A disposable electrochemical magnetic immunosensor for the rapid and sensitive detection of 5-formylcytosine and 5-carboxylcytosine in DNA.

5-formylcytosine (5 fC) and 5-carboxylcytosine (5caC) serve as key intermediates in DNA demethylation process with significant implications for gene regulation and disease progression. In this study, we introduce a novel electrochemical sensing platform specifically designed for the sensitive and selective detection of 5 fC and 5caC in DNA. Protein A-modified magnetic beads (ProtA-MBs) coupled with specific antibodies facilitate the immunorecognition and enrichment of these modified bases. Signal amplification is achieved through several chemical reactions involving the interaction between N3-kethonaxl and guanine, copper-free click chemistry for the attachment of dibenzocyclooctyne (DBCO)-Biotin, and the subsequent recognition by streptavidin-conjugated horseradish peroxidase (SA-HRP). The assay's readout is performed on a disposable laser-induced graphene (LIG) electrode, modified with the bead-antibody-DNA complex in a magnetic field, and analyzed using differential pulse voltammetry in a system employing hydroquinone (HQ) as the redox mediator and H2O2 as the substrate. This immunosensor displayed excellent sensitivity, with detection limits of 14.8 fM for 5 fC across a 0.1-1000 pM linear range and 87.4 fM for 5caC across a 0.5-5000 pM linear range, and maintained high selectivity even in the presence of interferences from other DNA modifications. Successful application in quantifying 5 fC and 5caC in genomic DNA from cell extracts, with recovery rates between 97.7% to 102.9%, underscores its potential for clinical diagnostics. N3-kethoxal was used for the first time in an electrochemical sensor. This work not only broadens the toolkit for detecting DNA modifications but also provides a fresh impetus for the development of point-of-care testing (POCT) technologies.

Electrochemical chiral sensor for recognition of amino acid enantiomers with cyclodextrin-based microporous organic networks.

BACKGROUND: Chirality is a ubiquitous phenomenon in nature, but enantiomers exhibit different pharmacological activities and toxicological effects. Therefore, Chiral recognition plays a pivotal role in various fields such as life sciences, chemical synthesis, drug development, and materials science. The synthesis of novel chiral composites with well-defined loading capabilities and ordered structures holds significant potential for electrochemical chiral recognition applications. However, the design of selective and stable electrochemical chiral recognition materials remains a challenging task. RESULT: In this work, we construct a simple and rapid electrochemical sensing platform for tryptophan (Trp) enantiomer recognition using cyclodextrin-modified microporous organic network as chiral recognition agent. CD-MON with chiral microenvironment was prepared by Sonogashira-Hagihara coupling reaction of the chiral molecule heptyl-6-iodo-6-deoxyß-cyclodextrin and 1, 4-Diethynylbenzene. The adhesion of BSA makes CD-MON firmly fixed on the electrode surface, and as a chiral protein, it can improve the chiral recognition ability through synergistic effect. Chiral amino acids are in full contact with the chiral microenvironment during pore conduction of MON, and L-Trp is more stably bound to CD-MON/BSA due to steric hindrance, host-guest recognition and hydrogen bonding. Therefore, the electrochemical sensor can effectively identify tryptophan enantiomers (IL-Trp/ID-Trp = 2.02), and it exhibits a detection limit of 2.6 µM for L-Trp. UV-Vis spectroscopy confirmed the adsorption capacity of CD-MON towards tryptophan enantiomers in agreement with electrochemistry results. SIGNIFICANCE: The prepared chiral sensor has excellent stability, reproducibility (RSD = 3.7%) and selectivity, realizes the quantitative detection of single isomer in tryptophan racemic and quantitative analysis in real samples with 94.0%-101.0% recovery. This work represents the first application of MON in chiral electrochemistry which expands the application scope of chiral sensors and holds great significance in separation science and electrochemical sensing.

CA IX-targeted Ag2S quantum dots bioprobe for NIR-II imaging-guided hypoxia tumor chemo-photothermal therapy.

Hypoxia is the common characteristic of almost all solid tumors, which prevents therapeutic drugs from reaching the tumors. Therefore, the development of new targeted agents for the accurate diagnosis of hypoxia tumors is widely concerned. As carbonic anhydrase IX (CA IX) is abundantly distributed on the hypoxia tumor cells, it is considered as a potential tumor biomarker. 4-(2-Aminoethyl)benzenesulfonamide (ABS) as a CA IX inhibitor has inherent inhibitory activity and good targeting effect. In this study, Ag2S quantum dots (QDs) were used as the carrier to prepare a novel diagnostic and therapeutic bioprobe (Ag2S@polyethylene glycol (PEG)-ABS) through ligand exchange and amide condensation reaction. Ag2S@PEG-ABS can selectively target tumors by surface-modified ABS and achieve accurate tumor imaging by the near infrared-II (NIR-II) fluorescence characteristics of Ag2S QDs. PEG modification of Ag2S QDs greatly improves its water solubility and stability, and therefore achieves high photothermal stability and high photothermal conversion efficiency (PCE) of 45.17%. Under laser irradiation, Ag2S@PEG-ABS has powerful photothermal and inherent antitumor combinations on colon cancer cells (CT-26) in vitro. It also has been proved that Ag2S@PEG-ABS can realize the effective treatment of hypoxia tumors in vivo and show good biocompatibility. Therefore, it is a new efficient integrated platform for the diagnosis and treatment of hypoxia tumors.

Health-Promoting Lifestyle and Its Predictors in Renal Transplant Recipients in Hunan, China: A Cross-Sectional Study.

Background: Kidney transplantation is a critical treatment for end-stage renal disease (ESRD), with health-promoting lifestyle (HPL) significantly impacting patient outcomes. HPL involves behaviors like regular exercise, balanced nutrition, stress management, and habit modification. However, few studies have analyzed the HPL of renal transplant recipients, addressing a significant gap in current research. Objective: This study aimed to determine the predictors of HPL in renal transplant recipients using the Chinese Health Promoting Lifestyle Profile (HPLP). Methods: This cross-sectional study enrolled renal transplant recipients completing the revised Chinese HPLP at organ transplant center in a tertiary hospital in Hunan Province of China between May 2022 and July 2022. Results: A total of 450 patients were included, comprising 256 males (56.9%), with a mean age of 44.85 ± 10.57 years. The mean score of self-actualization, health responsibility, interpersonal support, physical activity, stress management, nutrition, and overall HPLP were 15.27 ± 5.03 (possible range: 0-24), 11.41 ± 4.18 (possible range: 0-24), 11.61 ± 3.13 (possible range: 0-18), 7.53 ± 3.79 (possible range: 0-18), 12.68 ± 3.61 (possible range: 0-21), 11.17 ± 2.41 (possible range: 0-15), and 69.66 ± 16.98 (possible range: 0-120), respectively. Multivariate logistic regression analysis showed that urban residence (OR = 2.061, 95% CI: 1.350-3.148, P = 0.001), non-smoking after transplantation (OR = 2.010, 95% CI: 1.123-3.600, P = 0.019) and two post-transplant complications (OR=0.387, 95% CI: 0.218-0.689, P = 0.001). Conclusion: Although renal transplant recipients exhibit a moderate level of HPL, targeted interventions are essential to improve these behaviors. These interventions should focus especially on individuals from rural households, post-transplant smokers, and those experiencing post-transplant complications, to enhance their quality of life and clinical outcomes.

Roles of Cytokines in Alzheimer's Disease.

The neuroimmune system is a collection of immune cells, cytokines, and the glymphatic system that plays a pivotal role in the pathogenesis and progression of Alzheimer's disease (AD). Of particular focus are cytokines, a group of immune signaling molecules that facilitate communication among immune cells and contribute to inflammation in AD. Extensive research has shown that the dysregulated secretion of certain cytokines (IL-1ß, IL-17, IL-12, IL-23, IL-6, and TNF-α) promotes neuroinflammation and exacerbates neuronal damage in AD. However, anti-inflammatory cytokines (IL-2, IL-3, IL-33, and IL-35) are also secreted during AD onset and progression, thereby preventing neuroinflammation. This review summarizes the involvement of pro- and anti-inflammatory cytokines in AD pathology and discusses their therapeutic potential.

Etched stainless steel wire modified with conjugated microporous polymers-F6 for jacket-free stir bar sorptive extraction of benzoylureas in juice sample.

Benzoylurea (BU) insecticides have been widely used for pest control as third-generation insecticides. Considering that their residues in food may cause adverse effects on human health, the upper limits of BUs remaining in food have been set by the administration. Therefore, it is essential to develop a sensitive and efficient analytical method to determine the residues of BUs in food. Stir bar sorptive extraction (SBSE) is a novel sample preparation technique, and stainless steel wire (SSW) is an ideal substrate for an SBSE device. In this work, a novel SBSE device of SSW jacket-free stir bar with a dumbbell shape was designed and prepared. The conjugated microporous polymer CMP-F6, which possesses a porous structure, high hydrophobicity and rich fluorine-containing functional groups, was immobilized on the surface of SSW by the method of polyacrylonitrile glue adhesion. Compared with previous studies, which used SSW as a substrate, the method of etching partial SSW with hydrochloric acid, on the one hand, made the surface of SSW rough and easy to modify the extraction coating, and on the other hand, converted itself into a dumbbell-shaped structure, which is conducive to improving the extraction efficiency and stability of the SBSE device. The method of SBSE-HPLC-UV was established for determining five BUs. Owing to the hydrophobic interaction and F-F interaction between CMP-F6 and analytes, this method showed good extraction efficiency and had good linearity (R2 ≥ 0.9945) and high sensitivity (LODs in the range of 0.1-0.2 ng mL-1). It was used for the analysis of benzoylurea in an apple juice sample, and the recoveries were 74.3-117.9%.

Neuroplasticity of children in autism spectrum disorder.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that encompasses a range of symptoms including difficulties in verbal communication, social interaction, limited interests, and repetitive behaviors. Neuroplasticity refers to the structural and functional changes that occur in the nervous system to adapt and respond to changes in the external environment. In simpler terms, it is the brain's ability to learn and adapt to new environments. However, individuals with ASD exhibit abnormal neuroplasticity, which impacts information processing, sensory processing, and social cognition, leading to the manifestation of corresponding symptoms. This paper aims to review the current research progress on ASD neuroplasticity, focusing on genetics, environment, neural pathways, neuroinflammation, and immunity. The findings will provide a theoretical foundation and insights for intervention and treatment in pediatric fields related to ASD.

Deep-learning-based super-resolution for accelerating chemical exchange saturation transfer MRI.

Chemical exchange saturation transfer (CEST) MRI is a molecular imaging tool that provides physiological information about tissues, making it an invaluable tool for disease diagnosis and guided treatment. Its clinical application requires the acquisition of high-resolution images capable of accurately identifying subtle regional changes in vivo, while simultaneously maintaining a high level of spectral resolution. However, the acquisition of such high-resolution images is time consuming, presenting a challenge for practical implementation in clinical settings. Among several techniques that have been explored to reduce the acquisition time in MRI, deep-learning-based super-resolution (DLSR) is a promising approach to address this problem due to its adaptability to any acquisition sequence and hardware. However, its translation to CEST MRI has been hindered by the lack of the large CEST datasets required for network development. Thus, we aim to develop a DLSR method, named DLSR-CEST, to reduce the acquisition time for CEST MRI by reconstructing high-resolution images from fast low-resolution acquisitions. This is achieved by first pretraining the DLSR-CEST on human brain T1w and T2w images to initialize the weights of the network and then training the network on very small human and mouse brain CEST datasets to fine-tune the weights. Using the trained DLSR-CEST network, the reconstructed CEST source images exhibited improved spatial resolution in both peak signal-to-noise ratio and structural similarity index measure metrics at all downsampling factors (2-8). Moreover, amide CEST and relayed nuclear Overhauser effect maps extrapolated from the DLSR-CEST source images exhibited high spatial resolution and low normalized root mean square error, indicating a negligible loss in Z-spectrum information. Therefore, our DLSR-CEST demonstrated a robust reconstruction of high-resolution CEST source images from fast low-resolution acquisitions, thereby improving the spatial resolution and preserving most Z-spectrum information.

Effect of inhaled oxygen level on dynamic glucose-enhanced MRI in mouse brain.

PURPOSE: To investigate the effect of inhaled oxygen level on dynamic glucose enhanced (DGE) MRI in mouse brain tissue and CSF at 3 T. METHODS: DGE data of brain tissue and CSF from mice under normoxia or hyperoxia were acquired in independent and interleaved experiments using on-resonance variable delay multi-pulse (onVDMP) MRI. A bolus of 0.15 mL filtered 50% D-glucose was injected through the tail vein over 1 min during DGE acquisition. MRS was acquired before and after DGE experiments to confirm the presence of D-glucose. RESULTS: A significantly higher DGE effect under normoxia than under hyperoxia was observed in brain tissue (p = 0.0001 and p = 0.0002 for independent and interleaved experiments, respectively), but not in CSF (p > 0.3). This difference is attributed to the increased baseline MR tissue signal under hyperoxia induced by a shortened T1 and an increased BOLD effect. When switching from hyperoxia to normoxia without glucose injection, a signal change of ˜3.0% was found in brain tissue and a signal change of ˜1.5% was found in CSF. CONCLUSIONS: DGE signal was significantly lower under hyperoxia than that under normoxia in brain tissue, but not in CSF. The reason is that DGE effect size of brain tissue is affected by the baseline signal, which could be influenced by T1 change and BOLD effect. Therefore, DGE experiments in which the oxygenation level is changed from baseline need to be interpreted carefully.

Facile room-temperature synthesis of a spherical mesoporous covalent organic framework for capillary electrochromatography.

Herein, a spherical covalent organic framework COF TAPB-DMTP was facilely synthesized from 2,5-dimethoxyterephthalaldehyde (DMTP) and 1,3,5-tri-(4-aminophenyl)benzene (TAPB) as monomers. COF TAPB-DMTP with regular mesoporous and excellent mass transfer ability was first introduced into the capillary and immobilized on the inner wall of the capillary through a simple in situ growth method. Through various characterization results, COF TAPB-DMTP was successfully prepared and modified onto the capillary inner wall. The separation performance and potential of COF TAPB-DMTP modified capillary column was explored. The new developed COF modified column achieved a highly efficiency and selective separation between analytes with different properties, including halogeno benzenes, alkylbenzenes, phenols and sulfonamides. Satisfactory stability and reproducibility were observed on COF TAPB-DMTP modified columns. The intraday, interday and three batch columns relative standard deviations were all less than 1.85 % for the retention time. The separation performance of prepared column has no significant change after 90 continuous runs. Additionally, the COF TAPB-DMTP modified capillary column was successfully used for separation and detection of triazole antifungal drugs in human plasma, and the recoveries of three antifungal drugs (fluconazole, isavuconazole and posaconazole) in spiked samples were in the range of 98.6-100.8 %, 92.4-102.1 % and 99.9-107.5 %, respectively. This self-made column showed excellent application potential in chromatography separation science.

Fetal overgrowth and weight trajectories during infancy and adiposity in early childhood.

BACKGROUND: Large-for-gestational age (LGA), a marker of fetal overgrowth, has been linked to obesity in adulthood. Little is known about how infancy growth trajectories affect adiposity in early childhood in LGA. METHODS: In the Shanghai Birth Cohort, we followed up 259 LGA (birth weight >90th percentile) and 1673 appropriate-for-gestational age (AGA, 10th-90th percentiles) children on body composition (by InBody 770) at age 4 years. Adiposity outcomes include body fat mass (BFM), percent body fat (PBF), body mass index (BMI), overweight/obesity, and high adiposity (PBF >85th percentile). RESULTS: Three weight growth trajectories (low, mid, and high) during infancy (0-2 years) were identified in AGA and LGA subjects separately. BFM, PBF and BMI were progressively higher from low- to mid-to high-growth trajectories in both AGA and LGA children. Compared to the mid-growth trajectory, the high-growth trajectory was associated with greater increases in BFM and the odds of overweight/obesity or high adiposity in LGA than in AGA children (tests for interactions, all P < 0.05). CONCLUSIONS: Weight trajectories during infancy affect adiposity in early childhood regardless of LGA or not. The study is the first to demonstrate that high-growth weight trajectory during infancy has a greater impact on adiposity in early childhood in LGA than in AGA subjects. IMPACT: Large-for-gestational age (LGA), a marker of fetal overgrowth, has been linked to obesity in adulthood, but little is known about how weight trajectories during infancy affect adiposity during early childhood in LGA subjects. The study is the first to demonstrate a greater impact of high-growth weight trajectory during infancy (0-2 years) on adiposity in early childhood (at age 4 years) in subjects with fetal overgrowth (LGA) than in those with normal birth size (appropriate-for-gestational age). Weight trajectory monitoring may be a valuable tool in identifying high-risk LGA children for close follow-ups and interventions to decrease the risk of obesity.

The effect of aquaporin-4 inhibition on cerebrospinal fluid-tissue water exchange in mouse brain detected by magnetization transfer indirect spin labeling MRI.

The fluid transport of cerebrospinal fluid (CSF) and interstitial fluid in surrounding tissues plays an important role in the drainage pathway that facilitates waste clearance from the brain. This pathway is known as the glymphatic or perivascular system, and its functions are dependent on aquaporin-4 (AQP4). Recently, magnetization transfer indirect spin labeling (MISL) magnetic resonance imaging (MRI) has been proposed as a noninvasive and noncontrast-enhanced method for detecting water exchange between CSF and brain tissue. In this study, we first optimized the MISL sequence at preclinical 3 T MRI, and then studied the correlation of MISL in CSF with magnetization transfer (MT) in brain tissue, as well as the altered water exchange under AQP4 inhibition, using C57BL/6 mice. Results showed a strong correlation of MISL signal with MT signal. With the AQP4 inhibitor, we observed a significant decrease in MISL value (P < 0.05), suggesting that the hampered AQP4 activity led to decreased water exchange between CSF and brain tissue or the impairment of the glymphatic function. Overall, our findings demonstrate the potential application of MISL in assessing brain water exchange at 3 T MRI and its potential clinical translation.

Melatonin, a potentially effective drug for the treatment of infected bone nonunion.

Osteomyelitis (OM), characterized by heterogeneity and complexity in treatment, has a high risk of infection recurrence which may cause limb disability. Management of chronic inactive osteomyelitis (CIOM) without typical inflammatory symptoms is a great challenge for orthopedic surgeons. On the basis of data analysis of 1091 OM cases, we reported that latent osteogenic decline in CIOM patients was the main cause of secondary surgery. Our research shows that impairment of osteoblasts capacity in CIOM patients is associated with ferroptosis of osteoblasts caused by internalization of Staphylococcus aureus. Further studies show that melatonin could alleviate ferroptosis of osteoblasts in infected states through Nox4/ROS/P38 axis and protect the osteogenic ability of CIOM patients. Knockout of NADPH oxidase 4 (Nox4) in vivo could effectively relieve ferroptosis of osteoblasts in the state of infection and promote osteogenesis. Through a large number of clinical data analyses combined with molecular experiments, this study clarified that occult osteogenic disorders in CIOM patients were related to ferroptosis of osteoblasts. We revealed that melatonin might be a potential therapeutic drug for CIOM patients and provided a new insight for the treatment of OM.

Caregiver-child interaction as an effective tool for identifying autism spectrum disorder: evidence from EEG analysis.

BACKGROUND: Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder that affects individuals across their lifespan. Early diagnosis and intervention are crucial for improving outcomes. However, current diagnostic methods are often time-consuming, and costly, making them inaccessible to many families. In the current study, we aim to test caregiver-child interaction as a potential tool for screening children with ASD in clinic. METHODS: We enrolled 85 preschool children (Mean age: 4.90 ± 0.65 years, 70.6% male), including ASD children with or without developmental delay (DD), and typical development (TD) children, along with their caregivers. ASD core symptoms were evaluated by Childhood Autism Rating Scale (CARS) and Autism Diagnostic Observation Schedule-Calibrated Severity Scores (ADOS-CSS). Behavioral indicators were derived from video encoding of caregiver-child interaction, including social involvement of children (SIC), interaction time (IT), response of children to social cues (RSC), time for caregiver initiated social interactions (GIS) and time for children initiated social interactions (CIS)). Power spectral density (PSD) values were calculated by EEG signals simultaneously recorded. Partial Pearson correlation analysis was used in both ASD groups to investigate the correlation among behavioral indicators scores and ASD symptom severity and PSD values. Receiver operating characteristic (ROC) analysis was used to describe the discrimination accuracy of behavioral indicators. RESULTS: Compared to TD group, both ASD groups demonstrated significant lower scores of SIC, IT, RSC, CIS (all p values < 0.05), and significant higher time for GIS (all p values < 0.01). SIC scores negatively correlated with CARS (p = 0.006) and ADOS-CSS (p = 0.023) in the ASD with DD group. Compared to TD group, PSD values elevated in ASD groups (all p values < 0.05), and was associated with SIC (theta band: p = 0.005; alpha band: p = 0.003) but not IQ levels. SIC was effective in identifying both ASD groups (sensitivity/specificity: ASD children with DD, 76.5%/66.7%; ASD children without DD, 82.6%/82.2%). CONCLUSION: Our results verified the behavioral paradigm of caregiver-child interaction as an efficient tool for early ASD screening.

GGT1 Suppresses the Development of Ferroptosis and Autophagy in Mouse Retinal Ganglion Cell Through Targeting GCLC.

Background: Glaucoma is a neurodegenerative disorder characterized with optic nerve injury and the loss of retinal ganglion cells (RGCs). Ferroptosis has been proved to be associated with the degradation of RGCs. The aim of this study is to elucidate the relationship between ferroptosis and glaucoma pathogenesis, and unveil the underlying mechanism. Methods: Methyl thiazolyl tetrazolium (MTT) assay was used to evaluate the proliferation of RGCs. The accumulation of cellular iron was measured by Iron assay kit, and the level of reactive oxygen species (ROS) was detected by fluorescence probe. The mitochondrial morphology and autophagosomes were analysed by using transmission electron microscopy (TEM). The contents of glutathione (GSH) and malondialdehyde (MDA) were tested by a GSH assay kit and an MDA detection kit, respectively. The expression of autophagy-related proteins was detected by Western blotting. Results: A serious cell damage, aberrant iron homeostasis, and oxidative stress was shown in RGC-5 after oxygen-glucose deprivation/reoxygenation (OGD/R) treatment and gamma-Glutamyl transpeptidase 1 (GGT1) knockdown, but these effects were significantly alleviated by overexpression of GGT1 or ferroptosis inhibitors. The TEM and immunofluorescent results indicated that mitochondria impairment and autophagosome accumulation in OGD/R-treated cells was improved after GGT1 overexpression, while the phenomenon in GGT1-silenced cells was aggravated. Furthermore, we found that GGT1 can interact with glutamate cysteine ligase catalytic subunit (GCLC) to inhibit autophagy and ferroptosis in RGC-5 cells. Conclusion: GGT1 represses autophagy in RGC-5 cells by targeting GCLC, which further restrains the development of ferroptosis in cells.

A laser-induced graphene-based electrochemical immunosensor for nucleic acid methylation detection.

The detection of methylation in DNA and RNA is essential for the diagnosis and treatment of a wide range of diseases. A one-step fabricated laser-induced graphene (LIG) electrode has received increasing attention due to its good electrical conductivity, large specific surface area, ease of miniaturization, low cost and flexibility. Herein, a potential biosensor for N6-methyladenosine (m6A-RNA) and 5-methylcystosine-single strand DNA (5mC-ssDNA) detection was designed. The aim of this paper is to address the problem of detecting the m6A-RNA and 5mC-ssDNA content in cells. By stepwise modification of gold nanoparticles (AuNPs), sulfhydryl-modified nucleic acid chains, biotin-modified antibodies, and streptavidin-modified horseradish peroxidase (SA-HRP) at the LIG electrode, the peak current responses exhibited an increase proportional to the concentration of m6A-RNA and 5mC-ssDNA in the hydrogen peroxide-hydroquinone (H2O2-HQ) system. This method demonstrated a low detection limit of 2.81 pM for m6A-RNA and 9.53 pM for 5mC-ssDNA, with a linear detection range of 0.01 nM to 10 nM for both targets. The regression equation was determined as ΔI = 4.83 log c + 12.32 (R2 = 0.9980) for m6A-RNA and ΔI = 9.82 log c + 22.09 (R2 = 0.9903) for 5mC-ssDNA. Our method has good selectivity toward different detection targets of nucleic acid chains, stability for long-term storage and consecutive scanning (RSD of 9.42% and 2.08%, respectively) and reproducibility of 5 electrodes (RSD of 6.85%). This method utilizes gold-sulfur bonding to immobilize the detection target, which improves the conductivity of the LIG electrode and introduces an amplified portion of the signal by taking advantage of antigen-antibody specific binding. Thus, dual detection of m6A-RNA and 5mC-ssDNA was realized. Importantly, this approach is successfully applied for the detection of targets in spiked samples extracted from HeLa cells, suggesting its potential for clinical applications and providing a new perspective for the development of point-of care testing (POCT) techniques.

A novel catalyst derived from Co-ZIFs to grow N-doped carbon nanotubes for all-solid-state supercapacitors with high performance.

Carbon nanotubes (CNTs) have been widely used as electrode materials for electrochemical energy storage devices (e.g., supercapacitors) due to their excellent chemical and physical properties. However, conventional approaches (e.g., electron-beam vapor deposition and atomic layer deposition) to fabricate catalysts for the growth of CNTs are complex and demand high energy consumption. Herein, we report a facile method to synthesize catalysts derived from cobalt-containing zeolitic imidazolate frameworks (Co-ZIFs), which is exploited to in situ construct the three-dimensional (3D) CNT hybrid materials for all-solid-state supercapacitors. In brief, Co-ZIFs with a controllable structure is first grown on the inner porous surface of carbon foams pyrolyzed from commercial melamine foams, followed by thermal annealing and chemical vapor deposition to grow CNTs, achieving 3D free-standing CNT-based hybrids. The well-distributed Co-ZIFs in the carbon foam enable the grown CNTs with uniform structures and morphologies. Using the fabricated CNT-based hybrid as electrodes, the assembled all-solid-state supercapacitors show a high specific capacitance of 19.4 mF cm-2 at a current density of 0.5 mA cm-2, which could be further optimized to as high as 871.8 mF cm-2 by incorporating the pseudocapacitive material of manganese dioxide in CNT-based hybrids. This study provides a facile solution approach to fabricate the catalyst for the growth of a CNT inner porous substrate; the resultant 3D free-standing hybrids could be used as efficient electrodes for high-performance energy storage devices beyond supercapacitors.

A green versatile packaging based on alginate and anthocyanin via incorporating bacterial cellulose nanocrystal-stabilized camellia oil Pickering emulsions.

This study aims to develop a versatile intelligent packaging based on alginate (Alg) and anthocyanin (Ant) by incorporating bacterial cellulose nanocrystal-stabilized camellia oil Pickering emulsions. Firstly, bacterial cellulose nanocrystals (BCNs) matrix produced from kombucha was incorporated with camellia oil into via ultrasonic triggering, forming a stable and multifunctional camellia oil-bacterial cellulose nanocrystal Pickering nanoemulsions (CBPE). The microstructure and rheology results of the emulsion confirmed the stabilized preparation of CBPE. Subsequently, the CBPE was integrated into the three-dimensional network structure composed of alginate/anthocyanin. The composite film (Alg-Ant-CBPE) was designed through Ca2+ crosslinking, intermolecular hydrogen bonding and dehydration condensation. The fabricated color indicator films with different concentrations of CBPE (0.1 %-0.4 %), showed varying degree of improvement in hydrophobicity, UV shielding, mechanical strength, thermal stability, water vapor barrier properties and antioxidant capacities. When applied to yogurt, the Alg-Ant-CBPE4 exhibited more pronounced color changes compared to Alg-Ant, enabling visual detection of food freshness. In conclusion, the incorporation of Pickering nanoemulsion provides an effective and promising approach to enhance the performance of polysaccharide-based intelligent packaging.

The screening of lipase inhibitors based on the metal-organic framework Zeolitic Imidazolate Framework-8-immobilized enzyme microreactor.

An online capillary electrophoresis method based-lipase immobilized enzyme microreactor was developed for lipase kinetic study and inhibitor screening from compounds from natural products. Zeolitic Imidazolate Framework-8 (ZIF-8) has the advantages of large pore size, mild synthesis conditions and good biocompatibility. Lipase was immobilized on the inner wall of capillary with the help of the metal-organic framework ZIF-8. The results of electron microscopy showed that lipase could be aggregated and fixed on the inner wall of capillary by ZIF-8. After the experimental conditions including electrophoretic separation and enzymatic reaction were optimized, the baseline separation of substrate p-nitrophenyl acetate (pNPA) and product p-nitrophenol (pNP) was achieved within 3 min. The immobilized enzyme microreactor showed good repeatability and stability, and the determined Michaelis-Menten constant (Km) of lipase was 2.75 mM, which was lower than the kinetic constant determined in off-line reaction, indicating that the immobilized enzyme had a high affinity with the substrate. In addition, the IC50 value of the positive control compound orlistat on lipase inhibition was 7.26 nM, which was consistent with the literature. Then the inhibitory activity of 10 compounds from natural products on lipase was evaluated by the ZIF-8-IMER. Among them, 7 compounds including baicalein, luteolin, epicatechin gallic acid, and chlorogenic acid, had a certain inhibitory effect on lipase. The molecular docking technology proved the interaction between the enzyme and the screened inhibitor, which provides a new method for the screening of lipase inhibitors.

Cuprizone drives divergent neuropathological changes in different mouse models of Alzheimer's disease.

Myelin degradation is a normal feature of brain aging that accelerates in Alzheimer's disease (AD). To date, however, the underlying biological basis of this correlation remains elusive. The amyloid cascade hypothesis predicts that demyelination is caused by increased levels of the ß-amyloid (Aß) peptide. Here we report on work supporting the alternative hypothesis that early demyelination is upstream of amyloid. We challenged two different mouse models of AD (R1.40 and APP/PS1) using cuprizone-induced demyelination and tracked the responses with both neuroimaging and neuropathology. In oppose to amyloid cascade hypothesis, R1.40 mice, carrying only a single human mutant APP (Swedish; APP SWE ) transgene, showed a more abnormal changes of magnetization transfer ratio and diffusivity than in APP/PS1 mice, which carry both APP SWE and a second PSEN1 transgene (delta exon 9; PSEN1 dE9 ). Although cuprizone targets oligodendrocytes (OL), magnetic resonance spectroscopy and targeted RNA-seq data in R1.40 mice suggested a possible metabolic alternation in axons. In support of alternative hypotheses, cuprizone induced significant intraneuronal amyloid deposition in young APP/PS1, but not in R1.40 mice, and it suggested the presence of PSEN deficiencies, may accelerate Aß deposition upon demyelination. In APP/PS1, mature OL is highly vulnerable to cuprizone with significant DNA double strand breaks (53BP1 + ) formation. Despite these major changes in myelin, OLs, and Aß immunoreactivity, no cognitive impairment or hippocampal pathology was detected in APP/PS1 mice after cuprizone treatment. Together, our data supports the hypothesis that myelin loss can be the cause, but not the consequence, of AD pathology. SIGNIFICANCE STATEMENT: The causal relationship between early myelin loss and the progression of Alzheimer's disease remains unclear. Using two different AD mouse models, R1.40 and APP/PS1, our study supports the hypothesis that myelin abnormalities are upstream of amyloid production and deposition. We find that acute demyelination initiates intraneuronal amyloid deposition in the frontal cortex. Further, the loss of oligodendrocytes, coupled with the accelerated intraneuronal amyloid deposition, interferes with myelin tract diffusivity at a stage before any hippocampus pathology or cognitive impairments occur. We propose that myelin loss could be the cause, not the consequence, of amyloid pathology during the early stages of Alzheimer's disease.