Because most studies have focused on the intrinsic carcinogenic pathways of tumors, the underlying role of N6-methyladenosine (m6A) methylation in tumor immune microenvironment (TIME) remains ...elusive. Herein, we systematically explored the correlations of prominent m6A regulators with PD-L1 and immune infiltrates in 769 head and neck squamous cell carcinomas (HNSCCs; The Cancer Genome Atlas TCGA cohort, n = 499; GSE65858 cohort, n = 270). The PD-L1 expression evidently associated with m6A regulators. Two molecular subtypes (cluster1/2) were identified by consensus clustering for 15 m6A regulators. The cluster2 preferentially associated with favorable prognosis, upregulated PD-L1 expression, higher immunoscore, and distinct immune cell infiltration. The hallmarks of G2M checkpoint, mTORC1 signaling, and PI3K/AKT/mTOR signaling were remarkably enriched in the cluster1. A prognostic risk score was constructed using seven m6A regulator-associated signatures that represented an independent prognosis factor for HNSCC. Patients with low-risk score exhibited higher immunoscore and upregulated PD-L1 expression than patients with high-risk score. Consistently, m6A regulators showed the same influence on immune modulation and survival in external GSE65858 cohort. Further analysis revealed that m6A regulator-based signatures were implicated in TIME and their copy-number alterations dynamically affected the abundance of tumor-infiltrating immune cells. Collectively, our study elucidated the important role of m6A methylation in TIME of HNSCC. The proposed m6A regulator-based signatures might serve as crucial mediators of TIME in HNSCC, representing promising therapeutic targets in improving immunotherapeutic efficacy.
Display omitted
Because most studies focus on tumor-intrinsic oncogenic pathways, potential roles of the m6A methylation in tumor immune microenvironment remain unclear. This study highlights the important role of m6A methylation in immune microenvironment of HNSCC. The proposed m6A regulator-based signatures might serve as promising therapeutic targets for improving immunotherapeutic efficacy.
The efficient extraction of targets from complex surfaces is vital for technological applications ranging from environmental pollutant monitoring to analysis of explosive traces and pesticide ...residues. In our present study, we proposed a proof-of-concept surface enhance Raman scattering (SERS) active substrate serving directly to the rapid extraction and detection of target molecules. The novel substrate was constructed by decorating the commercial tape with colloidal gold nanoparticles (Au NPs), which simultaneously provides SERS activity and “sticky” of adhesive. The utility of SERS tape was demonstrated by directly extracting pesticide residues in fruits and vegetables via a simple and viable “paste and peel off” approach. The obtained strong and easily distinguishable SERS signals allow us to detect various pesticide residues such as parathion-methyl, thiram, and chlorpyrifos in the real samples with complex surfaces including green vegetable, cucumber, orange, and apple.
The metal-organic framework (MOF) was first utilized as the sensing platform for assaying biomolecules. It has also been demonstrated that this novel strategy is effective and reliable for detection ...of HIV DNA and thrombin with high sensitivity and selectivity.
Gold nanoparticles (AuNPs) have been frequently utilized for the construction of diverse colorimetric biosensors. Normally, AuNPs with sharp edges could have better sensitivity. However, the poor ...monodipersity of AuNPs with sharp edges seriously confines their utility for colorimetric biosensing. Herein, we demonstrate the utility of highly uniform gold nanobipyramids (Au NBPs) for ultrasensitive colorimetric detection of H5N1 virus. The proposed method is based on the fact that alkaline phosphatase (ALP) could catalyze the decomposition of 4-aminophenyl phosphate (4-APP) to generate 4-aminophenol (4-AP), which would then reduce silver nitrate to metal silver and then deposited on Au NBPs. The metal silver shell coated on the Au NBPs changed the refractive index of gold and thus resulted in a blue shift of longitudinal localized surface plasmon resonance (LSPR) and accompanied a vivid color change. This method exhibited a higher sensitivity than that of other Au NPs such as gold nanorods due to the high-index-faceted on the tips of the Au NBPs. This method was used to detect the activity of ALP. It exhibited a linear range of 0.1–5 mU/mL with a limit of detection (LOD) of 0.086 mU/mL. Finally, the proposed method was used in immunoassay to detect H5N1 virus. The results showed that the corresponding linear range for the detection of H5N1 virus antigen was 0.001–2.5 ng/mL, and the LOD was determined to be 1 pg/mL, which is more sensitive than those in most of the colorimetric biosensors reported previously.
► The sandwich complex enhanced the LSPR peak shift more than 150%. ► The use of DNA aptamers as thrombin capture units makes the sensor reusable. ► Calibration curve and sample detection were ...achieved by a single nanoparticle. ► An averaged LOD of 1.6 pM was achieved for thrombin detection.
Herein we demonstrate a sensitive approach for protein detection based on peak shifts of localized surface plasmon resonance (LSPR) induced by aptamer–antigen–antibody sandwich structures. The applicability of the proposed method is demonstrated using human α-thrombin as a model analyte. While the binding of thrombin to its specific receptor, thrombin binding aptamer (TBA) modified on Au nanorods (AuNRs), causes a measurable LSPR shift, a subsequent binding of an anti-thrombin antibody to the captured thrombin can exhibit a nearly 150% amplification in the LSPR response. This enhanced signal essentially leads to an improvement of limit of detection (LOD) by more than one order of magnitude. In addition, the use of TBA as thrombin recognition units makes the biosensor reusable. The feasibility of the proposed method was further exploited by the detection of thrombin in human serum, opening the possibility of a real application for diagnostics and medical investigations.
Display omitted
•For the first time, the combination of BNQDs with in situ grown AuNPs is used for fluorescence biosensing.•The sensing mechanism is based on FRET principle, showing a high ...specificity and good selectivity toward target, and effective anti-interference ability.•This strategy offers a convenient “mix and detect” approach for the simultaneous detection of AChE activity and paraoxon, which is easy-operation, fast and efficient.•The sensing platform is successfully applied for the detection of serum samples.
A rapid, label-free, and highly sensitive fluorescence biosensing platform has been fabricated for effectively detecting acetylcholinesterase (AChE) activity via fluorescence resonance energy transfer (FRET) between boron nitride quantum dots (BNQDs) and gold nanoparticles (AuNPs). In this work, AChE hydrolyzed acetylthiocholine (ATCh) to generate thiocholine (TCh), which can reduce chloroauric acid (HAuCl4) into AuNPs and in situ formation of TCh-BNQDs/AuNPs aggregates, resulting in fluorescence quenching of BNQDs. Moreover, paraoxon, a organophosphorus pesticide, was used to lower the activity of AChE and hinder the enzymatic hydrolysis reaction, hence weakened the fluorescence quenching of BNQDs. Based on these findings, a simple ‘one-pot’ FRET-based biosensor has been constructed to assess AChE activity and its inhibitor by measuring the fluorescence intensity of BNQDs. The linear range toward AChE was from 0.05 to 6.0 mU/mL with the lower detection limit of 0.0212 mU/mL, indicating the biosensor out-performs most of the reported sensors. Since the activity of AChE has been connected to a number of diseases, this convenient ‘mix and detect’ approach has potentially extensive application in clinic diagnosis. On the other hand, the inhibition effect by paraoxon was evaluated, and the corresponding half maximal inhibitory concentration (IC50) toward AChE was estimated to be 2.987 μg/L.As far as we known, the proposed biosensing platform based on TCh-BNQDs/AuNPs nanocomposites is the first time to demonstrate the application of BNQDs for fluormetric assays of enzyme activity and inhibiting effect. It also opens up a novel pathway of using BNQDs to develop optical biosensors for analyzing many other analytes.
Proliferating cells known as neoblasts include pluripotent stem cells (PSCs) that sustain tissue homeostasis and regeneration of lost body parts in planarians. However, the lack of markers to ...prospectively identify and isolate these adult PSCs has significantly hampered their characterization. We used single-cell RNA sequencing (scRNA-seq) and single-cell transplantation to address this long-standing issue. Large-scale scRNA-seq of sorted neoblasts unveiled a novel subtype of neoblast (Nb2) characterized by high levels of PIWI-1 mRNA and protein and marked by a conserved cell-surface protein-coding gene, tetraspanin 1 (tspan-1). tspan-1-positive cells survived sub-lethal irradiation, underwent clonal expansion to repopulate whole animals, and when purified with an anti-TSPAN-1 antibody, rescued the viability of lethally irradiated animals after single-cell transplantation. The first prospective isolation of an adult PSC bridges a conceptual dichotomy between functionally and molecularly defined neoblasts, shedding light on mechanisms governing in vivo pluripotency and a source of regeneration in animals.
Display omitted
Display omitted
•piwi-1 RNA and protein expression defined spectrum of functional neoblast states•scRNA-seq defined 12 neoblast sub-types; sub-type Nb2 contains pluripotent stem cells•Transplantation of single TSPAN-1+ Nb2 cells rescued lethally irradiated animals•Nb2 transcriptome differs during homeostasis, sublethal irradiation, and regeneration
Transplantation of a single pluripotent neoblast can restore regenerative ability and viability to lethally irradiated Planaria.
Genetic regulation of gene expression underlies variation in disease risk and other complex traits. The effect of expression quantitative trait loci (eQTLs) varies across cell types; however, the ...complexity of mammalian tissues makes studying cell-type eQTLs highly challenging. We developed a novel approach in the model nematode
that uses single-cell RNA sequencing to map eQTLs at cellular resolution in a single one-pot experiment. We mapped eQTLs across cell types in an extremely large population of genetically distinct
individuals. We found cell-type-specific
eQTL hotspots that affect the expression of core pathways in the relevant cell types. Finally, we found single-cell-specific eQTL effects in the nervous system, including an eQTL with opposite effects in two individual neurons. Our results show that eQTL effects can be specific down to the level of single cells.
Display omitted
•Ni3(HITP)2 sensor had high conductivity and large effective surface area.•A novel composite of CMOF-MIPIL was prepared with Ni3(HITP)2 as supporter.•Compared with Ni3(HITP)2, ...MIPIL-based sensors, CMOF-MIPIL sensor exhibited the highest peak current response.•Low detection limit and high selectivity of CMOF-MIPIL sensor for bisphenol A were achieved.
A novel composite of conductive metal organic framework and molecularly imprinted poly (ionic liquid) (CMOF-MIPIL) was prepared for highly sensitive detection of bisphenol A (BPA). Ni-based CMOFs with various organic ligands, i.e., 2,3,6,7,10,11-hexaiminotriphenylene, hexa-aminobenzene, and 2,3,6,7,10,11-hexahydroxytriphenylene were synthesized. The electrochemical properties of the obtained Ni-based CMOFs were investigated. The results demonstrated that Ni3(HITP)2 had the highest conductivity and largest effective surface area. CMOF-MIPIL was then prepared with Ni3(HITP)2 as supporter, BPA as template, and ILs as monomer and cross-linker. Under optimal conditions, CMOF-MIPIL sensor exhibited a linear range of BPA detection from 0.005 to 5.0 μM. The detection limit was 4.0 nM. Compared with MIPIL, Ni3(HITP)2, and CMOF-NIPIL-based sensors, the performance of this sensor for BPA detection was superior due to the excellent conductivity and the presence of specific recognition sites. In addition, CMOF-MIPIL sensor had excellent selectivity for BPA. The proposed assay was used for detection of BPA in environmental water samples, plastic bottle and fresh liquid milk samples with success.
Herein, an electrochemiluminescence (ECL) biosensor for ultrasensitive and specific detection of Kras mutant genes has been developed on the basis of the high discrimination capability of locked ...nucleic acid (LNA) and dual signal amplification techniques including DNA walkers and hyperbranched rolling circle amplification (HRCA).
PDF
