Multiple-ResNet GAN: An enhanced high-resolution image generation method for translation from fundus structure image to fluorescein angiography.

Fluorescein angiography (FA) is a diagnostic method for observing the vascular circulation in the eye. However, it poses a risk to patients. Therefore, generative adversarial networks have been used to convert retinal fundus structure images into FA images. Existing high-resolution image generation methods employ complex deep network models that are challenging to optimize, which leads to issues such as blurred lesion boundaries and poor capture of microleakage and microvessels. In this study, we propose a multiple-ResNet generative adversarial network (GAN) to improve model training, thereby enhancing the ability to generate high-resolution FA images. First, the structure of the multiple-ResNet generator is designed to enhance detail generation in high-resolution images. Second, the Gaussian error linear unit (GELU) activation function is used to help the model converge rapidly. The effectiveness of the multiple-ResNet is verified using the publicly available Isfahan MISP dataset. Experimental results show that our method outperforms other methods, achieving better quantitative results with a mean structural similarity of 0.641, peak signal-to-noise ratio of 18.25, and learned perceptual image patch similarity of 0.272. Compared with state-of-the-art methods, the results showed that using the multiple-ResNet framework and GELU activation function can improve the generation of detailed regions in high-resolution FA images.

Efficacy and safety of Vonoprazan-based treatment of Helicobacter pylori infection: a systematic review and network meta-analysis.

OBJECTIVE: The aim of this study was to evaluate the effectiveness and safety of the nine most widely studied Vonoprazan (VPZ)-based treatment regimens along with traditional Proton pump inhibitor (PPI)-based treatment regimens in eradicating Helicobacter pylori (H. pylori) infection. DESIGN: Through searching PubMed, Embase, Cochrane Library, Web of Science, we exclusively included randomized controlled trials (RCTs) to investigate the efficacy of VPZ-based and PPI-based therapies for H. pylori infection. The included studies were evaluated for methodological quality using the Cochrane bias risk assessment tool, and the data analysis software was used to analyze the data accordingly. RESULTS: The RCTs were collected from the earliest available date up to August 2023. Twenty-one RCTs were included, with a total sample size of 5481. The results of the network meta-analysis showed that the eradication rate of the VPZ-based quadruple 14-day (VPZ-Q14) treatment regimen in Intention-to-treat (ITT) analysis was the highest (SUCRA: 0.874); The eradication rate of the VPZ-based quadruple 10-day (VPZ-Q10) treatment plan in Per-protocol (PP) analysis was the highest (SUCRA: 0.849). All regimens were well tolerated without significant differences. According to the probability ranking of safety, high-dose VPZ-based dual 14-day therapy (H-VPZ-D14) ranked first in SUCRA, reaching 0.952. This indicates that H-VPZ-D14 treatment is the safest with a relatively low incidence of adverse effect. Therefore, VPZ-based therapies not only have a higher eradication rate, but also possess satisfactory safety. CONCLUSION: Compared with traditional PPI-based therapies, VPZ-based therapies have shown superior eradication effects. Based on the Ranking Plot of the Network, the VPZ-Q14 or VPZ-Q10 treatment regimen for H. pylori has a higher eradication rate and acceptable differences compared to other treatment regimens. In addition, for regions with high antibiotic resistance rates, we recommend a 14-day quadruple therapy with bismuth based on VPZ.

Nanoplastics exposure-induced mitochondrial dysfunction contributes to disrupted stem cell differentiation in human cerebral organoids.

Nanoplastics are ubiquitous in our daily lives, raising concerns about their potential impact on the human brain. Many studies reported that nanoplastics permeate the blood-brain barrier and influence cellular processes in mouse models. However, the neurotoxic effects of ingesting nanoplastics on human brain remain poorly understood. Here, we treated cerebral organoids with polystyrene nanoplastics to model the effects of nanoplastic exposure on human brain. Importantly, we found that mitochondria might be the significant organelles affected by polystyrene nanoplastics using immunostaing and RNA-seq analysis. Subsequently, we observed the increased cell death and decreased cell differentiation in our cerebral organoids. In conclusion, our findings shed insights on the mechanisms underlying the toxicity of nanoplastics on human brain organoids, providing an evaluation system in detection potential environmental toxicity on human brain.

Clinical features and immunotherapy outcomes in antibody-negative autoimmune encephalitis: a retrospective case-control study.

Objective: This study aimed to compare clinical features, laboratory findings, and immunotherapy responses between antibody-positive and antibody-negative Autoimmune encephalitis (AE) patients. Methods: A retrospective analysis of clinical data from 60 AE patients (33 antibody-positive, 27 antibody-negative) diagnosed at Zhongshan Hospital of Xiamen University between January 1, 2016, and March 1, 2024 was conducted. Disease severity and treatment response were assessed using the modified Rankin Scale (mRS) and the Clinical Assessment Scale for Autoimmune Encephalitis (CASE). Results: Antibody-positive AE patients more frequently presented with multiple symptoms (≥4 symptoms: 39.4% vs. 14.8%, p = 0.036). They demonstrated significantly elevated serum IgG concentrations (p = 0.010) and cerebrospinal fluid (CSF) leukocyte counts (p = 0.014). Conversely, antibody-negative AE patients presented with higher CSF total protein levels (p = 0.025) and albumin quotients (p = 0.018), indicative of more severe blood-brain barrier disruption. Antibody-positive AE patients more frequently received combination first-line immunotherapy (75.8% vs. 48.1%, p = 0.027) and exhibited superior treatment outcomes (90.9% vs. 70%, p = 0.022). Among critically ill patients (peak mRS score: 4-5), improvement in CASE scores was markedly greater in the antibody-positive cohort (median: 4.50 vs. 1.00, p = 0.024). Conclusion: Antibody-positive AE patients manifested a more diverse symptom spectrum, elevated serum IgG concentrations and CSF leukocyte counts, and superior responses to immunotherapy. In contrast, antibody-negative AE patients demonstrated more severe blood-brain barrier dysfunction, as evidenced by higher CSF total protein concentrations and albumin quotients.

Reperfusion Therapy for Trousseau Syndrome-Related Cerebral Infarction: A Case-Control Analysis of Efficacy and Prognosis.

OBJECTIVE: To evaluate the efficacy and prognostic significance of reperfusion therapy in patients with Trousseau syndrome-related cerebral infarction. STUDY DESIGN: Descriptive study. Place and Duration of the Study: Department of Neurology, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China, and The Second Affiliated Hospital of Xiamen Medical College, Xiamen, China, between January 2017 and December 2023. METHODOLOGY: Patients with Trousseau-associated cerebral infarction who were treated at two hospitals were included in the study. Clinical outcomes, including early neurological deterioration, intracranial haemorrhage, in-hospital mortality, 90-day modified Rankin scale (mRS) score, 90-day mortality, initial and discharge National Institutes of Health Stroke Scale (NIHSS) score, and ΔNIHSS (difference between the initial and discharge NIHSS score), were compared between the reperfusion-treated group (n = 9) and the conventionally treated group (n = 23). RESULTS: Patients who received reperfusion therapy demonstrated significant neurological improvement at discharge, with a statistically significant difference in their ΔNIHSS scores compared to those of the conventionally treated group (p <0.001). No significant differences were observed in early neurological deterioration (11.10% vs. 13.00%, p = 1.000), intracranial haemorrhage (33.33% vs. 8.70%, p = 0.121), in-hospital mortality (22.20% vs. 26.10%, p = 1.000), 90-day mortality (55.60% vs. 87.00%, p = 0.076), or 90-day mRS score (p = 0.052) between the two groups. CONCLUSION: Despite the high mortality rate within 90 days, reperfusion therapy has the potential to improve the quality of life of surviving cancer patients with Trousseau-associated cerebral infarction. KEY WORDS: Trousseau syndrome-related cerebral infarction, Reperfusion therapy, Intravenous thrombolysis, Mechanical thrombectomy, Acute cerebral infarction.

Neuronal Membrane-Derived Nanodiscs for Broad-Spectrum Neurotoxin Detoxification.

Neurotoxins pose significant challenges in defense and healthcare due to their disruptive effects on nervous tissues. Their extreme potency and enormous structural diversity have hindered the development of effective antidotes. Motivated by the properties of cell membrane-derived nanodiscs, such as their ultrasmall size, disc shape, and inherent cell membrane functions, here, we develop neuronal membrane-derived nanodiscs (denoted "Neuron-NDs") as a countermeasure nanomedicine for broad-spectrum neurotoxin detoxification. We fabricate Neuron-NDs using the plasma membrane of human SH-SY5Y neurons and demonstrate their effectiveness in detoxifying tetrodotoxin (TTX) and botulinum toxin (BoNT), two model toxins with distinct mechanisms of action. Cell-based assays confirm the ability of Neuron-NDs to inhibit TTX-induced ion channel blockage and BoNT-mediated inhibition of synaptic vesicle recycling. In mouse models of TTX and BoNT intoxication, treatment with Neuron-NDs effectively improves survival rates in both therapeutic and preventative settings. Importantly, high-dose administration of Neuron-NDs shows no observable acute toxicity in mice, indicating its safety profile. Overall, our study highlights the facile fabrication of Neuron-NDs and their broad-spectrum detoxification capabilities, offering promising solutions for neurotoxin-related challenges in biodefense and therapeutic applications.

Compound heterozygous CFTR variants (Q1352H and 5T; TG13) in a Chinese patient with cystic fibrosis.

Cystic fibrosis (CF) is an autosomal recessive inherited disease caused by variants of cystic fibrosis transmembrane conductance regulation (CFTR) gene. This report presents a case of a Chinese boy diagnosed with CF, attributed to the presence of two specific CFTR gene variations: 4056G > C (NM_000492.4) (p.Gln1352His, legacy: Q1352H) and c.1210-34TG[13]T[5] (NM_000492.4)(legacy: 5T; TG13). A ten-year-old boy was admitted to the hospital due to recurrent pneumonia, cough, and intermittent fever for seven years. Lung auscultation revealed rales, and a lung CT scan indicated parenchymal transformation with infection in both lungs. Whole Exome Sequencing (WES) identified two CFTR gene variants, Q1352H and 5T; TG13, which were significantly associated with clinical phenotype. Following a two-year course of azithromycin combined with inhalation therapy with budesonide, the patient experienced no further episodes of respiratory infections. Moreover, significant improvements were observed in pulmonary function, pulmonary infection, and bronchiectasis. The occurrence of combined variations, Q1352H and 5T; TG13, in the CFTR gene is rare and specific to Chinese populations. WES proves to be a valuable diagnostic tool for detecting CFTR gene variants.

Identification of Dementia & Mild Cognitive Impairment in Chinese Elderly Using Machine Learning.

OBJECTIVE: To assess the role of Machine Learning (ML) in identification critical factors of dementia and mild cognitive impairment. METHODS: 371 elderly individuals were ultimately included in the ML analysis. Demographic information (including gender, age, parity, visual acuity, auditory function, mobility, and medication history) and 35 features from 10 assessment scales were used for modeling. Five machine learning classifiers were used for evaluation, employing a procedure involving feature extraction, selection, model training, and performance assessment to identify key indicative factors. RESULTS: The Random Forest model, after data preprocessing, Information Gain, and Meta-analysis, utilized three training features and four meta-features, achieving an area under the curve of 0.961 and a accuracy of 0.894, showcasing exceptional accuracy for the identification of dementia and mild cognitive impairment. CONCLUSIONS: ML serves as a identification tool for dementia and mild cognitive impairment. Using Information Gain and Meta-feature analysis, Clinical Dementia Rating (CDR) and Neuropsychiatric Inventory (NPI) scale information emerged as crucial for training the Random Forest model.

Nanopore-based targeted next-generation sequencing of tissue samples for tuberculosis diagnosis.

Objective: Diagnosing tuberculosis (TB) can be particularly challenging in the absence of sputum for pulmonary tuberculosis cases and extrapulmonary TB (EPTB). This study evaluated the utility of nanopore-based targeted next-generation sequencing (tNGS) for diagnosing TB in tissue samples, and compared its efficacy with other established diagnostic methods. Methods: A total of 110 tissue samples from clinical cases were examined. The sensitivity and specificity of tNGS were benchmarked against a range of existing diagnostic approaches including hematoxylin and eosin (HE) staining in conjunction with acid-fast bacilli (AFB) detection, HE staining combined with PCR, HE staining paired with immunohistochemistry (IHC) using anti-MPT64, and the Xpert Mycobacterium tuberculosis (MTB)/rifampicin (RIF) assay. Results: The sensitivity and specificity of tNGS were 88.2 and 94.1%, respectively. The respective sensitivities for HE staining combined with AFB, HE staining combined with PCR, HE staining combined with IHC using anti-MPT64, and Xpert MTB/RIF were 30.1, 49.5, 47.3, and 59.1%. The specificities for these methods were 82.4, 88.2, 94.1, and 94.1%, respectively. Analysis of drug resistance based on tNGS results indicated that 10 of 93 TB patients (10.75%) had potential drug resistance. Conclusion: Targeted next-generation sequencing achieved higher accuracy than other established diagnostic methods, and can play a crucial role in the rapid and accurate diagnosis of TB, including drug-resistant TB.

Medicinal plants used by minority ethnic groups in China: Taxonomic diversity and conservation needs.

ETHNOPHARMACOLOGICAL RELEVANCE: Indigenous communities have long relied on medicinal plants (MPs) for primary healthcare. The ethnomedicinal knowledge are different among ethnic groups since the local flora and people's health beliefs generally vary among biocultural backgrounds. China with its diverse biocultural environment is rich in culturally important plant species including MPs. They are also essential in the context of conservation of plant resources and the related traditional medical knowledge, requiring an integrated perspective on these MPs. AIM OF THE STUDY: Focusing on the MPs used by the minority ethnic groups, this study assesses the diversity of MPs in China used in local indigenous traditions, as well as their conservation needs. MATERIALS AND METHODS: The MPs used by the 18 selected minority ethnic groups were extracted from an ethnic MP dictionary. After standardizing, the names then were compiled as an inventory. Next, following statistics were computed: the number of species in each order and family, species used by each ethnic group, species documented in the national herbal resource dataset, species adopted in drug standards, and species at different levels of conservation lists. The overall similarity of the MPs used by the ethnic groups included was achieved using a cluster and principal component analysis. RESULTS: In total 5886 vascular plant species are reported as medicines in the 18 ethnic groups, which belong to 1657 genera and 243 families. It is found that 3195 species are used exclusively by one ethnic group, indicating their cultural salience and potential restrictedness in ecological terms. Moreover, 1159 species are included in national/regional drug standards, indicating their importance in the national medical flora. However, only 3541 species of them are documented in the national herbal resource dataset, and 761 species are at different levels of threatened status, highlighting the conservation needs of Chinese MPs and the related traditional medical knowledge. CONCLUSIONS: Using a quantitative approach, for the first time the present study reveals the high level of taxonomic diversity of MPs used by minority ethnic groups of China. However, of these species, 40% are still not inventoried in the national herbal resource dataset, and more than half are used exclusively by one ethnic group, and around 13% are included in the conservation lists of different levels. These together urge the conservation of MP resources and related traditional medical knowledge. Additionally, we recommend fostering the cross-cultural communication the regional ethnomedicinal knowledge, for the purpose of maximizing the benefits of regional plants to human.

Synthesis and antibacterial medicinal evaluation of carbothioamido hydrazonyl thiazolylquinolone with multitargeting antimicrobial potential to combat increasingly global resistance.

The global microbial resistance is a serious threat to human health, and multitargeting compounds are considered to be promising to combat microbial resistance. In this work, a series of new thiazolylquinolones with multitargeting antimicrobial potential were developed through multi-step reactions using triethoxymethane and substituted anilines as start materials. Their structures were confirmed by 1H NMR, 13C NMR and HRMS spectra. Antimicrobial evaluation revealed that some of the target compounds could effectively inhibit microbial growth. Especially, carbothioamido hydrazonyl aminothiazolyl quinolone 8a showed strong inhibitory activity toward drug-resistant Staphylococcus aureus with MIC value of 0.0047 mM, which was 5-fold more active than that of norfloxacin. The highly active compound 8a exhibited negligible hemolysis, no significant toxicity in vitro and in vivo, low drug resistance, as well as rapidly bactericidal effects, which suggested its favorable druggability. Furthermore, compound 8a was able to effectively disrupt the integrity of the bacterial membrane, intercalate into DNA and inhibit the activity of topoisomerase IV, suggesting multitargeting mechanism of action. Compound 8a could form hydrogen bonds and hydrophobic interactions with DNA-topoisomerase IV complex, indicating the insertion of aminothiazolyl moiety was beneficial to improve antibacterial efficiency. These findings indicated that the active carbothioamido hydrazonyl aminothiazolyl quinolone 8a as a chemical therapeutic candidate demonstrated immense potential to tackle drug-resistant bacterial infections.

Biohybrid microrobots regulate colonic cytokines and the epithelium barrier in inflammatory bowel disease.

Cytokines have been identified as key contributors to the development of inflammatory bowel disease (IBD), yet conventional treatments often prove inadequate and carry substantial side effects. Here, we present an innovative biohybrid robotic system, termed "algae-MΦNP-robot," for addressing IBD by actively neutralizing colonic cytokine levels. Our approach combines moving green microalgae with macrophage membrane-coated nanoparticles (MΦNPs) to efficiently capture proinflammatory cytokines "on the fly." The dynamic algae-MΦNP-robots outperformed static counterparts by enhancing cytokine removal through continuous movement, better distribution, and extended retention in the colon. This system is encapsulated in an oral capsule, which shields it from gastric acidity and ensures functionality upon reaching the targeted disease site. The resulting algae-MΦNP-robot capsule effectively regulated cytokine levels, facilitating the healing of damaged epithelial barriers. It showed markedly improved prevention and treatment efficacy in a mouse model of IBD and demonstrated an excellent biosafety profile. Overall, our biohybrid algae-MΦNP-robot system offers a promising and efficient solution for IBD, addressing cytokine-related inflammation effectively.

Scalable Compliant Graphene Fiber-Based Thermal Interface Material with Metal-Level Thermal Conductivity via Dual-Field Synergistic Alignment Engineering.

High-performance thermal interface materials (TIMs) are highly desired for high-power electronic devices to accelerate heat dissipation. However, the inherent trade-off conflict between achieving high thermal conductivity and excellent compliance of filler-enhanced TIMs results in the unsatisfactory interfacial heat transfer efficiency of existing TIM solutions. Here, we report the graphene fiber (GF)-based elastic TIM with metal-level thermal conductivity via mechanical-electric dual-field synergistic alignment engineering. Compared with state-of-the-art carbon fiber (CF), GF features both superb high thermal conductivity of ∼1200 W m-1 K-1 and outstanding flexibility. Under dual-field synergistic alignment regulation, GFs are vertically aligned with excellent orientation (0.88) and high array density (33.5 mg cm-2), forming continuous thermally conductive pathways. Even at a low filler content of ∼17 wt %, GF-based TIM demonstrates extraordinarily high through-plane thermal conductivity of up to 82.4 W m-1 K-1, exceeding most CF-based TIMs and even comparable to commonly used soft indium foil. Benefiting from the low stiffness of GF, GF-based TIM shows a lower compressive modulus down to 0.57 MPa, an excellent resilience rate of 95% after compressive cycles, and diminished contact thermal resistance as low as 7.4 K mm2 W-1. Our results provide a superb paradigm for the directed assembly of thermally conductive and flexible GFs to achieve scalable and high-performance TIMs, overcoming the long-standing bottleneck of mechanical-thermal mismatch in TIM design.

Dual-Modal Cellular Nanoparticles for Continuous Neurotoxin Detoxification.

Neurotoxins are known for their extreme lethality. However, due to their enormous diversity, effective and broad-spectrum countermeasures are lacking. This study presents a dual-modal cellular nanoparticle (CNP) formulation engineered for continuous neurotoxin neutralization. The formulation involves encapsulating the metabolic enzyme N-sulfotransferase (SxtN) into metal-organic framework (MOF) nanoparticle cores and coating them with a natural neuronal membrane, termed "Neuron-MOF/SxtN-NPs". The resulting nanoparticles combine membrane-enabled broad-spectrum neurotoxin neutralization with enzyme payload-enabled continuous neurotoxin neutralization. The studies confirm the protection of the enzyme payload by the MOF core and validate the continuous neutralization of saxitoxin (STX). In vivo studies conducted using a mouse model of STX intoxication reveal markedly improved survival rates compared with control groups. Furthermore, acute toxicity assessments show no adverse effects associated with the administration of Neuron-MOF/SxtN-NPs in healthy mice. Overall, Neuron-MOF/SxtN-NPs represent a unique biomimetic nanomedicine platform poised to effectively neutralize neurotoxins, marking an important advancement in the field of countermeasure nanomedicine.

Biohybrid microrobots locally and actively deliver drug-loaded nanoparticles to inhibit the progression of lung metastasis.

Lung metastasis poses a formidable challenge in the realm of cancer treatment, with conventional chemotherapy often falling short due to limited targeting and low accumulation in the lungs. Here, we show a microrobot approach using motile algae for localized delivery of drug-loaded nanoparticles to address lung metastasis challenges. The biohybrid microrobot [denoted "algae-NP(DOX)-robot"] combines green microalgae with red blood cell membrane-coated nanoparticles containing doxorubicin, a representative chemotherapeutic drug. Microalgae provide autonomous propulsion in the lungs, leveraging controlled drug release and enhanced drug dispersion to exert antimetastatic effects. Upon intratracheal administration, algae-NP(DOX)-robots efficiently transport their drug payload deep into the lungs while maintaining continuous motility. This strategy leads to rapid drug distribution, improved tissue accumulation, and prolonged retention compared to passive drug-loaded nanoparticles and free drug controls. In a melanoma lung metastasis model, algae-NP(DOX)-robots exhibit substantial improvement in therapeutic efficacy, reducing metastatic burden and extending survival compared to control groups.

Macrophage-Mimicking Cellular Nanoparticles Scavenge Proinflammatory Cytokines in Specimens of Patients with Inflammatory Disorders.

Effectively neutralizing inflammatory cytokines is crucial for managing a variety of inflammatory disorders. Current techniques that target only a subset of cytokines often fall short due to the intricate nature of redundant and compensatory cytokine networks. A promising solution to this challenge is using cell membrane-coated nanoparticles (CNPs). These nanoparticles replicate the complex interactions between cells and cytokines observed in disease pathology, providing a potential avenue for multiplex cytokine scavenging. While the development of CNPs using experimental animal models has shown great promise, their effectiveness in scavenging multiple cytokines in human diseases has yet to be demonstrated. To bridge this gap, this study selected macrophage membrane-coated CNPs (MФ-CNPs) and assessed their ability to scavenge inflammatory cytokines in serum samples from patients with COVID-19, sepsis, acute pancreatitis, or type-1 diabetes, along with synovial fluid samples from patients with rheumatoid arthritis. The results show that MФ-CNPs effectively scavenge critical inflammatory cytokines, including interleukin (IL)-6, IL-8, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α, in a dose-dependent manner. Overall, this study demonstrates MФ-CNPs as a multiplex cytokine scavenging formulation with promising applications in clinical settings to treat a range of inflammatory disorders.

Argon gas poisoning leading to persistent memory impairment: A 2-year case report.

RATIONALE: Argon gas poisoning is an often overlooked yet critical public health concern with the potential for severe and persistent neurological consequences. Current treatment protocols primarily focus on acute-phase management, but a comprehensive understanding of the long-term neurological effects remains incomplete. PATIENT CONCERNS: A 22-year-old male worker was found unconscious in the furnace room of an argon production facility. After regaining consciousness, he presented with symptoms of dizziness, headache, fatigue, and irritability. Neurological examination revealed impairments in both recent and remote memory, notably pronounced short-term memory deficits and reduced arithmetic skills. DIAGNOSIS: Argon gas poisoning, hypoxic encephalopathy, and mild hepatic and renal dysfunction. INTERVENTIONS: Upon admission, symptomatic supportive measures included oxygen therapy via nasal cannula (3 L/min), daily hyperbaric oxygen therapy (1.5 ATA, 60 minutes), oral neurotrophic methylcobalamin (0.5 mg, 3 times daily), and intravenous vitamin C infusion (2 g daily) to scavenge oxygen free radicals. OUTCOME: A 2-year telephone follow-up indicated persistent short-term memory impairment, particularly with memorizing numbers. In a memory test, he achieved a digit span forward of 5 but a digit span backward of 2, indicating impairment. Despite these challenges, his daily life and work performance remained largely unaffected. LESSON: This case offers valuable insights into the biological mechanisms underlying prolonged neurological sequelae following asphyxiating gas exposure, specifically the persistent impairment of hippocampal function.

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.

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.