MiR-29 and MiR-140 regulate TRAIL-induced drug tolerance in lung cancer.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has chemotherapeutic potential as a regulator of an extrinsic apoptotic ligand, but its effect as a drug is limited by innate and acquired resistance. Recent findings suggest that an intermediate drug tolerance could mediate acquired resistance, which has made the main obstacle for limited utility of TRAIL as an anti-cancer therapeutics. We propose miRNA-dependent epigenetic modification drives the drug tolerant state in TRAIL-induced drug tolerant (TDT). Transcriptomic analysis revealed miR-29 target gene activation in TDT cells, showing oncogenic signature in lung cancer. Also, the restored TRAIL-sensitivity was associated with miR-29ac and 140-5p expressions, which is known as tumor suppressor by suppressing oncogenic protein RSK2 (p90 ribosomal S6 kinase), further confirmed in patient samples. Moreover, we extended this finding into 119 lung cancer cell lines from public data set, suggesting a significant correlation between TRAIL-sensitivity and RSK2 mRNA expression. Finally, we found that increased RSK2 mRNA is responsible for NF-κB activation, which we previously showed as a key determinant in both innate and acquired TRAIL-resistance. Our findings support further investigation of miR-29ac and -140-5p inhibition to maintain TRAIL-sensitivity and improve the durability of response to TRAIL in lung cancer.

Development of a Novel, Potent, and Selective Sialyltransferase Inhibitor for Suppressing Cancer Metastasis.

Sialyltransferase-catalyzed membrane protein and lipid glycosylation plays a vital role as one of the most abundant post-translational modifications and diversification reactions in eukaryotes. However, aberrant sialylation has been associated with cancer malignancy and metastasis. Sialyltransferases thus represent emerging targets for the development of small molecule cancer drugs. Herein, we report the inhibitory effects of a recently discovered lithocholic acid derivative FCW393 on sialyltransferase catalytic activity, integrin sialyation, cancer-associated signal transduction, MDA-MB-231 and B16F10 cell migration and invasion, and in in vivo studies, on tumor growth, metastasis, and angiogenesis. FCW393 showed effective and selective inhibition of the sialyltransferases ST6GAL1 (IC50 = 7.8 µM) and ST3GAL3 (IC50 = 9.45 µM) relative to ST3GAL1 (IC50 > 400 µM) and ST8SIA4 (IC50 > 100 µM). FCW393 reduced integrin sialylation in breast cancer and melanoma cells dose-dependently and downregulated proteins associated with the integrin-regulated FAK/paxillin and GEF/Rho/ROCK pathways, and with the VEGF-regulated Akt/NFκB/HIF-1α pathway. FCW393 inhibited cell migration (IC50 = 2.6 µM) and invasion in in vitro experiments, and in in vivo studies of tumor-bearing mice, FCW393 reduced tumor size, angiogenesis, and metastatic potential. Based on its demonstrated selectivity, cell permeability, relatively low cytotoxicity (IC50 = 55 µM), and high efficacy, FCW393 shows promising potential as a small molecule experimental tool compound and a lead for further development of a novel cancer therapeutic.

Acute kidney disease following COVID-19 vaccination: a single-center retrospective study.

Background: Rare cases of de novo or relapsed kidney diseases associated with vaccination against coronavirus disease 2019 (COVID-19) have been increasingly reported. The aim of this study was to report the incidence, etiologies, and outcomes of acute kidney disease (AKD) following COVID-19 vaccination. Methods: This retrospective study extracted cases from renal registry of a single medical center from 1 March 2021 to 30 April 2022, prior to the significant surge in cases of the Omicron variant of COVID-19 infection in Taiwan. Adult patients who developed AKD after COVID-19 vaccination were included. We utilized the Naranjo score as a causality assessment tool for adverse vaccination reactions and charts review by peer nephrologists to exclude other causes. The etiologies, characteristics, and outcomes of AKD were examined. Results: Twenty-seven patients (aged 23 to 80 years) with AKD were identified from 1,897 vaccines (estimated rate of 13.6 per 1000 patient-years within the renal registry). A majority (77.8%) of vaccine received messenger RNA-based regimens. Their median (IQR) Naranjo score was 8 (6-9) points, while 14 of them (51.9%) had a definite probability (Naranjo score ≥ 9). The etiologies of AKD included glomerular disease (n = 16) consisting of seven IgA nephropathy, four anti-neutrophil cytoplasmic antibodies-associated glomerulonephritis (AAN), three membranous glomerulonephritis, two minimal change diseases, and chronic kidney disease (CKD) with acute deterioration (n = 11). Extra-renal manifestations were found in four patients. Over a median (IQR) follow-up period of 42 (36.5-49.5) weeks, six patients progressed to end-stage kidney disease (ESKD). Conclusion: Besides glomerulonephritis (GN), the occurrence of AKD following COVID-19 vaccination may be more concerning in high-risk CKD patients receiving multiple doses. Patients with the development of de novo AAN, concurrent extra-renal manifestations, or pre-existing moderate to severe CKD may exhibit poorer kidney prognosis.

Bisphenol A detection based on nano gold-doped molecular imprinting electrochemical sensor with enhanced sensitivity.

A facile electrochemical sensor based on nano gold-doped molecularly imprinted polymer (MIP) was proposed to realize the selective detection of bisphenol A (BPA) with enhanced sensitivity. Initially, gold-doped MIP (Au@MIP) film was constructed by electropolymerizing p-aminobenzoic acid (PABA) and BPA with in situ gold reduction to distribute gold nanoparticles nearby the imprinted cavities. Subsequently, the template molecules were further extracted from the polymer film, then the MIP could rebind with the template molecules to achieve specific detection of BPA. The nano gold-doped MIP increased the effective surface area and promoted conductivity when BPA was oxidized in the imprinted cavities, which improved the determination sensitivity. Under optimal conditions, the prepared sensor displayed a linear range from 0.5 to 100 µM for BPA detection with a detection limit of 52 nM. The designed sensor was further used to detect BPA in food samples, obtaining satisfactory recoveries from 96.7% to 107.6%.

Lucidumol A, Purified Directly from Ganoderma lucidum, Exhibits Anticancer Effect and Cellular Inflammatory Response in Colorectal Cancer.

Colorectal cancer (CRC) is a deadly disease regardless of sex, and a few therapeutic approaches have been fully developed at advanced stages, even if some strategies have durable clinical benefits, such as immunotherapy and chemotherapy. Ganoderma lucidum has been recognized as an organism that suppresses tumors and inflammation; however, the molecular mechanisms induced by a triterpenoid in Ganoderma lucidum, Lucidumol A, have not yet been fully explored in CRC and inflammatory responses. To this end, we extracted Lucidumol A from Ganoderma lucidum and analyzed its anticancer effect and anti-inflammatory potential in CRC cell lines and RAW264.7 macrophage-derived cell lines, respectively. A series of in vitro experiments including cell survival, wound healing, and migration assays were performed to determine the role of Lucidumol A in the CRC cell line. We also analyzed inflammatory responses using qRT-PCR, Western Blot, and ELISA in RAW 264.7 macrophaged-derived cell lines exposed to various concentrations of Lucidumol A. Lucidumol A efficiently suppressed the metastatic potential of CRC at very low concentrations. Furthermore, significant anti-inflammatory activities were observed in Lucidumol A-treated RAW264.7 cells through modulation of inflammation-associated marker genes and cytokines. In conclusion, Lucidumol A plays an important role in Ganoderma lucidum-dependent tumor suppression and anti-inflammation, suggesting different strategies to treat CRC patients, and other diseases evoked by proinflammatory cytokines, despite the need to explore further its mechanism of action.

The association of pericardial fat and peri-aortic fat with severity of nonalcoholic fatty liver disease.

Visceral adipose tissue (VAT) is associated with central obesity, insulin resistance and metabolic syndrome. However, the association of body-site specific adiposity and non-alcoholic fatty liver disease (NAFLD) has not been well characterized. We studies 704 consecutive subjects who underwent annual health survey in Taiwan. All subjects have been divided into three groups including normal (341), mild (227) and moderate and severe (136) NAFLD according to ultrasound finding. Pericardial (PCF) and thoracic peri-aortic adipose tissue (TAT) burden was assessed using a non-contrast 16-slice multi-detector computed tomography (MDCT) dataset with off-line measurement (Aquarius 3DWorkstation, TeraRecon, SanMateo, CA, USA). We explored the relationship between PCF/TAT, NAFLD and cardiometabolic risk profiles. Patients with moderate and mild NAFLD have greater volume of PCF (100.7 ± 26.3vs. 77.1 ± 21.3 vs. 61.7 ± 21.6 ml, P < 0.001) and TAT (11.2 ± 4.1 vs. 7.6 ± 2.6 vs. 5.5 ± 2.6 ml, P < 0.001) when compared to the normal groups. Both PCF and TAT remained independently associated with NAFLD after counting for age, sex, triglyceride, cholesterol and other cardiometabolic risk factors. In addition, both PCF and TAT provided incremental prediction value for NAFLD diagnosis. (AUROC: 0.85 and 0.87, 95%, confidence interval: 0.82-0.89 and 0.84-0.90). Both visceral adipose tissues strongly correlated with the severity of NAFLD. Compared to PCF, TAT is more tightly associated with NAFLD diagnosis in a large Asian population.

SARS-CoV-2 versus other minor viral infection on kidney injury in asymptomatic and mildly symptomatic patients.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has become a global pandemic since December 2019. Most of the patients are mild or asymptomatic and recovered well as those suffered from other respiratory viruses. SARS-CoV-2 infection is supposed to demonstrate more sequelae. Acute kidney injury (AKI) is common among COVID-19 patients and is associated with disease severity and outcomes. Only a few studies focused on a detailed analysis of kidney damage in asymptomatic or mildly symptomatic COVID-19 patients. Whether any minor viral infection is likely to exhibit similar minor effect on renal function as COVID-19 is still unclear, and the definite pathophysiology of viral invasion is not fully understood. Currently, the proposed mechanisms of AKI include direct effects of virus on kidney, dysregulated immune response, or as a result of multi-organs failure have been proposed. This study will discuss the difference between COVID-19 and other viruses, focusing on proposed mechanisms, biomarkers and whether it matters with clinical significance.

Crevice Corrosion Behavior of Alloy 690 in High-Temperature Aerated Chloride Solution.

Crevice corrosion behavior of Alloy 690 in high-temperature aerated chloride solution was studied using a self-designed crevice device. The SEM, EDS, XRD, and XPS analyses results indicated that the oxide films outside the crevice consisted of Ni-Cr oxides containing a small amount of hydroxides, and the oxide films on crevice mouth consisted of a (Ni,Fe)(Fe,Cr)2O4 spinel oxides outer layer and a Cr(OH)3 inner layer, and the oxide films inside the crevice consisted of a α-CrOOH outer layer and a Cr(OH)3 inner layer. When crevice corrosion occurred, the hydrolysis of Cr3+ led to the formation of Cr(OH)3 inside the crevice, and caused the pH value of crevice solution to decrease, and Cl- migrated from outside the crevice into inside the crevice due to electrical neutrality principle and accumulation. When the water chemistry inside the crevice reached the critical value of active dissolution of metal, the active dissolution of metal inside the crevice occurred. In addition, (Ni,Fe)(Fe,Cr)2O4 spinel oxides on the crevice mouth were formed by the deposition of metal ions migrated from inside the crevice. The mechanism of crevice corrosion and the formation mechanism of oxide films at different regions were also discussed.

Electrochemical Self-Assembled Gold Nanoparticle SERS Substrate Coupled with Diazotization for Sensitive Detection of Nitrite.

The accurate determination of nitrite in food samples is of great significance for ensuring people's health and safety. Herein, a rapid and low-cost detection method was developed for highly sensitive and selective detection of nitrite based on a surface-enhanced Raman scattering (SERS) sensor combined with electrochemical technology and diazo reaction. In this work, a gold nanoparticle (AuNP)/indium tin oxide (ITO) chip as a superior SERS substrate was obtained by electrochemical self-assembled AuNPs on ITO with the advantages of good uniformity, high reproducibility, and long-time stability. The azo compounds generated from the diazotization-coupling reaction between nitrite, 4-aminothiophenol (4-ATP), and N-(1-naphthyl) ethylenediamine dihydrochloride (NED) in acid condition were further assembled on the surface of AuNP/ITO. The detection of nitrite was realized using a portable Raman spectrometer based on the significant SERS enhancement of azo compounds assembled on the AuNP/ITO chip. Many experimental conditions were optimized such as the time of electrochemical self-assembly and the concentration of HAuCl4. Under the optimal conditions, the designed SERS sensor could detect nitride in a large linear range from 1.0 × 10-6 to 1.0 × 10-3 mol L-1 with a low limit of detection of 0.33 µmol L-1. Additionally, nitrite in real samples was further analyzed with a recovery of 95.1-109.7%. Therefore, the proposed SERS method has shown potential application in the detection of nitrite in complex food samples.

Serum Fractalkine Levels Were Positively Associated with Disease Severity of Liver Cirrhosis.

OBJECTIVE: The chemokine receptor CX3CR1 and its specific ligand fractalkine (CX3CL1, FKN) has been implicated in modulating inflammatory and fibroproliferative diseases. The current study was performed to investigate the correlation of serum fractalkine levels with disease severity of liver fibrosis/cirrhosis (LC). METHODS: 162 LC patients and 140 healthy controls well enrolled in our study. Serum fractalkine levels were detected using commercial ELISA kit. Liver biopsy specimens were obtained using 16 G disposable needle in LC patients. The Child-Pugh grade was recorded to assess liver function. ROC curve analysis was performed to assess the potential diagnostic power of serum fractalkine with regard to the disease severity of Child-Pugh grade system. Pathological assessment of cirrhotic severity was performed by Laennec staging system. The L3 skeletal muscle index (L3SMI) was applicated to assess the nutrition status. RESULTS: Serum fractalkine levels were significantly higher in LC patients compared with healthy controls. The case group included 50 Child-Pugh A patients, 59 Child-Pugh B patients, and 53 Child-Pugh C patients. Cirrhosis patients with Child-Pugh C had drastically higher serum fractalkine levels compared with those with Child-Pugh B and A. Child-Pugh B patients showed significantly higher serum PACAP concentrations compared with those with Child-Pugh A. ROC curve analysis demonstrated that serum fractalkine may act as a potential indicator for disease progression of LC determined by Child-Pugh classification. Besides, serum fractalkine levels were positively related to ALT and AST concentrations and negatively related to L3SMI. CONCLUSION: Serum fractalkine levels were positively associated with disease severity of LC.

Sleeping, Smoking, and Kidney Diseases: Evidence From the NHANES 2017-2018.

Study Objectives: Smoking and sleep are modifiable factors associated with the chronic kidney diseases. However, the interaction of smoking and sleep on the renal function are still unclear. Therefore, we aimed to evaluate the interactive impacts of smoking and sleep on the renal function. Methods: Data were obtained from the National Health and Nutrition Examination Survey. The study population were categorized into nine subgroups by smoking (smoking every day, sometimes, and non-smokers recently) and sleep duration (short duration ≤ 6 h, normal duration 6-9 h, and longer duration ≥ 9 h on the weekdays). Results: The study group with a short sleep duration had significantly higher serum cotinine and hydrocotinine levels compared with the other two sleep groups. After adjusting the demographic characteristics (age, race, body mass index, and marital status), sleep quality (snoring or breathing cessation), and comorbidities (diabetes mellitus, hypertension, high cholesterol, anemia, congestive heart failure, coronary heart disease, and stroke), non-smokers with short or long sleep duration had significant lower estimated glomerular filtration rate (eGFR) levels than the study group who smoked every day and slept ≤ 6 h. The effects of sleep duration on eGFR levels varied with smoking status. For the study group smoking every day, eGFR levels increased as sleep duration decreased, whereas for the study group smoking sometimes, eGFR levels increased as sleep duration increased. The U-shaped effects of eGFR levels were observed among non-smokers whose normal sleep duration was associated with better eGFR levels. Normal sleep duration was an important protective factor of the renal function for non-smokers than smokers. Conclusions: The effects of sleep duration on eGFR levels varied with smoking status. Normal sleep duration was a protective factor and more crucial for non-smokers than for smokers.

CircCCT3 Acts as a Sponge of miR-613 to Promote Tumor Growth of Pancreatic Cancer Through Regulating VEGFA/VEGFR2 Signaling.

BACKGROUND: Circular RNAs (CircRNAs) have been recently implicated in the progression of pancreatic cancer (PC). AIMS: To investigate the involvement of CircCCT3 in PC and studying its interactions and functioning during the progression of PC in vitro and in vivo, using methods of molecular biology and bioinformatics. STUDY DESIGN: Experimental study. METHODS: The expressions of CircCCT3 and miR-613 in pancreatic carcinoma tissues and cell lines were evaluated by quantitative real-time polymerase chain reaction (PCR). The relationship between clinical pathologic features as well as the survival rate and CircCCT3 expression was analyzed with chi-square test and the Kaplan-Meier method. CCK-8, wound healing, transwell assays, and the fluorescein isothiocyanate- AnnexinV/propidium iodide (FITC-AnnexinV/PI) assay were used to assess cell proliferation, migration, invasion, and apoptosis after CircCCT3 overexpression or downregulation. The Dual- Luciferase reporter assay, RNA immunoprecipitation (RIP), RNA pull-down and fluorescence in situ hybridization (FISH) assays were performed to validate the potential interaction of CircCCT3, miR-613, and vascular endothelial growth factor (VEGFA). The nude mouse xenograft tumor assay was used to detect CircCCT3 effects on pancreatic tumorigenesis in vivo. Western blotting analysis was performed to examine the VEGFA and the vascular endothelial growth factor receptor 2 (VEGFR2) protein expressions following. RESULTS: CircCCT3 expression was significantly increased in PC tissues (3.41 ± 0.57 vs. 1.00 ± 0.10, P < .01) and cell lines (Patu8988 2.57 ± 0.20; SW1990 2.88 ± 0.10; BxPC-3 2.45 ± 0.20; Panc02 2.99 ± 0.10 vs. H6c7 1.00 ± 0.10; all P < .001). CircCCT3 expression was negatively correlated with miR-613 expression. PC patients with high CircCCT3 expression exhibited significantly poorer overall survival rate than those patients with low CircCCT3 expression (P = .013). Moreover, it was found that CircCCT3 promoted cell proliferation, migration, and invasion, and inhibited cell apoptosis in PC cells. The CircCCT3 acted as a sponge for the miR-613 to facilitate VEGFA and VEGFR2 expression. si-CirCCT3 also inhibited tumor growth of PC in nude mice. si-CircCCT3 reduced VEGFA and VEGFR2 expression, whereas overexpression of CircCCT3 increased VEGFA and VEGFR2 expression. CONCLUSION: Increased CircCCT3 suggests a poor prognosis for PC patients and promotes the migration and invasion through targeting VEGFA/VEGFR2 signaling. CircCCT3 may serve as a potential and promising therapeutic target for PC treatment.

Development of Highly Sensitive Immunosensor for Detection of Staphylococcus aureus Based on AuPdPt Trimetallic Nanoparticles Functionalized Nanocomposite.

The rapid and sensitive detection of Staphylococcus aureus (S. aureus) is essential to ensure food safety and protect humans from foodborne diseases. In this study, a sensitive and facile electrochemical immunosensor using AuPdPt trimetallic nanoparticles functionalized multi-walled carbon nanotubes (MWCNTs-AuPdPt) as the signal amplification platform was designed for the label-free detection of S. aureus. The nanocomposite of MWCNTs-AuPdPt was prepared by an in situ growth method of loading AuPdPt trimetallic nanoparticles on the surface of MWCNTs. The synthesized MWCNTs-AuPdPt featured good conductivity and superior catalytic performance for hydrogen peroxide. The nanocomposite of MWCNTs-AuPdPt with good biocompatibility and high specific surface area was further functionalized by anti-S. aureus antibodies. The immobilized antibodies could efficiently capture S. aureus to the modified electrode by an immune reaction, which resulted in the change of catalytic current intensity to realize the sensitive detection of S. aureus. The designed immunosensor could detect S. aureus in a linear range from 1.1 × 102 to 1.1 × 107 CFU mL-1 with a low detection limit of 39 CFU mL-1. Additionally, the proposed immunosensor was successfully applied to determine S. aureus in actual samples with acceptable results. This strategy provided a promising platform for highly sensitive determination of S. aureus and other pathogens in food products.

Quantitative analysis of colony number in mouldy wheat based on near infrared spectroscopy combined with colorimetric sensor.

Current work presented a novel method based on colorimetric sensor (CS) combined with visible/near-infrared spectroscopy (VNIRs) for the detection of volatile markers in wheat infected by Aspergillus glaucus. Wheat samples with different mouldy degree was cultivated for backup under temperature of 25-28 °C in incubator. The total colony number was determined by flat colony counting method. Through employing chemo-responsive dyes including 8-(4-nitrophenyl)-4, 4-difluoro-BODIPY (NO2BDP), 8-(4-bromophenyl)-4,4-difluoro-BODIPY(BrBDP) and 8-phenyl-4,4-difluoro- BODIPY(HBDP) as capture probes of colorimetric sensor for volatile organic compounds (VOCs). The spectral data of CS-VNIRs were scanned and used to build synergic interval partial least squares (Si-PLS) models. The optimized Si-PLS model based on HBDP sensor gave a better detection performance, and the correlation coefficient of the prediction set Rp = 0.9387. The achieved high correlation rates imply that the technique may be deployed as a panacea to identify and quantify the colony number of different mouldy wheat.

Grain boundary oxidation of proton-irradiated nuclear grade stainless steel in simulated primary water of pressurized water reactor.

Grain boundary (GB) oxidation of proton-irradiated 304 nuclear grade stainless steel in primary water of pressurized water reactor was investigated. The investigation was conducted by studying microstructure of the oxide and oxide precursor formed at GB on an "atom-by-atom" basis by a combination of atom-probe tomography and transmission electron microscope. The results revealed that increasing irradiation dose promoted the GB oxidation, in correspondence with a different oxide and oxide precursor formed at the GB. Correlation of the oxide and oxide precursor with the GB oxidation behavior has been discussed in detail.

Sialyltransferase Inhibitors Suppress Breast Cancer Metastasis.

We report the synthesis and evaluation of a series of cell-permeable and N- versus O-selective sialyltransferase inhibitors. Inhibitor design entailed the functionalization of lithocholic acid at C(3) and at the cyclopentane ring side chain. Among the series, FCW34 and FCW66 were shown to inhibit MDA-MB-231 cell migration as effectively as ST3GALIII-gene knockdown did. FCW34 was shown to inhibit tumor growth, reduce angiogenesis, and delay cancer cell metastasis in animal models. Furthermore, FCW34 inhibited vessel development and suppressed angiogenic activity in transgenic zebrafish models. Our results provide clear evidence that FCW34-induced sialyltransferase inhibition reduces cancer cell metastasis by decreasing N-glycan sialylation, thus altering the regulation of talin/integrin/FAK/paxillin and integrin/NFκB signaling pathways.

Electrochemical immunosensor based on self-assembled gold nanorods for label-free and sensitive determination of Staphylococcus aureus.

An electrochemical immunosensor based on self-assembled gold nanorods on glassy carbon electrode was developed for label-free and sensitive detection of Staphylococcus aureus (S. aureus). The gold nanorods were firstly assembled on the electrode surface by using poly-(diallyldimethylammonium chloride) (PDDA) and poly-(styrenesulfonate) (PSS) as the linkers, followed by the functionlization of anti-S. aureus antibodies. The immobilized antibodies on self-assembled gold nanorods could efficiently capture S. aureus to the modified electrode by the specific immune reaction, which clearly blocked the electron transfer of electrochemical probes on the electrode surface due to the resistance of S. aureus. Atomic force microscopy and electrochemical impedance spectroscopy were used to verify the stepwise assembly of the immunosensor fabrication. The immunosensor could detect S. aureus in a linear range from 1.8 × 103 to 1.8 × 107 CFU mL-1 with a low detection limit of 2.4 × 102 CFU mL-1. Furthermore, the designed electrochemical immunosensor was successfully used to determine S. aureus in milk samples with acceptable results. The proposed immunosensor could be further expanded to sensitive detect other pathogens with the addition of specific antibodies.

Simple electrochemical sensing for mercury ions in dairy product using optimal Cu2+-based metal-organic frameworks as signal reporting.

A convenient sensor is developed for electrochemical assay of Hg2+ in dairy product using the optimal Cu2+-based metal-organic frameworks (Cu-MOFs) as signal reporting. Benefiting from specific recognition between Hg2+ and thymine (T)-rich DNA strands, the interferences of milk matrices are effectively eliminated, thereby greatly improving the accuracy of test results. Moreover, the suitable Cu-MOFs offer an efficient carrier for probe design, and the contained Cu2+ ions could be directly detected to output electrochemical signal of Hg2+ presence without labor- or time-intensive operations. Compared with previous methods, this sensor substantially simplifies the process of electrochemical measurement and facilitates highly sensitive, selective and rapid analysis of Hg2+ with detection limit of 4.8 fM, offering a valuable means for monitoring dairy product contamination with Hg2+.