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1.
Artículo en Inglés | MEDLINE | ID: mdl-39177447

RESUMEN

Due to the slow diffusion of photovoltaic molecules, in particular, small-molecule acceptors (SMAs), under light and heating, the morphology of the active layer in organic solar cells (OSCs) prefers to deviate from the favorably metastable status, leading to the challenge of stability during long-term operation. Employing materials with a high glass transition temperature (Tg) as the third component to suppress molecular diffusion is an efficient method to achieve the balance of efficiency and stability of OSCs. Herein, a dimerized small-molecule acceptor denoted as F6D is synthesized by introducing a polyfluoride moiety as the linker to enhance the Tg. Benefitting from a rational molecular design, F6D not only exhibits a higher Tg, complementary absorption, and cascade energy levels with the host materials of the polymer donor PM6 and the SMA Y6 but also has excellent miscibility and multiple intermolecular interactions with Y6. As a result, a champion power conversion efficiency of 17.52% is achieved in the optimal PM6:Y6:F6D-based device. More importantly, the ternary device exhibits superior stability under continuous heating and lighting compared with the binary device.

2.
Bioconjug Chem ; 2024 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-39159059

RESUMEN

Drug delivery to the esophagus through systemic administration remains challenging, as minimal drug reaches the desired target. Local delivery offers the potential for improved efficacy while minimizing off-target toxicities but necessitates bioadhesive properties for mucosal delivery. Herein, we describe the synthesis of two new mucoadhesive amphiphilic copolymers prepared by sequential ring-opening copolymerization or postpolymerization click conjugation. Both strategies yield block copolymers containing a hydrophilic amine-functionalized poly-amido-saccharide and either a hydrophobic alkyl derivatized poly-amido-saccharide or poly(lactic acid), respectively. The latter resulting copolymers readily self-assemble into spherical, ≈200 nm diameter, positively charged mucoadhesive nanoparticles. The NPs entrap ultrahigh levels of paclitaxel via encapsulation of free paclitaxel and paclitaxel conjugated to a biodegradable, biocompatible poly(1,2-glycerol carbonate). Paclitaxel-loaded NPs rapidly enter cells, release paclitaxel, are cytotoxic to esophageal OE33 and OE19 tumor cells in vitro, and, importantly, demonstrate improved mucoadhesion compared to conventional poly(ethylene glycol)-poly(lactic acid) nanoparticles to ex vivo esophageal tissue.

3.
Sci Rep ; 14(1): 19215, 2024 08 19.
Artículo en Inglés | MEDLINE | ID: mdl-39160177

RESUMEN

The aim of this study was to develop a medical imaging and comprehensive stacked learning-based method for predicting high- and low-risk thymoma. A total of 126 patients with thymomas and 5 patients with thymic carcinoma treated at our institution, including 65 low-risk patients and 66 high-risk patients, were retrospectively recruited. Among them, 78 patients composed the training cohort, while the remaining 53 patients formed the validation cohort. We extracted 1702 features each from the patients' arterial-, venous-, and plain-phase images. Pairwise subtraction of these features yielded 1702 arterial-venous, arterial-plain, and venous-plain difference features each. The Mann‒Whitney U test and least absolute shrinkage and selection operator (LASSO) and SelectKBest methods were employed to select the best features from the training set. Six models were built with a stacked learning algorithm. By applying stacked ensemble learning, three machine learning algorithms (XGBoost, multilayer perceptron (MLP), and random forest) were combined by XGBoost to produce the the six basic imaging models. Then, the XGBoost algorithm was applied to the six basic imaging models to construct a combined radiomic model. Finally, the radiomic model was combined with clinical information to create a nomogram that could easily be used in clinical practice to predict the thymoma risk category. The areas under the curve (AUCs) of the combined radiomic model in the training and validation cohorts were 0.999 (95% CI 0.988-1.000) and 0.967 (95% CI 0.916-1.000), respectively, while those of the nomogram were 0.999 (95% CI 0.996-1.000) and 0.983 (95% CI 0.990-1.000). This study describes the application of CT-based radiomics in thymoma patients and proposes a nomogram for predicting the risk category for this disease, which could be advantageous for clinical decision-making for affected patients.


Asunto(s)
Aprendizaje Automático , Timoma , Neoplasias del Timo , Tomografía Computarizada por Rayos X , Humanos , Timoma/diagnóstico por imagen , Timoma/patología , Masculino , Femenino , Persona de Mediana Edad , Tomografía Computarizada por Rayos X/métodos , Neoplasias del Timo/diagnóstico por imagen , Neoplasias del Timo/patología , Adulto , Estudios Retrospectivos , Anciano , Medición de Riesgo/métodos , Algoritmos , Nomogramas , Radiómica
5.
Artículo en Inglés | MEDLINE | ID: mdl-39090454

RESUMEN

Given China's prohibition on the utilization of antibiotics as feed additives in 2020, we aim to investigate nutrition additives that are both efficient and safe. Lactobacillus, a well-recognized beneficial probiotic, has explicitly been investigated for its effects on health status of the host and overall impact on food industry. To evaluate effects of Lactobacillus plantarum (LW) supplementation on broiler chicken, we conducted comprehensive multi-omics analysis, growth performance evaluation, RT-qPCR analysis, and immunofluorescence. The findings revealed that LW supplementation resulted in a substantial progress in growth performance (approximately 205 g increase in final body weight in comparison to the control group (p < 0.01)). Additionally, LW exhibited promising potential for enhancing antioxidant properties of serum and promoting gut integrity and growth as evidenced by improved antioxidant indices (p < 0.01), intestinal villus morphology (p < 0.01), and enhanced gut barrier function (p < 0.01). Meanwhile, the multi-omics analysis, including 16S rRNA sequencing and liquid chromatography-tandem mass spectrometry, revealed an enrichment of beneficial microbes in the gut of broilers that were supplemented with LW, while simultaneously depleting harmful microorganisms. Moreover, a noteworthy modification was observed in gut metabolic profiling subsequent to the execution of the probiotic strategy. Specifically, variations were noticed in the levels of metabolites and metabolic pathways such as parathyroid hormone synthesis, inflammatory mediator regulation of TRP channels, oxidative phosphorylation, and mineral absorption. Taken together, our findings validate that LW administration produces valuable effects on the health and growth performance of broilers owing to its capability to boost the gut microbiota homeostasis and intestinal metabolism. Present findings signify the potential of LW as a dietary additive to promote growth and development in broiler chickens.

6.
BMC Cardiovasc Disord ; 24(1): 335, 2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-38961354

RESUMEN

BACKGROUND: The efficacy of optimal medical therapy (OMT) with or without revascularization therapy in patients with stable coronary artery disease (SCAD) remains controversial. We performed a meta-analysis of randomized controlled trials (RCTs) that compared OMT with or without revascularization therapy for SCAD patients. METHODS: Studies were searched in PubMed, EMBASE, and the Cochrane Central Register of Clinical Trials from January 1, 2005, to December 30, 2023. The main efficacy outcome was a composite of all-cause death, myocadiac infarction, revascularization, and cerebrovascular accident. Results were pooled using random effects model and fixed effects model and are presented as odd ratios (ORs) with 95% confidence intervals (CI). RESULTS: Ten studies involving 12,790 participants were included. The arm of OMT with revascularization compared with OMT alone was associated with decreased risks for MACCE (OR 0.55 [95% CI 0.38-0.80], I²=93%, P = 0.002), CV death (OR 0.84 [95% CI 0.73-0.97], I²=36%, P = 0.02), revascularization (OR 0.32 [95% CI 0.20-0.50], I²=92%, P < 0.001), and MI (OR 0.85 [95% CI 0.76-0.96], I²=45%, P = 0.007). While there was no significant difference between OMT with revascularization and OMT alone in the odds of all-cause death (OR 0.94 [95% CI 0.84-1.05], I²=0%, P = 0.30). CONCLUSIONS: The current updated meta-analysis of 10 RCTs shows that in patients with SCAD, OMT with revascularization would reduce the risk for MACCE, cardiovascular death, and MI. However, the invasive strategy does not decrease the risks for all-cause mortality when comparing with OMT alone.


Asunto(s)
Enfermedad de la Arteria Coronaria , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Enfermedad de la Arteria Coronaria/mortalidad , Enfermedad de la Arteria Coronaria/terapia , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Resultado del Tratamiento , Factores de Riesgo , Femenino , Masculino , Anciano , Persona de Mediana Edad , Fármacos Cardiovasculares/uso terapéutico , Fármacos Cardiovasculares/efectos adversos , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/mortalidad , Medición de Riesgo , Revascularización Miocárdica/efectos adversos , Revascularización Miocárdica/mortalidad , Factores de Tiempo
7.
Plant Sci ; 347: 112182, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39019090

RESUMEN

Photosynthesis is the main source of energy for plants to sustain growth and development. Abnormalities in photosynthesis may cause defects in plant development. The elaborate regulatory mechanism underlying photosynthesis remains unclear. In this study, we identified a natural mutant from the Greater Khingan Mountains and named it as "1-T". This mutant had variegated leaf with irregular distribution of yellow and green. Chlorophyll contents and photosynthetic capacity of 1-T were significantly reduced compared to other poplar genotypes. Furthermore, a transcriptome analysis revealed 3269 differentially expressed genes (DEGs) in 1-T. The products of the DEGs were enriched in photosystem I and photosystem II. Three motifs were significantly enriched in the promoters of these DEGs. Yeast one-hybrid, Electrophoretic mobility shift assays and tobacco transient transformation experiments indicated that PdGLKs may bind to the three motifs. Further analysis indicated that these photosystem related genes were also significantly down-regulated in PdGLK-RNAi poplars. Therefore, we preliminarily concluded that the down-regulation of PdGLKs in 1-T may affect the expression of photosystem-related genes, resulting in abnormal photosystem development and thus affecting the growth and development. Our results provide new insights into the molecular mechanism of photosynthesis regulating plant growth.


Asunto(s)
Perfilación de la Expresión Génica , Fotosíntesis , Populus , Populus/genética , Populus/metabolismo , Populus/crecimiento & desarrollo , Fotosíntesis/genética , Regulación de la Expresión Génica de las Plantas , Complejo de Proteína del Fotosistema II/metabolismo , Complejo de Proteína del Fotosistema II/genética , Transcriptoma , Complejo de Proteína del Fotosistema I/metabolismo , Complejo de Proteína del Fotosistema I/genética , Mutación , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
8.
Comput Biol Med ; 179: 108823, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38991322

RESUMEN

BACKGROUND AND OBJECTIVE: Stroke is a disease with high mortality and disability. Importantly, the fatality rate demonstrates a significant increase among patients afflicted by recurrent strokes compared to those experiencing their initial stroke episode. Currently, the existing research encounters three primary challenges. The first is the lack of a reliable, multi-omics image dataset related to stroke recurrence. The second is how to establish a high-performance feature extraction model and eliminate noise from continuous magnetic resonance imaging (MRI) data. The third is how to integration multi-omics data and dynamically weighted for different omics data. METHODS: We systematically compiled MRI and conventional detection data from a cohort comprising 737 stroke patients and established PSTSZC, a multi-omics dataset for predicting stroke recurrence. We introduced the first-ever Integrated Multi-omics Prediction Model for Stroke Recurrence, MPSR, which is based on ResNet, Lnet-transformer, LSTM and dynamically weighted DNN. The MPSR model comprises two principal modules, the Feature Extraction Module, and the Integrated Multi-Omics Prediction Module. In the Feature Extraction module, we proposed a novel Lnet regularization layer, which effectively addresses noise issues in MRI data. In the Integrated Multi-omics Prediction Module, we propose a dynamic weighted mechanism based on evaluators, which mitigates the noise impact brought about by low-performance omics. RESULTS: We compared seven single-omics models and six state-of-the-art multi-omics stroke recurrence models. The experimental results demonstrate that the MPSR model exhibited superior performance. The accuracy, AUROC, specificity, and sensitivity of the MPSR model can reach 0.96, 0.97, 1, and 0.94, respectively, which is higher than the results of contrast model. CONCLUSION: MPSR is the first available high-performance multi-omics prediction model for stroke recurrence. We assert that the MPSR model holds the potential to function as a valuable tool in assisting clinicians in accurately diagnosing individuals with a predisposition to stroke recurrence.


Asunto(s)
Imagen por Resonancia Magnética , Recurrencia , Accidente Cerebrovascular , Humanos , Accidente Cerebrovascular/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Masculino , Femenino , Anciano , Genómica/métodos , Persona de Mediana Edad , Multiómica
9.
Sci Rep ; 14(1): 15152, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38956404

RESUMEN

Removing texture while preserving the main structure of an image is a challenging task. To address this, this paper propose an image smoothing method based on global gradient sparsity and local relative gradient constraints optimization. To reduce the interference of complex texture details, adopting a multi-directional difference constrained global gradient sparsity decomposition method, which provides a guidance image with weaker texture detail gradients. Meanwhile, using the luminance channel as a reference, edge-aware operator is constructed based on local gradient constraints. This operator weakens the gradients of repetitive and similar texture details, enabling it to obtain more accurate structural information for guiding global optimization of the image. By projecting multi-directional differences onto the horizontal and vertical directions, a mapping from multi-directional differences to bi-directional gradients is achieved. Additionally, to ensure the consistency of measurement results, a multi-directional gradient normalization method is designed. Through experiments, we demonstrate that our method exhibits significant advantages in preserving image edges compared to current advanced smoothing methods.

10.
Environ Sci Technol ; 58(31): 13929-13939, 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-38978502

RESUMEN

The migration and risk of organophosphate esters (OPEs) in agricultural air-soil-plant multimedia systems due to plastic film application remain unclear. This study investigates the multimedia distribution of traditional OPEs (TOPEs), novel OPEs (NOPEs), and their transformation products (POPEs) in plastic and solar greenhouses. The total concentration of OPE-associated contaminants in air and airborne particles ranged from 594 to 1560 pg/m3 and 443 to 15600 ng/g, respectively. Significant correlations between air OPE concentrations and those in polyolefin film (P < 0.01) indicate plastic film as the primary source. Contaminants were also found in soils (96.8-9630 ng/g) and vegetables (197-7540 ng/g). The primary migration pathway for NOPEs was particle dry deposition onto the soil and leaf, followed by plant accumulation. Leaf absorption was the main uptake pathway for TOPEs and POPEs, influenced by vegetable specific leaf surface area. Moreover, total exposure to OPE-associated contaminants via vegetable intake was assessed at 2250 ng/kg bw/day for adults and 2900 ng/kg bw/day for children, with an acceptable hazard index. However, a high ecological risk was identified for NOPE compounds (median risk quotient, 975). This study provides the first evidence of the multimedia distribution and potential threat posed by OPE-associated contaminants in agricultural greenhouses.


Asunto(s)
Ésteres , Plásticos , Verduras , Verduras/química , Organofosfatos , Humanos , Suelo/química
11.
Iran J Basic Med Sci ; 27(9): 1155-1161, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39055877

RESUMEN

Objectives: The material used for bone tissue repair needs to be simultaneously osteoconductive, osteoinductive, and osteogenic. To overcome this problem, researchers combine hydroxyapatite (HA) with natural materials to improve properties. This paper compares the effects of angiogenesis and osteogenesis with different composites through in vivo experiments and characterization analysis. Materials and Methods: Chitosan/nHA (CS/nHA) and sodium alginate/nHA (SA/nHA) microspheres were synthesized via reverse-phase emulsification crosslinking and analyzed using scanning electron microscopy (SEM), energy dispersion spectroscopy (EDS), and X-ray diffraction (XRD). Implanted into mouse thigh muscles, their angiogenic and osteogenic potentials were assessed after 8 and 12 weeks through various staining methods and immunohistochemistry. Results: The mean vascular density (MVD) of CS/nHA, CaP/nHA, and SA/nHA groups was (134.92±35.30) n/mm2, (159.09±22.14) n/mm2, (160.31±42.23) n/mm2 at 12 weeks, respectively. The MVD of the CaP/nHA and SA/nHA groups were significantly higher than that of the CS/nHA group. The collagen volume fractions (CVF) were 34.13%, 51.53%, and 54.96% in the CS/nHA, CaP/nHA, and SA/nHA groups, respectively. In addition, the positive expression area ratios of OPN and CD31 in the CaP/nHA and SA/nHA groups were also significantly higher than those in the CS/nHA group. Conclusion: The ability of SA/nHA composite microspheres in osteogenesis and angiogenesis is clearly superior to that of the CS/nHA group and is comparable to that of CaP/nHA, which has superior osteogenesis ability, indicating that SA/nHA composite microspheres have greater application prospects in bone tissue engineering.

12.
Curr Issues Mol Biol ; 46(7): 7169-7186, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-39057068

RESUMEN

Clostridium perfringens (C. perfringens) is an important veterinary pathogen and a noteworthy threat to human and animal health. Recently, there has been a significant rise in the number of moose fatalities caused by this rare, endemic species in China. Currently, there is an increasing trend in conducting whole-genome analysis of C. perfringens strains originating from pigs and chickens, whereas fewer studies have been undertaken on Elaphurus davidianus-originating strains at the whole-genome level. Our laboratory has identified and isolated five C. perfringens type A from affected Elaphurus davidianus. The current study identified the most potent strain of C. perfringens, which originated from Elaphurus davidianus, and sequenced its genome to reveal virulence genes and pathogenicity. Our findings show that strain CX1-4 exhibits the highest levels of phospholipase activity, hemolytic activity, and mouse toxicity compared to the other four isolated C. perfringens type A strains. The chromosome sequence length of the CX1-4 strain was found to be 3,355,389 bp by complete genome sequencing. The current study unveils the genomic characteristics of C. perfringens type A originating from Elaphurus davidianus. It provides a core foundation for further investigation regarding the prevention and treatment of such infectious diseases in Elaphurus davidianus.

13.
BMC Public Health ; 24(1): 1934, 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39026285

RESUMEN

BACKGROUND: Many effective therapies for psoriasis are being applied in clinical practice in recent years, however, some patients still can't achieve satisfied effect even with biologics. Therefore, it is crucial to identify factors associated with the treatment efficacy among psoriasis patients. This study aims to explore factors influencing the treatment efficacy of psoriasis patients based on decision tree model and logistic regression. METHODS: We implemented an observational study and recruited 512 psoriasis patients in Shanghai Skin Diseases Hospital from 2021 to 2022. We used face-to-face questionnaire interview and physical examination to collect data. Influencing factors of treatment efficacy were analyzed by using logistic regression, and decision tree model based on the CART algorithm. The receiver operator curve (ROC) was plotted for model evaluation and the statistical significance was set at P < 0.05. RESULTS: The 512 patients were predominately males (72.1%), with a median age of 47.5 years. In this study, 245 patients achieved ≥ 75% improvement in psoriasis area and severity index (PASI) score in week 8 and was identified as treatment success (47.9%). Logistic regression analysis showed that patients with senior high school and above, without psoriasis family history, without tobacco smoking and alcohol drinking had higher percentage of treatment success in patients with psoriasis. The final decision tree model contained four layers with a total of seventeen nodes. Nine classification rules were extracted and five factors associated with treatment efficacy were screened, which indicated tobacco smoking was the most critical variable for treatment efficacy prediction. Model evaluation by ROC showed that the area under curve (AUC) was 0.79 (95%CI: 0.75 ~ 0.83) both for logistic regression model (0.80 sensitivity and 0.69 specificity) and decision tree model (0.77 sensitivity and 0.73 specificity). CONCLUSION: Psoriasis patients with higher education, without tobacco smoking, alcohol drinking and psoriasis family history had better treatment efficacy. Decision tree model had similar predicting effect with the logistic regression model, but with higher feasibility due to the nature of simple, intuitive, and easy to understand.


Asunto(s)
Árboles de Decisión , Psoriasis , Humanos , Psoriasis/terapia , Femenino , Masculino , Persona de Mediana Edad , China , Modelos Logísticos , Adulto , Resultado del Tratamiento , Encuestas y Cuestionarios , Índice de Severidad de la Enfermedad
14.
J Asian Nat Prod Res ; : 1-11, 2024 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-38945152

RESUMEN

Histone deacetylase 6 (HDAC6) was a potential target for Alzheimer's disease (AD). In this study, a series of novel oxyevodiamine-based HDAC6 inhibitors with a variety of linker moieties were designed, synthesized and evaluated. Compound 12 with a benzyl linker was identified as a high potent and selective HDAC6 inhibitor. It inhibited HDAC6 with an IC50 value of 6.2 nM and was more than 200 fold selectivity over HDAC1. It also had lower cytotoxicity and higher anti-H2O2 activity in vitro comparing with other derivatives. Compound 12 might be a good lead as novel HDAC6 inhibitor for the treatment of AD.

15.
Virology ; 597: 110150, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38917690

RESUMEN

Coronaviruses (CoVs) comprise a group of important human and animal pathogens that threaten public health because of their interspecies transmission potential to humans. However, virus-like particles (VLPs) constitute versatile tools in CoVs vaccine development due to their favorable immunological characteristics. Here, we engineered the VLPs composed of the spike (S), membrane (M), and envelope (E) structural proteins of the Porcine deltacoronavirus (PDCoV) and examined their immune responses in mice. Neutralization assays and flow Cytometry demonstrated that PDCoV VLPs induced highly robust neutralizing antibodies (NAbs) and elicited cellular immunity. To assess the protective efficacy of VLPs in newborn piglets, pregnant sows received vaccinations with either a PDCoV-inactivated vaccine or VLPs at 40 and 20 days before delivery. Five days post-farrowing, piglets were orally challenged with the PDCoV strain. Severe diarrhea, high viral RNA copies, and substantial intestinal villus atrophy were detected in piglets born to unimmunized sows. However, piglets from sows immunized with VLPs exhibited high NAbs titers and markedly reduced microscopic damage to the intestinal tissues, with no piglet showing diarrhea. Hence, the results indicate that the VLPs are a potential clinical candidate for PDCoV vaccination, while the strategy may serve as a platform for developing other coronavirus vaccines.


Asunto(s)
Anticuerpos Neutralizantes , Anticuerpos Antivirales , Infecciones por Coronavirus , Deltacoronavirus , Enfermedades de los Porcinos , Vacunas de Partículas Similares a Virus , Vacunas Virales , Animales , Porcinos , Vacunas de Partículas Similares a Virus/inmunología , Vacunas de Partículas Similares a Virus/administración & dosificación , Infecciones por Coronavirus/prevención & control , Infecciones por Coronavirus/veterinaria , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/virología , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , Enfermedades de los Porcinos/prevención & control , Enfermedades de los Porcinos/virología , Enfermedades de los Porcinos/inmunología , Vacunas Virales/inmunología , Vacunas Virales/administración & dosificación , Femenino , Deltacoronavirus/inmunología , Ratones , Embarazo , Glicoproteína de la Espiga del Coronavirus/inmunología , Glicoproteína de la Espiga del Coronavirus/genética , Animales Recién Nacidos
16.
Vet Sci ; 11(6)2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38921977

RESUMEN

Bovine coronavirus (BCoV), bovine rotavirus, bovine viral diarrhea virus, and bovine astrovirus are the most common intestinal pathogenic viruses causing diarrhea in cattle. We collected 1646 bovine fecal samples from January 2020 to August 2023. BCoV was the major pathogen detected, with a positive rate of 34.02% (560/1646). Of the 670 diarrheal samples and 976 asymptomatic samples, 209 and 351 were BCoV-positive, respectively. Studying the relevance of diarrhea associated with BCoV has shown that the onset of diarrheal symptoms post-infection is strongly correlated with the cattle's age and may also be related to the breed. We amplified and sequenced the hemagglutinin esterase (HE), spike protein, and whole genomes of the partially positive samples and obtained six complete HE sequences, seven complete spike sequences, and six whole genomes. Molecular characterization revealed that six strains were branched Chinese strains, Japanese strains, and partial American strains from the GⅡb subgroup. Strains HBSJZ2202 and JSYZ2209 had four amino acid insertions on HE. We also analyzed ORF1a and found disparities across various regions within GIIb, which were positioned on separate branches within the phylogenetic tree. This work provides data for further investigating the epidemiology of BCoV and for understanding and analyzing BCoV distribution and dynamics.

18.
J Invest Dermatol ; 2024 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-38909841

RESUMEN

Nagashima-type palmoplantar keratoderma is an autosomal recessive genodermatosis caused by loss-of-function variants in SERPINB7 and is the most prevalent form of inherited palmoplantar keratodermas among Asians. However, there is currently no effective therapy for Nagashima-type palmoplantar keratoderma because its pathogenesis remains unclear. In this study, Serpinb7-/- mice were generated and spontaneously developed a disrupted skin barrier, which was further exacerbated by acetone-ether-water treatment. The skin of these Serpinb7-/- mice showed weakened cytoskeletal proteins. In addition, SERPINB7 deficiency consistently led to decreased epidermal differentiation in a 3-dimensional human epidermal model. We also demonstrated that SERPINB7 was an inhibitory serpin that mainly inhibited the protease legumain. SERPINB7 bound directly with legumain and inhibited legumain activity both in vitro and in vivo. Furthermore, we found that SERPINB7 inhibited legumain in a protease-substrate manner and identified the cleavage sites of SERPINB7 as Asn71 and Asn343. Overall, we found that SERPINB7 showed the nature of a cysteine protease inhibitor and identified legumain as a key target protease of SERPINB7. Loss of SERPINB7 function led to overactivation of legumain, which might disrupt cytoskeletal proteins, contributing to the impaired skin barrier in Nagashima-type palmoplantar keratoderma. These findings may lead to the development of therapeutic strategies for Nagashima-type palmoplantar keratoderma.

19.
Artículo en Inglés | MEDLINE | ID: mdl-38889028

RESUMEN

Deep learning associated with neurological signals is poised to drive major advancements in diverse fields such as medical diagnostics, neurorehabilitation, and brain-computer interfaces. The challenge in harnessing the full potential of these signals lies in the dependency on extensive, high-quality annotated data, which is often scarce and expensive to acquire, requiring specialized infrastructure and domain expertise. To address the appetite for data in deep learning, we present Neuro-BERT, a self-supervised pre-training framework of neurological signals based on masked autoencoding in the Fourier domain. The intuition behind our approach is simple: frequency and phase distribution of neurological signals can reveal intricate neurological activities. We propose a novel pre-training task dubbed Fourier Inversion Prediction (FIP), which randomly masks out a portion of the input signal and then predicts the missing information using the Fourier inversion theorem. Pre-trained models can be potentially used for various downstream tasks such as sleep stage classification and gesture recognition. Unlike contrastive-based methods, which strongly rely on carefully hand-crafted augmentations and siamese structure, our approach works reasonably well with a simple transformer encoder with no augmentation requirements. By evaluating our method on several benchmark datasets, we show that Neuro-BERT improves downstream neurological-related tasks by a large margin.

20.
J Ethnopharmacol ; 333: 118475, 2024 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-38908496

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: The pathophysiological mechanism of thromboinflammation involves the intricate interplay between the inflammatory responses and coagulation cascades. Rhubarb is frequently used in traditional Chinese medicine to treat thromboinflammatory diseases. The scorched rhubarb (prepared by stir-baking the dried raw rhubarb till it partly turns to charcoal) is believed to possess enhanced blood-cooling and stasis-removing functions compared to the raw rhubarb, thereby augmenting the therapeutic effects on thromboinflammation. AIM OF THE STUDY: This study aimed to explore the chemical and pharmacological foundations of the scorch processing of rhubarb in order to ensure and enhance the efficacy and safety of the scorched rhubarb for treating thromboinflammatory diseases. MATERIALS AND METHODS: The dried raw rhubarb pieces were subjected to stir-baking at 180 °C for 10∼80 min to obtain the rhubarbs with varying degrees of scorching. Typical ingredients present in rhubarb pieces and extracts were determined by high-performance liquid chromatography. The therapeutic effects of the raw and scorched rhubarb on thromboinflammation were evaluated using a rat model. Proteomics analysis was employed to screen potential biological pathways associated with thromboinflammation treatment by the raw and scorched rhubarb, which were further verified using a cell model. RESULTS: Morphological properties indicated that the rhubarb baked at 180 °C for 50 min in this research showed the optimal degree of scorching. Compared to the raw rhubarb, the properly scorched rhubarb exhibited lower levels of anthraquinone glucosides, higher levels of anthraquinone aglycones, superior anti-thromboinflammatory effects, and no purgative side effects. Proteomics analysis revealed that the complement and coagulation cascades pathway played a significant role in mediating the therapeutic effects of the raw and scorched rhubarb on thromboinflammation. Furthermore, it was found that anthraquinone aglycones were more effective than their glucoside counterparts in restoring the impaired vascular endothelial cells as well as regulating the complement and coagulation cascades pathway. CONCLUSIONS: Proper scorch processing may augment the therapeutic effects of rhubarb on thromboinflammation via relieving inflammation and oxidative stress, repairing vascular endothelial cells, restoring coagulation cascades and blood rheology, and regulating some other biological processes. This may be partly caused by the scorch-induced thermolysis of anthraquinone glucosides into their aglycone counterparts that seemed to perform better in regulating the complement and coagulation cascades pathway.


Asunto(s)
Antraquinonas , Coagulación Sanguínea , Glucósidos , Ratas Sprague-Dawley , Rheum , Animales , Rheum/química , Antraquinonas/farmacología , Coagulación Sanguínea/efectos de los fármacos , Masculino , Glucósidos/farmacología , Glucósidos/química , Ratas , Inflamación/tratamiento farmacológico , Trombosis/tratamiento farmacológico , Antiinflamatorios/farmacología , Proteínas del Sistema Complemento/metabolismo , Modelos Animales de Enfermedad , Extractos Vegetales/farmacología , Extractos Vegetales/química
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