Clinical features and associated factors of impaired ventilatory efficiency: findings from the ECOPD study in China.

BACKGROUND: Impaired ventilatory efficiency during exercise is a predictor of mortality in chronic obstructive pulmonary disease. However, little is known about the clinical features and associated factors of impaired ventilatory efficiency in China. METHODS: We conducted a cross-sectional community-based study in China and collected demographic and clinical information, cardiopulmonary exercise testing, spirometry, and CT data. Impaired ventilatory efficiency was defined by a nadir ventilatory equivalent for CO2 production above the upper limit of normal. Multivariable linear and logistic regression models were used to explore the clinical features and associated factors of impaired ventilatory efficiency. RESULTS: The final analyses included 941 subjects, 702 (74.6%) of whom had normal ventilatory efficiency and 239 (25.4%) had impaired ventilatory efficiency. Participants with impaired ventilatory efficiency had more chronic respiratory symptoms, poorer lung function and exercise capacity, and more severe emphysema (natural logarithm transformation of the low-attenuation area of the lung with attenuation values below -950 Hounsfield units, logLAA-950: 0.19±0.65 vs -0.28±0.63, p<0.001) and air trapping (logLAA-856: 1.03±0.65 vs 0.68±0.70, p<0.001) than those with normal ventilatory efficiency. Older age (60-69 years, OR 3.10 (95% CI 1.33 to 7.21), p=0.009 and 70-80 years, OR 6.48 (95% CI 2.56 to 16.43), p<0.001 vs 40-49 years) and smoking (former, OR 3.19 (95% CI 1.29 to 7.86), p=0.012; current, OR 4.27 (95% CI 1.78 to 10.24), p=0.001 vs never) were identified as high risk factors of impaired ventilatory efficiency. CONCLUSIONS: Impaired ventilatory efficiency was associated with poorer respiratory characteristics. Longitudinal studies are warranted to explore the progression of individuals with impaired ventilatory efficiency.

PIM1-HDAC2 axis modulates intestinal homeostasis through epigenetic modification.

The mucosal barrier is crucial for intestinal homeostasis, and goblet cells are essential for maintaining the mucosal barrier integrity. The proviral integration site for Moloney murine leukemia virus-1 (PIM1) kinase regulates multiple cellular functions, but its role in intestinal homeostasis during colitis is unknown. Here, we demonstrate that PIM1 is prominently elevated in the colonic epithelia of both ulcerative colitis patients and murine models, in the presence of intestinal microbiota. Epithelial PIM1 leads to decreased goblet cells, thus impairing resistance to colitis and colitis-associated colorectal cancer (CAC) in mice. Mechanistically, PIM1 modulates goblet cell differentiation through the Wnt and Notch signaling pathways. Interestingly, PIM1 interacts with histone deacetylase 2 (HDAC2) and downregulates its level via phosphorylation, thereby altering the epigenetic profiles of Wnt signaling pathway genes. Collectively, these findings investigate the unknown function of the PIM1-HDAC2 axis in goblet cell differentiation and ulcerative colitis/CAC pathogenesis, which points to the potential for PIM1-targeted therapies of ulcerative colitis and CAC.

Anti-Eimeria tenella activity of Ethanamizuril in vitro and in vivo.

The prevalence of chicken coccidiosis in the poultry industry is a significant concern, further exacerbated by the emergence of drug-resistant coccidia resulting from the indiscriminate use of medications. Ethanamizuril, a novel triazine anti-coccidial compound, has been used to combat drug resistance. Currently, it is known that Ethanamizuril acts on the second-generation merozoites and early gametogenesis stages of Eimeria. Limited information exists regarding its impact on the early merozoites and exogenous stage of Eimeria. In the present study, the anti-coccidial properties of Ethanamizuril were evaluated both in vitro and in vivo. The in vitro experiments demonstrated that Ethanamizuril effectively inhibits the sporulation of E. tenella oocysts in a dose-dependent manner and significantly reduces the sporozoite excystation rate. Furthermore, in vivo tests revealed that treatment with 10 mg/L Ethanamizuril in drinking water significantly decreased the copy number of first-generation and secondary-generation merozoites in the chicken cecum, indicating that it can inhibit the development of whole schizonts development. Moreover, treatment with Ethanamizuril demonstrated excellent protective efficacy with an anti-coccidial index (ACI) of 180, which was manifested through higher body weight gains, lighter cecal lesion, lower fecal oocyst shedding score and reduced liver index. Collectively, this study suggests that Ethanamizuril effectively treats E. tenella infection by inhibiting both endogenous and exogenous stages development.

Modulating the electronic structure of VS2via Ru decoration for an efficient pH-universal electrocatalytic hydrogen evolution reaction.

High-efficiency water electrolysis over a broad pH range is desirable but challenging. Herein, Ru-decorated VS2 on carbon cloth (Ru-VS2/CC) has been in situ synthesized, which features the regulated electronic structure of VS2 by introducing Ru. It is remarkable that the optimal Ru-VS2/CC displays excellent electrocatalytic hydrogen evolution activity with overpotentials of 89 and 87 mV at -10 mA cm-2 in 0.5 M H2SO4 and 1.0 M KOH, respectively. Theoretical calculations and electrocatalytic measurements have demonstrated that introducing Ru induces an enhanced charge density around the Fermi level, facilitating charge transfer and speeding up the electrocatalytic HER kinetics. The Gibbs free energy of the hydrogen intermediate (ΔGH*) of Ru-VS2/CC (0.23 eV) is much closer to zero than that of pure VS2 (0.51 eV) and Ru (-0.37 eV), demonstrating an easier hydrogen adsorption and desorption process for Ru-VS2/CC. The more favorable ΔGH*, differential charge density and the d-band center endow Ru-VS2 with enhanced intrinsic electrocatalytic activity. This study presents a feasible strategy for enhancing electrocatalytic HER activity by the regulation of the electronic structure and the rational integration of dual active components.

Clinical Characteristics and 2-Year Outcomes of Chronic Obstructive Pulmonary Disease Patients With High Blood Eosinophil Counts: A Population-based Prospective Cohort Study in China.

BACKGROUND: High blood eosinophil count (BEC) is a useful biomarker for guiding inhaled corticosteroid therapy in patients with chronic obstructive pulmonary disease (COPD), yet its implications in a community setting remain underexplored. This study aimed to elucidate the clinical characteristics and outcomes of COPD patients with high BEC within the Chinese community. METHODS: We obtained baseline and 2-year follow-up data from COPD patients (post-bronchodilator forced expiratory volume in 1 second/forced vital capacity <0.70) in the early COPD study. Patients with a BEC ≥300cells/µL were classified as the high BEC group. We assessed differences in the clinical characteristics and outcomes between high and low BEC patients. Subgroup analyses were conducted on COPD patients without a history of corticosteroid use or asthma. RESULTS: Of the 897 COPD patients, 205 (22.9%) had high BEC. At baseline, high BEC patients exhibited a higher proportion of chronic respiratory symptoms, lower lung function, and more severe small airway dysfunction than low BEC patients. Over the 2-year period, high BEC patients experienced a significantly higher risk of acute exacerbations (relative risk: 1.28, 95% confidence interval: 1.09-1.49; P=0.002), even after adjusting for confounders. No significant difference was observed in lung function decline rates. The subgroup analysis yielded consistent results. CONCLUSIONS: COPD patients with high BEC in a Chinese community exhibited poorer health status, more severe small airway dysfunction, and a higher risk of exacerbations. Future research should explore the pathological mechanisms underlying the poorer prognosis in patients with high BEC.

Type I Cystatin Derived from Cysticercus pisiformis-Stefins, Suppresses LPS-Mediated Inflammatory Response in RAW264.7 Cells.

Cysticercus pisiformis is a kind of tapeworm larvae of Taenia pisiformis, which parasitizes the liver envelope, omentum, mesentery, and rectum of rodents such as rabbits. Cysteine protease inhibitors derived from helminth were immunoregulatory molecules of intermediate hosts and had an immunomodulatory function that regulates the production of inflammatory factors. Thus, in the present research, the recombinant Stefin of C. pisiformis was confirmed to have the potential to fight inflammation in LPS-Mediated RAW264.7 murine macrophages. CCK8 test showed that rCpStefin below 50 µg/mL concentration did not affect cellular viability. Moreover, the NO production level determined by the Griess test was decreased. In addition, the secretion levels of IL-1ß, IL-6, and TNF-α as measured by ELISA were decreased. Furthermore, it exerted anti-inflammatory activity by decreasing the production of proinflammatory cytokines and proinflammatory mediators, including IL-1ß, IL-6, TNF-α, iNOS, and COX-2 at the gene transcription level, as measured by qRT-PCR. Therefore, Type I cystatin derived from C. pisiformis suppresses the LPS-Mediated inflammatory response of the intermediate host and is a potential candidate for the treatment of inflammatory diseases.

Clinical features and 1-year outcomes of variable obstruction in participants with preserved spirometry: results from the ECOPD study in China.

BACKGROUND: There are limited data on the clinical features and longitudinal prognosis of variable obstruction, particularly among never smokers and different variable obstruction types. Therefore, we aimed to evaluate the clinical characteristics of the participants with variable obstruction and determine the relationship between variable obstruction and the development of chronic obstructive pulmonary disease (COPD) and the decline of lung function in a community-dwelling study of Chinese, especially among never smokers and different variable obstruction subtypes. METHODS: Participants with preserved spirometry (postbronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ≥0.70) at baseline from the Early COPD cohort were included in our analysis. Participants with variable obstruction (prebronchodilator FEV1/FVC <0.70) were compared with those without variable obstruction (prebronchodilator FEV1/FVC ≥0.70). We performed subgroup analyses in never smokers, former and current smokers, and different variable obstruction types (postbronchodilator FVC

Recent advances in nucleic acid signal amplification-based aptasensors for sensing mycotoxins.

Mycotoxin contamination in food products may cause serious health hazards and economic losses. The effective control and accurate detection of mycotoxins have become a global concern. Even though a variety of methods have been developed for mycotoxin detection, most conventional methods suffer from complicated operation procedures, low sensitivity, high cost, and long assay time. Therefore, the development of simple and sensitive methods for mycotoxin assay is highly needed. The introduction of nucleic acid signal amplification technology (NASAT) into aptasensors significantly improves the sensitivity and facilitates the detection of mycotoxins. Herein, we give a comprehensive review of the recent advances in NASAT-based aptasensors for assaying mycotoxins and summarize the principles, features, and applications of NASAT-based aptasensors. Moreover, we highlight the challenges and prospects in the field, including the simultaneous detection of multiple mycotoxins and the development of portable devices for field detection.

Clinical characterization and outcomes of impulse oscillometry-defined bronchodilator response: an ECOPD cohort-based study.

BACKGROUND: The clinical significance of the impulse oscillometry-defined small airway bronchodilator response (IOS-BDR) is not well-known. Accordingly, this study investigated the clinical characteristics of IOS-BDR and explored the association between lung function decline, acute respiratory exacerbations, and IOS-BDR. METHODS: Participants were recruited from an Early Chronic Obstructive Pulmonary Disease (ECOPD) cohort subset and were followed up for two years with visits at baseline, 12 months, and 24 months. Chronic obstructive pulmonary disease (COPD) was defined as a post-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio < 0.70. IOS-BDR was defined as meeting any one of the following criteria: an absolute change in respiratory system resistance at 5 Hz ≤ - 0.137 kPa/L/s, an absolute change in respiratory system reactance at 5 Hz ≥ 0.055 kPa/L/s, or an absolute change in reactance area ≤ - 0.390 kPa/L. The association between IOS-BDR and a decline in lung function was explored with linear mixed-effects model. The association between IOS-BDR and the risk of acute respiratory exacerbations at the two-year follow-up was analyzed with the logistic regression model. RESULTS: This study involved 466 participants (92 participants with IOS-BDR and 374 participants without IOS-BDR). Participants with IOS-BDR had higher COPD assessment test and modified Medical Research Council dyspnea scale scores, more severe emphysema, air trapping, and rapid decline in FVC than those without IOS-BDR over 2-year follow-up. IOS-BDR was not associated with the risk of acute respiratory exacerbations at the 2-year follow-up. CONCLUSIONS: The participants with IOS-BDR had more respiratory symptoms, radiographic structural changes, and had an increase in decline in lung function than those without IOS-BDR. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1900024643. Registered on 19 July, 2019.

Engineering Covalent Organic Frameworks Toward Advanced Zinc-Based Batteries.

Zinc-based batteries (ZBBs) have demonstrated considerable potential among secondary batteries, attributing to their advantages including good safety, environmental friendliness, and high energy density. However, ZBBs still suffer from issues such as the formation of zinc dendrites, occurrence of side reactions, retardation of reaction kinetics, and shuttle effects, posing a great challenge for practical applications. As promising porous materials, covalent organic frameworks (COFs) and their derivatives have rigid skeletons, ordered structures, and permanent porosity, which endow them with great potential for application in ZBBs. This review, therefore, provides a systematic overview detailing on COFs structure pertaining to electrochemical performance of ZBBs, following an in depth discussion of the challenges faced by ZBBs, which includes dendrites and side reactions at the anode, as well as dissolution, structural change, slow kinetics, and shuttle effect at the cathode. Then, the structural advantages of COF-correlated materials and their roles in various ZBBs are highlighted. Finally, the challenges of COF-correlated materials in ZBBs are outlined and an outlook on the future development of COF-correlated materials for ZBBs is provided. The review would serve as a valuable reference for further research into the utilization of COF-correlated materials in ZBBs.

Understanding the role of DNA methylation in colorectal cancer: Mechanisms, detection, and clinical significance.

Colorectal cancer (CRC) is one of the deadliest malignancies worldwide, ranking third in incidence and second in mortality. Remarkably, early stage localized CRC has a 5-year survival rate of over 90%; in stark contrast, the corresponding 5-year survival rate for metastatic CRC (mCRC) is only 14%. Compounding this problem is the staggering lack of effective therapeutic strategies. Beyond genetic mutations, which have been identified as critical instigators of CRC initiation and progression, the importance of epigenetic modifications, particularly DNA methylation (DNAm), cannot be underestimated, given that DNAm can be used for diagnosis, treatment monitoring and prognostic evaluation. This review addresses the intricate mechanisms governing aberrant DNAm in CRC and its profound impact on critical oncogenic pathways. In addition, a comprehensive review of the various techniques used to detect DNAm alterations in CRC is provided, along with an exploration of the clinical utility of cancer-specific DNAm alterations.

Elongation and Ligation-Mediated Differential Coding for Label-Free and Locus-Specific Analysis of 8-Oxo-7,8-dihydroguanine in DNA.

Oxidative DNA damage is closely associated with the occurrence of numerous human diseases and cancers. 8-Oxo-7,8-dihydroguanine (8-oxoG) is the most prevalent form of DNA damage, and it has become not only an oxidative stress biomarker but also a new epigenetic-like biomarker. However, few approaches are available for the locus-specific detection of 8-oxoG because of the low abundance of 8-oxoG damage in DNA and the limited sensitivity of existing assays. Herein, we demonstrate the elongation and ligation-mediated differential coding for label-free and locus-specific analysis of 8-oxoG in DNA. This assay is very simple without the involvement of any specific labeled probes, complicated steps, and large sample consumption. The utilization of Bsu DNA polymerase can specifically initiate a single-base extension reaction to incorporate dATP into the opposite position of 8-oxoG, endowing this assay with excellent selectivity. The introduction of cascade amplification reaction significantly enhances the sensitivity. The proposed method can monitor 8-oxoG with a limit of detection of 8.21 × 10-19 M (0.82 aM), and it can identify as low as 0.001% 8-oxoG damage from a complex mixture with excessive undamaged DNAs. This method can be further applied to measure 8-oxoG levels in the genomic DNA of human cells under diverse oxidative stress, holding prospect potential in the dynamic monitoring of critical 8-oxoG sites, early clinical diagnosis, and gene damage-related biomedical research.

Ligase detection reaction amplification-activated CRISPR-Cas12a for single-molecule counting of FEN1 in breast cancer tissues.

We construct a simple fluorescent biosensor for single-molecule counting of flap endonuclease 1 (FEN1) based on ligase detection reaction (LDR) amplification-activated CRISPR-Cas12a. This biosensor exhibits excellent selectivity and high sensitivity with a detection limit (LOD) of 1.31 × 10-8 U. Moreover, it can be employed to screen the FEN1 inhibitors and quantitatively measure the FEN1 activity in human cells and breast cancer tissues, holding great promise in clinical diagnosis and drug discovery.

Construction of a label-free fluorescent biosensor for homogeneous detection of m6A eraser FTO in breast cancer tissues.

Fat mass and obesity-associated protein (FTO) is a crucial eraser of RNA N6- methyladenosine (m6A) modification, and abnormal FTO expression level is implicated in pathogenesis of numerous cancers. Herein, we demonstrate the construction of a label-free fluorescent biosensor for homogeneous detection of m6A eraser FTO in breast cancer tissues. When FTO is present, it specifically erases the methyl group in m6A, inducing the cleavage of demethylated DNA by endonuclease DpnII and the generation of a single-stranded DNA (ssDNA) with a 3'-hydroxyl group. Subsequently, terminal deoxynucleotidyl transferase (TdT) promotes the incorporation of dTTPs into the ssDNA to obtain a long polythymidine (T) DNA sequence. The resultant long poly (T) DNA sequence can act as a template to trigger hyperbranched strand displacement amplification (HSDA), yielding numerous DNA fragments that may be stained by SYBR Gold to produce an enhanced fluorescence signal. This biosensor processes ultrahigh sensitivity with a detection limit of 1.65 × 10-10 mg/mL (2.6 fM), and it can detect the FTO activity in a single MCF-7 cell. Moreover, this biosensor can screen the FTO inhibitors, evaluate enzyme kinetic parameters, and discriminate the FTO expression levels in the tissues of breast cancer patients and healthy persons.

Near-room temperature ferromagnetism and a tunable anomalous Hall effect in atomically thin Fe4CoGeTe2.

Itinerant ferromagnetism at room temperature is a key factor for spin transport and manipulation. Here, we report the realization of near-room temperature itinerant ferromagnetism in Co doped Fe5GeTe2 thin flakes. The ferromagnetic transition temperature TC (∼323 K-337 K) is almost unchanged when the thickness is as low as 12 nm and is still about 284 K at 2 nm (bilayer thickness). Theoretical calculations further indicate that the ferromagnetism persists in monolayer Fe4CoGeTe2. In addition to the robust ferromagnetism down to the ultrathin limit, Fe4CoGeTe2 exhibits an unusual temperature- and thickness-dependent intrinsic anomalous Hall effect. We propose that it could be ascribed to the dependence of the band structure on thickness that changes the Berry curvature near the Fermi energy level subtly. The near-room temperature ferromagnetism and tunable anomalous Hall effect in atomically thin Fe4CoGeTe2 provide opportunities to understand the exotic transport properties of two-dimensional van der Waals magnetic materials and explore their potential applications in spintronics.

Host protein EPCAM interacting with EtMIC8-EGF is essential for attachment and invasion of Eimeria tenella in chickens.

The five epidermal growth factor-like domains (EGF) of Eimeria tenella microneme protein 8 (EtMIC8) (EtMIC8-EGF) plays a vital role in host cell attachment and invasion. These processes require interactions between parasite proteins and receptors on the surface of host cells. In this study, five chicken membrane proteins potentially interacting with EtMIC8-EGF were identified using the GST pull-down assay and mass spectrometry analysis, and only chicken (Gallus gallus) epithelial cell adhesion molecule (EPCAM) could bind to EtMIC8-EGF. EPCAM-specific antibody and recombinant EPCAM protein (rEPCAM) inhibited the EtMIC8-EGF binding to host cells in a concentration-dependent manner. Furthermore, the rEPCAM protein showed a binding activity to sporozoites in vitro, and a significant reduction of E. tenella invasion in DF-1 cells was further observed after pre-incubation of sporozoites with rEPCAM. The specific anti-EPCAM antibody further significantly decreased weight loss, lesion score and oocyst output during E. tenella infection, displaying partial inhibition of E. tenella infection. These results indicate that chicken EPCAM is an important EtMIC8-interacting host protein involved in E. tenella-host cell adhesion and invasion. The findings will contribute to a better understanding of the role of adhesion-associated microneme proteins in E. tenella.

Demethylation-activated light-up dual-color RNA aptamersensor for label-free detection of multiple demethylases in lung tissues.

Methylation is one of the most prevalent epigenetic modifications in natural organisms, and the processes of methylation and demethylation are closely associated with cell growth, differentiation, gene transcription and expression. Abnormal methylation may lead to various human diseases including cancers. Simultaneous analysis of multiple DNA demethylases remains a huge challenge due to the requirement of diverse substrate probes and scarcity of proper signal transduction strategies. Herein, we propose a sensitive and label-free method for simultaneous monitoring of multiple DNA demethylases on the basis of demethylation-activated light-up dual-color RNA aptamers. The presence of targets AlkB homologue-3 (ALKBH3) and fat mass and obesity-associated enzyme (FTO) erases the methyl group in DNA substrate probes, activating the ligation-mediate bidirectional transcription amplification reaction to produce enormous Spinach and Mango aptamers. The resulting RNA aptamers (i.e., Spinach and Mango aptamers) can bind with their cognate nonfluorescent fluorogens (DFHBI and TO1-biotin) to significantly improve the fluorescence signals. This aptamersensor shows high specificity and sensitivity with a limit of detection (LOD) of 8.50 × 10-14 M for ALKBH3 and 6.80 × 10-14 M for FTO, and it can apply to screen DNA demethylase inhibitors, evaluate DNA demethylase kinetic parameters, and simultaneously measure multiple endogenous DNA demethylases in a single cell. Importantly, this aptamersensor can accurately discriminate the expressions of ALKBH3 and FTO between healthy tissues and non-small cell lung cancer (NSCLC) patient tissues, offering a powerful platform for clinical diagnosis and drug discovery.

Integrative analysis of transcriptome and proteome profiles in primary and recurrent glioblastoma.

PURPOSE: Glioblastoma (GBM) is the most common and aggressive primary brain tumor characterized by poor prognosis and high recurrence. The underlying molecular mechanism that drives tumor progression and recurrence is unclear. This study is intended to look for molecular and biological changes that play a key role in GBM recurrence. EXPERIMENTAL DESIGN: An integrative transcriptomic and proteomic analysis was performed on three primary GBM and three recurrent GBM tissues. Omics analyses were conducted using label-free quantitative proteomics and whole transcriptome sequencing. RESULTS: A significant difference was found between primary GBM and recurrent GBM at the transcriptional level. Similar to other omics studies of cancer, a weak overlap was observed between transcriptome and proteome, and Procollagen C-Endopeptidase Enhancer 2 (PCOLCE2) was observed to be upregulated at mRNA and protein levels. Analysis of public cancer database revealed that high expression of PCOLCE2 is associated with poor prognosis of patients with GBM and that it may be a potential prognostic indicator. Functional and environmental enrichment analyses revealed significantly altered signaling pathways related to energy metabolism, including mitochondrial ATP synthesis-coupled electron transport and oxidative phosphorylation. CONCLUSIONS AND CLINICAL RELEVANCE: This study provides new insights into the recurrence process of GBM through combined transcriptomic and proteomic analyses, complementing the existing GBM transcriptomic and proteomic data and suggesting that integrated multi-omics analyses may reveal new disease features of GBM.

A candidate virulence factor of Eimeria tenella (EtROP30) predicted by virulence enhancement of transgenic Toxoplasma gondii.

Difficulties of in vitro culture and genetic manipulation of Eimeria tenella have hindered the screening of virulence factors in this parasite. In this study, the E. tenella rhoptry protein 30 (EtROP30) was expressed in Toxoplasma gondii (RH∆Ku80-EtROP30), and its effect on the proliferation and virulence of parasites was investigated. The results revealed that the expression of EtROP30 had no impact on the invasion and egress processes. However, the RH∆Ku80-EtROP30 strain formed larger plaques compared to the RH∆Ku80, indicating that the EtROP30 expression promotes T. gondii proliferation. Furthermore, the RH∆Ku80-EtROP30 strain exhibited greater pathogenicity, resulting in earlier mortality and shorter overall survival time compared to RH∆Ku80. These results imply that EtROP30 expression facilitates parasite intracellular proliferation and virulence in mice, suggesting that EtROP30 might be a candidate virulence factor of E. tenella.

Construction of a Dual-Mode Biosensor with Ferrocene as Both a Signal Enhancer and a Signal Tracer for Electrochemiluminescent and Electrochemical Enantioselective Recognition.

We demonstrate for the first time the construction of a dual-mode biosensor for electrochemiluminescent (ECL) and electrochemical chiral recognition of l- and d-isomers of amino acids, with ferrocene (Fc) as both a signal enhancer and a signal tracer. With the dissolved oxygen as a coreactant, ZnIn2S4 acts as the ECL emitter to generate a weak cathodic ECL signal. Fc can enter into the ß-cyclodextrin (ß-CD) cavity on ZnIn2S4-modified electrode as a result of host-guest interaction. Since Fc can promote H2O and O2 to produce abundant reactive oxygen species (ROS) (e.g., O2·- and ·OH), the ECL signal of ZnIn2S4 can be further amplified with Fc as a coreaction accelerator. Meanwhile, Fc molecules on the ß-CD/ZnIn2S4-modified electrode can be electrochemically oxidized to Fc+ to produce a remarkable oxidation peak current. When l-histidine (l-His) is present, the matching of the l-His configuration with the ß-CD cavity leads to the entrance of more l-His into the cavity of ß-CD than d-histidine (d-His), and the subsequent competence of l-His with Fc on the Fc/ß-CD/ZnIn2S4-modified electrode induces the decrease in both Fc peak current and ZnIn2S4-induced ECL intensity. This dual-mode biosensor can efficiently discriminate l-His from d-His, and it can sensitively monitor l-His with a detection limit of 7.60 pM for ECL mode and 3.70 pM for electrochemical mode. Moreover, this dual-mode biosensor can selectively discriminate l-His from other l- and d-isomers (e.g., threonine, phenylalanine, and glutamic acid), with potential applications in the chiral recognition of nonelectroactive chiral compounds, bioanalysis, and disease diagnosis.