Iodine Status and Its Influencing Factors in Hospitalized and Healthy Preschool-Age Children.

Iodine is a trace element necessary for synthesizing thyroid hormones. It is especially crucial for the neurodevelopment and intellectual development of children. Preschool-age children admitted to the hospital tend to have more fragile physical and mental health, but few studies demonstrate their iodine status. Our study aimed to investigate the iodine status of hospitalized and healthy preschool-age children and to explore the factors influencing them. From January to December 2021, 426 children aged 3-6 years were admitted to the respiratory department for pneumonia, bronchopneumonia, or bronchiectasis, but they could eat normally and were recruited as hospitalized children. Six hundred ten healthy children aged 3-6 years were included. We collected anthropometric measurements and urine samples from hospitalized and healthy preschool-age children, and iodine status was assessed through urinary iodine concentration (UIC) and urinary iodine/creatinine ratio (UI/Cr). UIC was 40.1 and 166.1 µg/L for hospitalized and healthy preschool-age children, respectively (P < 0.001). Urinary creatinine concentration (UCr) was 0.2 and 0.8 g/L for hospitalized and healthy preschool-age children, respectively (P < 0.001). UIC decreased with increasing height z-scores in hospitalized children (Spearman's rho = -0.11, P = 0.022). A significantly increased risk of UIC < 100 µg/L was found in hospitalized children (OR = 9.1 (6.8, 12.2), P < 0.001) when compared to healthy children. In conclusion, hospitalized preschool-age children are likelier to have iodine insufficiency than healthy preschool-age children, especially those with good linear growth. Measures should be implemented to ensure adequate iodine intake of preschool-age children during hospitalization to avoid affecting their intellectual and physical development. Due to lower UCr in hospitalized children, creatinine is not appropriate for assessing iodine status in hospitalized children.

A genetically engineered neuronal membrane-based nanotoxoid elicits protective immunity against neurotoxins.

Given their dangerous effects on the nervous system, neurotoxins represent a significant threat to public health. Various therapeutic approaches, including chelating agents, receptor decoys, and toxin-neutralizing antibodies, have been explored. While prophylactic vaccines are desirable, it is oftentimes difficult to effectively balance their safety and efficacy given the highly dangerous nature of neurotoxins. To address this, we report here on a nanovaccine against neurotoxins that leverages the detoxifying properties of cell membrane-coated nanoparticles. A genetically modified cell line with constitutive overexpression of the α7 nicotinic acetylcholine receptor is developed as a membrane source to generate biomimetic nanoparticles that can effectively and irreversibly bind to α-bungarotoxin, a model neurotoxin. This abrogates the biological activity of the toxin, enabling the resulting nanotoxoid to be safely delivered into the body and processed by the immune system. When co-administered with an immunological adjuvant, a strong humoral response against α-bungarotoxin is generated that protects vaccinated mice against a lethal dose of the toxin. Overall, this work highlights the potential of using genetic modification strategies to develop nanotoxoid formulations against various biological threats.

Unique aminothiazolyl coumarins as potential DNA and membrane disruptors towards Enterococcus faecalis.

Aminothiazolyl coumarins as potentially new antimicrobial agents were designed and synthesized in an effort to overcome drug resistance. Biological activity assay revealed that some target compounds exhibited significantly inhibitory efficiencies toward bacteria and fungi including drug-resistant pathogens. Especially, aminothiazolyl 7-propyl coumarin 8b and 4-dichlorobenzyl derivative 11b exhibited bactericidal potential (MBC/MIC = 2) toward clinically drug-resistant Enterococcus faecalis with low cytotoxicity to human lung adenocarcinoma A549 cells, rapidly bactericidal effects and no obvious bacterial resistance development against E. faecalis. The preliminary antibacterial action mechanism studies suggested that compound 11b was able to disturb E. faecalis membrane effectively, and interact with bacterial DNA isolated from resistant E. faecalis through noncovalent bonds to cleave DNA, thus inhibiting the growth of E. faecalis strain. Further molecular modeling indicated that compounds 8b and 11b could bind with SER-1084 and ASP-1083 residues of gyrase-DNA complex through hydrogen bonds and hydrophobic interactions. Moreover, compound 11b showed low hemolysis and in vivo toxicity. These findings of aminothiazolyl coumarins as unique structural scaffolds might hold a large promise for the treatments of drug-resistant bacterial infection.

Efficient Full-Frequency GW Calculations Using a Lanczos Method.

The GW approximation is widely used for reliable and accurate modeling of single-particle excitations. It also serves as a starting point for many theoretical methods, such as its use in the Bethe-Salpeter equation (BSE) and dynamical mean-field theory. However, full-frequency GW calculations for large systems with hundreds of atoms remain computationally challenging, even after years of efforts to reduce the prefactor and improve scaling. We propose a method that reformulates the correlation part of the GW self-energy as a resolvent of a Hermitian matrix, which can be efficiently and accurately computed using the standard Lanczos method. This method enables full-frequency GW calculations of material systems with a few hundred atoms on a single computing workstation. We further demonstrate the efficiency of the method by calculating the defect-state energies of silicon quantum dots with diameters up to 4 nm and nearly 2,000 silicon atoms using only 20 computational nodes.

Gastrin-Releasing Peptide/Gastrin-Releasing Peptide Receptor Participation in Itch Sensation Signaling in the Spinal Cord of Uremic Pruritus Mice.

Background: Uremic pruritus is a prevalent clinical symptom in maintenance dialysis patients. Existing evidence establishes a connection between itch transmission and the gastrin-releasing peptide/gastrin-releasing peptide receptor signaling pathway. Objective: To investigate the involvement of the gastrin-releasing peptide/gastrin-releasing peptide receptor in itch sensation signaling within the spinal cord of uremic pruritus. Design: An animal study was conducted. Setting: The research was conducted at the First Hospital of Hebei Medical University. Participants: A total of 50 male C57BL/6J mice (weight: 30-40 g) were acquired from Beijing Weitonglihua Laboratory Animal Center. Interventions: Mice were categorized into five groups: normal, sham, Y, A, and B. The Y group received intrathecal injections of saline (5 ul). The A group received intrathecal injections of gastrin-releasing peptide (0.1 nmol, 5 ul), and the B group received intrathecal injections of the gastrin-releasing peptide receptor antagonist RC-3095 (0.3 mmol, 5 ul). Primary Outcome Measures: (1) Pruritus behavior of mice and (2) expression of gastrin-releasing peptide, gastrin-releasing peptide receptor, and inositol trisphosphate. Results: Scratching times in the Y group significantly surpassed those of normal and sham groups, increasing over time. Gastrin-releasing peptide and receptor expression rose in the uremic pruritus mouse model compared to normal and sham groups (P < .05). Expression of gastrin-releasing peptide and its receptor was significantly elevated in the uremic pruritus mouse model compared to the normal and sham groups (P < .05). Inositol trisphosphate expression in the dorsal spinal horn of Y group mice increased compared to normal and sham groups. Intrathecal gastrin-releasing peptide heightened inositol trisphosphate expression, while the peptide receptor antagonist RC-3095 reduced it. Y group scratching times were higher than normal and sham groups, increasing after intrathecal gastrin-releasing peptide but decreasing after RC-3095 injection. Conclusion: The gastrin-releasing peptide/gastrin-releasing peptide receptor signaling pathway is involved in the development of uremic pruritus.

Cell membrane-coated nanoparticles for targeting carcinogenic bacteria.

The etiology of cancers is multifactorial, with certain bacteria established as contributors to carcinogenesis. As the understanding of carcinogenic bacteria deepens, interest in cancer treatment through bacterial eradication is growing. Among emerging antibacterial platforms, cell membrane-coated nanoparticles (CNPs), constructed by enveloping synthetic substrates with natural cell membranes, exhibit significant promise in overcoming challenges encountered by traditional antibiotics. This article reviews recent advancements in developing CNPs for targeting carcinogenic bacteria. It first summarizes the mechanisms of carcinogenic bacteria and the status of cancer treatment through bacterial eradication. Then, it reviews engineering strategies for developing highly functional and multitasking CNPs and examines the emerging applications of CNPs in combating carcinogenic bacteria. These applications include neutralizing virulence factors to enhance bacterial eradication, exploiting bacterium-host binding for precise antibiotic delivery, and modulating antibacterial immunity to inhibit bacterial growth. Overall, this article aims to inspire technological innovations in developing CNPs for effective cancer treatment through oncogenic bacterial targeting.

Longitudinal Associations between Metacognition and Spontaneous and Deliberate Mind Wandering During Early Adolescence.

Although metacognition plays a pivotal role in theoretical accounts of mind wandering, their longitudinal relationships have not yet been investigated during the important developmental period of early adolescence. This study aimed to examine the developmental trajectories of spontaneous and deliberate mind wandering and the dynamic associations between metacognition and two types of mind wandering in early adolescence. A sample of 4302 Chinese students beginning in Grade 4 (47.4% female; initial Mage = 9.84, SDage = 0.47) completed questionnaires on five occasions over 2.5 years. The results showed that deliberate mind wandering, but not spontaneous mind wandering, gradually increased from Grade 4 to Grade 6. Metacognition was negatively related to spontaneous mind wandering but positively related to deliberate mind wandering. These findings provide empirical evidence for theoretical viewpoints from both individual differences and developmental perspectives.

Nanoarchitectonics of Bimetallic Cu-/Co-Doped Nitrogen-Carbon Nanozyme-Functionalized Hydrogel with NIR-Responsive Phototherapy for Synergistic Mitigation of Drug-Resistant Bacterial Infections.

Superbug infections and transmission have become major challenges in the contemporary medical field. The development of novel antibacterial strategies to efficiently treat bacterial infections and conquer the problem of antimicrobial resistance (AMR) is extremely important. In this paper, a bimetallic CuCo-doped nitrogen-carbon nanozyme-functionalized hydrogel (CuCo/NC-HG) has been successfully constructed. It exhibits photoresponsive-enhanced enzymatic effects under near-infrared (NIR) irradiation (808 nm) with strong peroxidase (POD)-like and oxidase (OXD)-like activities. Upon NIR irradiation, CuCo/NC-HG possesses photodynamic activity for producing singlet oxygen(1O2), and it also has a high photothermal conversion effect, which not only facilitates the elimination of bacteria but also improves the efficiency of reactive oxygen species (ROS) production and accelerates the consumption of GSH. CuCo/NC-HG shows a lower hemolytic rate and better cytocompatibility than CuCo/NC and possesses a positive charge and macroporous skeleton for restricting negatively charged bacteria in the range of ROS destruction, strengthening the antibacterial efficiency. Comparatively, CuCo/NC and CuCo/NC-HG have stronger bactericidal ability against methicillin-resistant Staphylococcus aureus (MRSA) and ampicillin-resistant Escherichia coli (AmprE. coli) through destroying the cell membranes with a negligible occurrence of AMR. More importantly, CuCo/NC-HG plus NIR irradiation can exhibit satisfactory bactericidal performance in the absence of H2O2, avoiding the toxicity from high-concentration H2O2. In vivo evaluation has been conducted using a mouse wound infection model and histological analyses, and the results show that CuCo/NC-HG upon NIR irradiation can efficiently suppress bacterial infections and promote wound healing, without causing inflammation and tissue adhesions.

Sodium tanshinone IIA sulfonate suppresses microglia polarization and neuroinflammation possibly via regulating miR-125b-5p/STAT3 axis to ameliorate neuropathic pain.

The spinal cord microglia play a pivotal role in neuroinflammation and neuropathic pain (NP). Sodium tanshinone IIA sulfonate (STS), a derivative of tanshinone IIA, has anti-inflammatory and anti-hyperalgesic effects. However, its underlying mechanism in NP remains unclear. This study aimed to investigate the effect of STS and elucidate possible mechanisms in a rat model of spared nerve injury. In vivo experiments, STS and AG490 were administered intraperitoneally once daily for 14 consecutive days after surgery. The results showed that the expression of miR-125b-5p in the spinal dorsal horn was substantially reduced, whereas signal transducer and activator of transcription 3 (STAT3) signaling was increased. After treatment with STS, the mechanical thresholds, expression of miR-125b-5p, and microglial M2 marker such as Arg-1 in the spinal cord horn increased significantly, whereas multiple pro-inflammatory cytokines and apoptosis were significantly reduced. Moreover, STAT3 pathway-related proteins and expression of the microglial M1 marker, CD68, were appreciably inhibited. In vitro, lipopolysaccharide (LPS) was used to induce an inflammatory response in BV-2 microglial cells. STS pretreatment inhibited LPS-stimulated pro-inflammatory cytokine secretion, reduced STAT3 pathway related-proteins and apoptosis, increased miR-125b-5p and proopiomelanocortin expression, and enhanced microglia transformation from M1 to M2 phenotype in BV-2 cells. These effects were reversed after the inhibition of miR-125b-5p expression in BV-2 cells. A dual-luciferase reporter assay confirmed that STAT3 binds to miR-125b-5p. In summary, these results suggest that STS exerts anti-hyperalgesic and anti-neuroinflammatory effects in rats with NP possibly via the miR-125b-5p/STAT3 axis.

Progesterone induces neuroprotection associated with immune/inflammatory modulation in experimental traumatic brain injury.

An imbalance of immune/inflammatory reactions aggravates secondary brain injury after traumatic brain injury (TBI) and can deteriorate clinical prognosis. So far, not enough therapeutic avenues have been found to prevent such an imbalance in the clinical setting. Progesterone has been shown to regulate immune/inflammatory reactions in many diseases and conveys a potential protective role in TBI. This study was designed to investigate the neuroprotective effects of progesterone associated with immune/inflammatory modulation in experimental TBI. A TBI model in adult male C57BL/6J mice was created using a controlled contusion instrument. After injury, the mice received consecutive progesterone therapy (8 mg/kg per day, i.p.) until euthanized. Neurological deficits were assessed via Morris water maze test. Brain edema was measured via the dry-wet weight method. Immunohistochemical staining and flow cytometry were used to examine the numbers of immune/inflammatory cells, including IBA-1 + microglia, myeloperoxidase + neutrophils, and regulatory T cells (Tregs). ELISA was used to detect the concentrations of IL-1ß, TNF-α, IL-10, and TGF-ß. Our data showed that progesterone therapy significantly improved neurological deficits and brain edema in experimental TBI, remarkably increased regulatory T cell numbers in the spleen, and dramatically reduced the activation and infiltration of inflammatory cells (microglia and neutrophils) in injured brain tissue. In addition, progesterone therapy decreased the expression of the pro-inflammatory cytokines IL-1ß and TNF-α but increased the expression of the anti-inflammatory cytokine IL-10 after TBI. These findings suggest that progesterone administration could be used to regulate immune/inflammatory reactions and improve outcomes in TBI.

Mechanically and Thermally Guided, Honeycomb-like Nanocomposites with Strain-Insensitive High Thermal Conductivity for Stretchable Electronics.

Thermal management materials have become increasingly crucial for stretchable electronic devices and systems. Drastically different from conventional thermally conductive materials, which are applied at static conditions, thermal management materials for stretchable electronics additionally require strain-insensitive thermal conductivity, as they generally undergo cyclic deformation. However, realizing such a property remains challenging mainly because conventional thermally conductive polymer composites generally lack a mechanically guided design. Here, we report a honeycomb-like nanocomposite with a three-dimensional (3D) thermally conductive network fabricated by an arrayed ice-templating technique followed by elastomer infiltration. The hexagonal honeycomb-like structure with thin, compact walls (≈ 40 µm) endows our composite with a high through-plane thermal conductivity (≈ 1.54 W m-1 K-1) at an ultralow boron nitride nanosheet (BNNS) loading (≈ 0.85 vol %), with an enhancement factor of thermal conductivity up to 820% and thermal-insensitive strain up to 200%, which are 2.7 and 2 times higher than those reported in the literature. We report an intelligent strategy for the development of advanced thermal management materials for high-performance stretchable electronics.

Biocompatible N-carbazoleacetic acid decorated CuxO nanoparticles as self-cascading platforms for synergistic single near-infrared triggered phototherapy treating microbial infections.

In this work, positively charged N-carbazoleacetic acid decorated CuxO nanoparticles (CuxO-CAA NPs) as novel biocompatible nanozymes have been successfully prepared through a one-step hydrothermal method. CuxO-CAA can serve as a self-cascading platform through effective GSH-OXD-like and POD-like activities, and the former can induce continuous generation of H2O2 through the catalytic oxidation of overexpressed GSH in the bacterial infection microenvironment, which in turn acts as a substrate for the latter to yield ˙OH via Fenton-like reaction, without introducing exogenous H2O2. Upon NIR irradiation, CuxO-CAA NPs possess a high photothermal conversion effect, which can further improve the enzymatic activity for increasing the production rate of H2O2 and ˙OH. Besides, the photodynamic performance of CuxO-CAA NPs can produce 1O2. The generated ROS and hyperthermia have synergetic effects on bacterial mortality. More importantly, CuxO-CAA NPs are more stable and biosafe than Cu2O, and can generate electrostatic adsorption with negatively charged bacterial cell membranes and accelerate bacterial death. Antibacterial results demonstrate that CuxO-CAA NPs are lethal against methicillin-resistant Staphylococcus aureus (MRSA) and ampicillin-resistant Escherichia coli (AREC) through destroying the bacterial membrane and disrupting the bacterial biofilm formation. MRSA-infected animal wound models show that CuxO-CAA NPs can efficiently promote wound healing without causing toxicity to the organism.

Rational design and synthesis of triazene-amonafide derivatives as novel potential antitumor agents causing oxidative damage towards DNA through intercalation mode.

In this work, we rationally designed and synthesized two novel triazene-amonafide derivatives 2-(2-(diisopropylamino)ethyl)-5-(3,3-dimethyltriaz-1-en-1-yl)-1H-benzo[de]isoquinoline-1,3(2H)-dione (D-11) and 5-(3,3-diethyltriaz-1-en-1-yl)-2-(2-(diisopropylamino)ethyl)-1H-benzo[de]isoquinoline-1,3(2H)-dione (D-12) as potential antitumor agents. The DNA damage induced by the intercalation mode of D-11 (D-12) towards DNA was electrochemically detected through the construction of efficient biosensors. The consecutive processes of reversible redox of naphthylimide ring and irreversible oxidation of triazene moiety were elucidated on the surface of glassy carbon electrode (GCE) by CV, SWV, and DPV methods. Electrochemical biosensors were obtained through the immobilization of ctDNA, G-quadruplexes, poly(dG), and poly(dA), respectively, on the clean surface of GCE. After the incubation of biosensors with D-11 or D-12, the peaks of dGuo and dAdo decreased prominently, and the peak of 8-oxoGua appeared at +0.50 V, suggesting that the interaction between D-11 (D-12) and DNA could result in the oxidative damage of guanine. Unexpected, the as-prepared DNA biosensor possessed satisfactory anti-interference property and good practicability in real samples. UV-vis and fluorescence spectra, and gel electrophoresis assays were employed to further confirm the intercalation mode of D-11 (D-12) towards DNA base pairs. Moreover, D-11 was proved to exhibit stronger anti-proliferation activity than mitionafide and amonafide against both A549 and HeLa cell lines.

Treatment outcomes of retreated patients with isoniazid/rifampicin resistant pulmonary tuberculosis.

BACKGROUND: About 8% of TB cases worldwide are estimated to have rifampicin-susceptible, isoniazid-resistant tuberculosis (Hr-TB), ranging from 5 to 11% regions. However, Hr-TB has not received much attention while comparing to be given high priority to the management of rifampicin-resistant tuberculosis (RR-TB). This study aimed to compare the differences of treatment effects for Hr-TB and RR-TB, so as to intensify the treatment and management of Hr-TB. METHODS: A retrospective study was used to collect bacteriologically positive retreated patients with isoniazid/rifampicin resistant pulmonary tuberculosis, who were conducted at 29 tuberculosis control institutions in China from July 2009 to June 2021. We assessed effectiveness and safety of retreated patients with isoniazid/ rifampicin resistant pulmonary tuberculosis. RESULTS: A total of 147 with either positive smear or cultures were enrolled, and 80 cases were in Hr-TB group and 67 cases were in RR-TB group. There was no significant difference in terms of age, sex, body mass, type of retreatment and comorbid diabetes between the two groups (P > 0.05). The rate of number of lesions involving lung fields ≥ 3 in Hr-TB group 75.9% (60/79) was significantly higher than RR-TB group 56.7% (38/67) (χ2 = 6.077, P = 0.014). There was no statistically significant difference (P = 0.166) with regard to the treatment outcomes of the two groups, the cure rates were 54.7% (41/75) and 53.6% (30/56), respectively, and the failure rate in Hr-TB group 22.7% (17/75) was 10% higher than RR-TB group 10.7% (6/56). The rate of negative sputum smear at the end of the second month (65.7%) in the Hr-TB group was significantly lower than that in the RR-TB group (85.7%) (P = 0.025). There were no significant differences in the incidences of serious adverse reactions and chest X-ray changes between the two groups (P > 0.05). During the 5-year follow-up, recurrence in the Hr-TB group (7 cases, 14.9%) was no significantly lower than that in the RR-TB group (4 cases, 11.8%) (P = 0.754). CONCLUSION: The treatment of retreated Hr-TB patients was difficult and could be statistically similar or considerably worse than RR-TB. It's urgent to conduct further evaluation of the treatment status quo to guide the guideline development and clinical practice of Hr-TB patients.

Allelopathy and Identification of Volatile Components from the Roots and Aerial Parts of Astragalus mongholicus Bunge.

The volatile compounds produced by plants play an important role in plant growth, plant communication, and resistance to biological and abiotic stresses. Astragalus membranaceus var. mongholicus (AM) is a perennial herbaceous plant (Leguminosae) that is widely cultivated in northwest China. The bioactive compounds in its root have shown various pharmacological activities. Root rot disease caused by Fusarium spp. often occurs in AM planting with increasing severity in continuous monoculture. It is currently still unclear what are the effects of the volatile compounds produced by fresh AM on itself, other crops cultivated on the same field after AM, pathogen, and rhizobia. In this study, we found that seed germination and seedling growth of AM, lettuce (Lactuca sativa L.), and wheat (Triticum aestivum L.) could be affected if they were in an enclosed space with fresh AM tissue. Additionally, 90 volatile compounds were identified by SPME-GC-MS from whole AM plant during the vegetative growth, 36 of which were specific to aerial parts of AM (stems and leaves, AMA), 17 to roots (AMR), and 37 were found in both AMA and AMR. To further identify the allelopathic effects of these volatile compounds, five compounds (1-hexanol, (E)-2-hexenal, (E,E)-2,4-decadienal, hexanal, and eugenol) with relatively high content in AM were tested on three receptor plants and two microorganisms. We found that (E,E)-2,4-decadienal and (E)-2-hexenal showed significant inhibitory effects on the growth of AM and lettuce. One-hexanol and hexanal suppressed the growth of wheat, while eugenol showed a similar effect on all three plant species. Moreover, the activities of these compounds were dose dependent. Notably, we discovered that (E)-2-hexenal and eugenol also inhibited the growth of the pathogen Fusarium solani by as high as 100%. Meanwhile, all five compounds tested suppressed the rhizobia Sinorhizobium fredii. In summary, this study furthered our understanding of the comprehensive allelopathic effects of the main volatile components of AM.

A modular approach to enhancing cell membrane-coated nanoparticle functionality using genetic engineering.

Since their initial development, cell membrane-coated nanoparticles (CNPs) have become increasingly popular in the biomedical field. Despite their inherent versatility and ability to enable complex biological applications, there is considerable interest in augmenting the performance of CNPs through the introduction of additional functionalities. Here we demonstrate a genetic-engineering-based modular approach to CNP functionalization that can encompass a wide range of ligands onto the nanoparticle surface. The cell membrane coating is engineered to express a SpyCatcher membrane anchor that can readily form a covalent bond with any moiety modified with SpyTag. To demonstrate the broad utility of this technique, three unique targeted CNP formulations are generated using different classes of targeting ligands, including a designed ankyrin repeat protein, an affibody and a single-chain variable fragment. In vitro, the modified nanoparticles exhibit enhanced affinity towards cell lines overexpressing the cognate receptors for each ligand. When formulated with a chemotherapeutic payload, the modularly functionalized nanoparticles display strong targeting ability and growth suppression in a murine tumour xenograft model of ovarian cancer. Our data suggest genetic engineering offers a feasible approach for accelerating the development of multifunctional CNPs for a broad range of biomedical applications.

Construction of Mn-N-C nanoparticles with multienzyme-like properties and photothermal performance for the effective treatment of bacterial infections.

In this work, we successfully constructed Mn-coordinated nitrogen-carbon nanoparticles (Mn-N-C NPs) exhibiting multienzyme-like activities. In a bacterial infectious microenvironment, the POD-like and OXD-like activities of Mn-N-C NPs could synergistically trigger the generation of ROS (˙OH and O2˙-), causing oxidative damage to the bacterial cell membrane for killing bacteria. Alternatively, in neutral or weak alkaline normal tissues, the excessive O2˙- could be converted into O2 and H2O2via the SOD-like ability of Mn-N-C NPs, and subsequently their CAT-like activity catalyzed excess H2O2 into H2O and O2 for protecting normal cells through the antioxidant defense. Mn-N-C NPs also possessed a good NIR-photothermal performance, which could enhance their POD-like and OXD-like activities. Furthermore, Mn-N-C NPs could facilitate the GSH oxidation process and disrupt the intrinsic balance in the bacterial protection microenvironment with the assistance of H2O2, which is beneficial for rapid bacterial death. Undoubtedly, the Mn-N-C NPs + H2O2 system showed the highest antibacterial activity when irradiated with an 808 nm laser, destroying the bacterial membrane and causing the efflux of proteins. Moreover, the Mn-N-C NPs + H2O2 system was immune to the development of bacterial resistance and could efficiently disrupt the formation of a bacterial biofilm with negligible cytotoxicity and low hemolysis ratio. Finally, Mn-N-C NPs exhibited an excellent antibacterial performance in vivo and could accelerate wound healing without cellular inflammation production. Therefore, due to their significant therapeutic effects, Mn-N-C NPs show great potential in fighting antibiotic-resistant bacteria.

Protein-Loaded Cellular Nanosponges for Dual-Biomimicry Neurotoxin Countermeasure.

Neurotoxins present a substantial threat to human health and security as they disrupt and damage the nervous system. Their potent and structurally diverse nature poses challenges in developing effective countermeasures. In this study, a unique nanoparticle design that combines dual-biomimicry mechanisms to enhance the detoxification efficacy of neurotoxins is introduced. Using saxitoxin (STX), one of the deadliest neurotoxins, and its natural binding protein saxiphilin (Sxph) as a model system, human neuronal membrane-coated and Sxph-loaded metal-organic framework (MOF) nanosponges (denoted "Neuron-MOF/Sxph-NS") are successfully developed. The resulting Neuron-MOF/Sxph-NS exhibit a biomimetic design that not only emulates host neurons for function-based detoxification through the neuronal membrane coating, but also mimics toxin-resistant organisms by encapsulating the Sxph protein within the nanoparticle core. The comprehensive in vitro assays, including cell osmotic swelling, calcium flux, and cytotoxicity assays, demonstrate the improved detoxification efficacy of Neuron-MOF/Sxph-NS. Furthermore, in mouse models of STX intoxication, the application of Neuron-MOF/Sxph-NS shows significant survival benefits in both therapeutic and prophylactic regimens, without any apparent acute toxicity. Overall, the development of Neuron-MOF/Sxph-NS represents an important advancement in neurotoxin detoxification, offering promising potential for treating injuries and diseases caused by neurotoxins and addressing the current limitations in neurotoxin countermeasures.

Lightweight and multi-lesion segmentation model for diabetic retinopathy based on the fusion of mixed attention and ghost feature mapping.

Diabetic retinopathy is the main cause of blindness, and lesion segmentation is an important basic work for the diagnosis of this disease. The main lesions include soft and hard exudates, microaneurysms, and hemorrhages. However, the segmentation of these four types of lesions is difficult because of their variability in size and contrast, and high intertype similarity. Currently, many network models have problems, such as a large number of parameters and complex calculations, and most segmentation models for diabetic retinopathy focus only on one type of lesion. In this study, a lightweight algorithm based on BiSeNet V2 was proposed for the segmentation of multiple lesions in diabetic retinopathy fundus. First, a hybrid attention module was embedded in the semantic branch of BiSeNet V2 for 8- and 16-fold downsampling, which helped reassign deep feature-map weights and enhanced the ability to extract local key features. Second, a ghost feature-mapping unit was used to optimize the traditional convolution layers and further reduce the computational cost. Third, a new loss function based on the dynamic threshold loss function was applied to supervise the training by adjusting the training weights of the high-loss difficult samples, which enhanced the model's attention to small goals. In experiments on the IDRiD dataset, we conducted an ablation study to verify the effectiveness of each component and compared the proposed model, BiSeNet V2-Pro, with several state-of-the-art models. In comparison with the baseline BiSeNet V2, the segmentation performance of BiSeNet V2-Pro improved by 12.17 %, 11.44 %, and 8.49 % in terms of Sensitivity (SEN), Intersection over Union (IoU), and Dice coefficient (DICE), respectively. Specifically, IoU of MA reaches 0.5716. Compared with other methods, the segmentation speed was significantly improved while ensuring segmentation accuracy, and the number of model parameters was lower. These results demonstrate the superiority of BiSeNet V2-Pro in the multi-lesion segmentation of diabetic retinopathy.