Utilization of magnetic pomelo peel-derived biochar for extraction and liquid chromatography-mass spectrometry determination of opioid drugs in wastewaters.

In this study, magnetic pomelo peel-derived biochar composite was fabricated and applied as a low-cost adsorbent for the simultaneous extraction of morphine-like opioids named morphine, codeine, and 6-monoacetylmorphine from wastewaters, prior to their determination via liquid chromatography-mass spectrometry. A total of four biochar products were synthesized under different pyrolytic temperatures of 400, 500, 600, and 700°C, respectively, and the 400°C biochar was found to have the greatest extraction ability, with enrichment factors of 34, 58, and 61 for the three drugs. The primary adsorption mechanism includes π-π interaction and H-bonding. Parameters affecting the extraction of opioids were optimized. Under optimum conditions (such as pH = 7; adsorbent amount = 15 mg; sample volume = 20 ml; eluent solvent, 200 µl of methanol), the method was proved to be linear in the range of 0.05-10.0 µg/L, with coefficients of determination greater than 0.99, and the limits of detection were 0.006-0.010 µg/L. In-batch and inter-batch precisions were 1.8%-6.5% and 4.8%-10.6%, respectively. The method was successfully applied to the determination of the target opioids in the samples of influent and effluent wastewater. The developed method by using magnetic pomelo peel-derived biochar could potentially be applied for the effective estimation of illicit drug consumption.

Preparation of bamboo-derived magnetic biochar for solid-phase microextraction of fentanyls from urine.

In this study, a biochar-based magnetic solid-phase microextraction method, coupled with liquid chromatography-mass spectrometry, was developed for analyzing fentanyl analogs from urine sample. Magnetic biochar was fabricated through a one-step pyrolysis carbonization and magnetization process, followed by an alkali treatment. In order to achieve desired extraction efficiency, feed stocks (wood and bamboo) and different pyrolysis temperatures (300-700°C) were optimized. The magnetic bamboo biochar pyrolyzed at 400°C was found to have the greatest potential for extraction of fentanyls, with enrichment factors ranging from 58.9 to 93.7, presumably due to H-bonding and π-π interactions between biochar and fentanyls. Various extraction parameters, such as type and volume of desorption solvent, pH, and extraction time, were optimized, respectively, to achieve the highest extraction efficiency for the target fentanyls. Under optimized conditions, the developed method was found to have detection limits of 3.0-9.4 ng/L, a linear range of 0.05-10 µg/L, good precisions (1.9-9.4% for intrabatch, 2.9-9.9% for interbatch), and satisfactory recoveries (82.0-111.3%). The developed method by using magnetic bamboo biochar as adsorbent exhibited to be an efficient and promising pretreatment procedure and could potentially be applied for drug analysis in biological samples.

Identification and characterization of invertase family genes reveal their roles in vacuolar sucrose metabolism during Pyrus bretschneideri Rehd. fruit development.

23 invertase (PbrInvs) genes, including eight vacuolar invertases (PbrvacInvs), five cell wall invertases (PbrcwInvs) and 10 alkaline/neutral invertases (PbrA/N-Invs), were identified from P. bretschneideri Rehd. genome, with diverse chromosome locations, cis-acting elements, gene structures and motifs. Their expression profiles were tissue-specific, and postharvest light or temperature treatment would alter their expression profiles. During 'Dangshansuli' pear development, in association with visual/inner quality change was the alternations of invertase activity and the expression profiles of PbrInvs. In combination with results of subcellular sugar distribution as well as correlation analysis among sugar content, invertase activity and PbrInv mRNA abundance, PbrvacInv1 might be involved in sucrose decomposition during pear development. PbrvacInv1-GFP fusion protein mainly accumulated on the tonoplast (vacuolar membrane); meanwhile, transient overexpression of PbrvacInv1 in pear fruit would upregulate vacInv activity, causing higher fructose and lower sucrose when compared with that of the control. Furthermore, invertase inhibitor 5 (PbrInvInh5) could interact with PbrvacInv1.

Controlling and optimizing the morphology and microstructure of 3D interconnected activated carbons for high performance supercapacitors.

For an active electrode material, the morphology, microstructure and the effective specific surface area derived from them, have a dominant effect for the high performance supercapacitors. In this study, 3D interconnected activated carbons with controlled and optimized morphologies and porous structures were prepared from accessible carbon source and graphene oxide by a hydrothermal carbonization and following an activation method. Through optimizing the ratios of the precursors and reaction conditions, an electrode material with excellent specific surface area of 2318 m2 g-1, meso-/macro-pore ratio of 63.2% (meso-/macro-pore volume reached to 0.83 cm3 g-1), as well as an outstanding electrical conductivity of 46.6 S m-1, was obtained. The materials exhibit superior double-layer capacitive performances on a symmetric supercapacitor, delivering superior specific capacitance of 157 F g-1 in organic electrolyte system at current density of 0.5 A g-1, excellent energy density of 37.6 W h kg-1 with a power density of 7.1 kW kg-1 and good cycling stability of capacitance retention of 94% over 7000 cycles. These results offer a practical method to prepare the desired carbon electrode materials with controlled morphology and structure for high efficiency electrochemical energy storage devices.

Defective Zr-based metal-organic frameworks as sorbent for the determination of fungicides in environmental water samples by rapid dispersive micro-solid-phase extraction coupled to liquid chromatography/mass spectrometry.

In this work, defective Zr-based metal-organic framework was successfully synthesized and evaluated as a dispersive micro-solid-phase extraction sorbent for efficient preconcentration and determination of fungicides in complex water samples. The defective Zr-based metal-organic framework crystal with increased adsorption capacity was successfully synthesized by employing formic acid as the modulator. The extraction conditions, including the pH, extraction time, desorption solvent and desorption time, were comprehensively investigated. Under optimum conditions, it was found that dispersive micro-solid-phase extraction method, coupled with liquid chromatography/mass spectrometry, exhibited a good linear relationship with correlation coefficients greater than 0.9980. The relative standard deviations of inter-day and intra-day precisions ranged from 2.6 to 9.2% and the limits of detection ranged from 0.004 to 0.036 µg/L. These merits, combined with their satisfactory recoveries (>80%), suggested the great potential of defective Zr-based metal-organic framework as a new adsorbent for efficient extraction of trace fungicides. This method exhibits good application potential for the pretreatment of fungicides from environmental water samples.

Development and validation of a solid-phase competition ELISA based on virus-like particles of foot-and-mouth disease virus serotype A for antibody detection.

Foot-and-mouth disease (FMD), caused by FMD virus (FMDV), is a highly contagious epidemic disease, which is controlled primarily by prophylactic vaccination and serological monitoring after vaccination. Here, we have developed a solid-phase competition ELISA (SPCE) method based on virus-like particles (VLPs) of FMDV serotype A. The use of VLPs in the SPCE assay as a replacement for inactivated FMDV provides a high level of biosafety. The SPCE showed high concordance rates when compared with the virus neutralization test and liquid-phase blocking ELISA for testing clinical serum samples and successive serological monitoring (kappa = 0.925). Thus, this SPCE is an alternative method for post-immunization detection of antibodies against FMDV serotype A, with high specificity and sensitivity.

Genome-wide analysis of polygalacturonase gene family from pear genome and identification of the member involved in pear softening.

BACKGROUND: Polygalacturonase (PG), as an important hydrolase participating in the degradation of pectin, plays an important role in softening process of fruit. However, information on PG gene family in pear genome and the specific member involved in fruit softening is still rudimentary. RESULTS: In this study, a total of 61 PG genes, which could be divided into six subclasses, were identified from the pear genome with diverse chromosome locations, gene structures, motifs and cis-acting elements. Most PbrPGs were derived from WGD/segmental duplication blocks, and purifying selection was the main driving force for their expansion. The expression profiles of PbrPGs in pear were tissue/development-stage/cultivar-dependent. During 'Housui' pear storage, associated with the reduction of firmness was the accumulation of PG activity. Totally, 28 PbrPGs were expressed during fruit storage, which could be classified into five categories based on different expression patterns; most demonstrated an increased trend. Of these, PbrPG6 were proposed to account for pear softening in combination of the phylogenetic and correlation analysis among firmness, PG activity and PbrPGs. By constructing the silencing vector, a higher firmness was observed in PbrPG6-silenced fruit when compared with that of the control (empty vector). In a further study, we found that the expression of PbrPG6 was regulated by postharvest 1-MCP/ethrel treatment, and several PbrERFs might function in this process. CONCLUSIONS: We identified 61 PbrPG genes from pear genome; of these, PbrPG6 was involved in fruit softening process; furthermore, the expression of PbrPG6 might be under the control of PbrERF. This study provides a foundation for future work aimed at elucidating the molecular mechanism underlying pear softening.

Preparation of metal-organic framework UiO-66-incorporated polymer monolith for the extraction of trace levels of fungicides in environmental water and soil samples.

A zirconium terephthalate metal-organic framework-incorporated poly(N-vinylcarbazole-co-divinylbenzene) monolith was fabricated in a capillary by a thermal polymerization method. The optimized monolith had a homogeneous structure, good permeability, and stability. The monolith could be used for the effective enrichment of fungicides through π-π interactions, electrostatic forces, and hydrogen bonds. The potential factors that affect the extraction efficiency, including ionic strength, solution pH, sample volume, and eluent volume, were investigated in detail. The monolith-based in-tube solid-phase microextraction coupled with ultra-high-performance liquid chromatography and high-resolution Orbitrap mass spectrometry was performed for the analysis of five fungicides (pyrimethanil, tebuconazole, hexaconazole, diniconazole, and flutriafol) in environmental samples. Under the optimized conditions, the linear ranges were 0.005-5 ng/mL for pyrimethanil, 0.01-5 ng/mL for flutriafol, and 0.05-5 ng/mL for other fungicides, respectively, with coefficients of determination ≥0.9911. The limits of detection were 1.34-14.8 ng/L. The columns showed good repeatability (relative standard deviations ≤9.3%, n = 5) and desirable column-to-column reproducibility (relative standard deviations 5.3-9.4%, n = 5). The proposed method was successfully applied for the simultaneous detection of five fungicides in water and soil samples, with recoveries of 90.4-97.5 and 84.0-95.3%, respectively.

Fabrication of magnetic zinc adeninate metal-organic frameworks for the extraction of benzodiazepines from urine and wastewater.

In this study, an alternative method for synthesizing magnetic cobalt adeninate metal-organic frameworks was developed, and the synthesized materials were examined for their potential application for separating and enriching benzodiazepines from complex samples. Benzodiazepines, widely used as hypnotics, muscle relaxants, sedatives, and anxiolytics, are a class of drugs that require accurate detection and monitoring. Results showed that Fe3 O4 nanoparticles could be well anchored onto the external surface of cobalt adeninate metal-organic frameworks by using amino-silane as a linkage. Their adsorption of benzodiazepines was mainly promoted by intermolecular hydrogen binding, π-π interactions and electrostatic attraction. Their potential application was evaluated by extraction of benzodiazepines in urine and wastewater samples prior to liquid chromatography with mass spectrometry. Under optimum conditions, the calibration curves were linear with a correlation coefficient of ≥0.9928 in the concentration range of 10-5000 ng/L for lorazepam and 5-5000 ng/L for estazolam, chlordiazepoxide, alprazolam, midazolam and triazolam. The limits of detection were in the range of 0.71-2.49 ng/L. The percent of extraction recoveries were 80.2-94.5% for urine and 84.1-94.4% for wastewater, respectively. Results suggested that magnetic cobalt adeninate metal-organic frameworks could potentially be a promising material for enriching benzodiazepines from urine and wastewater with high accuracy and precision.

Poly(methacrylic acid-ethylene glycol dimethacrylate-N-vinylcarbazole) monolithic column for the enrichment of trace benzodiazepines from urine and beer samples.

A sensitive microextraction method based on a new poly(methacrylic acid-ethylene glycol dimethacrylate-N-vinylcarbazole) monolithic capillary column, coupled with gas chromatography and electron capture detection, was established for the determination of three benzodiazepines (estazolam, alprazolam, and triazolam) in urine and beer samples. Owing to the abundant π electrons and polar surface of N-vinylcarbazole, N-vinylcarbazole-incorporated monolith showed a higher extraction performance than neat poly(methacrylic acid-ethylene glycol dimethacrylate) because of the enhanced π-π stacking interactions derived from the π-electron-rich benzene groups from N-vinylcarbazole. The monolith exhibited a homogeneous and continuous structure, good permeability, and a long lifetime. Factors affecting the extraction such as solution pH, salt concentration, sample volume, desorption solvent, and desorption volume were investigated. Under the optimized conditions, limits of detection of 0.011-0.026 ng/mL were obtained. The one-column and column-to-column precision values were ≤7.2 and ≤9.8%, respectively. The real samples were first diluted with deionized water and then treated by the monolith microextraction before gas chromatography analysis. The recoveries were 81.4-93.3 and 83.3-94.7% for the spiked samples, with relative standard deviations of 4.1-8.1 and 3.8-8.5%, respectively. This method provides an accurate, simple, and sensitive detection platform for drug analysis.

Determination of tetracycline antibiotics in fatty food samples by selective pressurized liquid extraction coupled with high-performance liquid chromatography and tandem mass spectrometry.

For the determination of trace residues of tetracycline antibiotics in fatty food samples, selective pressurized liquid extraction coupled with high-performance liquid chromatography and tandem mass spectrometry was applied in this study. Copper(II) isonicotinate was first used as online cleanup adsorbent in the selective pressurized liquid extraction process. The adsorbent to sample ratio, extraction temperature, extraction time, and recycle times, etc. were optimized. The tetracyclines in food samples of pork, chicken meat, and clam meat were detected by liquid chromatography with tandem mass spectrometry. Tetracycline was found at levels of 0.32 and 0.53 µg/g and oxytetracycline was found at 0.14 and 0.21 µg/g in chicken meat and clam meat, respectively, while chlorotetracycline and deoxytetracycline were below the detection limit. The detection limit (S/N = 3) for these four tetracyclines were from 0.2 to 3.3 ng/g, the recoveries were from 75.8 to 110.5%, and relative standard deviations were from 5.5 to 13.6%. Copper(II) isonicotinate showed a higher purification capacity than other cleanup adsorbents for extraction of antibiotics in fatty food and the recovery showed predominance compared with a pressurized liquid extraction method without adsorbent. The study demonstrated that copper(II) isonicotinate would be a promising cleanup adsorbent in pressurized liquid extraction for the analysis of trace organic pollutants in complicated samples.

Review of fruits flavor deterioration in postharvest storage: Odorants, formation mechanism and quality control.

Fruits flavor deterioration is extremely likely to occur during post-harvest storage, which not only damages quality but also seriously affects its market value. This work focuses on the study of fruits deterioration odorants during storage by describing their chemical compositions (i.e., alcohols, aldehydes, acids, and sulfur-containing compounds). Besides, the specific flavor deterioration mechanisms (i.e., fermentation metabolism, lipid oxidation, and amino acid degradation) inducing by factors (temperature, oxygen, microorganisms, ethylene) are summarized. Moreover, quality control strategies to mitigate fruits flavor deterioration by physical (temperature control, hypobaric treatment, UV-C, CA) and chemical (1-MCP, MT, NO, MeJA) techniques are also proposed. This review will provide useful references for fruits flavor control technologies development.

Synthesis of polyethylene glycol-grafted magnetic nanoparticles for the fast and efficient extraction of anabolic substances from human urine.

Anabolic steroids and ß-agonists are commonly prohibited substances found in doping control studies; therefore, the determination of anabolic substances in biological samples is crucial. To analyze the anabolic compounds in urine, an adsorbent, polyethylene glycol (PEG)-grafted magnetic nanoparticle material (Fe3O4@SiO2-PEG), with low toxicity and strong biocompatibility was prepared in this investigation. Compared to those of Fe3O4 and Fe3O4@SiO2, the grafted PEG chains (approximately 5.4 wt.%) on the magnetic nanoparticles improved the extraction efficiencies by factors of 3.9-17.0 and 2.5-2.9, respectively, likely due to the electrostatic attraction and hydrogen bonding. To achieve maximum extraction efficiency, several extraction parameters were optimized, including the kind and volume of desorption solvent, pH, and the extraction and desorption time. The standard curves were linear within the range of 0.5-20 µg/L for methyltestosterone and trenbolone, and 0.02-5 µg/L for clenbuterol. The limits of detection for the three drugs were 0.01-0.12 µg/L. The limits of quantification were 0.02-0.40 µg/L. The levels of precision of the optimized method were assessed based on the respective intra- and inter-day and batch-to-batch relative standard deviations in the ranges of 3.2-5.2 % (n = 5), 5.9-11.3 % (n = 4), and 6.7-9.2 % (n = 3). The Fe3O4@SiO2-PEG nanoparticles could exclude urine matrix interferences (matrix effect of 91.8-98.1 %) and achieve satisfactory recoveries (75.5-116.1 %), affording sensitive and accurate determination of trace anabolic substances in urine.

Screening and Stability Evaluation of Freeze-Dried Protective Agents for a Live Recombinant Pseudorabies Virus Vaccine.

Infection of pigs with the pseudorabies virus (PRV) causes significant economic losses in the pig industry. Immunization with live vaccines is a crucial aspect in the prevention of pseudorabies in swine. The TK/gE/gI/11k/28k deleted pseudorabies vaccine is a promising alternative for the eradication of epidemic pseudorabies mutant strains. This study optimized the lyophilization of a heat-resistant PRV vaccine to enhance the quality of a live vaccine against the recombinant PRV rHN1201TK-/gE-/gI-/11k-/28k-. The A4 freeze-dried protective formulation against PRV was developed by comparing the reduction in virus titer after lyophilization and after seven days of storage at 37 °C. The formulation contains 1% gelatin, 5% trehalose, 0.5% poly-vinylpyrimidine (PVP), 0.5% thiourea, and 1% sorbitol. The A4 freeze-dried vaccine demonstrated superior protection and thermal stability. It experienced a freeze-dried loss of 0.31 Lg post-freeze-drying and a heat loss of 0.42 Lg after being stored at a temperature of 37 °C for 7 consecutive days. The A4 freeze-dried vaccine was characterized through XRD, FTIR, and SEM analyses, which showed that it possessed an amorphous structure with a consistent porous interior. The trehalose component of the vaccine formed stable hydrogen bonds with the virus. Long-term and accelerated stability studies were also conducted. The A4 vaccine maintained viral titer losses of less than 1.0 Lg when exposed to 25 °C for 90 days, 37 °C for 28 days, and 45 °C for 7 days. The A4 vaccine had a titer loss of 0.3 Lg after storage at 2-8 °C for 24 months, and a predicted shelf life of 6.61 years at 2-8 °C using the Arrhenius equation. The A4 freeze-dried vaccine elicited no side effects when used to immunize piglets and produced specific antibodies. This study provides theoretical references and technical support to improve the thermal stability of recombinant PRV rHN1201TK-/gE-/gI-/11k-/28k- vaccines.

Development and comprehensive SBSE-GC/Q-TOF-MS analysis optimization, comparison, and evaluation of different mulberry varieties volatile flavor.

Optimization of seven parameters of stir bar sorptive extraction (SBSE) on mulberry volatile components for the first time. A total of 347 volatile components were identified and quantified in 14 mulberry varieties, predominantly encompassing esters, aldehydes, terpenoids, hydrocarbons, ketones, alcohols, heterocyclics, acids, and phenols. Hexanal and (E)-2-hexenal were the dominant volatiles. Furthermore, 79 volatile compounds characterized by odor activity values (OAVs) > 1 were identified, making a significant contribution to the distinctive mulberry flavor. "Green" notes were the most intense, followed by "fatty" and "fruity". Utilizing odor ring charts, the volatile flavor characteristics of the 14 mulberry varieties could be intuitively distinguished. This study not only established a viable methodology for differentiating mulberry varieties but also laid a theoretical foundation for the quality evaluation and variety breeding of mulberry flavor.

Rapid and simple determination of organophosphorus pesticides in urine using polydopamine-modified monolithic spin column extraction combined with liquid chromatography-mass spectrometry.

The determination of organophosphorus pesticides in urine is useful for evaluating human exposure. In this study, a simple micro-solid-phase extraction method based on a polydopamine-modified monolithic spin column combined with liquid chromatography-mass spectrometry (LC-MS) was developed for the determination of six organophosphorus pesticides (dimethoate, dichlorvos, carbofuran, methidathion, phosalone, and chlorpyrifos) in urine samples. A methacrylate polymer monolithic support was prepared in situ in the spin column, and dopamine solution was repeatedly passed through the monolith matrix via centrifugation to generate a polydopamine layer in the polymeric network. All extraction steps were performed via centrifugation. The monolith exhibited good permeability, which enabled high-flow-rate sample loading and significantly reduced the sample pre-treatment time. The addition of polydopamine significantly improved the extraction efficiency of the monolithic spin column owing to the catechol and amine groups in dopamine, which can enhance hydrogen bonding and π-π stacking. Factors affecting the extraction, including the solution pH, centrifugation speed, and desorption solvent, were investigated to determine the optimal extraction conditions. Under the optimal conditions, the OPP detection limits were 0.02-1.32 µg/L. The relative standard deviations of the single column (n = 5) and column-to-column (n = 3) precision for the extraction method were <11%. The monolithic spin column exhibited high stability and could be used for more than 40 extraction cycles. The recoveries for spiked urine samples were 72.1-109.3% (RSDs: 1.6-7.9%). The developed method was successfully applied to the simple and rapid analysis of organophosphorus pesticides in urine samples.

Efficacy and mechanism of nourishing yin and purging fire therapy for central precocious puberty based on meta-analysis and network pharmacology.

BACKGROUND: Central precocious puberty (CPP) is due to the early activation of the hypothalamus-pituitary-gonadal axis, and its incidence is on the rise. A number of studies have shown that nourishing yin and purging fire (NYPF) therapy can be beneficial for CPP. Therefore, we conducted this review to investigate the efficacy, safety, and mechanism of NYPF therapy for CPP. METHODS: Electronic databases including PubMed, the Cochrane Library, Web of Science, EMBASE, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, Wan-fang Database, and China Scientific Technical Journals Database and 2 platforms including Clinical Trials and Chinese Clinical Trial Registry were searched for randomized controlled trials of NYPF therapy for CPP. A meta-analysis was conducted using RevMan 5.3 and Stata 17.0 software. The core herb pair of NYPF was identified by data mining using IBM SPSS Modeler 18.0 software. The active ingredients and targets of the core herb pair were obtained through the TCMSP database. The main targets of CPP were acquired form the GeneCards, Disgenet and TTD databases. A protein-protein interaction network was carried out to select the core genes by using STRING platform and Cytoscape 3.7.2 software. Metascape platform was used to conduct gene ontology (GO) and KEGG enrichment analysis. The results were verified utilizing molecular docking. RESULTS: A total of 23 studies were included. Meta-analysis shows the NYPF therapy could significantly improve the clinical efficacy rate and secondary sexual indicators (uterine volume, ovarian volume, breast nucleus diameter, follicular diameter), reduce TCM syndrome scores and serum sex hormone (FSH, LH, E2), and slow down bone age maturation compared to GnRHa therapy group. In addition, NYPF therapy was safe and has no obvious adverse events. Data mining revealed that the core herb pair of NYPF was "Anemarrhenae Rhizoma (Zhimu) - Phellodendri Chinensis Cortex (Huangbai)." Network pharmacology predicted that quercetin, kaempferol, beta-sitosterol, etc were the key components of Zhimu-Huangbai for treating CPP. The core targets were TP53, JUN, AKT1, ESR1, TNF, IL6, CCND1, MAPK1, BCL2, EGFR, IL1B, and PTGS2. They played a pivotal role in modulating multiple signaling pathways, such as Endocrine resistance, MAPK signaling pathway, and PI3K-Akt signaling pathway. CONCLUSION: This article revealed that NYPF therapy is effective and safe against CPP. The mechanism of the core herb pair of NYPF therapy for CPP through muti-components, muti-targets and muti-pathways.

Bacteria-Derived Outer-Membrane Vesicles Hitchhike Neutrophils to Enhance Ischemic Stroke Therapy.

The treatment of reperfusion injury after ischemic stroke remains unsatisfactory since the blood-brain barrier (BBB) prevents most neuroprotective agents from entering the brain. Here, a strategy is proposed based on bacteria-derived outer-membrane vesicle (OMV) hitchhiking on the neutrophils for enhanced brain delivery of pioglitazone (PGZ) to treat ischemic stroke. By encapsulating PGZ into OMV, the resulting OMV@PGZ nanoparticles inherit the functions associated with the bacterial outer membrane, making them ideal decoys for neutrophil uptake. The results show that OMV@PGZ simultaneously inhibits the activation of nucleotide oligomerization-like receptor protein 3 (NLRP3) inflammasomes and ferroptosis and reduces the reperfusion injury to exert a neuroprotective effect. Notably, the transcription factors Pou2f1 and Nrf1 of oligodendrocytes are identified for the first time to be involved in this process and promoted neural repair by single-nucleus RNA sequencing (snRNA-seq).

Cell membrane-specific self-assembly of peptide nanomedicine induces tumor immunogenic death to enhance cancer therapy.

Immunogenic cell death (ICD), as an unusual cell death pattern, mediates cancer cells to release a series of damage-associated molecular patterns (DAMPs), and is widely used in the field of cancer immunotherapy. Injuring the cell membrane can serve as a novel ICD initiation strategy. In this study, a peptide nanomedicine (PNpC) is designed using the fragment CM11 of cecropin, which is effective in disrupting cell membranes because of its α-helical structure. PNpC self-assembles in situ in the presence of high levels of alkaline phosphatase (ALP) on the tumor cell membrane, transforming from nanoparticles to nanofibers, which reduces the cellular internalization of the nanomedicine and increases the interaction between CM11 and tumor cell membranes. Both in vitro and in vivo results indicate that PNpC plays a significant role in killing tumor cells by triggering ICD. The ICD induced by the destruction of the cancer cell membrane is accompanied by the release of DAMPs, which promotes the maturation of DCs and facilitates the presentation of tumor-associated antigens (TAA), resulting in the infiltration of CD8+ T cells. We believe that PNpC can trigger ICD while killing cancer cells, providing a new reference for cancer immunotherapy.

Sonoactivated Cascade Fenton Reaction Enhanced by Synergistic Modulation of Electron-Hole Separation for Improved Tumor Therapy.

Chemodynamic therapy (CDT) is an emerging targeted treatment technique for tumors via the generation of highly cytotoxic hydroxyl radical (·OH) governed by tumor microenvironment-assisted Fenton reaction. Despite high effectiveness, it faces limitations like low reaction efficiency and limited endogenous H2 O2 , compromising its therapeutic efficacy. This study reports a novel platform with enhanced CDT performance by in situ sono-activated cascade Fenton reaction. A piezoelectric g-C3 N4 (Au-Fe-g-C3 N4 ) nanosheet is developed via sono-activated synergistic effect/H2 O2 self-supply mediated cascade Fenton reaction, realizing in situ ultrasound activated cascade Fenton reaction kinetics by synergistic modulation of electron-hole separation. The nanosheets consist of piezoelectric g-C3 N4 nanosheet oxidizing H2 O to highly reactive H2 O2 from the valence band, Fe3+ /Fe2+ cycling activated by conduction band to generate ·OH, and Au nanoparticles that lower the bandgap and further adopt electrons to generate more 1 O2 , resulting in improved CDT and sonodynamic therapy (SDT). Moreover, the Au-Fe-g-C3 N4 nanosheet is further modified by the targeted peptide to obtain P-Au-Fe-g-C3 N4 , which inhibits tumor growth in vivo effectively by generating reactive oxygen species (ROS). These results demonstrated that the sono-activated modulation translates into a high-efficiency CDT with a synergistic effect using SDT for improved anti-tumor therapy.