Correction: Promoter-regulated in vivo asymmetric self-assembly strategy to synthesize heterogeneous nanoparticles for signal amplification.

Correction for 'Promoter-regulated in vivo asymmetric self-assembly strategy to synthesize heterogeneous nanoparticles for signal amplification' by Chen Chen et al., Nanoscale, 2022, 14, 16180-16184, https://doi.org/10.1039/D2NR04661J.

Validation of a Simplified Model for Subarachnoid Hemorrhage in Mice.

BACKGROUND: Subarachnoid hemorrhage (SAH) represents a severe injury to the brain and is associated with a high mortality (40%). Several experimental SAH models are described in the literature requiring specialized equipment and a high degree of surgical expertise. Our goal was to validate a simplified, cost-effective model to permit future studies of SAH. METHODS: SAH was induced by injection of homologous blood into the cisterna magna. Perfusion-fixation then perfusion of gelatinous India ink was performed. Brains and brainstems were collected and imaged for analysis of cerebral vasospasm. Triphenyl tetrazolium chloride (TTC) staining was used to analyze brain tissue cell death 24 hours following stroke. A composite neuroscore was utilized to assess SAH-related neurologic deficits. RESULTS: Anterior cerebral artery and basilary artery diameters were significantly reduced at 24 hours post SAH induction. Middle cerebral artery diameter was also reduced; however, the results were not significant. TTC staining showed no infarcted tissue. Neuroscores were significantly lower in the SAH mice, indicating the presence of functional deficits. CONCLUSIONS: This simplified model of SAH elicits pathological changes consistent with those described for more complex models in the literature. Therefore, it can be used in future preclinical studies examining the pathophysiology of SAH and novel treatment options.

mRNA Delivery Systems Based on Protein Nanocages: How Far Can We Go?

Messenger RNA (mRNA) therapeutics hold great potential in the prevention and treatment of many diseases owing to several unique advantages. Delivery of mRNA into target cells is a critical step in mRNA therapy. Efficient and safe delivery systems remain an urgent need. Here, we provide an overview of the current applications of protein nanocages (PNCs), which include different types of PNCs, such as viral capsids, nonviral PNCs, and artificial PNCs, in mRNA delivery. PNCs have the features of uniform size, controllable assembly, modifiable inner and outer surfaces, good biocompatibility, and biodegradability, making them ideal candidates for mRNA delivery. In this review, the properties, loading strategies, and delivery outcomes of each tested PNC are introduced. The challenges faced by PNC-based mRNA carriers are discussed. We also share our perspectives on possible strategies to address these challenges, emphasizing the opportunities brought by emerging technologies and disciplinary convergence.

Plasma Neurofilament Light Relates to Divergent Default and Salience Network Connectivity in Alzheimer's Disease and Behavioral Variant Frontotemporal Dementia.

Background: Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD) show differential vulnerability to large-scale brain functional networks. Plasma neurofilament light (NfL), a promising biomarker of neurodegeneration, has been linked in AD patients to glucose metabolism changes in AD-related regions. However, it is unknown whether plasma NfL would be similarly associated with disease-specific functional connectivity changes in AD and bvFTD. Objective: Our study examined the associations between plasma NfL and functional connectivity of the default mode and salience networks in patients with AD and bvFTD. Methods: Plasma NfL and neuroimaging data from patients with bvFTD (n = 16) and AD or mild cognitive impairment (n = 38; AD + MCI) were analyzed. Seed-based functional connectivity maps of key regions within the default mode and salience networks were obtained and associated with plasma NfL in these patients. RESULTS: We demonstrated divergent associations between NfL and functional connectivity in AD + MCI and bvFTD patients. Specifically, AD + MCI patients showed lower default mode network functional connectivity with higher plasma NfL, while bvFTD patients showed lower salience network functional connectivity with higher plasma NfL. Further, lower NfL-related default mode network connectivity in AD + MCI patients was associated with lower Montreal Cognitive Assessment scores and higher Clinical Dementia Rating sum-of-boxes scores, although NfL-related salience network connectivity in bvFTD patients was not associated with Neuropsychiatric Inventory Questionnaire scores. CONCLUSIONS: Our findings indicate that plasma NfL is differentially associated with brain functional connectivity changes in AD and bvFTD.

Waste-green infrastructure nexus: Green roof promotion by digestate and digestate biochar from food waste.

Waste-Green Infrastructure Nexus is crucial to mitigate carbon emissions in waste disposal and promote eco-functions of green infrastructure in a circular bio-economy. Our purpose is to verify the feasibility of the nexus via "food waste anaerobic digestion - digestate/digestate biochar - green roof promotion". The results found that food waste digestate and digestate biochar significantly promoted green roof plant growth, evapotranspiration, rainwater retention, runoff reduction, and prevention of nutrient leaching. Digestate treatments were better than digestate biochar for the green roof promotion. The promotion ranked consistently with 20 % digestate > 10 % digestate > 20 % digestate biochar > 10 % digestate biochar > control in stolon growth, leaf emergence, branching of Paspalum vaginatum, green roof establishment, rainwater retention, runoff reduction, and the leaching of nitrogen, phosphorus, potassium. This study demonstrated that food waste could be regenerated to promote urban green infrastructure to form a circular bio-economy by the Waste-Green Infrastructure Nexus.

Transcriptomic analysis of salt-tolerant and sensitive high-yield japonica rice (Oryza sativa L.) reveals complicated salt-tolerant mechanisms.

Developing and cultivating rice varieties is a potent strategy for reclaiming salinity-affected soils for rice production. Nevertheless, the molecular mechanisms conferring salt tolerance, especially in conventional high-yield japonica rice varieties, remain obscure. In this study, Zhendao 23309 (ZD23309) exhibited significantly less grain yield reduction under a salt stress gradient than the control variety Wuyunjing 30 (WYJ30). High positive correlations between grain yield and dry matter accumulation at the jointing, heading and maturity stages indicated that early salt tolerance performance is a crucial hallmark for yield formation. After a mild salt stress (85 mM NaCl) of young seedlings, RNA sequencing (RNA-seq) of shoot and root separately identified a total of 1952 and 3647 differentially expressed genes (DEGs) in ZD23309, and 2114 and 2711 DEGs in WYJ30, respectively. Gene ontology (GO) analysis revealed numerous DEGs in ZD23309 that play pivotal roles in strengthening salt tolerance, encompassing the response to stimulus (GO:0050896) in shoots and nucleoside binding (GO:0001882) in roots. Additionally, distinct expression patterns were observed in a fraction of genes in the two rice varieties under salt stress, corroborating the efficacy of previously reported salt tolerance genes. Our research not only offers fresh insights into the differences in salt stress tolerance among conventional high-yield rice varieties but also unveils the intricate nature of salt tolerance mechanisms. These findings lay a solid groundwork for deciphering the mechanisms underlying salt tolerance.

Diallyl disulfide antagonizes DJ-1 mediated proliferation, epithelial-mesenchymal transition, and chemoresistance in gastric cancer cells.

Diallyl disulfide (DADS), an organic component of allicin abstracted from garlic, possesses multi-target antitumor activity. DJ-1 performs a vital function in promoting AKT aberrant activation via down-regulating phosphatase and tensin homologue (PTEN) in tumors. It is unknown the involvement of DJ-1 in epithelial-mesenchymal transition (EMT) of gastric cancer (GC) cells. The purpose of this study is to investigate whether diallyl disulfide (DADS) intervenes in the role of DJ-1 in GC. Based on the identification that the correlation between high DJ-1 and low PTEN expression in GC was implicated in clinical progression, we illuminated that down-regulation of DJ-1 by DADS aided in an increase in PTEN expression and a decrease in phosphorylated AKT levels, which was in line with the results manifested in the DJ-1 knockdown and overexpressed cells, concurrently inhibiting proliferation, EMT, migration, and invasion. Furthermore, the antagonistic effects of DADS on DJ-1 were observed in in vivo experiments. Additionally, DADS mitigated the DJ-1-associated drug resistance. The current study revealed that DJ-1 is one of potential targets for DADS, which hopefully provides a promising strategy for prevention and adjuvant chemotherapy of GC.

Sea Cucumber and Blueberry Extracts Suppress Inflammation and Reduce Acute Lung Injury through the Regulation of NF-κB/MAPK/JNK Signaling Pathway in Lipopolysaccharide-Treated C57BL/6 Mice.

Acute lung injury (ALI) represents a life-threatening condition with high morbidity and mortality despite modern mechanical ventilators and multiple pharmacological strategies. Therefore, there is a need to develop efficacious interventions with minimal side effects. The anti-inflammatory activities of sea cucumber (Cucumaria frondosa) and wild blueberry (Vaccinium angustifolium) extracts have been reported recently. However, their anti-inflammatory activities and the mechanism of action against ALI are not fully elucidated. Thus, the present study aims to understand the mechanism of the anti-inflammatory activity of sea cucumber and wild blueberry extracts in the context of ALI. Experimental ALI was induced via intranasal lipopolysaccharide (LPS) instillation in C57BL/6 mice and the anti-inflammatory properties were determined by cytokine analysis, histological examination, western blot, and qRT-PCR. The results showed that oral supplementation of sea cucumber extracts repressed nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways, thereby downregulating the expression of interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF) in the lung tissue and in the plasma. Wild blueberry extracts also suppressed the expression of IL-4. Furthermore, the combination of sea cucumber and wild blueberry extracts restrained MAPK signaling pathways by prominent attenuation of phosphorylation of NF-κB, c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK) while the levels of pro-inflammatory cytokines were significantly suppressed. Moreover, there was a significant and synergistic reduction in varying degrees of ALI lesions such as distorted parenchyma, increased alveoli thickness, lymphocyte and neutrophil infiltrations, fibrin deposition, pulmonary emphysema, pneumonia, intra-alveolar hemorrhage, and edema. The anti-inflammatory effect of the combination of sea cucumber and wild blueberry extracts is associated with suppressing MAPK and NF-κB signaling pathways, thereby significantly reducing cytokine storm in LPS-induced experimental ALI.

A muti-modal feature fusion method based on deep learning for predicting immunotherapy response.

Immune checkpoint therapy (ICT) has greatly improved the survival of cancer patients in the past few years, but only a small number of patients respond to ICT. To predict ICT response, we developed a multi-modal feature fusion model based on deep learning (MFMDL). This model utilizes graph neural networks to map gene-gene relationships in gene networks to low dimensional vector spaces, and then fuses biological pathway features and immune cell infiltration features to make robust predictions of ICT. We used five datasets to validate the predictive performance of the MFMDL. These five datasets span multiple types of cancer, including melanoma, lung cancer, and gastric cancer. We found that the prediction performance of multi-modal feature fusion model based on deep learning is superior to other traditional ICT biomarkers, such as ICT targets or tumor microenvironment-associated markers. In addition, we also conducted ablation experiments to demonstrate the necessity of fusing different modal features, which can improve the prediction accuracy of the model.

Peripheral nerve injury associated with JEV infection in high endemic regions, 2016-2020: a multicenter retrospective study in China.

Previously, we reported a cohort of Japanese encephalitis (JE) patients with Guillain-Barré syndrome. However, the evidence linking Japanese encephalitis virus (JEV) infection and peripheral nerve injury (PNI) remains limited, especially the epidemiology, clinical presentation, diagnosis, treatment, and outcome significantly differ from traditional JE. We performed a retrospective and multicenter study of 1626 patients with JE recorded in the surveillance system of the Chinese Center for Disease Control and Prevention, spanning the years 2016-2020. Cases were classified into type 1 and type 2 JE based on whether the JE was combined with PNI or not. A comparative analysis was conducted on demographic characteristics, clinical manifestations, imaging findings, electromyography data, laboratory results, and treatment outcomes. Among 1626 laboratory confirmed JE patients, 230 (14%) were type 2 mainly located along the Yellow River in northwest China. In addition to fever, headache, and disturbance of consciousness, type 2 patients experienced acute flaccid paralysis of the limbs, as well as severe respiratory muscle paralysis. These patients presented a greater mean length of stay in hospital (children, 22 years [range, 1-34]; adults, 25 years [range, 0-183]) and intensive care unit (children, 16 years [range, 1-30]; adults, 17 years [range, 0-102]). The mortality rate was higher in type 2 patients (36/230 [16%]) compared to type 1 (67/1396 [5%]). The clinical classification of the diagnosis of JE may play a crucial role in developing a rational treatment strategy, thereby mitigating the severity of the disease and potentially reducing disability and mortality rates among patients.

In-vivo whole-cortex marker of excitation-inhibition ratio indexes cortical maturation and cognitive ability in youth.

A balanced excitation-inhibition ratio (E/I ratio) is critical for healthy brain function. Normative development of cortex-wide E/I ratio remains unknown. Here we non-invasively estimate a putative marker of whole-cortex E/I ratio by fitting a large-scale biophysically-plausible circuit model to resting-state functional MRI (fMRI) data. We first confirm that our model generates realistic brain dynamics in the Human Connectome Project. Next, we show that the estimated E/I ratio marker is sensitive to the GABA-agonist benzodiazepine alprazolam during fMRI. Alprazolam-induced E/I changes are spatially consistent with positron emission tomography measurement of benzodiazepine receptor density. We then investigate the relationship between the E/I ratio marker and neurodevelopment. We find that the E/I ratio marker declines heterogeneously across the cerebral cortex during youth, with the greatest reduction occurring in sensorimotor systems relative to association systems. Importantly, among children with the same chronological age, a lower E/I ratio marker (especially in association cortex) is linked to better cognitive performance. This result is replicated across North American (8.2 to 23.0 years old) and Asian (7.2 to 7.9 years old) cohorts, suggesting that a more mature E/I ratio indexes improved cognition during normative development. Overall, our findings open the door to studying how disrupted E/I trajectories may lead to cognitive dysfunction in psychopathology that emerges during youth.

Examining the associations between microglia genetic capacity, early life exposures and white matter development at the level of the individual.

There are inter-individual differences in susceptibility to the influence of early life experiences for which the underlying neurobiological mechanisms are poorly understood. Microglia play a role in environmental surveillance and may influence individual susceptibility to environmental factors. As an index of neurodevelopment, we estimated individual slopes of mean white matter fractional anisotropy (WM-FA) across three time-points (age 4.5, 6.0, and 7.5 years) for 351 participants. Individual variation in microglia reactivity was derived from an expression-based polygenic score(ePGS) comprised of Single Nucleotide Polymorphisms (SNPs) functionally related to the expression of microglia-enriched genes.A higher ePGS denotes an increased genetic capacity for the expression of microglia-related genes, and thus may confer a greater capacity to respond to the early environment and to influence brain development. We hypothesized that this ePGS would associate with the WM-FA index of neurodevelopment and moderate the influence of early environmental factors.Our findings show sex dependency, where a significant association between WM-FA and microglia ePGS was only obtained for females.We then examined associations with perinatal factors known to decrease (optimal birth outcomes and familial conditions) or increase (systemic inflammation) the risk for later mental health problems.In females, individuals with high microglia ePGS showed a negative association between systemic inflammation and WM-FA and a positive association between more advantageous environmental conditions and WM-FA. The microglia ePGS in females thus accounted for variations in the influence of the quality of the early environment on WM-FA.Finally, WM-FA slopes mediated the association of microglia ePGS with interpersonal problems and social hostility in females. Our findings suggest the genetic capacity for microglia function as a potential factor underlying differential susceptibility to early life exposuresthrough influences on neurodevelopment.

Illumina and Nanopore sequencing in culture-negative samples from suspected lower respiratory tract infection patients.

Objective: To evaluate the diagnostic value of metagenomic sequencing technology based on Illumina and Nanopore sequencing platforms for patients with suspected lower respiratory tract infection whose pathogen could not be identified by conventional microbiological tests. Methods: Patients admitted to the Respiratory and Critical Care Medicine in Shanghai Ruijin Hospital were retrospectively studied from August 2021 to March 2022. Alveolar lavage or sputum was retained in patients with clinically suspected lower respiratory tract infection who were negative in conventional tests. Bronchoalveolar lavage fluid (BALF) samples were obtained using bronchoscopy. Sputum samples were collected, while BALF samples were not available due to bronchoscopy contraindications. Samples collected from enrolled patients were simultaneously sent for metagenomic sequencing on both platforms. Results: Thirty-eight patients with suspected LRTI were enrolled in this study, consisting of 36 parts of alveolar lavage and 2 parts of sputum. According to the infection diagnosis, 31 patients were confirmed to be infected with pathogens, while 7 patients were diagnosed with non-infectious disease. With regard to the diagnosis of infectious diseases, the sensitivity and specificity of Illumina and Nanopore to diagnose infection in patients were 80.6% vs. 93.5% and 42.9 vs. 28.6%, respectively. In patients diagnosed with bacterial, Mycobacterium, and fungal infections, the positive rates of Illumina and Nanopore sequencer were 71.4% vs. 78.6%, 36.4% vs. 90.9%, and 50% vs. 62.5%, respectively. In terms of pathogen diagnosis, the sensitivity and specificity of pathogens detected by Illumina and Nanopore were 55.6% vs. 77.8% and 42.9% vs. 28.6%, respectively. Among the patients treated with antibiotics in the last 2 weeks, 61.1% (11/18) and 77.8% (14/18) cases of pathogens were accurately detected by Illumina and Nanopore, respectively, among which 8 cases were detected jointly. The consistency between Illumina and diagnosis was 63.9% (23/36), while the consistency between Nanopore and diagnosis was 83.3% (30/36). Between Illumina and Nanopore sequencing methods, the consistency ratio was 55% (22/42) based on pathogen diagnosis. Conclusion: Both platforms play a certain value in infection diagnosis and pathogen diagnosis of CMT-negative suspected LRTI patients, providing a theoretical basis for clinical accurate diagnosis and symptomatic treatment. The Nanopore platform demonstrated potential advantages in the identification of Mycobacterium and could further provide another powerful approach for patients with suspected Mycobacterium infection.

Light-Initiated Imprinted Membrane-Based Biomimetic SERS Sensor toward Selective Detection of Trace MC-LR.

Microcystin-LR (MC-LR) is a severe threat to human and animal health; thus, monitoring it in the environment is essential, especially in water quality protections. Herein, in this work, we synthesize PVDF/CNT/Ag molecular imprinted membranes (PCA-MIMs) via an innovative combination of surface-enhanced Raman spectroscopy (SERS) detection, membrane separation, and molecular-imprinted technique toward the analysis of MC-LR in water. In particular, a light-initiated imprint is employed to protect the chemical structure of the MC-LR molecules. Furthermore, in order to ensure the detection sensitivity, the SERS substrates are combined with the membrane via the assistance of magnetism. The effect of synthesis conditions on the SERS sensitivity was investigated in detail. It is demonstrated from the characteristic results that the PCA-MIMs present high sensitivity to the MC-LR molecules with excellent selectivity against the interfere molecules. Results clearly show that the as-prepared PCA-MIMs hold great potential applications to detect trace MC-LR for the protection of water quality.

Genome-wide association study identified five quantitative trait loci and two candidate genes for digestive traits in Suhuai pigs.

This work aimed to identify markers and candidate genes underlying porcine digestive traits. In total, 331 pigs were genotyped by 80 K Chip data or 50 K Chip data. For apparent neutral detergent fiber digestibility, a total of 19 and 21 candidate single nucleotide polymorphisms (SNP) were respectively identified using a genome-wide efficient mixed-model association algorithm and linkage-disequilibrium adjusted kinship. Among them, three quantitative trait locus (QTL) regions were identified. For apparent acid detergent fiber digestibility, a total of 16 and 17 SNPs were identified by these two methods, respectively. Of these, three QTL regions were also identified. Moreover, two candidate genes (MST1 and LATS1), which are functionally related to intestinal homeostasis and health, were detected near these significant SNPs. Taken together, our results could provide a basis for deeper research on digestive traits in pigs.

Rapid detection of monkeypox virus and differentiation of West African and Congo Basin strains using endonuclease restriction-mediated real-time PCR-based testing.

The ongoing multi-country outbreak of monkeypox virus (MPXV) has continuously attracted global attention, highlighting the critical need for timely and accurate methods to detect MPXV and differentiate its clades. Herein, we devised a novel multiplex ET-PCR (endonuclease restriction-mediated real-time PCR) assay that integrates PCR amplification, restriction endonuclease cleavage and real-time fluorescence detection to diagnose MPXV infection and distinguish the Congo Basin and West African MPXV strains. In the MPXV ET-PCR system, three sets of specific primers were designed for MPXV, Congo Basin and West African strains. A short sequence, which could be recognized by restriction endonuclease enzyme BstUI, was added to the 5'end of amplification primers. Then, the modified primers were assigned different reporter dyes and corresponding quenching dyes to each of the three targets, enabling real-time fluorescence reporting of the results and multiplex detection. The designed assay enabled the detection of single or three targets in a single tube, with excellent specificity and analytical sensitivity in terms of plasmid and pseudotyped virus. Moreover, the clinical feasibility of our assay was validated using artificially simulated plasma, nasopharyngeal swab and skin swab samples. In conclusion, the multiplex ET-PCR assay devised here had the advantages of simple primer design, cost-effectiveness, low contamination risk, excellent sensitivity, high specificity and multiplex detection, making it a valuable and dependable tool for curbing the extensive spread of MPXV.

Cannabis, Cannabinoids, and Stroke: Increased Risk or Potential for Protection-A Narrative Review.

Worldwide, approximately 15 million people per year suffer from stroke. With about 5 million deaths, stroke is the second most common cause of death and a major cause of long-term disability. It is estimated that about 25% of people older than 85 years will develop stroke. Cannabis sativa and derived cannabinoids have been used for recreational and medical purposes for many centuries. However, due to the legal status in the past, research faced restrictions, and cannabis use was stigmatized for potential negative impacts on health. With the changes in legal status in many countries of the world, cannabis and cannabis-derived substances such as cannabinoids and terpenes have gained more interest in medical research. Several medical effects of cannabis have been scientifically proven, and potential risks identified. In the context of stroke, the role of cannabis is controversial. The negative impact of cannabis use on stroke has been reported through case reports and population-based studies. However, potential beneficial effects of specific cannabinoids are described in animal studies under certain conditions. In this narrative review, the existing body of evidence regarding the negative and positive impacts of cannabis use prior to stroke will be critically appraised.

Insight into Cu (II) adsorption on pyrochar and hydrochar resultant from Acacia Senegal waste for wastewater decontamination.

Acacia Senegal waste (ASW) is remaining biomass following gum Arabic harvesting and has no use mentioned in the literature as of yet. This study aims to convert ASW into valuable biochar via two comparative thermal and hydrothermal techniques, which include pyrochar ASW at 300 °C (PC ASW300) and hydrochar ASW at 180 °C (HC ASW180), respectively, for Cu (II) adsorption from aqueous solutions. SEM-EDS, FTIR, XRD, and XPS were used to characterize the biochar. Adsorption performance was studied as a function of pH, contact time, and adsorbent concentration. Adsorption kinetics were best fit for a pseudo-second-order model. And thermodynamics studies revealed that Cu (II) on biochar was endothermic, spontaneous, and best fitted to the Langmuir isotherm model. Pyrochar adsorption capacity (31.93 mg g-1) was seven times that of hydrochar (5.45 mg g-1). ASW treated with phosphorus (PC H3PO4 and HC H3PO4) prior to the carbonization altered the pore structure and surface functional groups as well (O-P-O, P-CH3, and P-OH) of biochar. It was found that treating with phosphorous acid increased adsorption capacity to 141.7 mg g-1 and 22.24 mg g-1 for PC H3PO4 and HC H3PO4, respectively. The surface functional groups of biochar resulted from lignin, alkaloids, and polysaccharides combined with Cu (II) during the adsorption process via surface complexation accompanied by π-electron interaction and Cu (II) reduction. These findings shed light on the ASW biochar potential as a new green cost-effective adsorbent and drew an insightful understanding of Cu (II) adsorption performance and mechanism. It is concluded that ASW-derived biochar is highly effective and a promising alternative for Cu (II) decontamination from wastewater.

[Retracted] Interaction of YAP1 and mTOR promotes bladder cancer progression.

Following the publication of the above article, a concerned reader drew to the Editor's attention that certain of the immunohistochemical data shown in Fig. 1C on p. 236, and immunofluorescence data featured in Figs. 2G and 5G on p. 237 and 239 respectively, were strikingly similar to data that had appeared in other articles written by different authors at different research institutes which had already been published.  In view of the fact that certain of the data in the above article had already been published at the time of the paper's submission, the Editor of International Journal of Oncology has decided that this paper should be retracted from the publication. After having been in contact with the authors, they accepted the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Oncology 56: 232­242, 2020; DOI: 10.3892/ijo.2019.4922].

Online electrochemistry coupling liquid chromatography-mass spectrometry for rapid investigation on the phase I and phase II simulated metabolic reactions of flavonoids.

In this study, an online electrochemistry coupling high-performance liquid chromatography-mass spectrometry (EC-HPLC-MS) technology has been developed for simulating metabolic reactions and rapid analysis of metabolites of flavone, quercetin, and rutin, which are not only widely present compounds with pharmacological activity in nature, but also have structural similarity and variability. The simulated metabolic processes of the substrates (phase I and phase II metabolism) were implemented on the surface of glassy carbon electrode (GCE) by using different electrochemical methods. After online chromatographic separation, the products were transmitted to a mass spectrometer for detection, in order to speculate relevant reaction pathways and structural information of the reaction product. The main metabolites, including methylation, hydroxylation, hydrolysis, and conjugation reaction products, had been successfully identified through the designed in situ hyphenated technique. Furthermore, compared with metabolites produced by in vitro incubation of rat liver microsomes, it was found that the products of electrochemical simulated metabolism were more abundant with diverse metabolic pathways. The results indicated that the proposed method exhibited advantages in the sample pretreatment process and detection cycle without compromising the reliability and accuracy of the results.