Engagement of AKT and ERK signaling pathways facilitates infection of human neuronal cells with West Nile virus.

West Nile virus (WNV) is an important neurotropic virus that accounts for the emergence of human arboviral encephalitis and meningitis. The interaction of WNV with signaling pathways plays a key role in controlling WNV infection. We have investigated the roles of the AKT and ERK pathways in supporting WNV propagation and modulating the inflammatory response following WNV infection. WNV established a productive infection in neuronal cell lines originated from human and mouse. Expression of IL-11 and TNF-α was markedly up-regulated in the infected human neuronal cells, indicating elicitation of inflammation response upon WNV infection. WNV incubation rapidly activated signaling cascades of AKT (AKT-S6-4E-BP1) and ERK (MEK-ERK-p90RSK) pathways. Treatment with AKT inhibitor MK-2206 or MEK inhibitor U0126 abrogated WNV-induced AKT or ERK activation. Strong activation of AKT and ERK signaling pathways could be detectable at 24 h after WNV infection, while such activation was abolished at 48 h post infection. U0126 treatment or knockdown of ERK expression significantly increased WNV RNA levels and viral titers and efficiently decreased IL-11 production induced by WNV, suggesting the involvement of ERK pathway in WNV propagation and IL-11 induction. MK-2206 treatment enhanced WNV RNA replication accompanied with a moderate decrease in IL-11 production. These results demonstrate that engagement of AKT and ERK signaling pathways facilitates viral infection and may be implicated in WNV pathogenesis.

Effect of Placental Transfusion on Long-Term Neurodevelopmental Outcomes in Premature Infants: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: The pathophysiology and the potential risks of placental transfusion (PT) differ substantially in preterm infants, necessitating specific studies in this population. This study aimed to evaluate the safety and efficacy of PT in preterm infants from the perspective of long-term neurodevelopmental outcomes. METHODS: We conducted a systematic literature search using placental transfusion, preterm infant, and its synonyms as search terms. Cochrane Central Register of Controlled Trials, Medline, and Embase were searched until March 07, 2023. Two reviewers independently identified, extracted relevant randomized controlled trials, and appraised the risk of bias. The extracted studies were included in the meta-analysis of long-term neurodevelopmental clinical outcomes using fixed-effects models. RESULTS: A total of 5612 articles were identified, and seven randomized controlled trials involving 2551 infants were included in our meta-analysis. Compared with immediate cord clamping (ICC), PT may not impact adverse neurodevelopment events. No clear evidence was found of a difference in the risk of neurodevelopmental impairment (risk ratio [RR]: 0.89, 95% confidence interval [CI]: 0.76 to 1.03, P = 0.13, I2 = 0). PT was not associated with the incidence of cerebral palsy (RR: 1.23, 95% CI: 0.59 to 2.57, P = 0.79, I2 = 0). Analyses showed no differences between the two interventions in cognitive, language, and motor domains of neurodevelopment. CONCLUSIONS: From the perspective of long-term neurodevelopment, PT at preterm birth may be as safe as ICC. Future studies should focus on standardized, high-quality clinical trials and individual participant data to optimize cord management strategies for preterm infants after birth.

Pressure-Induced Amidine Formation via Side-Chain Polymerization in a Charge-Transfer Cocrystal.

Compression of small molecules can induce solid-state reactions that are difficult or impossible under conventional, solution-phase conditions. Of particular interest is the topochemical-like reaction of arenes to produce polymeric nanomaterials. However, high reaction onset pressures and poor selectivity remain significant challenges. Herein, the incorporation of electron-withdrawing and -donating groups into π-stacked arenes is proposed as a strategy to reduce reaction barriers to cycloaddition and onset pressures. Nevertheless, competing side-chain reactions between functional groups represent alternative viable pathways. For the case of a diaminobenzene:tetracyanobenzene cocrystal, amidine formation between amine and cyano groups occurs prior to cycloaddition with an onset pressure near 9 GPa, as determined using vibrational spectroscopy, X-ray diffraction, and first-principles calculations. This work demonstrates that reduced-barrier cycloaddition reactions are theoretically possible via strategic functionalization; however, the incorporation of pendant groups may enable alternative reaction pathways. Controlled reactions between pendant groups represent an additional strategy for producing unique polymeric nanomaterials.

Joint modeling approaches for censored predictors due to detection limits with applications to metabolites data.

Measures of substance concentration in urine, serum or other biological matrices often have an assay limit of detection. When concentration levels fall below the limit, exact measures cannot be obtained, and thus are left censored. The problem becomes more challenging when the censored data come from heterogeneous populations consisting of exposed and non-exposed subjects. If the censored data come from non-exposed subjects, their measures are always zero and hence censored, forming a latent class governed by a distinct censoring mechanism compared with the exposed subjects. The exposed group's censored measurements are always greater than zero, but less than the detection limit. It is very often that the exposed and non-exposed subjects may have different disease traits or different relationships with outcomes of interest, so we need to disentangle the two different populations for valid inference. In this article, we aim to fill the methodological gaps in the literature by developing a novel joint modeling approach to not only address the censoring issue in predictors, but also untangle different relationships of exposed and non-exposed subjects with the outcome. Simulation studies are performed to assess the numerical performance of our proposed approach when the sample size is small to moderate. The joint modeling approach is also applied to examine associations between plasma metabolites and blood pressure in Bogalusa Heart Study, and identify new metabolites that are highly associated with blood pressure.

Epigenetic Reprogramming Drives Epithelial Disruption in Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) remains a major public health challenge that contributes greatly to mortality and morbidity worldwide. Although it has long been recognized that the epithelium is altered in COPD, there has been little focus on targeting it to modify the disease course. Therefore, mechanisms that disrupt epithelial cell function in patients with COPD are poorly understood. In this study, we sought to determine whether epigenetic reprogramming of the cell-cell adhesion molecule E-cadherin, encoded by the CDH1 gene, disrupts epithelial integrity. By reducing these epigenetic marks, we can restore epithelial integrity and rescue alveolar airspace destruction. We used differentiated normal and COPD-derived primary human airway epithelial cells, genetically manipulated mouse tracheal epithelial cells, and mouse and human precision-cut lung slices to assess the effects of epigenetic reprogramming. We show that the loss of CDH1 in COPD is due to increased DNA methylation site at the CDH1 enhancer D through the downregulation of the ten-eleven translocase methylcytosine dioxygenase (TET) enzyme TET1. Increased DNA methylation at the enhancer D region decreases the enrichment of RNA polymerase II binding. Remarkably, treatment of human precision-cut slices derived from patients with COPD with the DNA demethylation agent 5-aza-2'-deoxycytidine decreased cell damage and reduced air space enlargement in the diseased tissue. Here, we present a novel mechanism that targets epigenetic modifications to reverse the tissue remodeling in human COPD lungs and serves as a proof of concept for developing a disease-modifying target.

Carotid body denervation improves hyperglycemia in obese mice.

The carotid bodies (CBs) have been implicated in glucose abnormalities in obesity via elevation of activity of the sympathetic nervous system. Obesity-induced hypertension is mediated by insulin receptor (INSR) signaling and by leptin, which binds to the leptin receptor (LEPRb) in CB and activates transient receptor potential channel subfamily M member 7 (TRPM7). We hypothesize that in mice with diet-induced obesity, hyperglycemia, glucose intolerance, and insulin resistance will be attenuated by the CB denervation (carotid sinus nerve dissection, CSND) and by knockdown of Leprb, Trpm7, and Insr gene expression in CB. In series of experiments in 75 male diet-induced obese (DIO) mice, we performed either CSND (vs. sham) surgeries or shRNA-induced suppression of Leprb, Trpm7, or Insr gene expression in CB, followed by blood pressure telemetry, intraperitoneal glucose tolerance and insulin tolerance tests, and measurements of fasting plasma insulin, leptin, corticosterone, glucagon and free fatty acids (FFAs) levels, hepatic expression of gluconeogenesis enzymes phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6-phosphatase (G-6-Pase) mRNA and liver glycogen levels. CSND decreased blood pressure, fasting blood glucose levels and improved glucose tolerance without any effect on insulin resistance. CSND did not affect any hormone levels and gluconeogenesis enzymes, but increased liver glycogen level. Genetic knockdown of CB Leprb, Trpm7, and Insr had no effect on glucose metabolism. We conclude that CB contributes to hyperglycemia of obesity, probably by modulation of the glycogen-glucose equilibrium. Diabetogenic effects of obesity on CB in mice do not occur via activation of CB Leprb, Trpm7, and Insr.NEW & NOTEWORTHY This paper provides first evidence that carotid body denervation abolishes hypertension and improves fasting blood glucose levels and glucose tolerance in mice with diet-induced obesity. Furthermore, we have shown that this phenomenon is associated with increased liver glycogen content, whereas insulin sensitivity and enzymes of gluconeogenesis were not affected.

Study on the Relationship Between the Number of Adverse Drug Reactions of Essential Drugs and Visits: Based on Vector Autoregressive Model.

Objective: To analyse the relationship between the adverse drug reactions (ADRs) of essential drugs and visits, based on the recorded annual increase in ADRs associated with essential medicines in China, to provide a reliable theoretical basis for further analysis and optimization of the safety of essential drugs. Methods: The data of adverse reactions of essential drugs in China from 2011 to 2020, time series analysis was conducted, and vector autoregressive (VAR) model was established. The relationship between the number of ADRs and visits was explored empirically through Granger causality test, impulse response function and variance decomposition. Results: There was a long-term cointegration relationship and one-way causality between the number of visits and ADRs caused by essential medicines. In the initial stage, the ADR response to the number of visits increased sharply, but with an increase in the number of lag periods, the impact remained basically stable, even showing a slight decreasing trend. Conclusion: The number of visits impacts ADRs caused by essential medicines, but this impact remains basically stable after reaching a certain level.

Inhibition of MMP-2 and MMP-9 attenuates surgery-induced cognitive impairment in aged mice.

BACKGROUND: The inhibition of matrix metalloproteinases (MMPs) has shown potential in the treatment of various neurodegenerative diseases, and perioperative neurocognitive disorders (PND) is accompanied by the increased expression of MMP-2 and MMP-9 in the hippocampus. However, the effect of inhibiting MMP-2 and MMP-9 on PND is not clear. In this study we aimed to evaluate the effects of inhibiting MMP-2 and MMP-9 on cognitive function in the aged mice after surgery, in order to find a possible target for the prevention and treatment of PND METHODS: In this study, 14-month-old C57BL/6 mice were used to establish a PND model by tibial fracture surgery and sevoflurane anesthesia. Three days later, part of the mice were subjected to cognitive assessment and the other was sacrificed for biochemical analysis. We used the Novel object recognition test and Fear conditioning test to evaluate the postoperative cognitive function of mice. The expression of mmp-2 and MMP-9 was detected by western blotting. We also examined the expression of claudin-5 and occludin using Western blotting, and the activation of microglia and astrocytes using immunofluorescence. RESULTS: The results showed that surgery increased the expression of MMP-2 and MMP-9 in the hippocampus of mice, accompanied by cognitive impairment, decreased expression of claudin-5 and occludin, and increased activation of microglia and astrocytes. However, inhibition of MMP-2 and MMP-9 expression by SB-3CT reversed these changes. CONCLUSIONS: Our study shows that inhibition of MMP-2 and MMP-9 alleviates anesthesia/surgery-induced cognitive decline by increasing BBB integrity and inhibiting glial cell activation.

Proinflammatory Bone Marrow Mesenchymal Stem Cell-Derived Exosomal miR-150-3p Suppresses Proinflammatory Polarization of Alveolar Macrophages in Sepsis by Targeting Inhibin Subunit Beta A.

Bone marrow mesenchymal stem cell (BMSC)-derived exosomes can protect lung tissues against sepsis, but its related mechanism remains elusive. BMSCs were primed with or without lipopolysaccharide (LPS) before extracting exosomes. The isolated exosomes were identified by transmission electron microscopy, nanoparticle tracking analysis, and western blot. LPS-stimulated macrophages were cocultured with exosomes for 24 h, followed by enzyme-linked immunosorbent assay, flow cytometry, and molecular experiments. Bioinformatics and luciferase assay were employed to investigate the interaction between miR-150-3p and inhibin subunit beta A (INHBA). MiR-150-3p expression was increased in exosomes in a proinflammatory environment. Exosomes suppressed proinflammatory polarization by downregulating IL-6, IL-1ß, iNOS, and CD86, as well as promoted anti-inflammatory polarization by upregulating IL-10, ARG-1, and CD206 in LPS-stimulated macrophages. Such effects were more pronounced by LPS-primed exosomes, which was reversed in the absence of miR-150-3p. MiR-150-3p targeted INHBA. INHBA silencing decreased CD86 expression and increased CD206 expression in macrophages, but these effects were reversed by exosomal miR-150-3p inhibition. Proinflammatory BMSC-derived exosomal miR-150-3p suppressed proinflammatory polarization and promoted anti-inflammatory polarization of alveolar macrophages to attenuate LPS-induced sepsis by targeting INHBA.

Progress in the treatment of neonatal hypoxic-ischemic encephalopathy with umbilical cord blood mononuclear cells.

Neonatal hypoxic-ischemic encephalopathy (HIE) is a common disease among newborns, which is a leading cause of neonatal death and permanent neurological sequelae. Therapeutic hypothermia (TH) is the only method for the treatment of HIE that has been recognized effective clinically at home and abroad, but the efficacy is limited. Recent research suggests that the cord blood-derived mononuclear cells (CB-MNCs), which the refer to blood cells containing one nucleus in the cord blood, exert anti-oxidative, anti-inflammatory, anti-apoptotic effects and play a neuroprotective role in HIE. This review focuses on safety and efficacy, the route of administration, dose, timing and combination treatment of CB-MNCs in HIE.

Dimethyl fumarate attenuates cholestatic liver injury by activating the NRF2 and FXR pathways and suppressing NLRP3/GSDMD signaling in mice.

The progression of cholestasis is characterized by excessive accumulation of bile acids (BAs) in the liver, which leads to oxidative stress (OS), inflammation and liver injury. There are currently limited treatments for cholestasis. Therefore, appropriate drugs for cholestasis treatment need to be developed. Dimethyl fumarate (DMF) has been widely used in the treatment of various diseases and exerts antioxidant and anti-inflammatory effects, but its effect on cholestatic liver disease remains unclarified. We fed mice 3,5-diethoxycarbonyl-1,4-dihydrocollidine or cholic acid to induce cholestatic liver injury and treated these mice with DMF to evaluate its protective ability. Alanine aminotransferase, aspartate aminotransferase, and total liver BAs were assessed as indicators of liver function. The levels of OS, liver inflammation, transporters and metabolic enzymes were also measured. DMF markedly altered the relative ALT and AST levels and enhanced the liver antioxidant capacity. DMF regulated the MST/NRF2 signaling pathway to protect against OS and reduced liver inflammation through the NLRP3/GSDMD signaling pathway. DMF also regulated the levels of BA transporters by promoting FXR protein expression. These findings provide new strategies for the treatment of cholestatic liver disorders.

COVID-19 vaccination likelihood among federally qualified health center patients: Lessons learned for future health crises.

BACKGROUND: To prepare for rollout of a COVID-19 vaccine in fall 2020, there was an urgent need to understand barriers to ensuring equitable access and addressing vaccine skepticism and resistance. This study aimed to understand the association between trusted sources of COVID-19 information and likelihood of vaccination during that time, focusing on lessons learned to prepare for future public health crises. METHODS: From December 2020-March 2021, we surveyed a probability-based, cross-sectional sample of 955 patients across seven federally qualified health centers (FQHCs) serving predominantly low-income, Black and White populations in southeastern Louisiana. Vaccination likelihood was measured on a 7-point scale; "very likely to vaccinate" was defined as score=7. Trust in healthcare provider was measured with a single survey item. High trust in personal contacts, government, and media, respectively, were defined as the highest tertiles of summative scores of trust items. Weighted multivariable logistic regression estimated adjusted odds ratios (aOR) and 95% confidence intervals (CI) for being very likely to vaccinate. RESULTS: Participants were 56% Black, 64% women, mean age 44.6 years; 33% were very likely to vaccinate. High trust in healthcare provider (aOR=4.14, 95% CI 2.26-7.57) and government sources (aOR=3.23, 95% CI 1.98-5.28) were associated with being very likely to vaccinate. CONCLUSIONS: During initial COVID-19 vaccination rollout, trust in healthcare providers and government sources of COVID-19 information was associated with likelihood to vaccinate in FQHC patients. To inform public health planning for future crises, we highlight lessons learned for translating community-relevant insights into direct action to reach those most impacted.

On testing proportional odds assumptions for proportional odds models.

Proportional odds models are commonly used to model ordinal responses, but the proportional odds assumption may not hold in practice, leading to biased inference. Tests such as score, Wald and likelihood ratio (LR) have been proposed to evaluate the proportional odds assumption based on models without the assumption. Brant has proposed an independent binary model-based Wald-type test, and Wolfe and Gould have extended the idea to propose an LR-type test. This paper provides a brief review of the Brant and Wolfe-Gould tests for evaluating the proportional odds assumption and evaluates their performance through simulation studies and a real data example. Sample programs are provided in SAS, SPSS and Stata to facilitate the implementation of these tests using standard statistical software packages. This study highlights the importance of evaluating the proportional odds assumption when using proportional odds models for ordinal responses. The sample programs provided in this paper make it easy for researchers to apply these tests in their own analyses using standard statistical software packages.

Estimating the individual singleton preterm birth risk: nomogram establishment and independent validation.

Background: To establish and independently validate nomograms for predicting singleton preterm birth (PTB) risk based on a large sample size comprising data from two independent datasets. Methods: This cohort study used data from 50 states and the District of Columbia in the National Vital Statistics System (NVSS) database between January 2016 and December 2020. Multivariate logistic regression analysis was used to confirm the independent risk factors for PTB. Statistically significant variables were incorporated into the logistic regression models to establish PTB prediction nomograms. The models were developed using the United States (US)-derived data and were independently validated using data from US Territories. Results: A total of 16,294,529 mother-newborn pairs from the US were included in the training set, and 54,708 mother-newborn pairs from the US Territories were included in the validation set. In all, 4 nomograms were built: 1 to predict PTB probability, and another 3 to predict moderately and late PTB probability, very PTB probability, and extremely PTB probability, respectively. Hypertensive eclampsia and infertility treatment were found to be the top 2 contributors to PTB. Conclusions: We developed and validated nomograms to predict the individualized probability of PTB, which could be useful to physicians for improved early identification of PTB and in making individualized clinical decisions.

Differences among fathers, mothers, and teachers in symptom assessment of ADHD patients.

Background: The Swanson Nolan, and Pelham scale version IV (SNAP-IV) is the most critical tool for ADHD screening and diagnosis, which has two scoring methods. ADHD requires symptom assessment in multiple scenarios, and parent and teacher reports are indispensable for diagnosing ADHD. But the differences of assessment results from fathers, mothers and teachers, and the consistency of results from different scoring methods are unknown. Therefore, we carried out this study to understand the differences in the scores of fathers, mothers and teachers using SNAP-IV for children with ADHD and to explore the differences in scoring results under different scoring methods. Methods: The SNAP-IV scale and Demographics Questionnaire and Familiarity Index were used to survey fathers, mothers and head teachers. Measurement data are expressed as the mean ± standard deviation (x ± s). The enumeration data were described by frequency and percentage. ANOVA was used to compare group differences in mothers', fathers', and teachers' mean SNAP-IV scores. The Bonferroni method was used for post hoc multiple comparison tests. Cochran's Q test was used to compare the differences in the abnormal rate of SNAP-IV score results of mothers, fathers and teachers. Dunn's test was used for post hoc multiple comparison tests. Results: There were differences in scores among the three groups, and the differences showed inconsistent trends across the different subscales. Differences between groups were calculated again with familiarity as a control variable. The results showed the familiarity of parents and teachers with the patients did not affect the differences in their scores. The evaluation results were different under two assessment methods. Conclusion: Results concluded that fathers did not appear to be an appropriate candidate for evaluation. When using the SNAP-V for assessment, it should be comprehensively considered from both the scorer and symptom dimensions.

Inhibition of tick-borne encephalitis virus in cell cultures by ribavirin.

Tick-borne encephalitis virus (TBEV) belonging to arboviruses is a major member of zoonotic pathogens. TBEV infection causes severe human encephalitis without specific antiviral drugs. Due to its use of antiviral drug against a wide range of viruses, we investigated antiviral effect of ribavirin against TBEV in susceptible human cell lines A549 and SH-SY5Y. Ribavirin displayed minor cytotoxicity on multiple cell lines. Ribavirin obviously impaired TBEV replication and protected the infected cells from cytopathic effect. Importantly, ribavirin markedly inhibited TBEV propagation, as evidenced by impairment of TBEV production and viral RNA replication. Treatment with ribavirin (co-treatment and post-treatment) led to a dose-dependent reduction in TBEV titers as well as the viral RNA levels. Antiviral protein myxovirus resistance A mRNA expression was significantly up-regulated and signal transducer and activator of transcription 3 was activated in TBEV-infected A549 cells upon the ribavirin treatment. Induction of inflammatory cytokine tumor necrosis factor alpha by TBEV was decreased in A549 cells with the treatment of ribavirin, whereas interleukin 1 beta release appeared to be unaffected. These results suggest that ribavirin might represent a promising safe and effective antiviral drug against TBEV.

Exercise-primed extracellular vesicles improve cell-matrix adhesion and chondrocyte health.

Extracellular vesicles (EVs) have been suggested to transmit the health-promoting effects of exercise throughout the body. Yet, the mechanisms by which beneficial information is transmitted from extracellular vesicles to recipient cells are poorly understood, precluding a holistic understanding of how exercise promotes cellular and tissue health. In this study, using articular cartilage as a model, we introduced a network medicine paradigm to simulate how exercise facilitates communication between circulating EVs and chondrocytes, the cells resident in articular cartilage. Using the archived small RNA-seq data of EV before and after aerobic exercise, microRNA regulatory network analysis based on network propagation inferred that circulating EVs activated by aerobic exercise perturb chondrocyte-matrix interactions and downstream cellular aging processes. Building on the mechanistic framework identified through computational analyses, follow up experimental studies interrogated the direct influence of exercise on EV-mediated chondrocyte-matrix interactions. We found that pathogenic matrix signaling in chondrocytes was abrogated in the presence of exercise-primed EVs, restoring a more youthful phenotype, as determined by chondrocyte morphological profiling and evaluation of chondrogenicity. Epigenetic reprograming of the gene encoding the longevity protein, α-Klotho, mediated these effects. These studies provide mechanistic evidence that exercise transduces rejuvenation signals to circulating EVs, endowing EVs with the capacity to ameliorate cellular health even in the presence of an unfavorable microenvironmental signals.

Sugammadex Is Associated With Reduced Pulmonary Complications in Patients With Respiratory Dysfunction.

INTRODUCTION: Use of sugammadex is associated with fewer postoperative pulmonary complications (PPCs). This study investigated the relationship between sugammadex and PPCs in specific patients with respiratory dysfunction. MATERIALS AND METHODS: We reviewed the electronic medical and anesthesia records of patients with respiratory dysfunction who underwent laparoscopic gastric or intestinal surgery at a single center between May 1, 2018 and December 31, 2019. The patients were divided into the sugammadex group and the nonsugammadex group, based on whether they received sugammadex or neostigmine. Binary logistic regression analyses were used to characterize the differences in incidence of PPC. RESULTS: A total of 112 patients were included, of which 46 patients (41.1%) received sugammadex. In the logistic regression analysis, the incidences of PPC were fewer in the sugammadex group. Postoperative fever (odds ratio [OR] 0.330; 95% confidence interval [CI] 0.137-0.793, P = 0.0213), postoperative intensive care unit admission (OR 0.204; 95% CI 0.065-0.644, P = 0.007), cough (OR 0.143; 95% CI 0.061- 0.333, P < 0.001), pleural effusion (all) (OR: 0.280; 95% CI 0.104- 0.759, P = 0.012), pleural effusion (massive) (OR: 0.142; 95% CI 0.031- 0.653, P = 0.012), and difficulty in breathing (OR: 0.111; 95% CI 0.014-0.849, P = 0.039) showed significant differences between the two groups. CONCLUSIONS: Sugammadex is associated with a reduction in PPC in patients with respiratory dysfunction.

Chemometrics and antioxidant activity assisted nontargeted metabolomics for the identification of ginger species.

An ultrahigh-performance liquid chromatography coupled with ion mobility quadrupole time-of-flight mass spectrometry method was developed for the separation and identification of phenols, organic acids, flavonoids and curcumin in different species of ginger. The parameters affecting the separation and response of liquid chromatography, including the stationary phase and mobile phase, were systematically investigated and optimized. To further identify the differential metabolites in the six types of samples, a chemometric approach was introduced. Principal component analysis, cluster analysis and partial least squares discriminant analysis were used to identify the major components in the samples and to compare the compositional differences between the various samples. In addition, antioxidant experiments were designed to investigate the differences in antioxidant activity among the six ginger samples. The method showed good linearity (R2 ≥0.9903), satisfactory precision (RSD% ≤ 4.59 %), low LOD (0.35-25.86 ng/mL) and acceptable recovery (78-109 %) and reproducibility (RSD% ≤ 4.20 %). Therefore, the method has great potential for application in the compositional analysis and quality control of ginger.

Magnetic quantum dots barcodes using Fe3O4/TiO2 with weak spectral absorption in the visible region for high-sensitivity multiplex detection of tumor markers.

Magnetic quantum dot (QD) barcode holds great potential for automatic suspension array and rapid point-of-care detection since it enables simultaneous target encoding, enrichment and separation. However, a serious obstacle to enhancing the encoding capacity of magnetic QD microbeads (MBs) is the fluorescence quenching of magnetic nanoparticles (MNPs) to quantum dots (QDs) in the visible wavelength range due to the broad and strong optical absorption spectrum of MNPs. Here, we report Fe3O4/TiO2 core/shell MNPs and CdSe/ZnS QDs for the construction of dual-function magnetic QD barcodes. Fe3O4/TiO2 MNPs can significantly inhibit fluorescence quenching because the weak absorption of visible light by the TiO2. The two-dimension barcode library of 30 magnetic QD barcodes was constructed based on Fe3O4/TiO2 MNPs and CdSe/ZnS QDs. Moreover, the magnetic QD barcodes showed high sensitivity for the multiplex detection of four tumor markers, cancer antigen 125 (CA125), cancer antigen 199 (CA199), alpha-fetoprotein (AFP), and neuron specific enolase (NSE) with detection limits of 0.89 KU/L, 0.72 KU/L, 0.05 ng/mL, and 0.15 ng/mL, respectively. This bifunctional magnetic QD barcodes are promising for automatic high-sensitivity multiplex bioassay.