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1.
Acta Pharm Sin B ; 14(6): 2402-2427, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38828146

ABSTRACT

Targeted protein degradation (TPD) represented by proteolysis targeting chimeras (PROTACs) marks a significant stride in drug discovery. A plethora of innovative technologies inspired by PROTAC have not only revolutionized the landscape of TPD but have the potential to unlock functionalities beyond degradation. Non-small-molecule-based approaches play an irreplaceable role in this field. A wide variety of agents spanning a broad chemical spectrum, including peptides, nucleic acids, antibodies, and even vaccines, which not only prove instrumental in overcoming the constraints of conventional small molecule entities but also provided rapidly renewing paradigms. Herein we summarize the burgeoning non-small molecule technological platforms inspired by PROTACs, including three major trajectories, to provide insights for the design strategies based on novel paradigms.

2.
Sleep Med ; 119: 526-534, 2024 May 24.
Article in English | MEDLINE | ID: mdl-38805860

ABSTRACT

BACKGROUND: Obstructive sleep apnea (OSA) is a common sleep disorder among chronic kidney disease (CKD) patients, associated with considerable morbidity. Various studies from around the globe have reported different prevalence rates. OBJECTIVE: This systematic review and meta-analysis aimed to determine the prevalence of OSA and quantify the relationship between OSA and mortality risk in patients with CKD. METHODS: Four databases were systematically searched, and additional references to relevant articles were manually searched. The prevalence of OSA and the mortality risk based on random-effects models were assessed using percentages and hazard ratio (HR) with a 95 % confidence interval (95 % CI). In addition, the heterogeneity between studies was assessed using I2 statistics. RESULTS: A total of 44 literature (47 studies with 223,967 participants) met the eligibility criteria for the meta-analysis. The results showed that the prevalence of OSA in CKD patients was reported to be 39.3 % (95 % CI, 32.3-46.7). Among study participants in different age groups, the highest prevalence of OSA was found in CKD respondents aged 60 years or older, at 47.1 % (95 % CI 34.4-60.3). Of the eight literature (10 cohorts) that provided survival data, the pooled estimates indicated a 26.5 % (HR: 1.265; 95 % CI 1.021-1.568) higher mortality risk in subjects with OSA than CKD patients without OSA. CONCLUSIONS: This systematic review and meta-analysis found that more than 1/3 of CKD patients have comorbid OSA, which increases the risk of early death in CKD patients. These results should help policymakers to provide adequate healthcare for this population. PROSPERO REGISTRATION ID: CRD42023465497.

3.
J Agric Food Chem ; 72(20): 11706-11715, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38728528

ABSTRACT

In this study, we devised a photothermally stable phytochemical dye by leveraging alizarin in conjunction with the metal-organic framework ZIF-8 (AL@ZIF-8). The approach involved grafting alizarin into the microporous structure of ZIF-8 through physical adsorption and hydrogen-bonding interactions. AL@ZIF-8 significantly enhanced the photostability and thermostability of alizarin. The nanoparticles demonstrate substantial color changes in various pH environments, showcasing their potential for meat freshness monitoring. Furthermore, we introduced an intelligent film utilizing poly(vinyl alcohol)-sodium alginate-AL@ZIF-8 (PA-SA-ZA) for detecting beef freshness. The sensor exhibited a superior water contact angle (52.34°) compared to the alizarin indicator. The color stability of the film was significantly enhanced under visible and UV light (ΔE < 5). During beef storage, the film displayed significant color fluctuations correlating with TVB-N (R2=0.9067), providing precise early warning signals for assessing beef freshness.


Subject(s)
Alginates , Colorimetry , Polyvinyl Alcohol , Alginates/chemistry , Animals , Polyvinyl Alcohol/chemistry , Cattle , Colorimetry/methods , Anthraquinones/chemistry , Food Packaging/instrumentation , Phytochemicals/chemistry , Red Meat/analysis , Metal-Organic Frameworks/chemistry
4.
Front Med ; 2024 May 21.
Article in English | MEDLINE | ID: mdl-38769281

ABSTRACT

Schistosoma infection is one of the major causes of liver fibrosis. Emerging roles of hepatic progenitor cells (HPCs) in the pathogenesis of liver fibrosis have been identified. Nevertheless, the precise mechanism underlying the role of HPCs in liver fibrosis in schistosomiasis remains unclear. This study examined how autophagy in HPCs affects schistosomiasis-induced liver fibrosis by modulating exosomal miRNAs. The activation of HPCs was verified by immunohistochemistry (IHC) and immunofluorescence (IF) staining in fibrotic liver from patients and mice with Schistosoma japonicum infection. By coculturing HPCs with hepatic stellate cells (HSCs) and assessing the autophagy level in HPCs by proteomic analysis and in vitro phenotypic assays, we found that impaired autophagy degradation in these activated HPCs was mediated by lysosomal dysfunction. Blocking autophagy by the autophagy inhibitor chloroquine (CQ) significantly diminished liver fibrosis and granuloma formation in S. japonicum-infected mice. HPC-secreted extracellular vehicles (EVs) were further isolated and studied by miRNA sequencing. miR-1306-3p, miR-493-3p, and miR-34a-5p were identified, and their distribution into EVs was inhibited due to impaired autophagy in HPCs, which contributed to suppressing HSC activation. In conclusion, we showed that the altered autophagy process upon HPC activation may prevent liver fibrosis by modulating exosomal miRNA release and inhibiting HSC activation in schistosomiasis. Targeting the autophagy degradation process may be a therapeutic strategy for liver fibrosis during Schistosoma infection.

5.
Small ; : e2312129, 2024 Apr 09.
Article in English | MEDLINE | ID: mdl-38593332

ABSTRACT

Lithium (Li) metal is widely recognized as a viable candidate for anode material in future battery technologies due to its exceptional energy density. Nevertheless, the commercial Li foils in common use are too thick (≈100 µm), resulting in a waste of Li resources. Herein, by applying the vacuum evaporation plating technology, the ultra-thin Li foils (VELi) with high purity, strong adhesion, and thickness of less than 10 µm are successfully prepared. The manipulation of evaporation temperature allows for convenient regulation of the thickness of the fabricated Li film. This physical thinning method allows for fast, continuous, and highly accurate mass production. With a current density of 0.5 mA cm-2 for a plating amount of 0.5 mAh cm-2, VELi||VELi cells can stably cycle for 200 h. The maximum utilization of Li is already more than 25%. Furthermore, LiFePO4||VELi full cells present excellent cycling performance at 1 C (1 C = 155 mAh g-1) with a capacity retention rate of 90.56% after 240 cycles. VELi increases the utilization of active Li and significantly reduces the cost of Li usage while ensuring anode cycling and multiplication performance. Vacuum evaporation plating technology provides a feasible strategy for the practical application of ultra-thin Li anodes.

6.
Anal Chim Acta ; 1304: 342515, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38637032

ABSTRACT

Aiming for sustainable crop productivity under changing climate conditions, it is essential to develop handy models for in-situ monitoring of reactive oxygen species (ROS). Herein, this work reports a simple electrochemical sensing toward hydrogen peroxide (H2O2) for tracking crop growth status sensitized with electron-migration nanostructure. To be specific, Cu-based metal-organic frameworks (MOFs) with high HOMO energy level are designed for H2O2 reduction on account of Cu(I)/Cu(II) redox switchability. Importantly, the sensing performance is improved by electrochemically reduced graphene oxide (GO) with ready to use feature. To overcome the shortcomings of traditional liquid electrolytes, conductive hydrogel as semi-solid electrolyte exhibits the adhesive property to the cut plant petiole surface. Benefitting from the preferred composite models and conductive hydrogel, the electrochemical sensing toward H2O2 with high sensitivity and good anti-interference against the coexistent molecules, well qualified for acquiring plant growth status.

7.
EClinicalMedicine ; 71: 102566, 2024 May.
Article in English | MEDLINE | ID: mdl-38686219

ABSTRACT

Background: Urine cytology is an important non-invasive examination for urothelial carcinoma (UC) diagnosis and follow-up. We aimed to explore whether artificial intelligence (AI) can enhance the sensitivity of urine cytology and help avoid unnecessary endoscopy. Methods: In this multicentre diagnostic study, consecutive patients who underwent liquid-based urine cytology examinations at four hospitals in China were included for model development and validation. Patients who declined surgery and lacked associated histopathology results, those diagnosed with rare subtype tumours of the urinary tract, or had low-quality images were excluded from the study. All liquid-based cytology slides were scanned into whole-slide images (WSIs) at 40 × magnification and the WSI-labels were derived from the corresponding histopathology results. The Precision Urine Cytology AI Solution (PUCAS) was composed of three distinct stages (patch extraction, features extraction, and classification diagnosis) and was trained to identify important WSI features associated with UC diagnosis. The diagnostic sensitivity was mainly used to validate the performance of PUCAS in retrospective and prospective validation cohorts. This study is registered with the ChiCTR, ChiCTR2300073192. Findings: Between January 1, 2018 and October 31, 2022, 2641 patients were retrospectively recruited in the training cohort, and 2335 in retrospective validation cohorts; 400 eligible patients were enrolled in the prospective validation cohort between July 7, 2023 and September 15, 2023. The sensitivity of PUCAS ranged from 0.922 (95% CI: 0.811-0.978) to 1.000 (0.782-1.000) in retrospective validation cohorts, and was 0.896 (0.837-0.939) in prospective validation cohort. The PUCAS model also exhibited a good performance in detecting malignancy within atypical urothelial cells cases, with a sensitivity of over 0.84. In the recurrence detection scenario, PUCAS could reduce 57.5% of endoscopy use with a negative predictive value of 96.4%. Interpretation: PUCAS may help to improve the sensitivity of urine cytology, reduce misdiagnoses of UC, avoid unnecessary endoscopy, and reduce the clinical burden in resource-limited areas. The further validation in other countries is needed. Funding: National Natural Science Foundation of China; Key Program of the National Natural Science Foundation of China; the National Science Foundation for Distinguished Young Scholars; the Science and Technology Planning Project of Guangdong Province; the National Key Research and Development Programme of China; Guangdong Provincial Clinical Research Centre for Urological Diseases.

8.
Cell Mol Biol (Noisy-le-grand) ; 70(3): 174-181, 2024 Mar 31.
Article in English | MEDLINE | ID: mdl-38650145

ABSTRACT

Ovarian cancer is a prevalent malignancy in the female reproductive system, representing a significantly fatal and incurable tumor. Chelerythrine (CHE), a natural benzopyridine alkaloid, has demonstrated a broad spectrum of anticancer activities. Nevertheless, the ovarian cancer inhibitory impact of CHE remains unclear. In this study, we investigated the cytotoxic mechanism and potential targets of CHE on in vitro cultures of A2780 and SKOV3 cells derived from ovarian cancer. Additionally, in vivo experiments were conducted to confirm the suppressive impact of CHE on tumor growth in nude mice. The findings revealed that CHE impeded the growth of A2780 and SKOV3 cells in a concentration-time-dependent manner and significantly suppressed the development of tumors in nude mice. CHE elevated the level of oxidative stress in tumor cells, prompted cell cycle halt in the S phase, and increased their mitochondrial membrane potential. Western blotting results demonstrated that CHE could modulate the expression of proteins associated with apoptotic and ferroptosis processes in A2780 and SKOV3 cells. Nrf2 was verified to be an upstream key target mediating the inhibitory impact of CHE on ovarian cancer cells. In summary, CHE exerts its anti-cancer effects on ovarian cancer by modulating Nrf2, inhibiting cellular proliferation, and promoting apoptosis and ferroptosis.


Subject(s)
Apoptosis , Benzophenanthridines , Cell Proliferation , Ferroptosis , Mice, Nude , NF-E2-Related Factor 2 , Ovarian Neoplasms , Female , Benzophenanthridines/pharmacology , Humans , Ovarian Neoplasms/metabolism , Ovarian Neoplasms/pathology , Ovarian Neoplasms/drug therapy , NF-E2-Related Factor 2/metabolism , Animals , Cell Line, Tumor , Ferroptosis/drug effects , Apoptosis/drug effects , Cell Proliferation/drug effects , Membrane Potential, Mitochondrial/drug effects , Mice , Xenograft Model Antitumor Assays , Mice, Inbred BALB C , Oxidative Stress/drug effects , Reactive Oxygen Species/metabolism
9.
Compr Rev Food Sci Food Saf ; 23(3): e13339, 2024 05.
Article in English | MEDLINE | ID: mdl-38578165

ABSTRACT

The importance of food quality and safety lies in ensuring the best product quality to meet consumer demands and public health. Advanced technologies play a crucial role in minimizing the risk of foodborne illnesses, contamination, drug residue, and other potential hazards in food. Significant materials and technological advancements have been made throughout the food supply chain. Among them, quantum dots (QDs), as a class of advanced nanomaterials with unique physicochemical properties, are progressively demonstrating their value in the field of food quality and safety. This review aims to explore cutting-edge research on the different applications of QDs in food quality and safety, including encapsulation of bioactive compounds, detection of food analytes, food preservation and packaging, and intelligent food freshness indicators. Moreover, the modification strategies and potential toxicities of diverse QDs are outlined, which can affect performance and hinder applications in the food industry. The findings suggested that QDs are mainly used in analyte detection and active/intelligent food packaging. Various food analytes can be detected using QD-based sensors, including heavy metal ions, pesticides, antibiotics, microorganisms, additives, and functional components. Moreover, QD incorporation aided in improving the antibacterial and antioxidant activities of film/coatings, resulting in extended shelf life for packaged food. Finally, the perspectives and critical challenges for the productivity, toxicity, and practical application of QDs are also summarized. By consolidating these essential aspects into this review, the way for developing high-performance QD-based nanomaterials is presented for researchers and food technologists to better capitalize upon this technology in food applications.


Subject(s)
Quantum Dots , Quantum Dots/toxicity , Food Contamination/prevention & control , Food Contamination/analysis , Food Microbiology , Food Quality , Food Packaging/methods
10.
EClinicalMedicine ; 71: 102580, 2024 May.
Article in English | MEDLINE | ID: mdl-38618206

ABSTRACT

Background: The pathological examination of lymph node metastasis (LNM) is crucial for treating prostate cancer (PCa). However, the limitations with naked-eye detection and pathologist workload contribute to a high missed-diagnosis rate for nodal micrometastasis. We aimed to develop an artificial intelligence (AI)-based, time-efficient, and high-precision PCa LNM detector (ProCaLNMD) and evaluate its clinical application value. Methods: In this multicentre, retrospective, diagnostic study, consecutive patients with PCa who underwent radical prostatectomy and pelvic lymph node dissection at five centres between Sep 2, 2013 and Apr 28, 2023 were included, and histopathological slides of resected lymph nodes were collected and digitised as whole-slide images for model development and validation. ProCaLNMD was trained at a dataset from a single centre (the Sun Yat-sen Memorial Hospital of Sun Yat-sen University [SYSMH]), and externally validated in the other four centres. A bladder cancer dataset from SYSMH was used to further validate ProCaLNMD, and an additional validation (human-AI comparison and collaboration study) containing consecutive patients with PCa from SYSMH was implemented to evaluate the application value of integrating ProCaLNMD into the clinical workflow. The primary endpoint was the area under the receiver operating characteristic curve (AUROC) of ProCaLNMD. In addition, the performance measures for pathologists with ProCaLNMD assistance was also assessed. Findings: In total, 8225 slides from 1297 patients with PCa were collected and digitised. Overall, 8158 slides (18,761 lymph nodes) from 1297 patients with PCa (median age 68 years [interquartile range 64-73]; 331 [26%] with LNM) were used to train and validate ProCaLNMD. The AUROC of ProCaLNMD ranged from 0.975 (95% confidence interval 0.953-0.998) to 0.992 (0.982-1.000) in the training and validation datasets, with sensitivities > 0.955 and specificities > 0.921. ProCaLNMD also demonstrated an AUROC of 0.979 in the cross-cancer dataset. ProCaLNMD use triggered true reclassification in 43 (4.3%) slides in which micrometastatic tumour regions were initially missed by pathologists, thereby correcting 28 (8.5%) missed-diagnosed cases of previous routine pathological reports. In the human-AI comparison and collaboration study, the sensitivity of ProCaLNMD (0.983 [0.908-1.000]) surpassed that of two junior pathologists (0.862 [0.746-0.939], P = 0.023; 0.879 [0.767-0.950], P = 0.041) by 10-12% and showed no difference to that of two senior pathologists (both 0.983 [0.908-1.000], both P > 0.99). Furthermore, ProCaLNMD significantly boosted the diagnostic sensitivity of two junior pathologists (both P = 0.041) to the level of senior pathologists (both P > 0.99), and substantially reduced the four pathologists' slide reviewing time (-31%, P < 0.0001; -34%, P < 0.0001; -29%, P < 0.0001; and -27%, P = 0.00031). Interpretation: ProCaLNMD demonstrated high diagnostic capabilities for identifying LNM in prostate cancer, reducing the likelihood of missed diagnoses by pathologists and decreasing the slide reviewing time, highlighting its potential for clinical application. Funding: National Natural Science Foundation of China, the Science and Technology Planning Project of Guangdong Province, the National Key Research and Development Programme of China, the Guangdong Provincial Clinical Research Centre for Urological Diseases, and the Science and Technology Projects in Guangzhou.

11.
Foods ; 13(7)2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38611406

ABSTRACT

In this work, a gelatin/chia mucilage (GN/CM) composite coating material doped with Lactococcus lactis (LS) was developed for strawberry preservation applications. The results of the scanning electron microscope and Fourier transform infrared spectroscopy stated that the enhanced molecular interaction between the CM and GN matrix strengthened the density and compactness of the GN film. Antifungal results indicated that the addition of LS significantly (p < 0.05) improved the ability of the GN coating to inhibit the growth of Botrytis cinerea (inhibition percentage = 62.0 ± 4.6%). Adding CM significantly (p < 0.05) decreased the water vapour permeability and oxygen permeability of the GN coating by 32.7 ± 4.0% and 15.76 ± 1.89%, respectively. In addition, the incorporated CM also significantly (p < 0.05) improved the LS viability and elongation at break of the film by 13.11 ± 2.05% and 42.58 ± 1.21%, respectively. The GN/CM/LS composite coating material also exhibited an excellent washability. The results of this study indicated that the developed GN/CM/LS coating could be used as a novel active material for strawberry preservation.

12.
Mol Neurobiol ; 2024 Mar 28.
Article in English | MEDLINE | ID: mdl-38546929

ABSTRACT

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the abnormal aggregation of α-synuclein (α-syn) and the loss of dopaminergic neurons. Although microbial infection has been implicated in the pathogenesis of PD, the associated virulence factors and the underlying molecular mechanisms require further elucidation. Here, we found that intestinal infection with Nocardia farcinica induced a series of PD-like symptoms in Caenorhabditis elegans, such as the accelerated degeneration of dopaminergic neurons, impaired locomotion capacity, and enhanced α-syn aggregation, through the disturbance of mitochondrial functions. To identify the potential virulence factors involved in these effects, we knocked out the nbtB/C and nbtS genes in N. farcinica, which are localized in the gene clusters responsible for nocobactin biosynthesis. The deletion of either gene partially rescued the degenerative effects of wild-type N. farcinica on dopaminergic neurons by attenuating mitochondrial dysfunction. LC-MS analysis further identified a decrease in the abundance of several siderophores in the two mutants, including nocobactin NA-a, nocobactin NA-b, and nocardimicin B. Collectively, our results demonstrated that intestinal N. farcinica infection in C. elegans facilitates PD-like pathogenesis and provides novel evidence for the involvement of pathogenic bacteria in neurodegenerative diseases via non-neuroinvasive mechanisms.

13.
Cancer Lett ; 587: 216728, 2024 Apr 10.
Article in English | MEDLINE | ID: mdl-38431036

ABSTRACT

Lysosomes are crucial organelles responsible for the degradation of cytosolic materials and bulky organelles, thereby facilitating nutrient recycling and cell survival. However, lysosome also acts as an executioner of cell death, including ferroptosis, a distinctive form of regulated cell death that hinges on iron-dependent phospholipid peroxidation. The initiation of ferroptosis necessitates three key components: substrates (membrane phospholipids enriched with polyunsaturated fatty acids), triggers (redox-active irons), and compromised defence mechanisms (GPX4-dependent and -independent antioxidant systems). Notably, iron assumes a pivotal role in ferroptotic cell death, particularly in the context of cancer, where iron and oncogenic signaling pathways reciprocally reinforce each other. Given the lysosomes' central role in iron metabolism, various strategies have been devised to harness lysosome-mediated iron metabolism to induce ferroptosis. These include the re-mobilization of iron from intracellular storage sites such as ferritin complex and mitochondria through ferritinophagy and mitophagy, respectively. Additionally, transcriptional regulation of lysosomal and autophagy genes by TFEB enhances lysosomal function. Moreover, the induction of lysosomal iron overload can lead to lysosomal membrane permeabilization and subsequent cell death. Extensive screening and individually studies have explored pharmacological interventions using clinically available drugs and phytochemical agents. Furthermore, a drug delivery system involving ferritin-coated nanoparticles has been specifically tailored to target cancer cells overexpressing TFRC. With the rapid advancements in understandings the mechanistic underpinnings of ferroptosis and iron metabolism, it is increasingly evident that lysosomes represent a promising target for inducing ferroptosis and combating cancer.


Subject(s)
Iron , Neoplasms , Humans , Cell Death , Iron/metabolism , Ferritins/metabolism , Neoplasms/drug therapy , Neoplasms/metabolism , Lysosomes/metabolism
14.
Int J Biol Macromol ; 265(Pt 1): 130466, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38432274

ABSTRACT

A novel colorimetric aerogel was developed by the complexation of carboxymethyl cellulose (CMC), sodium alginate (SA), and black goji anthocyanin (BGA) followed by freeze-drying for monitoring fish (Coho salmon) freshness during storage at 4 °C and 25 °C. The various aerogels (C/S/B3:1, C/S/B2:1, C/S/B1:1, C/S/B1:2, and C/S/B1:3) externally and internally were characterized using SEM, FTIR, XRD, DSC, and TGA. Among them, the aerogel composite C/S/B1:2 exhibited the most uniform pore size, largest specific surface area, rapid color changes in various alkaline vapors (5 µM and 50 µM), and better mechanical strength. Furthermore, the colorimetric aerogel became dark blue from light purple during fish storage at temperatures of 4 °C and 25 °C when it reached pH 7.49 and 7.33, TVC 8.9 × 107 CFU/g and 8.5 × 107 CFU/g, and TVB-N 33.8 mg/100 g and 26.12 mg/100 g, respectively, indicating fish completely deteriorated. Taken together, the colorimetric aerogel composite C/S/B1:2 was promising for determining fish freshness, which could be utilized as a non-destructive and useful intelligent sensor in monitoring various fish and meat freshness and/or quality.


Subject(s)
Alginates , Carboxymethylcellulose Sodium , Animals , Carboxymethylcellulose Sodium/chemistry , Anthocyanins/chemistry , Colorimetry , Food Packaging
15.
CNS Neurosci Ther ; 30(3): e14663, 2024 03.
Article in English | MEDLINE | ID: mdl-38439636

ABSTRACT

BACKGROUND: Epilepsy is a widespread and chronic disease of the central nervous system caused by a variety of factors. Mitochondrial ferritin (FtMt) refers to ferritin located within the mitochondria that may protect neurons against oxidative stress by binding excess free iron ions in the cytoplasm. However, the potential role of FtMt in epilepsy remains unclear. We aimed to investigate whether FtMt and its related mechanisms can regulate epilepsy by modulating ferroptosis. METHODS: Three weeks after injection of adeno-associated virus (AAV) in the skull of adult male C57BL/6 mice, kainic acid (KA) was injected into the hippocampus to induce seizures. Primary hippocampal neurons were transfected with siRNA using a glutamate-mediated epilepsy model. After specific treatments, Western blot analysis, immunofluorescence, EEG recording, transmission electron microscopy, iron staining, silver staining, and Nissl staining were performed. RESULTS: At different time points after KA injection, the expression of FtMt protein in the hippocampus of mice showed varying degrees of increase. Knockdown of the FtMt gene by AAV resulted in an increase in intracellular free iron levels and a decrease in the function of iron transport-related proteins, promoting neuronal ferroptosis and exacerbating epileptic brain activity in the hippocampus of seizure mice. Additionally, increasing the expression level of FtMt protein was achieved by AAV-mediated upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) gene in the hippocampus of seizure mice. CONCLUSIONS: In epilepsy, Nrf2 modulates ferroptosis by involving the expression of FtMt and may be a potential therapeutic mechanism of neuronal injury after epilepsy. Targeting this relevant process for treatment may be a therapeutic strategy to prevent epilepsy.


Subject(s)
Epilepsy , Ferroptosis , Male , Animals , Mice , Mice, Inbred C57BL , Kainic Acid/toxicity , NF-E2-Related Factor 2/genetics , Epilepsy/chemically induced , Seizures , Glutamic Acid , Dependovirus , Disease Models, Animal , Ferritins , Homeostasis
17.
Environ Res ; 251(Pt 2): 118708, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38493858

ABSTRACT

The mode of action (MOA) framework is proposed to inform a biological link between chemical exposures and adverse health effects. Despite a significant increase in knowledge and awareness, the application of MOA in human health risk assessment (RA) remains limited. This study aims to discuss the adoption of MOA for health RA within a regulatory context, taking our previously proposed but not yet validated MOA for lead neurotoxicity as an example. We first conducted a quantitative weight of evidence (qWOE) assessment, which revealed that the MOA has a moderate confidence. Then, targeted bioassays were performed within an in vitro blood-brain barrier (BBB) model to quantitatively validate the scientific validity of key events (KEs) in terms of essentiality and concordance of empirical support (dose/temporal concordance), which increases confidence in utilizing the MOA for RA. Building upon the quantitative validation data, we further conducted benchmark dose (BMD) analysis to map dose-response relationships for the critical toxicity pathways, and the lower limit of BMD at a 5% response (BMDL5) was identified as the point of departure (POD) value for adverse health effects. Notably, perturbation of the Aryl Hydrocarbon Receptor (AHR) signaling pathway exhibited the lowest POD value, measured at 0.0062 µM. Considering bioavailability, we further calculated a provisional health-based guidance value (HBGV) for children's lead intake, determining it to be 2.56 µg/day. Finally, the health risk associated with the HBGV was assessed using the hazard quotient (HQ) approach, which indicated that the HBGV established in this study is a relative safe reference value for lead intake. In summary, our study described the procedure for utilizing MOA in health RA and set an example for MOA-based human health risk regulation.


Subject(s)
Lead , Risk Assessment/methods , Humans , Lead/toxicity , Blood-Brain Barrier/drug effects , Neurotoxicity Syndromes/etiology , Dose-Response Relationship, Drug
18.
Food Chem ; 447: 138663, 2024 Jul 30.
Article in English | MEDLINE | ID: mdl-38489878

ABSTRACT

The combination of carbon dots (CDs) with covalent organic frameworks (COFs) was used to design an innovative sensor based on fluorescence resonance energy transfer (FRET) for the detection of Escherichia coli O157:H7 (E. coli O157:H7) in food samples. Carbon dots were used as fluorescence donors, covalent organic frameworks as fluorescence acceptors. The antibody (Ab) specific to E. coli O157:H7 was used to form a CD-Ab-COF immunosensor by linking CDs and COFs. The antibody was specifically bound with E. coli O157:H7, which caused the connection between CDs and COFs to be interrupted, and the carbon dots exhibited fluorescence restoration. The sensor exhibited a linear detection range spanning from 0 to 106 CFU/mL, with the limit of detection (LOD) of 7 CFU/mL. The analytical performance of the developed immunosensor was evaluated using spiked food samples with different concentrations of E. coli O157:H7, validating the capability of assessing risks in food testing.


Subject(s)
Biosensing Techniques , Escherichia coli O157 , Metal-Organic Frameworks , Fluorescence Resonance Energy Transfer , Carbon , Immunoassay , Antibodies
19.
Int J Biol Macromol ; 266(Pt 2): 131000, 2024 May.
Article in English | MEDLINE | ID: mdl-38521333

ABSTRACT

In recent years, the development of probiotic film by incorporating probiotics into edible polymers has attracted significant research attention in the field of active packaging. However, the influence of the external environment substantially reduces the vitality of probiotics, limiting their application. Therefore, to improve the probiotic activity, this study devised a novel nanofiber film incorporating chia mucilage protection solution (CPS), gum arabic (GA), pullulan (PUL), and Lactobacillus bulgaricus (LB). SEM images indicated the successful preparation of the nanofiber film incorporating LB. CPS incorporation significantly improved the survival ability of LB, with a live cell count reaching 7.62 log CFU/g after 28 days of storage at 4 °C - an increase of 1 log CFU/g compared to the fiber film without CPS. The results showed that the fiber film containing LB inhibited Escherichia coli and Staphylococcus aureus. Finally, the novel probiotic nanofiber film was applied to beef. The results showed that the shelf life of the beef during the experiments was extended for 2 days at 4 °C. Therefore, the novel probiotic film containing LB was suitable for meat preservation.


Subject(s)
Anti-Bacterial Agents , Glucans , Gum Arabic , Nanofibers , Nanofibers/chemistry , Glucans/chemistry , Glucans/pharmacology , Gum Arabic/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Salvia/chemistry , Lactobacillus delbrueckii , Probiotics/chemistry , Animals , Food Preservation/methods , Red Meat/microbiology , Staphylococcus aureus/drug effects , Plant Mucilage/chemistry , Escherichia coli/drug effects , Cattle , Food Packaging/methods
20.
Foods ; 13(3)2024 Feb 05.
Article in English | MEDLINE | ID: mdl-38338639

ABSTRACT

Accurate assessment of dough kneading is pivotal in pasta processing, where both under-kneading and over-kneading can detrimentally impact dough quality. This study proposes an innovative approach utilizing a cost-effective current sensor to ascertain the optimal kneading time for dough. Throughout the kneading process, the dough's tensile resistance gradually increases, reflecting the evolution of properties such as the gluten network. This leads to a discernible ascending phase in dough quality, evident through an increase in the load current of the mixing machine, succeeded by a subsequent decline beyond a certain threshold. The identification of this peak point enables the achievement of optimal dough consistency, thereby enhancing the overall quality of both the dough and subsequent pasta products. After the final product quality assessment, this novel method promises to be a valuable tool in optimizing pasta processing and ensuring consistent product quality.

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