence on the electrode interface. The DNA conformation on top of DNA tetrahedron changes accordingly, which can be further digested by Exonuclease T(Exo T), a type of single-strand specific nuclease. Electrochemical species are removed synchronously and the initial PSA level can thus be determined. A linear range from 0.5 pg mL^(-1) to50 ng mL^(-1) is achieved with the limit of detection(LOD) as low as 0.15 pg mL^(-1). Moreover, this proposed method is highly selective and is successfully applied to determine PSA in human serum samples.
基金This work was supported by National Natural Science Foundation of China(Grant Nos.81672297,Grant Nos.61701493)Policy Guidance project(International Science and Technology Cooperation)of Jiangsu Province of China(BZ2018040)+3 种基金the Natural Science Foundation of Tianjin,P.R.China(18JCYBJC42100)Hundred Talents Program of the Chinese Academy of SciencesProject Funded by China Postdoctoral Science Foundation(2019M651959)Postdoctoral Research Funding Program of Jiangsu Province(2018K004B).
文摘Background Chronic obstructive pulmonary disease(COPD)is a severe public health problem.Cigarette smoke(CS)is a risk factor for COPD and lung cancer.The underlying molecular mechanisms of CS-induced malignant transformation of bronchial epithelial cells remain unclear.In this study,we describe a lung-on-a-chip to explore the possible mechanistic link between cigarette smoke extract(CSE)-associated COPD and lung cancer.Methods An in vitro lung-on-a-chip model was used to simulate pulmonary epithelial cells and vascular endothelial cells with CSE.The levels of IL-6 and TNF-αwere tested as indicators of inflammation using an enzyme-linked immune sorbent assay.Apical junction complex mRNA expression was detected with qRT-PCR as the index of epithelial-to-mesenchymal transition(EMT).The effects of CSE on the phosphorylation of signal transduction and transcriptional activator 3(STAT3)were detected by Western blotting.Flow cytometry was performed to investigate the effects of this proto-oncogene on cell cycle distribution.Results Inflammation caused by CSE was achieved in a lung-on-a-chip model with a mimetic movement.CSE exposure induced the degradation of intercellular connections and triggered the EMT process.CSE exposure also activated the phosphorylation of proto-oncogene STAT3,while these effects were inhibited with HJC0152.Conclusions CSE exposure in the lung-on-a-chip model caused activation of STAT3 in epithelial cells and endothelial cells.HJC0152,an inhibitor of activated STAT3,could be a potential treatment for CS-associated COPD and lung cancer.
基金National Natural Science Foundation of China,Grant/Award Numbers:21875036,22135004Open Fund of theKeyLab of Organic Optoelec-tronics&Molecular EngineeringInnovation and Technology Commission,Grant/Award Number:ITC-CNERC14SC01。
文摘Light has been sought and explored by human since ancient times.As the most important form of light,fluorescence is significant to applications in bioimaging and optoelectronic devices.However,fluorescence quenching problem constitutes a serious bottleneck in materials creation.Inspired from the core–shell structure in nature,we report an effective strategy to overcome this long-standing problem by utilizing a molecular core–shell structure.With an emissive core and multifunctional shell fragments,these compounds show aggregation-induced delayed fluorescence(AIDF)properties by restricting singlet oxygen(^(1)O_(2))generation and suppressing the triplet–triplet annihilation(TTA).Protected by the functional shell,the aggregation-induced emission luminogens(AIEgens)exhibit strong emission with high photoluminescent quantum yield and exciton utilization.Furthermore,because the shell materials can form exciplex with electron-transport materials,the fully solution-processed organic light-emitting diodes(OLEDs)based on these core–shell materials show low turnon voltages,excellent device performance with current efficiency of 61.4 cd A–1 and power efficiency of 42.8 lm W–1,which is a record-breaking efficiency based on all-solution processed organic multilayer systems among the AIE-OLEDs so far.This simple visualization strategy based on molecular core–shell structure provides a promising platform for AIEgens used in the fully wet-processed optoelectronic field.
