High-performance fentanyl molecularly imprinted electrochemical sensing platform designed through molecular simulations.

BACKGROUND: Fentanyl and its derivatives are a type of potent opioid analgesics, with the characteristics of diverse structure, high toxicity, extremely low content, and high fatality rate. Currently, they have become one of the most serious problems in international drug abuse control due to their extensive use in drug production and use. Therefore, the development of a rapid, sensitive, and accurate method for detecting trace fentanyl is of great significance. In this study, in view of its complex structure and trace concentration, a new molecular imprinting electrochemical sensor was developed through molecular simulations followed by experimental validation to detect trace fentanyl. RESULTS: The process consisted of first obtaining the optimal functional monomer and its molar ratio through molecular simulations. The recognition sites of fentanyl-imprinted polymers were predicted to guide the synthesis of imprinted membranes with precision approach to ensure an efficient and accurate reaction process. Reduced graphene oxide (ErGO) was then deposited on glassy carbon electrode surface by electrochemical reduction to yield large numbers of active sites suitable for catalyzing reactions of fentanyl piperidine for promoted efficient electron transfer and amplified sensitivity of the sensor. Accordingly, fentanyl molecularly imprinted film was formed through one-step electropolymerization to yield greatly improved sensing selectivity due to the specific recognition of molecularly imprinted polymer. Under optimal experimental conditions, the fentanyl sensor showed an extended detection range of 3.84 × 10-9 mol L-1-1.72 × 10-6 mol L-1 and a detection limit of 1.28 × 10-9 mol L-1. SIGNIFICANCE: A distinctive feature of this sensor is its molecularly imprinted polymerized membrane, which offers excellent specific recognition, thereby boosting the sensor's selectivity. Throughout the sensor's development process, molecular simulations were employed to steer the synthesis of molecularly imprinted polymers and predict the recognition sites of fentanyl-imprinted polymers. The experimental outcomes proved to align with the simulation data. The final sensor exhibited outstanding selectivity, repeatability, stability, and high sensitivity. The sensor was effectively used to reliably track fentanyl in human serum samples, with acceptable analytical reliability, suggesting its potential for practical applications.

A simple polyarginine membrane electrochemical sensor for the determination of MDMA and MDA.

In this study, a simple electrochemical sensor based on l-arginine membrane (P-L-arg/GCE) was developed for rapid and sensitive detection of MDMA and MDA. A polyarginine membrane was obtained through one-step direct electropolymerization, which provides more reaction sites for the analyte and improves the sensitivity of the sensor. Following the optimized selection parameters, the MDMA detection range was established at 1.0 × 10-7∼3.5 × 10-5 mol L-1, with a detection limit of 3.3 × 10-8 mol L-1. Similarly, the detection range for MDA was established at 1.0 × 10-7∼5.3 × 10-5 mol L-1 with a detection limit of 3.3 × 10-8 mol L-1. Additionally, the potential oxidation mechanism of MDMA and MDA during the REDOX process was analyzed by cyclic voltammetry. Furthermore, the proposed sensor exhibited superior selectivity, excellent reproducibility, and satisfactory stability. The proposed sensors can be used for reliable monitoring of MDMA or MDA in human urine and hair samples, respectively, and it has acceptable analytical reliability and enormous potential for practical applications.

A novel hydrangea-like magnetic composite Fe3O4@MnO2@ZIF-67 for efficient selective adsorption of Pd(II) from metallurgical wastewater.

The selective adsorption of palladium from wastewater is a feasible solution to solving palladium pollution and resource scarcity. Because traditional solvent extraction methods often involve the use of considerable amounts of organic solvents, research is focused on investigating adsorption techniques that can selectively remove palladium from wastewater. In this paper, the magnetic composite Fe3O4@MnO2@ZIF-67 was synthesized and its performance for the adsorption of Pd(II) in acidic water was investigated. Fe3O4@MnO2@ZIF-67 was characterized by various analytical methods such as TEM, SEM, EDS, BET, XRD, FTIR, zeta potential analysis, VSM, and TGA. The effects of palladium ion concentration, contact time, pH, and temperature on adsorption were evaluated. The kinetics were shown to follow the pseudo-second-order kinetic model and Elovich model, and the rate-limiting step was chemisorption. Thermodynamic studies showed that increasing the temperature promoted the adsorption of Pd(II), and the maximum uptake capacity of Fe3O4@MnO2@ZIF-67 for Pd(II) was 531.91 mg g-1. Interestingly, Fe3O4@MnO2@ZIF-67 exhibited superior selectivity for Pd(II) in the presence of Ir(IV), Pt(IV), and Rh(III). The adsorbent can be used repeatedly for selective adsorption of palladium. Even at the fifth cycle, the uptake rate of Pd(II) remained as high as 83.1%, and it showed a favorable adsorption capacity and selectivity for Pd(II) in real metallurgical wastewater. The adsorption mechanism was analyzed by SEM, FTIR, XRD, XPS, and DFT calculations, which indicated that electrostatic interactions and coordination with nitrogen-containing groups were involved. Fe3O4@MnO2@ZIF-67 is a promising adsorbent for the efficient adsorption and selective separation of palladium ions.

A promising and highly sensitive electrochemical platform for the detection of fentanyl and alfentanil in human serum.

A novel electrochemical method has been developed, based on a covalent organic framework (COF) and reduced graphene oxide (rGO), to detect fentanyl and alfentanil. COF nanomaterials with chrysanthemum morphology obtained by solvothermal reaction contain rich active sites for electrochemical catalytic reaction, thus improving the detection performance of the designed sensor. Reduced graphene oxide improves the sensor's sensitivity due to enhanced electron transfer. Under optimized experimental conditions, the fabricated electrode presents a linear range of 0.02 to 7.26 µM for alfentanil and 0.1 to 6.54 µM for fentanyl, with detection limits of 6.7 nM and 33 nM, respectively. In addition, the sensor possesses excellent selectivity, outstanding reproducibility, and acceptable stability. The proposed sensor is feasible for the reliable monitoring of fentanyl and alfentanil in human serum samples, with acceptable reliability and high potential in real-world applications. Finally, the electrochemical characteristic fingerprint of fentanyl is investigated by studying the electrochemical behavior of alfentanil and fentanyl on the electrode surface.

A multifunctional adsorbent based on 2,3-dimercaptosuccinic acid/dopamine-modified magnetic iron oxide nanoparticles for the removal of heavy-metal ions.

Overexploitation of nature by humans has led to an increasingly serious issue of heavy-metal water pollution. To reduce the threat of water pollution to humans and the environment, it is imperative to develop or improve the water treatment technology for heavy-metal-containing wastewater. Functionalized Fe3O4 magnetic nanoparticles (Fe3O4 MNPs) have been widely used as effective adsorbents for the removal of heavy-metal ions from water owing to their high efficiency, low cost, selective adsorption ability, and recyclability. In this study, Fe3O4@DA-DMSA magnetic nanoparticles (FDDMs) were prepared by the functionalization of Fe3O4 MNPs with environmentally friendly dopamine (DA) and a heavy-metal detoxifying agent such as 2,3-dimercaptosuccinic acid (DMSA) for the efficient and rapid adsorption of Pb2+, Cu2+, and Cd2+, with maximum adsorption capacities of 187.62, 63.01, and 49.46 mg/g, respectively. FDDMs exhibited the best ability to remove Pb2+ with a maximum adsorption capacity than that of the most reported Fe3O4 MNP-related adsorbents. In actual wastewater and multi-component simulated water samples contaminated with Pb2+, Cu2+, and Cd2+, the as-prepared adsorbent maintained a good removal ability for Pb2+ with low influence by ionic strength and interfering ions, as well as exhibited an excellent selectivity. According to the results of batch experiments and X-ray photoelectron spectroscopy (XPS) analysis of the adsorbent before and after adsorption, the adsorption mechanism of the adsorbent for the removal of heavy-metal ions mainly involves coordination and ion exchange. In addition, the adsorbent exhibited a good regeneration performance. Therefore, FDDMs can be considered as a promising adsorbent for the treatment of heavy-metal wastewater.

MicroRNA-128-3p suppresses interleukin-1ß-stimulated cartilage degradation and chondrocyte apoptosis via targeting zinc finger E-box binding homeobox 1 in osteoarthritis.

Accumulating studies have suggested that microRNAs (miRNAs) play vital roles in the pathogenesis of osteoarthritis (OA). Nevertheless, the specific function of miR-128-3p in OA remains unknown. In this study, we demonstrated that miR-128-3p was decreased and ZEB1 was increased in OA. Additionally, miR-128-3p expression was negatively correlated with ZEB1. miR-128-3p overexpression or ZEB1 silencing attenuated extracellular matrix degradation and cell apoptosis, and increased the proliferation of IL-1ß-activated CHON-001 cells. Furthermore, ZEB1 was directly targeted by miR-128-3p. In addition, ZEB1 upregulation restored the effects of miR-128-3p overexpression on OA progression. Overall, our findings suggested that miR-128-3p might regulate the development of OA via targeting ZEB1.

Diagnostic Accuracy of Procalcitonin for Bacterial Infection in Liver Failure: A Meta-Analysis.

The purpose of our studies was to systematically assess the accuracy and clinical value of plasma calcitonin in patients with liver failure complicated with bacterial infection. In this study, we included prospective observational studies or randomized controlled trials on PCT. The quality of the studies was evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. Heterogeneity, pooled diagnostic odds ratio (DOR), pooled sensitivity, pooled specificity, pooled positive likelihood ratio, pooled negative likelihood ratio, the area under the summary receiver operating characteristic curve (SROC), and metaregression analysis were performed using Stata16.0 software. Consequently, the studies revealed substantial heterogeneity (I 2 = 96, 95% confidence interval (95% CI) = 94-99). The results of meta-analysis using random effect models suggested that the combined DOR was 10.67 (95% CI = 3.73-30.53). In addition, the threshold effect analysis showed that the threshold effect was 0.23 and the correlation coefficient was -0.48, indicating that there was no threshold effect. In the forest map, the DOR of each study and the combined DOR are not distributed along the same line, and Q = 2.2 × 1014, P ≤ 0.001. Furthermore, the metaregression analysis of PCT study design, bacterial infection site, and mean age displayed that the P values were >0.05. The combined sensitivity was 0.77 (95% CI = 0.54-0.90), the combined specificity was 0.76 (95% CI = 0.70-0.82), the combined positive likelihood ratio was 3.25 (95% CI = 2.33-4.52), the combined negative likelihood ratio was 0.30 (95% CI = 0.14-0.67), and the combined AUC was 0.80 (95% CI = 0.76-0.83). In conclusion, PCT has moderate diagnostic value for adult liver failure complicated with bacterial infection, and it is a better auxiliary diagnostic index for liver failure with bacterial infection. However, the results of procalcitonin must be carefully interpreted combined with medical history, physical examination, and microbiological assessment.

VEGF165 gene-modified human umbilical cord blood mesenchymal stem cells protect against acute liver failure in rats.

BACKGROUND: Human umbilical cord blood mesenchymal stem cells (HUCB-MSCs) can exert a protective effect in rat models of acute liver failure (ALF). Vascular endothelial growth factor 165 (VEGF165 ) is the predominant VEGF isoform and possesses a strong pro-angiogenic function. In the present study, HUCB-MSC served as the gene delivery vehicle for the VEGF165 gene, and we explored the therapeutic effects of this system on ALF. METHODS: HUCB-MSCs were infected with an adenovirus expressing green fluorescent protein (GFP)-VEFG fusion protein (Ad-VEGF165 ) to overexpress VEGF165 or an adenovirus expressing GFP (Ad-GFP) as control. The control and modified HUCB-MSCs were then transplanted into ALF model rats. Liver function and liver pathological changes were assessed by biochemical tests and liver histology. Immunohistochemistry was carried out to determine the expression of, CD34, Ki67 and VEGF. RESULTS: VEGF165 overexpression enhanced the multipotency of HUCB-MSCs and promoted the homing and colonization of HUCB-MSC in the liver tissues of ALF rats. Furthermore, although HUCB-MSC transplantation ameliorated liver damage and promoted liver regeneration to some extent in ALF rats, Ad-VEGF165 -HUCB-MSC transplantation showed stronger therapeutic effects on ALF. CONCLUSIONS: In summary, transplantation of VEGF165 -modified HUCB-MSCs exert stronger therapeutic effects on ALF than HUCB-MSCs. The present study provides a novel therapeutic approach for ALF.

Optimizing screening strategies for coronavirus disease 2019: A study from Middle China.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has been highly epidemic in China since January 2020. Rapid detection of the causative agent, severe acute respiratory coronavirus-2 (SARS-CoV-2), is very important due to its high rate of infectivity. This study aimed to clarify the epidemiology and clinical characteristics of COVID-19 outside of Hubei province, China, and to optimize screening strategies for COVID-19 in attempts to contain spread of the virus. METHODS: This retrospective study included all confirmed cases of COVID-19 in Hunan Provincial People's Hospital (Changsha, China) between January 22 and February 15, 2020. All cases were detected using a real-time reverse transcription polymerase chain reaction assay. The epidemiology and clinical characteristic of these cases were investigated according to outcome in attempts to optimize screening strategies for COVID-19. RESULTS: There were 24 confirmed cases of COVID-19 in the fever outpatient department of Hunan Provincial People's Hospital. Three patients were asymptomatic, and 3 exhibited mild and 3 moderate disease. There was a family cluster phenomenon. CONCLUSION: Individuals with COVID-19 can be asymptomatic or exhibit mild manifestations of disease. Close monitoring and an optimized screening strategy for COVID-19 could help deter spread of the virus.

Therapeutic effect of human umbilical cord blood mesenchymal stem cells combined with G-CSF on rats with acute liver failure.

Human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) have been used to facilitate healing in animal models of liver injury, while granulocyte colony-stimulating factor (G-CSF) has been shown to stimulate stem cell mobilization and these cells may contribute to liver repair. hUCB-MSCs were characterized by flow cytometry, and transplanted into rats with d-galactosamine (D-GalN)/lipopolysaccharides (LPS)-induced acute liver failure (ALF) together with granulocyte colony-stimulating factor (G-CSF). Liver function, oxidative stress and pro-inflammatory cytokines expressions were examined using enzyme-linked immunosorbent assay (ELISA). Hematoxylin-eosin (HE) staining was used to observe the morphological changes. Apoptosis was investigated by terminal dUTP nick end labeling (TUNEL) staining. Bromodeoxyuridine (BrdU) cell proliferation assay was analyzed by immunofluorescence and immunohistochemistry. In the results, cultured hUCB-MSCs displayed proliferation and adipogenic and osteogenic differentiation potentials. hUCB-MSCs in combination with G-CSF significantly attenuated ALF-induced liver function injury. Furthermore, hUCB-MSCs and G-CSF treatment remarkably suppressed the secretions of pro-inflammatory cytokines and MDA activation induced by ALF. In addition, inflammation, lesions and cell apoptosis in liver tissues were obviously ameliorated by application of hUCB-MSCs and G-CSF. In conclusion, hUCB-MSCs, alone or co-treatment with G-CSF could ameliorate ALF in rats by inhibiting liver function injury, production of pro-inflammatory cytokines, oxidative stress, and liver cell apoptosis.