Immune-checkpoint therapy (ICB) has conferred significant and durable clinical benefit to some cancer patients. However, most patients do not respond to ICB, and reliable biomarkers of ICB response are needed to improve patient stratification. Here, we performed a transcriptome-wide meta-analysis across 1,486 tumors from ICB-treated patients and tumors with expected ICB outcomes based on microsatellite status. Using a robust transcriptome deconvolution approach, we inferred cancer and stroma-specific gene expression differences and identified cell-type specific features of ICB response across cancer types. Consistent with current knowledge, stromal expression of CXCL9, CXCL13, and IFNG were the top determinants of favorable ICB response. In addition, we identified a group of potential immune-suppressive genes, including FCER1A, associated with poor response to ICB. Strikingly, PD-L1 expression in stromal cells, but not cancer cells, is correlated with ICB response across cancer types. Furthermore, the unbiased transcriptome-wide analysis failed to identify cancer-cell intrinsic expression signatures of ICB response conserved across tumor types, suggesting that cancer cells lack tissue-agnostic transcriptomic features of ICB response.
In response to the challenges of supporting fractured and weak surrounding rock in deep coal mines in the Huainan region of China, a self-moving hydraulic support system for roof support was designed and developed. This innovative solution addresses the difficulties encountered in providing continuous support to roof structures. Based on the theory of elastoplastic mechanics, a numerical analysis model was established to calculate the mechanical parameters such as the displacement, stress, and strain of hydraulic supports during the stepping process under multiple operating conditions. The results of the numerical simulation were compared and verified with those from an actual working site. The results show that the maximum equivalent stress is 245.33 MPa for operating condition 1, 246.82 MPa for operating condition 2, and 245.27 MPa for operating condition 3. The maximum stress values under the three working conditions do not exceed the yield strength of the material, satisfying the requirements for normal bracket support operations. These research findings can establish a theoretical framework for the comprehensive assessment of the reliability and stability of hydraulic supports and the optimization of construction processes.
Valid reference data are essential for reliable forensic age assessment procedures in the living, a fact that extends to the trait of mandibular third molar eruption in dental panoramic radiographs (PAN). The objective of this study was to acquire valid reference data for a northern Chinese population. The study was guided by the criteria for reference studies in age assessment.To this end, a study population from China comprising 917 panoramic radiographs obtained from 430 females and 487 males aged between 15.00 and 25.99 years was analysed. Of the 917 PANs, a total of 1230 mandibular third molars were evaluated.The PANs, retrospectively evaluated, were performed for medical indication during the period from 2016 to 2021. The assessment of mandibular third molars was conducted using the staging scale presented by Olze et al. in 2012. Two independent examiners, trained in assessing PANs for forensic age estimation, evaluated the images. In instances where the two examiners diverged in their assessments these were subsequently deliberated, and a consensus stage was assigned.The mean age increased with higher stages for both teeth and both sexes. The minimum age recorded for stage D, indicating complete tooth eruption, was 15.6 years in females and 16.1 years in males. Consequently, the completion of mandibular third molar eruption was observed in both sexes well before reaching the age of 18. In light of our results, it is evident that relying solely on the assessment of mandibular third molar eruption may not be sufficient for accurately determining the age of majority. Contrary to previous literature, this finding of a completed eruption of the mandibular third molars in northern Chinese individuals is only suitable for detecting the completion of the 16th year of life in males according to our results. However, as the results are inconsistent compared to other studies in the literature, the trait should not be used as the only decisive marker to prove this age threshold in males from northern China.
The surge in lithium-ion batteries has heightened concerns regarding metal resource depletion and the environmental impact of spent batteries. Battery recycling has become paramount globally, but conventional techniques, while effective at extracting transition metals like cobalt and nickel from cathodes, often overlook widely used spent LiFePO4 due to its abundant and low-cost iron content. Direct regeneration, a promising approach for restoring deteriorated cathodes, is hindered by practicality and cost issues despite successful methods like solid-state sintering. Hence, a smart prelithiation separator based on surface-engineered sacrificial lithium agents is proposed. Benefiting from the synergistic anionic and cationic redox, the prelithiation separator can intelligently release or intake active lithium via voltage regulation. The staged lithium replenishment strategy was implemented, successfully restoring spent LiFePO4's capacity to 177 mAh g-1 and a doubled life. Simultaneously, the separator can absorb excess active lithium up to approximately 600mAh g-1 below 2.5 V to prevent over-lithiation of the cathode This innovative, straightforward, and cost-effective strategy paves the way for the direct regeneration of spent batteries, expanding the possibilities in the realm of lithium-ion battery recycling.
Oncogenic overexpression or activation of C-terminal Src kinase (CSK) has been shown to play an important role in triple-negative breast cancer (TNBC) progression, including tumor initiation, growth, metastasis, drug resistance. This revelation has pivoted the focus toward CSK as a potential target for novel treatments. However, until now, there are few inhibitors designed to target the CSK protein. Responding to this, our research has implemented a comprehensive virtual screening protocol. By integrating energy-based screening methods with AI-driven scoring functions, such as Attentive FP, and employing rigorous rescoring methods like Glide docking and molecular mechanics generalized Born surface area (MM/GBSA), we have systematically sought out inhibitors of CSK. This approach led to the discovery of a compound with a potent CSK inhibitory activity, reflected by an IC50 value of 1.6 nM under a homogeneous time-resolved fluorescence (HTRF) bioassay. Subsequently, molecule 2 exhibits strong growth inhibition of MD anderson - metastatic breast (MDA-MB) -231, Hs578T, and SUM159 cells, showing a level of growth inhibition comparable to that observed with dasatinib. Treatment with molecule 2 also induced significant G1 phase accumulation and cell apoptosis. Furthermore, we have explored the explicit binding interactions of the compound with CSK using molecular dynamics simulations, providing valuable insights into its mechanism of action.
Pseudorabies virus (PRV) is recognized as the aetiological agent responsible for Aujeszky's disease, or pseudorabies, in swine populations. Rab6, a member of the small GTPase family, is implicated in various membrane trafficking processes, particularly exocytosis regulation. Its involvement in PRV infection, however, has not been documented previously. In our study, we observed a significant increase in the Rab6 mRNA and protein levels in both PK-15 porcine kidney epithelial cells and porcine alveolar macrophages, as well as in the lungs and spleens of mice infected with PRV. The overexpression of wild-type Rab6 and its GTP-bound mutant facilitated PRV proliferation, whereas the GDP-bound mutant form of Rab6 had no effect on viral propagation. These findings indicated that the GTPase activity of Rab6 was crucial for the successful spread of PRV. Further investigations revealed that the reduction in Rab6 levels through knockdown significantly hampered PRV proliferation and disrupted virus assembly and egress. At the molecular level, Rab6 was found to interact with the PRV glycoproteins gB and gE, both of which are essential for viral assembly and egress. Our results collectively suggest that PRV exploits Rab6 to expedite its assembly and egress and identify Rab6 as a promising novel target for therapeutic treatment for PRV infection.
Herpesvirus 1, Suid , Pseudorabies , Virus Release , rab GTP-Binding Proteins , Animals , Herpesvirus 1, Suid/physiology , Herpesvirus 1, Suid/genetics , Swine , rab GTP-Binding Proteins/metabolism , rab GTP-Binding Proteins/genetics , Mice , Pseudorabies/virology , Virus Assembly/physiology , Swine Diseases/virology , Cell Line
Gastric cancer (GC) is the fifth most common cancer worldwide and is a heterogeneous disease. Among GC subtypes, the mesenchymal phenotype (Mes-like) is more invasive than the epithelial phenotype (Epi-like). While gene expression of the epithelial-to-mesenchymal transition (EMT) has been studied, the regulatory landscape shaping this process is not fully understood. Here we use ATAC-seq and RNA-seq from a compendium of gastric cancer cell lines and primary tumors to detect drivers of regulatory state changes and their transcriptional responses. Using the ATAC-seq, we developed a machine learning approach to determine the transcription factors (TFs) regulating the subtypes of GC. We identified TFs driving the mesenchymal (RUNX2, ZEB1, SNAI2, AP-1 dimer) as well as the epithelial states (GATA4, GATA6, KLF5, HNF4A, FOXA2, GRHL2) in gastric cancer. We identified DNA copy number alterations associated with dysregulation of these TFs, specifically deletion of GATA4 and amplification of MAPK9 Comparisons with bulk and single-cell RNA-seq datasets identified activation toward fibroblast-like epigenomic and expression signatures in Mes-like GC. The activation of this mesenchymal fibrotic program is associated with differentially accessible DNA cis-regulatory elements flanking up-regulated mesenchymal genes. These findings establish a map of TF activity in GC and highlight the role of copy number driven alterations in shaping epigenomic regulatory programs as potential drivers of gastric cancer heterogeneity and progression.
To explore altered patterns of static and dynamic functional brain network connectivity (sFNC and dFNC) in Primary angle-closure glaucoma (PACG) patients. Clinically confirmed 34 PACG patients and 33 age- and gender-matched healthy controls (HCs) underwent evaluation using T1 anatomical and functional MRI on a 3 T scanner. Independent component analysis, sliding window, and the K-means clustering method were employed to investigate the functional network connectivity (FNC) and temporal metrics based on eight resting-state networks. Differences in FNC and temporal metrics were identified and subsequently correlated with clinical variables. For sFNC, compared with HCs, PACG patients showed three decreased interactions, including SMN-AN, SMN-VN and VN-AN pairs. For dFNC, we derived four highly structured states of FC that occurred repeatedly between individual scans and subjects, and the results are highly congruent with sFNC. In addition, PACG patients had a decreased fraction of time in state 3 and negatively correlated with IOP (p < 0.05). PACG patients exhibit abnormalities in both sFNC and dFNC. The high degree of overlap between static and dynamic results suggests the stability of functional connectivity networks in PACG patients, which provide a new perspective to understand the neuropathological mechanisms of optic nerve damage in PACG patients.
Glaucoma, Angle-Closure , Magnetic Resonance Imaging , Humans , Glaucoma, Angle-Closure/physiopathology , Glaucoma, Angle-Closure/diagnostic imaging , Female , Male , Middle Aged , Aged , Nerve Net/physiopathology , Nerve Net/diagnostic imaging , Case-Control Studies , Brain/diagnostic imaging , Brain/physiopathology , Brain/pathology
An abdominal aortic aneurysm (AAA) is a life-threatening cardiovascular disease. We identified plasma insulin-like growth factor 1 (IGF1) as an independent risk factor in patients with AAA by correlating plasma IGF1 with risk. Smooth muscle cell- or fibroblast-specific knockout of Igf1r, the gene encoding the IGF1 receptor (IGF1R), attenuated AAA formation in two mouse models of AAA induced by angiotensin II infusion or CaCl2 treatment. IGF1R was activated in aortic aneurysm samples from human patients and mice with AAA. Systemic administration of IGF1C, a peptide fragment of IGF1, 2 weeks after disease development inhibited AAA progression in mice. Decreased AAA formation was linked to competitive inhibition of IGF1 binding to its receptor by IGF1C and modulation of downstream alpha serine/threonine protein kinase (AKT)/mammalian target of rapamycin signaling. Localized application of an IGF1C-loaded hydrogel was developed to reduce the side effects observed after systemic administration of IGF1C or IGF1R antagonists in the CaCl2-induced AAA mouse model. The inhibitory effect of the IGF1C-loaded hydrogel administered at disease onset on AAA formation was further evaluated in a guinea pig-to-rat xenograft model and in a sheep-to-minipig xenograft model of AAA formation. The therapeutic efficacy of IGF1C for treating AAA was tested through extravascular delivery in the sheep-to-minipig model with AAA established for 2 weeks. Percutaneous injection of the IGF1C-loaded hydrogel around the AAA resulted in improved vessel flow dynamics in the minipig aorta. These findings suggest that extravascular administration of IGF1R antagonists may have translational potential for treating AAA.
Aortic Aneurysm, Abdominal , Disease Models, Animal , Insulin-Like Growth Factor I , Receptor, IGF Type 1 , Animals , Receptor, IGF Type 1/metabolism , Receptor, IGF Type 1/antagonists & inhibitors , Humans , Aortic Aneurysm, Abdominal/pathology , Aortic Aneurysm, Abdominal/drug therapy , Aortic Aneurysm, Abdominal/metabolism , Aortic Aneurysm, Abdominal/prevention & control , Insulin-Like Growth Factor I/metabolism , Male , Swine , Mice , Signal Transduction/drug effects , Mice, Inbred C57BL , Rats
Non-small cell lung cancer (NSCLC) accounts for approximately 80% of all lung cancers with a low five-year survival rate. Therefore, the mechanistic pathways and biomarkers of NSCLC must be explored to elucidate its pathogenesis. In this study, we examined TIPE3 expression in NSCLC cells and investigated the molecular mechanisms underlying NSCLC regulation in vivo and in vitro. We collected tissue samples from patients with NSCLC to examine TIPE3 expression and its association with patient metastasis and prognosis. Furthermore, we evaluated the expression level of TIPE3 in NSCLC cells. Cell lines with the highest expression were selected for molecular mechanism experiments, and animal models were established for in vivo verification. The results showed that TIPE3 was significantly increased in patients with NSCLC, and this increased expression was associated with tumor metastasis and patient prognosis. TIPE3 knockdown inhibited proliferation, migration, invasion, EMT, angiogenesis, and tumorsphere formation in NSCLC cells. Moreover, it reduced the metabolic levels of tumor cells. However, overexpression of TIPE3 has the opposite effect. The in vivo results showed that TIPE3 knockdown reduced tumor volume, weight, and metastasis. Furthermore, the results showed that TIPE3 may inhibit malignant progression of NSCLC via the regulation of Wnt/ß-catenin expression. These findings suggest that TIPE3 is significantly elevated in patients with NSCLC and that downregulation of TIPE3 can suppress the malignant progression of NSCLC, which could serve as a potential diagnostic and treatment strategy for NSCLC.
BACKGROUND & OBJECTIVE: Sex estimation is a critical aspect of forensic expertise. Some special anatomical structures, such as the maxillary sinus, can still maintain integrity in harsh environmental conditions and may be served as a basis for sex estimation. Due to the complex nature of sex estimation, several studies have been conducted using different machine learning algorithms to improve the accuracy of sex prediction from anatomical measurements. MATERIAL & METHODS: In this study, linear data of the maxillary sinus in the population of northwest China by using Cone-Beam Computed Tomography (CBCT) were collected and utilized to develop logistic, K-Nearest Neighbor (KNN), Support Vector Machine (SVM) and random forest (RF) models for sex estimation with R 4.3.1. CBCT images from 477 samples of Han population (75 males and 81 females, aged 5-17 years; 162 males and 159 females, aged 18-72) were used to establish and verify the model. Length (MSL), width (MSW), height (MSH) of both the left and right maxillary sinuses and distance of lateral wall between two maxillary sinuses (distance) were measured. 80% of the data were randomly picked as the training set and others were testing set. Besides, these samples were grouped by age bracket and fitted models as an attempt. RESULTS: Overall, the accuracy of the sex estimation for individuals over 18 years old on the testing set was 77.78%, with a slightly higher accuracy rate for males at 78.12% compared to females at 77.42%. However, accuracy of sex estimation for individuals under 18 was challenging. In comparison to logistic, KNN and SVM, RF exhibited higher accuracy rates. Moreover, incorporating age as a variable improved the accuracy of sex estimation, particularly in the 18-27 age group, where the accuracy rate increased to 88.46%. Meanwhile, all variables showed a linear correlation with age. CONCLUSION: The linear measurements of the maxillary sinus could be a valuable tool for sex estimation in individuals aged 18 and over. A robust RF model has been developed for sex estimation within the Han population residing in the northwestern region of China. The accuracy of sex estimation could be higher when age is used as a predictive variable.
Endogenous stimuli-responsive injectable hydrogels hold significant promise for practical applications due to their spatio-temporal controllable drug delivery. Herein, we report a facile strategy to construct a series of in situ formation polypeptide hydrogels with thermal responsiveness and enzyme-triggered dynamic self-assembly. The thermo-responsive hydrogels are from the diblock random copolymer mPEG-b-P(Glu-co-Tyr). The L-glutamic acid (Glu) segments with different γ-alkyl groups, including methyl, ethyl, and n-butyl, offer specific secondary structure, facilitating the formation of hydrogel. The L-tyrosine (Tyr) residues not only provide hydrogen-bond interactions and thus adjust the sol-gel transition temperatures, but also endow polypeptide enzyme-responsive properties. The PTyr segments could be phosphorylated, and the phosphotyrosine copolymers were amphiphilies, which could readily self-assemble into spherical aggregates and transform into sheet-like structures upon dephosphorylation by alkaline phosphatase (ALP). P(MGlu-co-Tyr/P) and P(MGlu-co-Tyr) copolymers showed good compatibility with both MC3T3-E1 and Hela cells, with cell viability above 80% at concentrations up to 1000 µg/mL. The prepared injectable polypeptide hydrogel and its enzyme-triggered self-assemblies show particular potential for biomedical applications.
The absolute structures of a pair of infinite Na(H2O)4+-connected ε-Keggin-Al13 species (Na-ε-K-Al13) that were inversion structures and mirror images of each other were determined. Single crystals obtained by adding A2SO4 (A = Li, Na, K, Rb, or Cs) solution to NaOH-hydrolyzed AlCl3 solution were subjected to X-ray structure analyses. The statistical results for 36 single crystals showed that all the crystals had almost the same unit cell parameter, belonged to the same F4Ì 3m space group, and possessed the same structural formula [Na(H2O)4AlO4Al12(OH)24(H2O)12](SO4)4·10H2O. However, the crystals had two inverse absolute structures (denoted A and B), which had a crystallization ratio of 1:1. From Li+ to Cs+, with increasing volume of the cation coexisting in the mother solution, the degree of disorder of the four H2O molecules in the Na(H2O)4+ hydrated ion continuously decreased; they became ordered when the cation was Cs+. Absolute structures A and B are the first two infinite aluminum polycations connected by statistically occupied [(Na1/4)4(H2O)4]+ hydrated ions. The three-dimensional structure of the infinite Na-ε-K-Al13 species can be regarded as the assembly of finite ε-K-Al13 species linked by [(Na1/4)4(H2O)4]+ in a 1:1 ratio. In this assembly, each [(Na1/4)4(H2O)4]+ is connected to four ε-K-Al13 and each ε-K-Al13 is also connected to four [(Na1/4)4(H2O)4]+ in tetrahedral orientations to form a continuous rigid framework structure, which has an inverse spatial orientation between absolute structure A and B. This discovery clarifies that the ε-K-Al13 (or ε-K-GaAl12) species in Na[MO4Al12(OH)24(H2O)12](XO4)4·nH2O (M = Al, Ga; X = S, Se; n = 10-20) exists as discrete groups and deepens understanding of the formation and evolution process of polyaluminum species in forcibly hydrolyzed aluminum salt solution. The reason why Na+ statistically occupies the four sites was examined, and a formation and evolution mechanism of the infinite Na-ε-K-Al13 species was proposed.
Two metal borate-carbonates, M6[Cd2(CO3)2(B12O18)(OH)6] [M = K (1), Rb (2)], were obtained under surfactant-thermal conditions. In 1 and 2, each cyclic [(B12O18)(OH)6]6- anion captures two CdCO3 in two sides of the rings and finally forms the unusual (CdCO3)2@[(B12O18)(OH)6] cluster. Both 1 and 2 show moderate birefringence. Density functional theory calculations indicate that carbonate groups have a major contribution to electron-related optical transition.
A new Co4-added polyoxometalate (CoAP) Cs4[(Co(H2O)5)2{(µ2-Co(H2O)4)2Co4(H2O)2(B-α-GeW9O34)2}]·6H2O (1) has been made using a lacunary directing strategy under hydrothermal conditions. Single-crystal X-ray diffraction analysis demonstrated that 1 is a one-dimensional (1D) chain, in which CoAP is linked by cobalt-oxygen octahedra to form a 1D structure with excellent chemical stability. The visible light-driven H2 evolution test demonstrated that 1 has high activity, with an H2 evolution rate of 1485.95 µmol h-1 g-1. PXRD and FT-IR tests demonstrated that compound 1 exhibits excellent heterogeneous catalytic stability.
High expression of ubiquitin-specific protease 10 (USP10) promote the proliferation of hepatocellular carcinoma (HCC), thus the development of USP10 inhibitors holds promise as a novel therapeutic approach for HCC treatment. However, the development of selective USP10 inhibitor is still limited. In this study, we developed a novel USP10 inhibitor for investigating the feasibility of targeting USP10 for the treatment of HCC. Due to high USP10 inhibition potency and prominent selectivity, compound D1 bearing quinolin-4(1H)-one scaffold was identified as a lead compound. Subsequent research revealed that D1 significantly inhibits cell proliferation and clone formation in HCC cells. Mechanistic insights indicated that D1 targets the ubiquitin pathway, facilitating the degradation of YAP (Yes-associated protein), thereby triggering the downregulation of p53 and its downstream protein p21. Ultimately, this cascade leads to S-phase arrest in HCC cells, followed by cell apoptosis. Collectively, our findings highlight D1 as a promising starting point for USP10-positive HCC treatment, underscoring its potential as a vital tool for unraveling the functional intricacies of USP10.
Adaptor Proteins, Signal Transducing , Antineoplastic Agents , Carcinoma, Hepatocellular , Cell Proliferation , Drug Discovery , Liver Neoplasms , Transcription Factors , Ubiquitin Thiolesterase , YAP-Signaling Proteins , Humans , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/metabolism , Liver Neoplasms/drug therapy , Liver Neoplasms/pathology , Liver Neoplasms/metabolism , Cell Proliferation/drug effects , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Ubiquitin Thiolesterase/antagonists & inhibitors , Ubiquitin Thiolesterase/metabolism , Transcription Factors/antagonists & inhibitors , Transcription Factors/metabolism , Structure-Activity Relationship , Adaptor Proteins, Signal Transducing/metabolism , Adaptor Proteins, Signal Transducing/antagonists & inhibitors , YAP-Signaling Proteins/metabolism , Molecular Structure , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Apoptosis/drug effects , Small Molecule Libraries/pharmacology , Small Molecule Libraries/chemistry , Small Molecule Libraries/chemical synthesis , Cell Line, Tumor
Ni-rich cathodes are some of the most promising candidates for advanced lithium-ion batteries, but their available capacities have been stagnant due to the intrinsic Li+ storage sites. Extending the voltage window down can induce the phase transition from O3 to 1T of LiNiO2-derived cathodes to accommodate excess Li+ and dramatically increase the capacity. By setting the discharge cutoff voltage of LiNi0.6Co0.2Mn0.2O2 to 1.4 V, we can reach an extremely high capacity of 393 mAh g-1 and an energy density of 1070 Wh kg-1 here. However, the phase transition causes fast capacity decay and related structural evolution is rarely understood, hindering the utilization of this feature. We find that the overlithiated phase transition is self-limiting, which will transform into solid-solution reaction with cycling and make the cathode degradation slow down. This is attributed to the migration of abundant transition metal ions into lithium layers induced by the overlithiation, allowing the intercalation of overstoichiometric Li+ into the crystal without the O3 framework change. Based on this, the wide-potential cycling stability is further improved via a facile charge-discharge protocol. This work provides deep insight into the overstoichiometric Li+ storage behaviors in conventional layered cathodes and opens a new avenue toward high-energy batteries.
Background: An increasing body of research has demonstrated a robust correlation between circulating inflammatory proteins and neuromyelitis optica spectrum disorders (NMOSD). However, whether this association is causal or whether immune cells act as mediators currently remains unclear. Methods: We employed bidirectional two-sample Mendelian randomization (TSMR) analysis to examine the potential causal association between circulating inflammatory proteins, immune cells, and NMOSD using data from genome-wide association studies (GWAS). Five different methods for Mendelian randomization analyses were applied, with the inverse variance-weighted (IVW) method being the primary approach. Sensitivity analyses were further performed to assess the presence of horizontal pleiotropy and heterogeneity in the results. Finally, a two-step Mendelian randomization (MR) design was employed to examine the potential mediating effects of immune cells. Results: A notable causal relationship was observed between three circulating inflammatory proteins (CSF-1, IL-24, and TNFRSF9) and genetically predicted NMOSD. Furthermore, two immune cell phenotypes, genetically predicted CD8 on naive CD8+ T cells, and Hematopoietic Stem Cell Absolute Count were negatively and positively associated with genetically predicted NMOSD, respectively, although they did not appear to function as mediators. Conclusion: Circulating inflammatory proteins and immune cells are causally associated with NMOSD. Immune cells do not appear to mediate the pathway linking circulating inflammatory proteins to NMOSD.
Herein, single-atom iron doped carbon dots (SA Fe-CDs) were successfully prepared as novel electrochemiluminescence (ECL) emitters with high ECL efficiency, and a biosensor was constructed to ultrasensitively detect microRNA-222 (miRNA-222). Importantly, compared with the conventional without single-atom doped CDs with low ECL efficiency, SA Fe-CDs exhibited strong ECL efficiency, in which single-atom iron as an advanced coreactant accelerator could significantly enhance the generation of reactive oxygen species (ROS) from the coreactant S2O82- for improving the ECL efficiency. Moreover, a neoteric amplification strategy combining the improved strand displacement amplification with Nt.BbvCI enzyme-induced target amplification (ISDA-EITA) could produce 4 output DNAs in every cycle, which greatly improved the amplification efficiency. Thus, a useful ECL biosensor was built with a detection limit of 16.60 aM in the range of 100 aM to 1 nM for detecting traces of miRNA-222. In addition, miRNA-222 in cancer cell lysate (MHCC-97L) was successfully detected by using the ECL biosensor. Therefore, this strategy provides highly efficient single-atom doped ECL emitters for the construction of sensitive ECL biosensing platforms in the biological field and clinical diagnosis.
Biosensing Techniques , Carbon , Electrochemical Techniques , Iron , Luminescent Measurements , MicroRNAs , Quantum Dots , MicroRNAs/analysis , Carbon/chemistry , Iron/chemistry , Electrochemical Techniques/methods , Quantum Dots/chemistry , Humans , Biosensing Techniques/methods , Limit of Detection
