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The spatial organization characteristics and redox status of the extracellular space (ECS) are crucial in the development of brain diseases. However, it remains a challenge to simultaneously capture dynamic changes in microstructural features and redox states at the submicron level within the ECS. Here, we developed a reversible glutathione (GSH)-responsive nanoprobe (RGN) for mapping the spatial organization features and redox status of the ECS in brain tissues with nanoscale resolution. The RGN is composed of polymer nanoparticles modified with GSH-responsive molecules and amino-functionalized methoxypoly(ethylene glycol), which exhibit exceptional single-particle brightness and excellent free diffusion capability in the ECS of brain tissues. Tracking single RGNs in acute brain slices allowed us to dynamically map spatial organizational features and redox levels within the ECS of brain tissues in disease models. This provides a powerful super-resolution imaging method that offers a potential opportunity to study the dynamic changes in the ECS microenvironment and to understand the physiological and pathological roles of the ECS in vivo.
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Encéfalo , Espacio Extracelular , Glutatión , Nanopartículas , Oxidación-Reducción , Encéfalo/metabolismo , Encéfalo/diagnóstico por imagen , Animales , Espacio Extracelular/metabolismo , Espacio Extracelular/química , Glutatión/química , Glutatión/metabolismo , Nanopartículas/química , Ratones , Polietilenglicoles/químicaRESUMEN
Background: To investigate the comparative effects of local anesthesia using lidocaine with adrenaline vs. articaine with adrenaline in endoscopic endonasal dacryocystorhinostomy (EN-DCR). Methods: This retrospective study included a total of 180 patients. These patients were categorized into two groups: the lidocaine group, which received 2% lidocaine (1:100,000 adrenaline), and the articaine group, which received 4% articaine (1:100,000 adrenaline) for local anesthesia. The study compared anesthesia efficacy, intraoperative pain levels, intraoperative bleeding, as well as differences in heart rate and blood pressure between the two groups. Results: The articaine group demonstrated a significantly lower visual analog scale (VAS) pain score when compared to the lidocaine group, measuring at 4.4 ± 0.6 cm vs. 5.0 ± 1.0 cm, respectively (P < 0.0001). Additionally, the articaine group exhibited a higher anesthesia efficacy compared to the lidocaine group (89.0% vs. 76.6%, p = 0.0487). Notably, the articaine group experienced less nasal mucosal bleeding during the surgery in contrast to the lidocaine group (p = 0.004). However, there were no statistically significant differences in changes in blood pressure and heart rate between the two groups (p > 0.05). Conclusion: This study demonstrated that 4% articaine (1:100,000 adrenaline) has superior clinical effectiveness in comparison to 2% lidocaine (1:100,000 adrenaline) in EN-DCR.
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Gene innovation plays an essential role in trait evolution. Rhizobial symbioses, the most important N2-fixing agent in agricultural systems that exists mainly in Leguminosae, is one of the most attractive evolution events. However, the gene innovations underlying Leguminosae root nodule symbiosis (RNS) remain largely unknown. Here, we investigated the gene gain event in Leguminosae RNS evolution through comprehensive phylogenomic analyses. We revealed that Leguminosae-gain genes were acquired by gene duplication and underwent a strong purifying selection. Kyoto Encyclopedia of Genes and Genomes analyses showed that the innovated genes were enriched in flavonoid biosynthesis pathways, particular downstream of chalcone synthase (CHS). Among them, Leguminosae-gain type â ¡ chalcone isomerase (CHI) could be further divided into CHI1A and CHI1B clades, which resulted from the products of tandem duplication. Furthermore, the duplicated CHI genes exhibited exon-intron structural divergences evolved through exon/intron gain/loss and insertion/deletion. Knocking down CHI1B significantly reduced nodulation in Glycine max (soybean) and Medicago truncatula; whereas, knocking down its duplication gene CHI1A had no effect on nodulation. Therefore, Leguminosae-gain type â ¡ CHI participated in RNS and the duplicated CHI1A and CHI1B genes exhibited RNS functional divergence. This study provides functional insights into Leguminosae-gain genetic innovation and sub-functionalization after gene duplication that contribute to the evolution and adaptation of RNS in Leguminosae.
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BACKGROUND: Polypoidal choroidal vasculopathy (PCV) is a hemorrhagic fundus disease that can lead to permanent vision loss. Predicting the treatment response to anti-VEGF monotherapy in PCV is consistently challenging. We aimed to conduct a prospective multicenter study to explore and identify the imaging biomarkers for predicting the anti-VEGF treatment response in PCV patients, establish predictive model, and undergo multicenter validation. METHODS: This prospective multicenter study utilized clinical characteristics and images of treatment naïve PCV patients from 15 ophthalmic centers nationwide to screen biomarkers, develop model, and validate its performance. Patients from Peking Union Medical College Hospital were randomly divided into a training set and an internal validation set. A nomogram was established by univariate, LASSO regression, and multivariate regression analysis. Patients from the other 14 centers served as an external test set. Area under the curve (AUC), sensitivity, specificity, and accuracy were calculated. Decision curve analysis (DCA) and clinical impact curve (CIC) were utilized to evaluate the practical utility in clinical decision-making. FINDINGS: The eye distribution for the training set, internal validation set, and external test set were 66, 31, and 71, respectively. The 'Good responder' exhibited a thinner subfoveal choroidal thickness (SFCT) (230.67 ± 61.96 vs. 314.42 ± 88.00 µm, p < 0.001), lower choroidal vascularity index (CVI) (0.31 ± 0.08 vs. 0.36 ± 0.05, p = 0.006), fewer choroidal vascular hyperpermeability (CVH) (31.0 vs. 62.2%, p = 0.012), and more intraretinal fluid (IRF) (58.6 vs. 29.7%, p = 0.018). SFCT (OR 0.990; 95% CI 0.981-0.999; p = 0.033) and CVI (OR 0.844; 95% CI 0.732-0.971; p = 0.018) were ultimately included as the optimal predictive biomarkers and presented in the form of a nomogram. The model demonstrated AUC of 0.837 (95% CI 0.738-0.936), 0.891 (95% CI 0.765-1.000), and 0.901 (95% CI 0.824-0.978) for predicting 'Good responder' in the training set, internal validation set, and external test set, respectively, with excellent sensitivity, specificity, and practical utility. INTERPRETATION: Thinner SFCT and lower CVI can serve as imaging biomarkers for predicting good treatment response to anti-VEGF monotherapy in PCV patients. The nomogram based on these biomarkers exhibited satisfactory performances.
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Inhibidores de la Angiogénesis , Biomarcadores , Tomografía de Coherencia Óptica , Factor A de Crecimiento Endotelial Vascular , Humanos , Masculino , Femenino , Estudios Prospectivos , Anciano , Persona de Mediana Edad , Inhibidores de la Angiogénesis/uso terapéutico , Inhibidores de la Angiogénesis/administración & dosificación , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Coroides/irrigación sanguínea , Coroides/diagnóstico por imagen , Neovascularización Coroidal/tratamiento farmacológico , Neovascularización Coroidal/diagnóstico por imagen , Resultado del Tratamiento , Nomogramas , Pólipos/tratamiento farmacológico , Pólipos/diagnóstico por imagen , Pólipos/diagnóstico , Angiografía con Fluoresceína/métodos , Enfermedades de la Coroides/tratamiento farmacológico , Enfermedades de la Coroides/diagnóstico por imagen , Enfermedades de la Coroides/diagnóstico , Vasculopatía Coroidea PolipoideaRESUMEN
Actin- and microtubule (MT)-based transport systems are essential for intracellular transport. During influenza A virus (IAV) infection, MTs provide long tracks for virus trafficking toward the nucleus. However, the role of the actin cytoskeleton in IAV entry and especially the transit process is still ambiguous. Here, by using quantum dot-based single-virus tracking, it was revealed that the actin cytoskeleton was crucial for the virus entry via clathrin-mediated endocytosis (CME). After entry via CME, the virus reached MTs through three different pathways: the virus (1) was driven by myosin VI to move along actin filaments to reach MTs (AF); (2) was propelled by actin tails assembled by an Arp2/3-dependent mechanism to reach MTs (AT); and (3) directly reached MTs without experiencing actin-related movement (NA). Therefore, the NA pathway was the main one and the fastest for the virus to reach MTs. The AT pathway was activated only when plenty of viruses entered the cell. The viruses transported by the AF and AT pathways shared similar moving velocities, durations, and displacements. This study comprehensively visualized the role of the actin cytoskeleton in IAV entry and transport, revealing different pathways for IAV to reach MTs after entry. The results are of great significance for globally understanding IAV infection and the cellular endocytic transport pathway.
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Endocitosis , Virus de la Influenza A , Microtúbulos , Puntos Cuánticos , Puntos Cuánticos/química , Microtúbulos/metabolismo , Microtúbulos/virología , Humanos , Virus de la Influenza A/fisiología , Internalización del Virus , Animales , Perros , Células de Riñón Canino Madin Darby , Citoesqueleto de Actina/metabolismoRESUMEN
INTRODUCTION: This study aimed to explore ocular manifestations in ANCA-associated vasculitis (AAV), focusing on granulomatosis with polyangiitis (GPA), eosinophilic granulomatosis with polyangiitis (EGPA), and microscopic polyangiitis (MPA) and to examine the associations with laboratory parameters and other systemic manifestations. METHODS: This retrospective study reviewed data from 533 AAV patients across two major Chinese medical centers from January 2016 to November 2023. Data including diagnosis, cranial manifestations of disease, ocular complications, and laboratory parameters were analyzed. Univariate and multivariable logistic regression analyses assessed associations across disease manifestations. Machine learning models were also utilized to predict the risk of retinal/eye involvement in AAV patients. RESULTS: Among 533 patients (210 GPA, 217 MPA, 99 EGPA, and 7 unclassified AAV), ocular complications were observed in 20.64% of them, with a distribution of 36.67% in GPA, 7.37% in MPA, and 18.18% in EGPA. The most common ocular manifestations included scleritis and retro-orbital mass/dacryocystitis, which were notably prevalent in GPA patients. Retinal involvement was observed in 9.09% of EGPA cases. The machine learning models yielded that eosinophil percentage (EOS%), high-sensitivity C-reactive protein (hsCRP), and CD4 + T cell/CD8 + T cell ratio (T4/T8) can predict retinal involvement. Furthermore, the white blood cell, EOS%, APTT, IgA, hsCRP, PR3-ANCA, and T4/T8 can predict eye involvement. CONCLUSION: Ocular manifestations are a prevalent complication across all forms of AAV. Predictive models developed through machine learning offer promising tools for early intervention and tailored patient care. This necessitates a multidisciplinary approach, integrating rheumatology and ophthalmology expertise for optimal patient outcomes.
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Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos , Humanos , Masculino , Estudios Retrospectivos , Femenino , Persona de Mediana Edad , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/complicaciones , China/epidemiología , Anciano , Adulto , Oftalmopatías/etiología , Poliangitis Microscópica/complicaciones , Granulomatosis con Poliangitis/complicaciones , Aprendizaje Automático , Proteína C-Reactiva/análisis , Escleritis/etiología , Escleritis/epidemiología , Pueblos del Este de AsiaRESUMEN
Nanozymes, nanostructured materials emulating natural enzyme activities, exhibit potential in catalyzing reactive oxygen species (ROS) production for cancer treatment. By facilitating oxidative reactions, elevating ROS levels, and influencing the tumor microenvironment (TME), nanozymes foster the eradication of cancer cells. Noteworthy are their superior stability, ease of preservation, and cost-effectiveness compared to natural enzymes, rendering them invaluable for medical applications. This comprehensive review intricately explores the interplay between ROS and tumor therapy, with a focused examination of metal-based nanozyme strategies mitigating tumor hypoxia. It provides nuanced insights into diverse catalytic processes, mechanisms, and surface modifications of various metal nanozymes, shedding light on their role in intra-tumoral ROS generation and applications in antioxidant therapy. The review concludes by delineating specific potential prospects and challenges associated with the burgeoning use of metal nanozymes in future tumor therapies.
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Neoplasias , Especies Reactivas de Oxígeno , Microambiente Tumoral , Humanos , Especies Reactivas de Oxígeno/metabolismo , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Animales , Microambiente Tumoral/efectos de los fármacos , Nanoestructuras/química , Antioxidantes/farmacología , Antioxidantes/química , Antineoplásicos/farmacología , Antineoplásicos/química , Metales/química , Hipoxia Tumoral/efectos de los fármacosRESUMEN
Seven species of the genus Toxorhina Loew, 1850 have been recorded from China, of which three are known to occur in Yunnan Province. Herein, all known species from Yunnan, China are reviewed with more detailed descriptions and illustrations of the male hypopygium. A species of Toxorhina belonging to the subgenus Ceratocheilus Wesché, 1910 from Yunnan, T. (C.) pianmicasp. nov., is described and illustrated as new to science.
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Acute methicillin-resistant Staphylococcus aureus (MRSA) pneumonia is a common and serious lung infection with high morbidity and mortality rates. Due to the increasing antibiotic resistance, toxicity, and pathogenicity of MRSA, there is an urgent need to explore effective antibacterial strategies. In this study, we developed a dry powder inhalable formulation which is composed of porous microspheres prepared from poly(lactic-co-glycolic acid) (PLGA), internally loaded with indocyanine green (ICG)-modified, heat-resistant phages that we screened for their high efficacy against MRSA. This formulation can deliver therapeutic doses of ICG-modified active phages to the deep lung tissue infection sites, avoiding rapid clearance by alveolar macrophages. Combined with the synergistic treatment of phage therapy and photothermal therapy, the formulation demonstrates potent bactericidal effects in acute MRSA pneumonia. With its long-term stability at room temperature and inhalable characteristics, this formulation has the potential to be a promising drug for the clinical treatment of MRSA pneumonia.
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Staphylococcus aureus Resistente a Meticilina , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Animales , Ratones , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Microesferas , Terapia Fototérmica , Neumonía Estafilocócica/terapia , Terapia de Fagos/métodos , Verde de Indocianina/química , Verde de Indocianina/farmacología , Verde de Indocianina/uso terapéutico , Verde de Indocianina/administración & dosificación , Antibacterianos/química , Antibacterianos/farmacología , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Administración por Inhalación , Humanos , Bacteriófagos/químicaRESUMEN
Nanoplastics (NPs, size <1000 nm) are ubiquitous plastic particles, potentially more abundant than microplastics in the environment; however, studies highlighting their distribution dynamics in freshwater are rare due to analytical limitations. Here, we investigated spatiotemporal levels of nine polymers of NPs in surface water samples (n = 30) from the full stretch of the Pearl River (sites, n = 15) using pyrolysis gas chromatography-mass spectrometry (Py-GC/MS). Six polymers were detected, including polystyrene (PS), polyvinyl chloride (PVC), nylon/polyamide 66 (PA66), polyester (PES), poly(methyl methacrylate) (PMMA) and polyethylene (PE), where three polymers showed high detection frequencies; PS (100 % in winter and summer), followed by PVC (73 % in winter and 87 % in summer) and PA66 (53 % in winter and 67 % in summer). The spatiotemporal distribution revealed the sites related to aquaculture (AQ) and shipping (SHP) showed higher NP levels than those of human settlement (HS) and wastewater treatment plants (WWTPs) (p = 0.004), and relatively high average levels of NPs in the urban sites compared to rural sites (p = 0.04), albeit showed no obvious seasonal differences (p = 0.78). For instance, the average PS levels in the Pearl River were in the following order: AQ 411.55 µg/L > SHP 81.75 µg/L > WWTP 56.66 µg/L > HS 47.75 µg/L in summer and HS 188.1 µg/L > SHP 103.55 µg/L > AQ 74.7 µg/L > WWTP 62.1 µg/L in winter. Source apportionment showed a higher contribution through domestic plastic waste emissions among urban sites, while rural sites showed an elevated contribution via aquaculture, agriculture, and surface run-off to the NP pollution. Risk assessment revealed that NPs at SHP and AQ sites posed a higher integrated risk in terms of pollution load index (PLI) than those at WWTP and HS sites. Regarding polymer hazard index (HI), 80 % of sampling sites in summer and 60 % of sampling sites in winter posed level III polymer risk, with PVC posing the highest risk. This study provides novel insights into the seasonal contamination and polymer risks of NP in the Pearl River, which will help to regulate the production and consumption of plastics in the region. ENVIRONMENTAL IMPLICATIONS: The contamination dynamics of field nanoplastics (NPs) in freshwater resources remain little understood, mainly attributed to analytical constraints. This study aims to highlight the spatiotemporal distribution of NPs in the Pearl River among various land use types, urban-rural comparison, seasonal comparison, their compositional profiles, potential sources, interaction with environmental factors, and ecological and polymer hazard assessments of investigated polymers in the full stretch of the Pearl River from Liuxi Reservoir to the Pearl River Delta (PRD) region. This study, with a comparatively large number of samples and NP polymers, will offer novel insights into the contamination profiles of nano-sized plastic particles in one of the important freshwater riverine systems in China.
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Nanoplastics (NPs) interact with cooccurring chemicals and natural organic matter (NOM) in the environment, forming complexes that can change their bioavailability and interfacial toxicity in aquatic organisms. This study aims to elucidate the single and combined impacts of 21-day chronic exposure to low levels of polystyrene NPs (size 80 nm) at 1 mg/L and 6:2 chlorinated polyfluorinated ether sulfonate (Cl-PFAES or F53B) at 200 µg/L in the presence and absence of NOM (humic acid-HA and bovine serum albumin-BSA at 10 mg/L) in adult zebrafish (Danio rerio). Our findings through multiple bioassays, revealed that the mixture group (M), comprising of NPs, F53B, HA, and BSA, caused a higher level of toxicity compared to the single NPs (AN), single F53B (AF), and combined NPs+F53B (ANF) groups. The mixture exposure caused the highest level of vacuolization and nuclear condensation in hepatocytes, and most of the intestinal villi were fused and highly reduced in villi length and crypt depth. Further, the T-AOC levels were significantly lower (p < 0.05), while the MDA levels in the liver and intestine were significantly higher (p < 0.05) in the M group with downregulation of nfkbiaa, while upregulation of prkcda, csf1ra, and il1b apoptosis genes in the liver. Pairwise comparison of gut microbiota showed significantly higher (p < 0.05) abundances of various genera in the M group, including Gordonia, Methylobacterium, Tundrisphaera, GKS98, Pedomicrobium, Clostridium, Candidatus and Anaerobacillus, as well as higher abundance of genera including pathogenic strains, while control group showed higher abundance of probiotic genus ZOR0006 than exposed group (p < 0.01). The transcriptomic analysis revealed highest number of DEGs in the M group (2815), followed by the AN group (506) and ANF group (206) with the activation of relaxin signaling pathway-RSP (slc9a1, slc9a2) and AMP-activated protein kinase (AMPK) pathway (plin1), and suppression of the toll-like receptor (TLR) pathway (tlr4a, tlr2, tlr1), cytokine-cytokine receptor interaction (CCRI) pathway (tnfb, il21r1, il21, ifng1), and peroxisome proliferator-activated receptors (PPAR) pathway (pfkfb3). Overall, toxicity in the M group was higher, indicating that the HA and BSA elevated the interfacial impacts of NPs and F53B in adult zebrafish after chronic environmentally relevant exposure, implying the revisitation of the critical interaction of NOM with co-occurring chemicals and associated impacts.
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Microbioma Gastrointestinal , Pez Cebra , Animales , Microbioma Gastrointestinal/efectos de los fármacos , Contaminantes Químicos del Agua/toxicidad , Nanopartículas/toxicidad , Nanopartículas/química , Microplásticos/toxicidad , Poliestirenos/toxicidad , Poliestirenos/química , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Transcriptoma/efectos de los fármacos , Perfilación de la Expresión Génica , Fluorocarburos/toxicidadRESUMEN
Membrane tension is an important physical parameter of describing cellular homeostasis, and it is widely used in the study of cellular processes involving membrane deformation and reorganization, such as cell migration, cell spreading, and cell division. Despite the importance of membrane tension, direct measurement remains difficult. In this work, we developed a ratiometric fluorescent probe sensitive to membrane tension by adjusting the carbon chain structure based on polarity-sensitive fluorophores. The probe is sensitive to changes in membrane tension after cells were subjected to physical or chemical stimuli, such as osmotic shock, lipid peroxidation, and mechanical stress. When the polarity of the plasma membrane increases (the green/red ratio decreases) and the membrane tension increases, the relative magnitude of the membrane tension can be quantitatively calculated by fluorescence ratio imaging. Thus, the probe proved to be an efficient and sensitive membrane tension probe.
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Membrana Celular , Colorantes Fluorescentes , Colorantes Fluorescentes/química , Membrana Celular/metabolismo , Humanos , Imagen Óptica/métodos , Animales , Presión Osmótica , Estrés MecánicoRESUMEN
The thermal properties, microstructure, and mechanical properties of Fe-18Mn-3Ti (wt%) were investigated, focusing on the effects of different heat-treatment processes. Results revealed that the 450 °C warm-rolling sample (450 WR) exhibited promising mechanical properties. Specifically, this sample displayed a yield strength of 988 MPa, an ultimate tensile strength of 1052 MPa, and total elongation of 15.49%. Consequently, a favorable strength-ductility balance was achieved. The strain-hardening ability surpassed that of the cold rolling sample (CR). Microstructure analysis indicated the simultaneous occurrence of dynamic equilibrium between grain deformation and re-crystallization because of the co-influence of thermal and strain in the warm rolling process. This desirable mechanical property was attributed to the presence of a multi-phase (α-martensite, austenite, and ε-martensite) and heterogeneous microstructure. The improvement of ultimate tensile strength was based on grain refinement, grain co-deformation, and the transformation-induced plasticity (TRIP) effect in the early stage of plastic deformation (stage â ). The improvement of ultimate elongation (TEL) was ascribed to the TRIP effect in the middle stage of plastic deformation (stage â ¡).
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In vivo real-time qualitative and quantitative analysis is essential for the diagnosis and treatment of diseases such as tumors. Near-infrared-II (NIR-II, 1000-1700 nm) bioimaging is an emerging visualization modality based on fluorescent materials. The advantages of NIR-II region fluorescent materials in terms of reduced photon scattering and low tissue autofluorescence enable NIR-II bioimaging with high resolution and increasing depth of tissue penetration, and thus have great potential for in vivo qualitative and quantitative analysis. In this review, we first summarize recent advances in NIR-II imaging, including fluorescent probe selection, quantitative analysis strategies, and imaging. Then, we describe in detail representative applications to illustrate how NIR-II fluorescence imaging has become an important tool for in vivo quantitative analysis. Finally, we describe the future possibilities and challenges of NIR-II fluorescence imaging.
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Colorantes Fluorescentes , Imagen Óptica , Colorantes Fluorescentes/química , Imagen Óptica/métodos , Humanos , Animales , Espectroscopía Infrarroja Corta/métodos , Neoplasias/diagnóstico por imagen , Rayos InfrarrojosRESUMEN
OBJECTIVES: Lung cancer is characterized by its high incidence and case fatality rate. Factors related to population composition and cancer prevention programme policy have an effect on the incidence and diagnosis of lung cancer. This study aims to provide scientific support for early diagnosis and treatment of lung cancer by investigating the clinic information, pathological, and imaging characteristics of surgical patients with lung cancer. METHODS: The data of 2 058 patients, who underwent surgery for lung cancer in the Department of Thoracic Surgery of Xiangya Hospital of Central South University from 2016 to 2019, were retrospectively collected to analyze changes in clinic information, pathological, and imaging characteristics. RESULTS: From 2016 to 2019, the number of patients per year was 280, 376, 524, and 878, respectively. Adenocarcinoma (68.1%) was the most common pathological type of surgical patients with lung cancer. From 2016 to 2019, the proportion of adenocarcinoma was increased from 55.5% to 74.1%. The proportion lung cancer patients in stage IA was increased from 38.9% to 62.3%, and the proportion of patients who underwent sublobar resection was increased from 1.8% to 8.6%. The proportion of lymph node sampling was increased in 2019. Compared with the rate in 2016, the detection rate of nodules with diameter≤1 cm detected by CT before surgery in 2019 was significantly improved (2.0% vs 18.2%), and the detection rate of nodules with diameter>3 cm was decreased (34.7% vs 18.3%). From 2016 to 2019, the proportion of lesions with pure ground-glass density and partial solid density detected by CT was increased from 2.0% and 16.6% to 20.0% and 37.3%, respectively. The proportion of solid density was decreased from 81.4% to 42.7%. CONCLUSIONS: The number of lung cancer surgery patients is rapidly increasing year by year, the proportion of CT-detected purely ground-glass density and partially solid density lesions are increasing, the proportion of patients with adenocarcinoma is rising, the proportion of early-stage lung cancer is increasing, smaller lung cancers are detected in earlier clinical stage leading to a more minimally invasive approach to the surgical methods.
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Adenocarcinoma , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/patología , Estudios Retrospectivos , Adenocarcinoma/cirugía , Adenocarcinoma/diagnóstico por imagen , Adenocarcinoma/patología , Femenino , Masculino , Tomografía Computarizada por Rayos X , Estadificación de Neoplasias , Adenocarcinoma del Pulmón/cirugía , Adenocarcinoma del Pulmón/diagnóstico por imagen , Adenocarcinoma del Pulmón/patología , Persona de Mediana Edad , AncianoRESUMEN
Developing small-molecule photothermal agents (PTAs) with good near-infrared-II (NIR-II) response for deeper tissue penetration and minimizing damage to healthy tissues has attracted much attention in photothermal therapy (PTT). However, concentrating ultra-long excitation wavelengths and high photothermal conversion efficiencies (PCEs) into a single organic small molecule is still challenging due to the lack of suitable molecular structures. Here, six polymethine cyanine molecules based on the structure of indocyanine green are synthesized by increasing the conjugated structure of the two-terminal indole salts and the number of rigid methine units, and incorporating longer alkyl side chains into the indole salts. Ultimately, IC-1224 is obtained with an absorption wavelength of more than 1200 nm, which has a high PCE up to 83.2% in the NIR-II window and exhibits excellent PTT tumor ablation performance. This provides a high-performance NIR-II-responsive PTA, and offers further possibilities for the application of PTT in biomedical fields.
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Terapia Fototérmica , Terapia Fototérmica/métodos , Animales , Ratones , Humanos , Carbocianinas/química , Verde de Indocianina/química , Verde de Indocianina/farmacología , Línea Celular Tumoral , Rayos Infrarrojos , Ratones Endogámicos BALB C , Fototerapia/métodos , FemeninoRESUMEN
Orthotopic glioblastoma (GBM) has an aggressive growth pattern and complex pathogenesis, becoming one of the most common and deadly tumors of the central nervous system (CNS). The emergence of RNA therapies offers promise for the treatment of GBM. However, the efficient and precise delivery of RNA drugs to specific tumor cells in the brain with high cellular heterogeneity remains ongoing. Here, a strategy is proposed to regulate protein conformation through lipid nanoenvironments to custom-design virus-mimicking nanoparticles (VMNs) with excellent selective cell targeting capabilities, leading to efficient and precise delivery of small interfering RNA for effective treatment of GBM. The optimized VMNs not only retain the ability to cross the blood-brain barrier and release the RNA by lysosomal escape like natural viruses but also ensure precise enrichment in the GBM area. This study lays the conceptual foundation for the custom design of VMNs with superior cell-selective targeting capabilities and opens up the possibility of RNA therapies for the efficient treatment of GBM and CNS tumors.
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Glioblastoma , Nanopartículas , ARN Interferente Pequeño , Glioblastoma/terapia , Glioblastoma/patología , Glioblastoma/metabolismo , ARN Interferente Pequeño/química , ARN Interferente Pequeño/metabolismo , Humanos , Nanopartículas/química , Línea Celular Tumoral , Animales , Conformación Proteica , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/patología , Ratones , Barrera Hematoencefálica/metabolismo , Materiales Biomiméticos/químicaRESUMEN
PURPOSE: The present study aimed to analyze the influence of muscle activation on lumbar injury under a specific +Gz load. METHODS: A hybrid finite element human body model with detailed lumbar anatomy and lumbar muscle activation capabilities was developed. Using the specific +Gz loading acceleration as input, the kinematic and biomechanical responses of the occupant's lower back were studied for both activated and deactivated states of the lumbar muscles. RESULTS: The results indicated that activating the major lumbar muscles enhanced the stability of the occupant's torso, which delayed the contact between the occupant's head and the headrest. Lumbar muscle activation led to higher strain and stress output in the lumbar spine under +Gz load, such as the maximum Von Mises stress of the vertebrae and intervertebral discs increased by 177.9% and 161.8%, respectively, and the damage response index increased by 84.5%. CONCLUSION: In both simulations, the occupant's risk of lumbar injury does not exceed 10% probability. Therefore, the activation of muscles could provide good protection for maintaining the lumbar spine and reduce the effect of acceleration in vehicle travel direction.
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Vértebras Lumbares , Humanos , Vértebras Lumbares/lesiones , Fenómenos Biomecánicos , Análisis de Elementos Finitos , Aceleración , Hipergravedad/efectos adversos , Músculo Esquelético/lesiones , Músculo Esquelético/fisiología , Músculo Esquelético/fisiopatología , Traumatismos Vertebrales/fisiopatología , Traumatismos Vertebrales/etiologíaRESUMEN
Cell membrane stiffness is critical for cellular function, with cholesterol and sphingomyelin as pivot contributors. Current methods for measuring membrane stiffness are often invasive, ex situ, and slow in process, prompting the need for innovative techniques. Here, we present a fluorescence resonance energy transfer (FRET)-based protein sensor designed to address these challenges. The sensor consists of two fluorescent units targeting sphingomyelin and cholesterol, connected by a linker that responds to the proximity of these lipids. In rigid membranes, cholesterol and sphingomyelin are in close proximity, leading to an increased FRET signal. We utilized this sensor in combination with confocal microscopy to explore changes in plasma membrane stiffness under various conditions, including differences in osmotic pressure, the presence of reactive oxygen species (ROS) and variations in substrate stiffness. Furthermore, we explored the impact of SARS-CoV-2 on membrane stiffness and the distribution of ACE2 after attachment to the cell membrane. This tool offers substantial potential for future investigations in the field of mechanobiology.
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Membrana Celular , Colesterol , Transferencia Resonante de Energía de Fluorescencia , SARS-CoV-2 , Esfingomielinas , Transferencia Resonante de Energía de Fluorescencia/métodos , Humanos , Membrana Celular/metabolismo , Membrana Celular/química , Esfingomielinas/análisis , Esfingomielinas/metabolismo , Colesterol/análisis , Colesterol/metabolismo , Microscopía Confocal/métodos , Especies Reactivas de Oxígeno/metabolismo , Especies Reactivas de Oxígeno/análisis , COVID-19/virología , Enzima Convertidora de Angiotensina 2/metabolismo , Técnicas Biosensibles/métodosRESUMEN
Nanoplastics (NPs) have emerged as global environmental pollutants with concerning implications for sustainable agriculture. Understanding the underlying mechanisms of NPs toxicity and devising strategies to mitigate their impact is crucial for crop growth and development. Here, we investigated the nanoparticles of zinc oxide (nZnO) to mitigate the adverse effects of 80 nm NPs on fragrant rice. Our results showed that optimized nZnO (25 mg L-1) concentration rescued root length and structural deficits by improving oxidative stress response, antioxidant defense mechanism and balanced nutrient levels, compared to seedlings subjected only to NPs stress (50 mg L-1). Consequently, microscopy observations, Zeta potential and Fourier transform infrared (FTIR) results revealed that NPs were mainly accumulated on the initiation joints of secondary roots and between cortical cells that blocks the nutrients uptake, while the supplementation of nZnO led to the formation of aggregates with NPs, which effectively impedes the uptake of NPs by the roots of fragrant rice. Transcriptomic analysis identified a total of 3973, 3513 and 3380 differentially expressed genes (DEGs) in response to NPs, nZnO and NPs+nZnO, respectively, compared to the control. Moreover, DEGs were significantly enriched in multiple pathways including biosynthesis of secondary metabolite, phenylpropanoid biosynthesis, amino sugar and nucleotide sugar metabolism, carotenoid biosynthesis, plant-pathogen interactions, MAPK signaling pathway, starch and sucrose metabolism, and plant hormone signal transduction. These pathways could play a significant role in alleviating NPs toxicity and restoring fragrant rice roots. Furthermore, metabolomic analysis demonstrated that nZnO application restored 2-acetyl-1-pyrroline (2-AP) pathways genes expression, enzymatic activities, and the content of essential precursors related to 2-AP biosynthesis under NPs toxicity, which ultimately led to the restoration of 2-AP content in the leaves. In conclusion, this study shows that optimized nZnO application effectively alleviates NPs toxic effects and restores both root structure and aroma production in fragrant rice leaves. This research offers a sustainable and practical strategy to enhance crop production under NPs toxicity while emphasizing the pivotal role of essential micronutrient nanomaterials in agriculture.