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OBJECTIVE: Alzheimer's disease (AD) has become a significant global concern, but effective drugs able to slow down AD progression is still lacked. Electroacupuncture (EA) has been demonstrated to ameliorate cognitive impairment in individuals with AD. However, the underlying mechanisms remains poorly understood. This study aimed at examining the neuroprotective properties of EA and its potential mechanism of action against AD. METHODS: APP/PS1 transgenic mice were employed to evaluate the protective effects of EA on Shenshu (BL 23) and Baihui (GV 20). Chemogenetic manipulation was used to activate or inhibit serotonergic neurons within the dorsal raphe nucleus (DRN). Learning and memory abilities were assessed by the novel object recognition and Morris water maze tests. Golgi staining, western blot, and immunostaining were utilized to determine EA-induced neuroprotection. RESULTS: EA at Shenshu (BL 23) and Baihui (GV 20) effectively ameliorated learning and memory impairments in APP/PS1 mice. EA attenuated dendritic spine loss, increased the expression levels of PSD95, synaptophysin, and brain-derived neurotrophic factor in hippocampus. Activation of serotonergic neurons within the DRN can ameliorate cognitive deficits in AD by activating glutamatergic neurons mediated by 5-HT1B. Chemogenetic inhibition of serotonergic neurons in the DRN reversed the effects of EA on synaptic plasticity and memory. CONCLUSION: EA can alleviate cognitive dysfunction in APP/PS1 mice by activating serotonergic neurons in the DRN. Further study is necessary to better understand how the serotonergic neurons-related neural circuits involves in EA-induced memory improvement in AD.
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Ferulic acid ethyl ester (FAEE) is an essential raw material for the formulation of drugs for cardiovascular and cerebrovascular diseases and leukopenia. It is also used as a fixed aroma agent for food production due to its high pharmacological activity. In this study, the interaction of FAEE with Human serum albumin (HSA) and Lysozyme (LZM) was characterized by multi-spectrum and molecular dynamics simulations at four different temperatures. Additionally, the quenching mechanism of FAEE-HSA and FAEE-LZM were explored. Meanwhile, the binding constants, binding sites, thermodynamic parameters, molecular dynamics, molecular docking binding energy, and the influence of metal ions in the system were evaluated. The results of Synchronous fluorescence spectroscopy, UV-vis spectroscopy, CD, three-dimensional fluorescence spectrum, and resonance light scattering showed that the microenvironment of HSA and LZM and the protein conformation changed in the presence of FAEE. Furthermore, the effects of some common metal ions on the binding constants of FAEE-HSA and FAEE-LZM were investigated. Overall, the experimental results provide a theoretical basis for promoting the application of FAEE in the cosmetics, food, and pharmaceutical industries and significant guidance for food safety, drug design, and development.
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Ácidos Cumáricos , Simulación del Acoplamiento Molecular , Muramidasa , Unión Proteica , Albúmina Sérica Humana , Espectrometría de Fluorescencia , Humanos , Muramidasa/química , Muramidasa/metabolismo , Ácidos Cumáricos/química , Ácidos Cumáricos/metabolismo , Albúmina Sérica Humana/metabolismo , Albúmina Sérica Humana/química , Simulación de Dinámica Molecular , Termodinámica , Sitios de Unión , Dicroismo Circular , Espectrofotometría Ultravioleta , Ácidos CafeicosRESUMEN
Purpose: To develop and validate a nomogram for assessing the risk of developing hypercapnic respiratory failure (HRF) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Patients and Methods: From January 2019 to August 2023, a total of 334 AECOPD patients were enrolled in this research. We employed the Least Absolute Shrinkage and Selection Operator (LASSO) regression and multivariate logistic regression to determine independent predictors and develop a nomogram. This nomogram was appraised by the area under the receiver operating characteristic curve (AUC), calibration curve, Hosmer-Lemeshow goodness-of-fit test (HL test), decision curve analysis (DCA), and clinical impact curve (CIC). The enhanced bootstrap method was used for internal validation. Results: Sex, prognostic nutritional index (PNI), hematocrit (HCT), and activities of daily living (ADL) were independent predictors of HRF in AECOPD patients. The developed nomogram based on the above predictors showed good performance. The AUCs for the training, internal, and external validation cohorts were 0.841, 0.884, and 0.852, respectively. The calibration curves and HL test showed excellent concordance. The DCA and CIC showed excellent clinical usefulness. Finally, a dynamic nomogram was developed (https://a18895635453.shinyapps.io/dynnomapp/). Conclusion: This nomogram based on sex, PNI, HCT, and ADL demonstrated high accuracy and clinical value in predicting HRF. It is a less expensive and more accessible approach to assess the risk of developing HRF in AECOPD patients, which is more suitable for primary hospitals, especially in developing countries with high COPD-related morbidity and mortality.
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Progresión de la Enfermedad , Hipercapnia , Nomogramas , Valor Predictivo de las Pruebas , Enfermedad Pulmonar Obstructiva Crónica , Insuficiencia Respiratoria , Humanos , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Masculino , Femenino , Anciano , Hipercapnia/diagnóstico , Hipercapnia/fisiopatología , Insuficiencia Respiratoria/diagnóstico , Insuficiencia Respiratoria/fisiopatología , Insuficiencia Respiratoria/etiología , Medición de Riesgo , Factores de Riesgo , Persona de Mediana Edad , Reproducibilidad de los Resultados , Pronóstico , Evaluación Nutricional , Anciano de 80 o más Años , Hematócrito , Estudios Retrospectivos , Factores Sexuales , Técnicas de Apoyo para la Decisión , Actividades Cotidianas , Estado NutricionalRESUMEN
BACKGROUND: Male androgenetic alopecia (MAA) is a multifactorial disease, with patients presenting at a younger age, which is a risk factor for many metabolic diseases. AIMS: To explore the risk factors associated with early-onset of MAA and its metabolic characteristics. METHODS: Forty patients with MAA and 45 healthy controls were collected. The serum levels of fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total testosterone (TT), uric acid (UA), and 25-hydroxyvitamin D (25(OH)D) were measured. Meanwhile, lipid metabolites were detected by ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). RESULTS: 37.50% MAA patients had metabolic syndrome, compared to 17.78% in control group (p < 0.05). The levels of HDL-C, UA, and 25(OH)D were decreased in patients with MAA compared to healthy controls (p < 0.05). However, there was no significant difference in the level of TT between the two groups. Additionally, there were no significant differences in the levels of HDL-C, UA, 25(OH)D, and TT among different grades of hair loss (p > 0.05). The lipid profile of early-onset MAA differed significantly from healthy controls. In early-onset MAA, the levels of ceramide (Cer) and sphingomyelin (SM) were significantly lower. Cer(d38:5) and TG(15:0/18:1/18:1) may be the biomarkers. CONCLUSION: Low HDL-C, UA, and 25(OH)D may be the independent risk factors for early-onset MAA. Abnormal lipid metabolism was observed in early-onset MAA, wherein Cer and SM may serve as protective factors.
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Low-rank tensor representation with the tensor nuclear norm has been rising in popularity in multi-view subspace clustering (MVSC), in which the tensor nuclear norm is commonly implemented using discrete Fourier transform (DFT). Unfortunately, existing DFT-oriented MVSC methods may provide unsatisfactory results since (1) DFT exploits complex arithmetic in the Fourier domain, usually resulting in high tubal tensor rank, and (2) local structural information is rarely considered. To solve these problems, in this paper, we propose a novel double discrete cosine transform (DCT)-oriented multi-view subspace clustering (D2CTMSC) method, in which the first DCT aims to derive the tensor nuclear norm without complex arithmetic while the second DCT aims to explore the local structure of the self-representation tensor, such that the essential low-rankness and sparsity embedding in multi-view features can be thoroughly exploited. Moreover, we design an effective alternating iteration strategy to solve the proposed model. Experimental results on four types of multi-view datasets (News stories, Face images, Scene images, and Generic objects) demonstrate the superiority of the D2CTMSC method compared with DFT-based methods and other state-of-the-art clustering methods.
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Despite of the recent advances in regulatory T cell (Treg) therapy, a limited number of available cells and specificity at the desired tissue site have severely compromised their efficacy. Herein, an injectable drug-releasing (MTK-TK-drug) microgel system in response to in situ stimulation by reactive oxygen species (ROS) was constructed with a coaxial capillary microfluidic system and UV curing. The spherical microgels with a size of 150 µm were obtained. The MTK-TK-drug microgels efficiently converted the pro-inflammatory Th17 cells into anti-inflammatory regulatory T cells (Treg) cells in vitro, and the ROS-scavenging materials synergistically enhanced the effect by modulating the inflammation microenvironment. Thus, the microgels significantly reduced cardiomyocyte apoptosis and decreased the inflammatory response in the early stages of post-myocardial infarction (MI) in vivo, thereby reducing fibrosis, promoting vascularization, and preserving cardiac function. Overall, our results indicate that the MTK-TK-drug microgels can attenuate the inflammatory response and improve MI therapeutic effects in vivo.
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Microgeles , Infarto del Miocardio , Humanos , Especies Reactivas de Oxígeno , Infarto del Miocardio/tratamiento farmacológico , Linfocitos T Reguladores , MicrofluídicaRESUMEN
Background: Androgenetic alopecia (AGA) is the most common form of hair loss. Studies have suggested a potential link to metabolic disorders, but with conflicting results. To elucidate the lipidomics profile and sex-specific variations in AGA, while exploring correlation between AGA and metabolic syndrome (MetS). Methods: The AGA patients (n = 83) and healthy controls (n = 84) were collected in the study. The lipid profiles were analyzed using ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS). Serum levels of important factors associated with AGA, namely dihydrotestosterone (DHT), prostaglandin D2 (PGD2) and transforming growth factor-ß1 (TGF-ß1) were quantified using ELISA. Results: Compared with controls, AGA patients had a higher probability of MetS (26.51% vs 11.9%, P < 0.05). Fifty-one differentially expressed lipids were identified in AGA. The kind of triglyceride (TG) were significantly increased, while phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylglycerol (PG), phosphatidylinositol (PI), and phosphatidylserine (PS) exhibited remarkable decrease. PC (16:2/21:6), PC (34:4p), PE (41:7), PE (44:12), PG (40:9), PI (32:2) and TG (15:0/18:1/18:1) were identified as potential biomarkers of AGA with the highest specificity. The levels of DHT, PGD2 and TGF-ß1 were significantly elevated in AGA. All seven lipids showed significant correlations with DHT, PC (34:4p) and TG (15:0/18:1/18:1) were significantly associated with PGD2, TGF-ß1 displayed exclusively correlation with TG (15:0/18:1/18:1) (all P < 0.05). Furthermore, these lipids were also significantly linked to systolic blood pressure and BMI, while some of them also showed significant associations with total cholesterol and HDL-C. In subgroups, forty-two differentially expressed lipids were identified in male AGA vs male control and eighty-one in female AGA vs female control. PC (16:2/21:6) was the only specific lipids common to both sexes. Conclusions: Aberrant lipid metabolism was observed in AGA, with distinct lipidomic profiles between male and female AGA. The potential biomarkers were closely related to DHT, PGD2, TGF-ß1 and MetS-related indicators. It provides the foundation for revealing the mechanisms of AGA.
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Ferulic acid (FA) and ferulic acid methyl ester (FAM) are important phenolic compounds in Baijiu. In this study, the interaction of FA and FAM with human serum albumin (HSA) and lysozyme (LZM) was investigated using multispectral methods and molecular dynamics simulation. FA and FAM could interact with HSA and LZM, changing the conformation and hydrophilicity of the protein. The quenching mechanisms of FA-HSA, FA-LZM, FAM-HSA, and FAM-LZM were all static-quenching. In the FA-HSA, FAM-HSA, and FA-LZM systems, the interaction forces were mainly hydrophobic interactions and hydrogen bonding. In the FAM-LZM system, the interaction forces were mainly hydrophobic interactions, hydrogen bonding, and van der Waals force. Common metal ions such as K+, Ca2+, Cu2+, Mg2+, and Mn2+ could affect the binding ability of FA and FAM to HSA and LZM. Moreover, FA and FAM could increase the stability of HSA and LZM, and the protein bound to FA/FAM was more stable than the free protein. FA and FAM had varying degrees of impact on the physiological activities of HSA and LZM. This study provides relevant information on the interactions and metabolic mechanisms of FA and its derivatives with endogenous proteins.
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The occurrence of osteoarthritis (OA) is highly associated with the inflammatory hypoxic microenvironment. Yet currently no attention has been paid to fabricating hypoxia-responsive platforms for OA treatment. Herein, an injectable hydrogel microsphere system (HAM-SA@HCQ) focusing on the hypoxic inflamed joint is prepared with methacrylate-modified sulfonated azocalix[4]arene (SAC4A-MA), methacrylated hyaluronic acid (HA-MA), and dithiol-terminated matrix metalloproteinase 13 (MMP-13) sensitive peptide via a microfluidic device and photo crosslinking technique, followed by encapsulation of the anti-inflammatory drug hydroxychloroquine (HCQ) through host-guest interaction. Owing to the hydrophobic deep cavity, phenolic units, and azo bonds of SAC4A-MA, the hydrogel microspheres show strong drug loading capacity, prominent reactive oxygen species (ROS) scavenging capability, and specific hypoxia-responsive drug release ability. In the OA tissue microenvironment, the hydrogel microspheres undergo degradation by excessive MMP-13 and release HCQ under the hypoxia condition, which synergizes with the ROS-scavenging calixarene to inhibit the inflammatory response of macrophages. After being injected into the OA-inflamed joint, the HAM-SA@HCQ can significantly attenuate the oxidative stress, downregulate the expression of hypoxia-induced factor-1α and inflammatory cytokines, and prevent the cartilage from being destroyed.
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Macropanax rosthornii (Harms) C. Y. Wu ex Hoo is an evergreen broadleaf species cultivated in subtropical China as an ornamental (Liang et al. 2015). In August 2020, leaf spot symptoms were observed on the campus of Jiangxi Agricultural University (28°45'56â³N, 115°50'21â³E), Jiangxi province, China. The early symptoms were small spots on the edge or tip of the leaves. The spots gradually expanded and became grayish brown with reddish egdes, eventually developing large irregular lesions. The disease incidence was estimated at 45%. Leaf pieces (5 × 5 mm) from the lesion borders were surface disinfested in 70% ethanol for 30 s, followed by 2% NaOCl for 1 min, and then rinsed three times with sterile water (Li et al. 2023). Tissues were placed on potato dextrose agar (PDA) and incubated at 25°C in the dark. Three representative single-spore isolates (DS-2, DS-3, and DS-5) were used for morphological studies and phylogenetic analyses. Colonies on PDA of the three isolates were white-to-gray with cottony mycelia. Conidia were single-celled, straight, hyaline, cylindrical, clavate, and measured 14.3-18.1 ×4.3-6.9 µm (15.8 ± 1.1 × 5.3 ± 0.2 µm, n = 100). Appressoria were brown to dark brown, ovoid to clavate, slightly irregular to irregular, and ranged from 5.6-9.4 × 4.5-6.9 µm (7.7 ± 0.3 × 5.5 ± 0.2 µm, n=100). Morphological features were similar to the Colletotrichum gloeosporioides species complex (Weir et al. 2012). The internal transcribed spacer (ITS) regions, calmodulin (CAL), actin (ACT), ß-tubulin 2 (TUB2), glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and chitin synthase (CHS-1) were amplified from genomic DNA for the three isolates using primers ITS1/ITS4, CL1/CL2, ACT-512F/ACT-783R, T1/Bt2b, GDF/GDR and CHS-79F/CHS-354R (Weir et al. 2012), respectively. Sequences were deposited in GenBank under nos. OL895315 - OL895316 (ITS), OL830190 - OL830192 (ACT), OL830181 - OL830183 (GAPDH), OL830178 - OL830180 (TUB2), OL830184 - OL830186 (CHS-1), and OL830187 - OL830189 (CAL). A maximum likelihood and Bayesian posterior probability analyses using IQtree v. 1.6.8 and Mr. Bayes v. 3.2.6 with the concatenated sequences placed DS-2, DS-3, and DS-5 in the clade of C. siamense. Based on the multi-locus phylogeny and morphology, three isolates were identified as C. siamense. Pathogenicity of the three isolates was verified on six 5-year-old Macropanax rosthornii plants, which were grown in the field. Three healthy leaves per plant were wounded using a sterile needle (Φ=0.5 mm) and inoculated with a 20-µL conidial suspension per leaf (106 conidia/mL). Another six control plants were treated with sterile water. Eighteen leaves were used for the pathogenicity test of three isolates. All leaves were covered with plastic bags to maintain humidity for 2 days. The inoculated leaves showed similar symptoms to those observed in the field, whereas control leaves were asymptomatic after 8 days. The fungi were consistently reisolated only from the inoculated and symptomatic leaves, fulfilling Koch's postulates. C. siamense can cause leaf diseases in a variety of hosts, including Liriodendron chinense × tulipifera (Zhu et al. 2019), Salix matsudana (Zhang et al. 2021), Carya illinoinensis (Zhuo et al. 2023). However, this is the first report of C. siamense infecting Macropanax rosthornii in China. This work provided crucial information for epidemiologic studies and appropriate control strategies for this newly emerging disease.
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OBJECTIVE: Although mini-plate fixation is an attractive treatment option for distal radius metaphyseal diaphysis junction (DRMDJ) fractures in children, the benefits of minimally invasive fixation (MIF) with pre-bent elastic stable intramedullary nails (MIF) remain underexplored. Therefore, this study aimed to evaluate the clinical efficacy of MIF administration in children with DRMDJ fractures. METHODS: This retrospective study enrolled 40 patients with DRMDJ fractures who underwent MIF or mini-plate fixation from January 2016 to January 2021. Radiographic parameters, such as palmar inclination and ulnar deflection angle, were examined postoperatively to assess the anatomical reduction of the wrist joint. Clinical outcomes, including the range of wrist flexion and back extension, were examined to analyze the recovery of the wrist range of motion. Additionally, the Gartland-Werley scoring system was used to assess the recovery status of wrist function and healing condition. The student t-test and χ2 test were used to compare differences among groups. RESULTS: All included patients successfully underwent the operation and were followed up for 12-24 months. Patients in the MIF group had a smaller surgical incision length (0.49 ± 0.06 cm) compared to those in the mini-plate fixation group (4.41 ± 0.73 cm) (t = 22.438, p = 0.000). Palmar inclination and ulnar deflection were within the normal range in patients of both groups, and the fractures were successfully anatomically reduced. Moreover, wrist flexion and back extension in the MIF group and mini-plate group were (72.50° ± 0.64° vs. 70.18° ± 0.56°) and (59.55° ± 1.75° vs. 60.04° ± 1.37°), and differences were statistically significant (t = 2.708, p = 0.010 and t = 0.885, p = 0.382, respectively). Furthermore, MIF treatment resulted in a higher proportion of excellent Gartland-Werley scores (94.44%) than mini-plate fixation (86.36%) (p = 0.390). In addition, one case in the mini-plate fixation group experienced re-fracture following the removal of the internal fixation, and the fracture healed after reduction and cast fixation. All patients achieved satisfactory bone healing without other complications. CONCLUSION: Compared with mini-plate fixation, MIF has the advantages of small incision length, superior range of motion of thr wrist joint, and better maintenance of the physiological radian, providing a promising approach for clinical and surgical treatment of DRMDJ fractures.
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Fijación Intramedular de Fracturas , Fracturas del Radio , Humanos , Niño , Diáfisis/cirugía , Estudios Retrospectivos , Radio (Anatomía) , Fracturas del Radio/diagnóstico por imagen , Fracturas del Radio/cirugía , Fijación Intramedular de Fracturas/métodos , Fijación Interna de Fracturas/métodos , Resultado del Tratamiento , Placas Óseas , Rango del Movimiento ArticularRESUMEN
Polygonatum cyrtonema Hua is a traditional Chinese medicine, which has anti-oxidant, anti-inflammatory, immunomodulatory, and other pharmacological effects (Lu et al. 2023). In June 2022, A disease of root rot was observed on P. cyrtonema plants in Tonggu County (28°63'89â³N, 114°48'07â³E), Jiangxi Province, China. The disease incidence was approximately 30% in a surveyed area of 3 hectares, which contained approximately 20,000 plants. Initially, the above-ground parts of the plants did not show any obvious symptoms. However, the underground roots exhibited red-brown spots that gradually expanded and sunken areas appeared, and the diseased plants presented leaf chlorosis and red-brown discoloration of the tubers, eventually leading to plant death. To identify the pathogen, symptomatic root tissues (0.5×0.5×0.5cm) from the lesion margin surface were sterilized with 75% ethanol for 30s, 3% NaClO for 3 min followed by rinsing three times with sterile water. The sterile root pieces were placed on potato dextrose agar (PDA) and incubated at 25â. Thirteen pure fungal isolates with the same morphological characteristics were obtained by monosporic isolation from 20 pieces of roots, and the representative isolates, HJGF1-1, HJGF1-2 were used for morphological studies and phylogenetic analyses. Initially, the two colonies on PDA appeared white with cotton-shaped aerial hyphae, which later turned light green to green and formed concentric rings. At the end of the conidiophores, 3 to 6 pear-shaped branches are irregularly gathered, and the angles between the branches are acute. The conidia were mostly solitary ellipsoid or obovate with the size of (3.7-5.9) × (3.6-4.5) µm (n=100). These morphological characteristics are consistent with the description of a Trichoderma spp. (Kamala et al. 2015). For molecular identification, the internal transcribed spacer (ITS), translation elongation factor 1-alpha (TEF-1α) and RNA polymerase II second largest subunit (RPB2) sequences were PCR amplified using primer pairs of ITS1/ITS4 (White et al. 1990), EF1-728F/EF1-986R (Carbone et al. 1999), and RPB2-5F2/RPB2-7cR (O'Donnell et al. 2022), respectively. BLAST analysis showed that the ITS, TEF-1α and RPB2 sequences of isolates HJGF1-1 (GenBank accession nos. OR229621, OR290791, OR334600) and HJGF1-2 (GenBank accession nos. OR229622, OR290792, OR334600) showed 99%-100% identity with multiple GenBank sequences of Trichoderma virens. A phylogenetic tree based on concatenated sequences of ITS, TEF-1α and RPB2 using maximum-likelihood analyses revealed that the two isolates HJGF1-1 and HJGF1-2 were in the same clade with T. virens strains. The two isolates were identified as T. virens based on the morphological characteristics and molecular phylogeny. To test pathogenicity, ten healthy P. cyrtonema plants (one tuber each, 5 tubers per isolate, n=10) in the field were pin-pricked with a sterile needle and pour-inoculated with 5 mL spore suspension per tuber (1× 107 conidia/ mL) with a temperature of about 28â. Another five tubers were were pin-pricked with a sterile needle, inoculated with sterile water and served as controls. The resulting symptoms were similar to those on the original infected plants in the field, and control tubers remained symptomless fourteen days after inoculation. T. virens was reisolated from the diseased tubers, nevertheless no pathogenic fungus was isolated from the control tubers. T. virens has been reported causing disease on tulip bulb (Lou et al. 2003) but has not previously been reported causing disease on P. cyrtonema. Although several species of Trichoderma are known to be beneficial microorganisms, the beneficial fungus may have had an evolutionary period of interaction with plants in which it behaved as a plant pathogen (Poveda et al. 2022). To our knowledge, this is the first report of T. virens infecting P. cyrtonema in China. This result may expanded the etiological study of T. virens and the control strategy of P. cyrtonema root rot.
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Bacterial infection causes lung inflammation and recruitment of several inflammatory factors that may result in acute lung injury (ALI). During bacterial infection, reactive oxygen species (ROS) and other signaling pathways are activated, which intensify inflammation and increase ALI-related mortality and morbidity. To improve the ALI therapy outcome, it is imperative clinically to manage bacterial infection and excessive inflammation simultaneously. Herein, a synergistic nanoplatform (AZI+IBF@NPs) constituted of ROS-responsive polymers (PFTU), and antibiotic (azithromycin, AZI) and anti-inflammatory drug (ibuprofen, IBF) was developed to enable an antioxidative effect, eliminate bacteria, and modulate the inflammatory milieu in ALI. The ROS-responsive NPs (PFTU NPs) loaded with dual-drugs (AZI and IBF) scavenged excessive ROS efficiently both in vitro and in vivo. The AZI+IBF@NPs eradicated Pseudomonas aeruginosa (PA) bacterial strain successfully. To imitate the entry of bacterial-derived compounds in body, a lipopolysaccharide (LPS) model was adopted. The administration of AZI+IBF@NPs via the tail veins dramatically reduced the number of neutrophils, significantly reduced cell apoptosis and total protein concentration in vivo. Furthermore, nucleotide oligomerization domain-like receptor thermal protein domain associated protein 3 (NLRP3) and Interleukin-1 beta (IL-1ß) expressions were most effectively inhibited by the AZI+IBF@NPs. These findings present a novel nanoplatform for the effective treatment of ALI.
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Lesión Pulmonar Aguda , Infecciones Bacterianas , Nanopartículas , Humanos , Azitromicina , Especies Reactivas de Oxígeno , Ibuprofeno/farmacología , Ibuprofeno/uso terapéutico , Polímeros , Lesión Pulmonar Aguda/tratamiento farmacológico , Lesión Pulmonar Aguda/metabolismo , Inflamación , Nanopartículas/uso terapéuticoRESUMEN
Advanced elastomers are highly in demand for the fabrication of medical devices for minimally invasive surgery (MIS). Herein, a shape memory and self-healing polyurethane (PCLUSe) composed of semi-crystalline poly(ε-caprolactone) (PCL) segments and interchangeable and antioxidative diselenide bonds was designed and synthesized. The excellent shape memory of PCLUSe contributed to the smooth MIS operation, leading to less surgical wounds than in the case of sternotomy. The diselenide bonds of PCLUSe contributed to the rapid self-healing under 405 nm irradiation within 60 s, and the alleviation of tissue oxidation post injury. After being delivered through a 10 mm diameter trocar onto a beating canine heart by MIS, two shape-recovered PCLUSe films self-assembled (self-healing) into a larger single patch (20 × 10 × 0.2 mm3) under the trigger of laser irradiation in situ, which could efficiently overcome the limited-size problem within MIS and meet a larger treatment area. The diselenide bonds in the PCLUSe cardiac patches protected the myocardium under oxidative stress post myocardial infarction (MI), and significantly maintained the cardiac functions.
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Infarto del Miocardio , Poliuretanos , Animales , Perros , Poliuretanos/química , Elastómeros , MiocardioRESUMEN
Multi-view subspace clustering aims to integrate the complementary information contained in different views to facilitate data representation. Currently, low-rank representation (LRR) serves as a benchmark method. However, we observe that these LRR-based methods would suffer from two issues: limited clustering performance and high computational cost since (1) they usually adopt the nuclear norm with biased estimation to explore the low-rank structures; (2) the singular value decomposition of large-scale matrices is inevitably involved. Moreover, LRR may not achieve low-rank properties in both intra-views and inter-views simultaneously. To address the above issues, this paper proposes the Bi-nuclear tensor Schatten- p norm minimization for multi-view subspace clustering (BTMSC). Specifically, BTMSC constructs a third-order tensor from the view dimension to explore the high-order correlation and the subspace structures of multi-view features. The Bi-Nuclear Quasi-Norm (BiN) factorization form of the Schatten- p norm is utilized to factorize the third-order tensor as the product of two small-scale third-order tensors, which not only captures the low-rank property of the third-order tensor but also improves the computational efficiency. Finally, an efficient alternating optimization algorithm is designed to solve the BTMSC model. Extensive experiments with ten datasets of texts and images illustrate the performance superiority of the proposed BTMSC method over state-of-the-art methods.
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Tumor necrosis factor α (TNF-α) is a leading proinflammatory cytokine as the master regulator of inflammation in chronic inflammation diseases. Although TNF-α antagonists such as small molecules and peptides are in development, comparable effectiveness in TNF-α neutralization is hardly achieved only with TNF-α capture. In this study, simplified α2-macroglobulin (SM) as a novel TNF-α inhibitor was fabricated to relieve inflammation response by TNF-α capture and internalization with lysosomal degradation. SM was prepared by conjugating a TNF-α-targeting peptide with a receptor binding domain (RBD) derived from α2-macroglobulin through a synthetic biology strategy. SM exhibited effective capture and bioactivity inhibition of TNF-α. Improved endocytosis of TNF-α into lysosomes was observed with SM in macrophages. Even challenged with LPS/IFNγ, the macrophages showed relieved inflammation response with SM treatment. When administrated in chronic inflammation injury in vivo, SM achieved comparable therapeutic efficacy with Infliximab, showing ameliorated cartilage degeneration with relieved inflammation in osteoarthritis (OA) and preserved cardiac function with mitigated myocardium injury in myocardial infarction (MI). These results suggest that SM functioning in TNF-α capture-internalization mechanism might be promising therapeutic alternatives of TNF-α antibodies.
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Infarto del Miocardio , Osteoartritis , alfa 2-Macroglobulinas Asociadas al Embarazo , Embarazo , Femenino , Humanos , Factor de Necrosis Tumoral alfa/metabolismo , Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio/patología , Inflamación/tratamiento farmacológico , Factores InmunológicosRESUMEN
BACKGROUND: The morphological classification of the upper eyelid in Asian people is complex and diverse and usually not consistent with what we know well. AIMS: To improve the classification of upper eyelid morphology and investigate the preferred double eyelid shape by Asian people. METHODS: An investigation of 640 patients' preferences for double eyelid shape was conducted, and the pre- and post-operative effects were assessed. The shapes of the natural eyelids of 247 people (485 eyes) who provided real photographs of the eyelids were counted. The chi-square test was used to analyze the differences. RESULTS: There were 10 eyelid shapes: single eyelid, parallel-shaped double eyelid, fan-shaped double eyelid, parallel fan-shaped double eyelid, opened fan-shaped double eyelid, crescent-shaped double eyelid, hidden-shaped double eyelid, horizontal-shaped double eyelid, triangle-shaped double eyelid, and multiple-fold eyelid. The difference in the shape of the natural eyelid between males and females was statistically significant (p < 0.05). The most popular eyelid shapes were single eyelid (24.9%), open fan-shaped double eyelid (21.0%), fan-shaped double eyelid (16.3%), and hidden-shaped double eyelid (12.6%). Men and women preferred a parallel fan-shaped double eyelid (18.0%), a parallel-shaped double eyelids (17.0%), and an open fan-shaped double eyelids (18.1%). CONCLUSIONS: The most popular upper eyelid shapes were single eyelid, open fan-shaped double eyelid, and fan-shaped double eyelid. The parallel fan-shaped, parallel-shaped, and open fan-shaped double eyelid were favored by men and women.
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Blefaroplastia , Masculino , Humanos , Femenino , Pueblo Asiatico , Párpados/cirugía , Prioridad del Paciente , Encuestas y Cuestionarios , Estudios RetrospectivosRESUMEN
Infectious diabetic ulcers (IDU) require anti-infection, angiogenesis, and nerve regeneration therapy; however, the latter has received comparatively less research attention than the former two. In particular, there have been few reports on the recovery of mechanical nociception. In this study, a photothermal controlled-release immunomodulatory hydrogel nanoplatform is tailored for the treatment of IDU. Due to a thermal-sensitive interaction between polydopamine-reduced graphene oxide (pGO) and the antibiotic mupirocin, excellent antibacterial efficacy is achieved through customized release kinetics. In addition, Trem2+ macrophages recruited by pGO regulate collagen remodeling and restore skin adnexal structures to alter the fate of scar formation, promote angiogenesis, accompanied by the regeneration of neural networks, which ensures the recovery of mechanical nociception and may prevent the recurrence of IDU at the source. In all, a full-stage strategy from antibacterial, immune regulation, angiogenesis, and neurogenesis to the recovery of mechanical nociception, an indispensable neural function of skin, is introduced to IDU treatment, which opens up an effective and comprehensive therapy for refractory IDU.
Asunto(s)
Diabetes Mellitus , Nocicepción , Humanos , Preparaciones de Acción Retardada , Úlcera , AntibacterianosRESUMEN
In this article, a unified multiview subspace learning model, called partial tubal nuclear norm-regularized multiview subspace learning (PTN 2 MSL), was proposed for unsupervised multiview subspace clustering (MVSC), semisupervised MVSC, and multiview dimension reduction. Unlike most of the existing methods which treat the above three related tasks independently, PTN 2 MSL integrates the projection learning and the low-rank tensor representation to promote each other and mine their underlying correlations. Moreover, instead of minimizing the tensor nuclear norm which treats all singular values equally and neglects their differences, PTN 2 MSL develops the partial tubal nuclear norm (PTNN) as a better alternative solution by minimizing the partial sum of tubal singular values. The PTN 2 MSL method was applied to the above three multiview subspace learning tasks. It demonstrated that these tasks organically benefited from each other and PTN 2 MSL has achieved better performance in comparison to state-of-the-art methods.