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Environmental endocrine disrupting chemical 4-tert-butylphenol (4-tBP), a widely-utilized surfactant in various industries, poses potential risks to aquatic organisms. Our previous sequencing results suggested that 4-tBP-induced common carp liver injury might be associated with Ca2+ signaling and autophagy. However, the intricate involvement of these pathways in 4-tBP-induced cytotoxic mechanisms remained unexplored. To bridge these knowledge gaps, this study focused on epithelioma papulosum cyprini (EPC) cells, a significant cell type in fish biology. Initial observations showed that 4-tBP induced a dose-dependent perturbation in Ca2+ levels. Further investigations, with siRNA and L-type Ca2+ channel agonist (BAYK8644), identified L-type calcium channel gene CACNA1D as a critical regulator of 4-tBP-induced Ca2+ overload. Predictive analysis using miRanda platform suggested a potential interaction between miR-363 and CACNA1D, which was subsequently verified through dual-luciferase reporter gene assays. We then established miR-363 mimic/inhibitor models, along with miR-363 and CACNA1D co-suppression models in EPC cells. Through TEM observation, immunofluorescence assay, Ca2+ staining, and qRT-PCR analysis, we evaluated the role of miR-363/CACNA1D axis in modulating the effects of 4-tBP on Ca2+ signaling and autophagy. Results showed that miR-363 inhibitor exacerbated 4-tBP-induced increase in CALM2, CAMKII, Calpain2, and p62 expression and also led to decrease in ATG5, ATG7, and LC3b expression. In contrast, miR-363 mimic notably alleviated these changes. Notably, siRNA CACNA1D effectively modulating miR-363 inhibitor's effect. Our study revealed that 4-tBP induced Ca2+ overload and subsequent autophagy impairment via miR-363/CACNA1D axis. These findings illuminated a profound understanding of molecular mechanisms underlying 4-tBP-induced cytotoxicity and spotlighted a potential therapeutic target.
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Autofagia , Calcio , Disruptores Endocrinos , MicroARNs , Animales , Autofagia/efectos de los fármacos , MicroARNs/metabolismo , MicroARNs/genética , Calcio/metabolismo , Disruptores Endocrinos/toxicidad , Carpas/metabolismo , Canales de Calcio Tipo L/metabolismo , Canales de Calcio Tipo L/genética , Fenoles/toxicidad , Contaminantes Químicos del Agua/toxicidad , Proteínas de Peces/metabolismo , Proteínas de Peces/genéticaRESUMEN
Currently, foliar diseases of chili have significantly impacted both yield and quality. Despite effective advancements in deep learning techniques for the classification of chili leaf diseases, most existing classification models still face challenges in terms of accuracy and practical application in disease identification. Therefore, in this study, an optimized and enhanced convolutional neural network model named MCCM (MCSAM-ConvNeXt-MSFFM) is proposed by introducing ConvNeXt. The model incorporates a Multi-Scale Feature Fusion Module (MSFFM) aimed at better capturing disease features of various sizes and positions within the images. Moreover, adjustments are made to the positioning, activation functions, and normalization operations of the MSFFM module to further optimize the overall model. Additionally, a proposed Mixed Channel Spatial Attention Mechanism (MCSAM) strengthens the correlation between non-local channels and spatial features, enhancing the model's extraction of fundamental characteristics of chili leaf diseases. During the training process, pre-trained weights are obtained from the Plant Village dataset using transfer learning to accelerate the model's convergence. Regarding model evaluation, the MCCM model is compared with existing CNN models (Vgg16, ResNet34, GoogLeNet, MobileNetV2, ShuffleNet, EfficientNetV2, ConvNeXt), and Swin-Transformer. The results demonstrate that the MCCM model achieves average improvements of 3.38%, 2.62%, 2.48%, and 2.53% in accuracy, precision, recall, and F1 score, respectively. Particularly noteworthy is that compared to the original ConvNeXt model, the MCCM model exhibits significant enhancements across all performance metrics. Furthermore, classification experiments conducted on rice and maize disease datasets showcase the MCCM model's strong generalization performance. Finally, in terms of application, a chili leaf disease classification website is successfully developed using the Flask framework. This website accurately identifies uploaded chili leaf disease images, demonstrating the practical utility of the model.
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In this study, we designed and synthesized a series of pleuromutilin derivatives containing thiazole. The in vitro antimicrobial efficacy of these synthesized compounds was examined by using four strains. Compared with tiamulin (MIC = 0.25 µg/mL), compound 14 exhibited potency in inhibiting MRSA growth (MIC = 0.0625 µg/mL) in these derivatives. Meanwhile, the time-killing kinetics further demonstrated that compound 14 could efficiently inhibit the MRSA growth. After exposure at 4 × MIC, the postantibiotic effect (PAE) of compound 14 was 1.29 h. Additionally, in thigh-infected mice, compound 14 exhibited a more potent antibacterial efficacy (-1.78 ± 0.28 log10 CFU/g) in reducing MRSA load compared to tiamulin (-1.21 ± 0.23 log10 CFU/g). Moreover, the MTT assay on RAW 264.7 cells demonstrated that compound 14 (8 µg/mL) had no significant cytotoxicity. Docking studies indicated the strong affinity of compound 14 toward the 50S ribosomal subunit, with a binding free energy of -9.63 kcal/mol. Taken together, it could be deduced that compound 14 was a promising candidate for treating MRSA infections.
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Antibacterianos , Diterpenos , Staphylococcus aureus Resistente a Meticilina , Pruebas de Sensibilidad Microbiana , Simulación del Acoplamiento Molecular , Pleuromutilinas , Compuestos Policíclicos , Infecciones Estafilocócicas , Tiazoles , Compuestos Policíclicos/farmacología , Compuestos Policíclicos/química , Diterpenos/farmacología , Diterpenos/química , Diterpenos/síntesis química , Animales , Ratones , Antibacterianos/farmacología , Antibacterianos/síntesis química , Antibacterianos/química , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Tiazoles/farmacología , Tiazoles/química , Tiazoles/síntesis química , Infecciones Estafilocócicas/tratamiento farmacológico , Diseño de Fármacos , Células RAW 264.7RESUMEN
14 novel pleuromutilin derivatives were designed and synthesized as inhibitors against Staphylococcus aureus (S. aureus). The modification was focused on the C22 position of pleuromutilin. We conducted the characterization, in vitro and in vivo biological assessment of the compounds. Compound 18 exhibited the best antibacterial effect against MRSA (MIC = 0.015 µg/mL, MBC = 0.125 µg/mL). Compound 18 was further studied by time-kill kinetic and post-antibiotic effect (PAE) approaches. Besides, most compounds exhibited low cytotoxicity to RAW 264.7 cells. Compound 18 displayed decent bactericidal activity in vivo (-0.51 log10 CFU/mL). Molecular docking study indicated that compound 18 could be located stably at the ribosome (ΔGb = -7.30 kcal/mol). The results revealed that compound 18 might be further developed into a novel antibiotic.
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Antibacterianos , Diterpenos , Pruebas de Sensibilidad Microbiana , Simulación del Acoplamiento Molecular , Pleuromutilinas , Compuestos Policíclicos , Compuestos Policíclicos/farmacología , Compuestos Policíclicos/química , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/síntesis química , Diterpenos/farmacología , Diterpenos/química , Ratones , Animales , Estructura Molecular , Células RAW 264.7 , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Diseño de Fármacos , Staphylococcus aureus/efectos de los fármacos , Infecciones Estafilocócicas/tratamiento farmacológicoRESUMEN
Gastric organoids are models created in the laboratory using stem cells and sophisticated three-dimensional cell culture techniques. These models have shown great promise in providing valuable insights into gastric physiology and advanced disease research. This review comprehensively summarizes and analyzes the research advances in culture methods and techniques for adult stem cells and induced pluripotent stem cell-derived organoids, and patient-derived organoids. The potential value of gastric organoids in studying the pathogenesis of stomach-related diseases and facilitating drug screening is initially discussed. The construction of gastric organoids involves several key steps, including cell extraction and culture, three-dimensional structure formation, and functional expression. Simulating the structure and function of the human stomach by disease modeling with gastric organoids provides a platform to study the mechanism of gastric cancer induction by Helicobacter pylori. In addition, in drug screening and development, gastric organoids can be used as a key tool to evaluate drug efficacy and toxicity in preclinical trials. They can also be used for precision medicine according to the specific conditions of patients with gastric cancer, to assess drug resistance, and to predict the possibility of adverse reactions. However, despite the impressive progress in the field of gastric organoids, there are still many unknowns that need to be addressed, especially in the field of regenerative medicine. Meanwhile, the reproducibility and consistency of organoid cultures are major challenges that must be overcome. These challenges have had a significant impact on the development of gastric organoids. Nonetheless, as technology continues to advance, we can foresee more comprehensive research in the construction of gastric organoids. Such research will provide better solutions for the treatment of stomach-related diseases and personalized medicine.
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In agricultural production activities, the growth of crops always accompanies the competition of weeds for nutrients and sunlight. In order to mitigate the adverse effects of weeds on yield, we apply semantic segmentation techniques to differentiate between seedlings and weeds, leading to precision weeding. The proposed EPAnet employs a loss function coupled with Cross-entropy loss and Dice loss to enhance attention to feature information. A multi-Decoder cooperative module based on ERFnet is designed to enhance information transfer during feature mapping. The SimAM is introduced to enhance position recognition. DO-CONV is used to replace the traditional convolution Feature Pyramid Networks (FPN) connection layer to integrate feature information, improving the model's performance on leaf edge processing, and is named FDPN. Moreover, the Overall Accuracy has been improved by 0.65%, the mean Intersection over Union (mIoU) by 1.91%, and the Frequency-Weighted Intersection over Union (FWIoU) by 1.19%. Compared to other advanced methods, EPAnet demonstrates superior image segmentation results in complex natural environments with uneven lighting, leaf interference, and shadows.
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Malezas , Plantones , Productos Agrícolas/crecimiento & desarrollo , Algoritmos , Procesamiento de Imagen Asistido por Computador/métodos , Semántica , Hojas de la Planta , Redes Neurales de la Computación , Fabaceae/fisiologíaRESUMEN
Bacterial wilt is a widespread and devastating disease that impacts the production of numerous crucial crops worldwide. The main causative agent of the disease is Ralstonia solanacearum. Due to the pathogen's broad host range and prolonged survival in the soil, it is challenging to control the disease with conventional strategies. Therefore, it is of great importance to develop effective alternative disease control strategies. In recent years, phage therapy has emerged as an environmentally friendly and sustainable biocontrol alternative, demonstrating significant potential in controlling this severe disease. This paper summarized basic information about isolated phages that infect R. solanacearum, and presented some examples of their application in the biocontrol of bacterial wilt. The risks of phage application and future prospect in this area were also discussed. Overall, R. solanacearum phages have been isolated from various regions and environments worldwide. These phages belong mainly to the Inoviridae, Autographiviridae, Peduoviridae, and Cystoviridae families, with some being unclassified. Studies on the application of these phages have demonstrated their ability to reduce pathogenicity of R. solanacearum through direct lysis or indirect alteration of the pathogen's physiological properties. These findings suggested bacteriophage is a promising tool for biocontrol of bacterial wilt in plants.
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Lead (Pb), a heavy metal environmental pollutant, poses a threat to the health of humans and birds. Inflammation is one of the most common pathological phenomena in the case of illness and poisoning. However, the underlying mechanisms of inflammation remain unclear. The cerebellum and the thalamus are important parts of the nervous system. To date, there have been no reports of Pb inducing inflammation in animal cerebellums or thalami. Selenium (Se) can relieve Pb poisoning. Therefore, we aimed to explore the mechanism by which Se alleviates Pb toxicity to the cerebellums and thalami of chickens by establishing a chicken Pb or/and Se treatment model. Our results demonstrated that exposure to Pb caused inflammatory damage in cerebellums and thalami, evidenced by the characteristics of inflammation, the decrease in anti-inflammatory factors (interleukin (IL)-2 and interferon-γ (INF-γ)), and the increase in pro-inflammatory factors (IL-4, IL-6, IL-12ß, IL-17, and nitric oxide (NO)). Moreover, we found that the IL-2/IL-17-NO pathway took part in Pb-caused inflammatory injury. The above findings were reversed by the supplementation of dietary Se, meaning that Se relieved inflammatory damage caused by Pb via the IL-2/IL-17-NO pathway. In addition, an up-regulated oxidative index malondialdehyde (MDA) and two down-regulated antioxidant indices (glutathione (GSH) and total antioxidant capacity (TAC)) were recorded after the chickens received Pb stimulation, indicating that excess Pb caused an oxidant/antioxidant imbalance and oxidative stress, and the oxidative stress mediated inflammatory damage via the GSH-IL-2 axis. Interestingly, exposure to Pb inhibited four glutathione peroxidase (GPx) family members (GPx1, GPx2, GPx3, and GPx4), three deiodinase (Dio) family members (Dio1, Dio2, and Dio3), and fifteen other selenoproteins (selenophosphate synthetase 2 (SPS2), selenoprotein (Sel)H, SelI, SelK, SelM, SelO, SelP1, SelPb, SelS, SelT, SelU, and selenoprotein (Sep)n1, Sepw1, Sepx1, and Sep15), suggesting that Pb reduced antioxidant capacity and resulted in oxidative stress involving the SPS2-GPx1-GSH pathway. Se supplementation, as expected, reversed the changes mentioned above, indicating that Se supplementation improved antioxidant capacity and mitigated oxidative stress in chickens. For the first time, we discovered that the SPS2-GPx1-GSH-IL-2/IL-17-NO pathway is involved in the complex inflammatory damage mechanism caused by Pb in chickens. In conclusion, this study demonstrated that Se relieved Pb-induced oxidative stress and inflammatory damage via the SPS2-GPx1-GSH-IL-2/IL-17-NO pathway in the chicken nervous system. This study offers novel insights into environmental pollutant-caused animal poisoning and provides a novel theoretical basis for the detoxification effect of Se against oxidative stress and inflammation caused by toxic pollutants.
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Extensive application of lead (Pb) brought about environmental pollution and toxic reactions of organisms. Selenium (Se) has the effect of antagonizing Pb poisoning in humans and animals. However, it is still unclear how Pb causes brainstem toxicity. In the present study, we wanted to investigate whether Se can alleviate Pb toxicity in chicken brainstems by reducing apoptosis. One hundred and eighty chickens were randomly divided into four groups, namely the control group, the Se group, the Pb group, and the Se/Pb group. Morphological examination, ultrastructural observation, relative mRNA expressions of genes on heat shock proteins (HSPs); selenoproteins; inflammatory cytokines; and apoptosis-related factors were investigated. The results showed that Pb exposure led to tissue damage and apoptosis in chicken brainstems. Furthermore, an atypical expression of HSPs (HSP27, HSP40, HSP60, HSP70, and HSP90); selenoprotein family glutathione peroxidase (GPx) 1, GPx2, GPx3, and GPx4), thioredoxin reductases (Txnrd) (Txnrd1, Txnrd2, and Txnrd3), dio selenoprotein famliy (diodothyronine deiodinases (Dio)1, Dio2, and Dio3), as well as other selenoproteins (selenoprotein (Sel)T, SelK, SelS, SelH, SelM, SelU, SelI, SelO, Selpb, selenoprotein n1 (Sepn1), Sepp1, Sepx1, Sepw1, 15-kDa selenoprotein (Sep15), and selenophosphate synthetases 2 (SPS2)); inflammatory cytokines (Interleukin 2 (IL-2), IL-4, IL-6, IL-12ß, IL-17, and Interferon-γ (IFN-γ)); and apoptosis-related genes (B-cell lymphoma-2 (Bcl-2), tumor protein 53 (p53), Bcl-2 Associated X (Bax), Cytochrome c (Cyt c), and Caspase-3) were identified. An inflammatory reaction and apoptosis were induced in chicken brainstems after exposure to Pb. Se alleviated the abnormal expression of HSPs, selenoproteins, inflammatory cytokines, and apoptosis in brainstem tissues of chickens treated with Pb. The results indicated that HSPs, selenoproteins, inflammatory, and apoptosis were involved in Se-resisted Pb poisoning. Overall, Se had resistance effect against Pb poisoning, and can be act as an antidote for Pb poisoning in animals.
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Selenio , Humanos , Animales , Selenio/farmacología , Pollos/metabolismo , Citocinas/genética , Plomo , Selenoproteínas/genética , Selenoproteínas/metabolismo , Proteínas de Choque Térmico/genética , Proteínas Proto-Oncogénicas c-bcl-2RESUMEN
OBJECTIVE: To investigate the mechanism of Anwei decoction (AWD) intervention on gastric intestinal metaplasia (GIM) using a rat model through the endoplasmic reticulum stress-autophagy pathway. METHODS: Gastric intestinal metaplasia was induced in rats using 1-methyl-3-nitro-1-nitrosoguanidine. The experiment included a normal control group, a model group, and low-, medium- and high-dose AWD groups. The specificity of intestinal epithelial cells was determined for model establishment and drug efficacy by detecting the protein expression of markers such as MUC2, VILLIN and CDX2 through western blotting (WB). The effects of AWD on endoplasmic reticulum stress and autophagy were evaluated by measuring the mRNA and protein expression levels of endoplasmic reticulum stress markers (PEPK, ATF6, CHOP and caspase-12) and autophagy markers (LC3â ¡ and Beclin-1) using reverse transcription polymerase chain reaction and the WB method. Furthermore, the ultrastructure of gastric mucosal cells and autophagosome status were observed using transmission electron microscopy. RESULTS: Compared with the model group, the AWD-treated rats exhibited significant improvement in body weight (P < 0.01), reduced protein expression of the intestine epithelial cell-specific markers MUC2, VILLIN, CDX2 and KLF4 (P < 0.01 for all) and increased SOX2 protein expression (P < 0.01). In addition, AWD suppressed the mRNA and protein expression of endoplasmic reticulum stress markers PEPK and ATF6 (P < 0.01 for all) and promoted the mRNA and protein expression of autophagy and apoptosis markers CHOP, caspase-12, LC3â ¡ and Beclin-1 (P < 0.01 for all). CONCLUSION: Anwei decoction effectively inhibits the further progression of GIM and prevents the occurrence of gastric mucosal carcinogenesis.
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Apoptosis , Transducción de Señal , Ratas , Animales , Beclina-1/genética , Beclina-1/farmacología , Caspasa 12 , ARN Mensajero , Autofagia , Estrés del Retículo Endoplásmico , MetaplasiaRESUMEN
Oxidative stress and inflammation responses are closely related to the occurrence and development of many diseases. Therefore, anti-oxidation and anti-inflammation have become hot spots in the treatment of diseases. A series of novel resveratrol derivatives which hybrid with benzoylhydrazines were designed, synthesized and assessed for their in vitro antioxidant and anti-inflammatory activity. Initially, the antioxidant abilities of resveratrol derivatives were investigated by DPPH, ABTS radical scavenging and FRAP assays. RAW 264.7 macrophages are routinely used to evaluate the antioxidant and anti-inflammatory activities of drugs, so we used it to construct cell models of oxidative stress and inflammation. Among all the derivatives, compound 5 exhibited superior ROS- and NO-inhibitory activities. The molecular mechanism detected by Western blotting showed that compound 5 could significantly activate the Nrf2 signaling pathway and up-regulate the expression of HO-1 to resist oxidative stress stimulated by H2O2. At the same time, it could down-regulate the expression of apoptosis-related proteins Caspase3 and PARP, alleviating cells damage and apoptosis. In addition, compound 5 dose-dependently inhibited the activation of NF-κB p65/iNOS and MAPKs signaling pathway.
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Antioxidantes , Peróxido de Hidrógeno , Ratones , Animales , Humanos , Antioxidantes/uso terapéutico , Resveratrol/farmacología , Resveratrol/uso terapéutico , Peróxido de Hidrógeno/farmacología , FN-kappa B/metabolismo , Células RAW 264.7 , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Inflamación/tratamiento farmacológico , Estrés Oxidativo , Lipopolisacáridos/farmacología , Factor 2 Relacionado con NF-E2/metabolismoRESUMEN
Flavonoids, which contain a benzo-γ-pyrone (C6-C3-C6) skeleton, have been reported to exhibit effective antioxidant ability. This study aimed to compare the antioxidant activities of 7,8-dihydroxyflavone (7,8-DHF) and 7-hydroxyflavone (7-HF) in H2 O2 , lipopolysaccharide (LPS), or tert-butyl hydroperoxide (t-BHP)-induced RAW264.7 cells, respectively. The antioxidant capacities of 7,8-DHF and 7-HF were firstly evaluated by 2,2-azinobis-3-ethyl-benzothiazoline-6-sulphonic acid (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) assays. Then, reactive oxygen species (ROS), super oxide dismutase (SOD), and malondialdehyde (MDA) productions in H2 O2 , LPS, or t-BHP-induced RAW264.7 cells were tested and compared, respectively. Finally, the antioxidant mechanisms of 7-HF and 7,8-DHF were initially investigated by western blot. Our results showed that 7,8-DHF possessed stronger free-radical scavenging capacity than 7-HF. Both 7,8-DHF and 7-HF suppressed MDA production and ROS accumulation, improved the activity of SOD in H2 O2 , LPS, or t-BHP-induced RAW264.7 cells, respectively. And 7,8-DHF exerted a better antioxidant effect than 7-HF, especially in t-BHP-induced oxidative stress. Mechanically, 7,8-DHF prevented the activation of poly ADP-ribosepolymerase and caspase-3, meanwhile markedly upregulated the expression of HO-1 protein in t-BHP-induced oxidative stress. These results suggested that 7,8-DHF might serve as a potential pharmaceutical drug against oxidative stress injury.
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Antioxidantes , Flavonas , Inhibidores de Poli(ADP-Ribosa) Polimerasas , Antioxidantes/farmacología , Antioxidantes/metabolismo , Caspasa 3/metabolismo , Lipopolisacáridos/toxicidad , Estrés Oxidativo , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacología , Especies Reactivas de Oxígeno/metabolismo , Superóxido Dismutasa/metabolismo , Animales , RatonesRESUMEN
A systemic treatment strategy is urgently demanded to suppress the rapid growth and easy metastasis characteristics of breast cancer. In this work, a chimeric peptide-engineered self-delivery nanomedicine (designated as ChiP-CeR) for photodynamic-triggered breast cancer immunotherapy by macrophage polarization. Among these, ChiP-CeR is composed of the photosensitizer of chlorine e6 (Ce6) and the TLR7/8 agonist of lmiquimod (R837), which is further modified with tumor matrix targeting peptide (Fmoc-K(Fmoc)-PEG8 -CREKA. ChiP-CeR is preferred to actively accumulate at the tumor site via specific recognition of fibronectin, which can eradicate primary tumor growth through photodynamic therapy (PDT). Meanwhile, the destruction of primary tumors would trigger immunogenic cell death (ICD) effects to release high-mobility group box-1(HMGB1) and expose calreticulin (CRT). Moreover, ChiP-CeR can also polarize M2-type tumor-associated macrophages (TAMs) into M1-type TAMs, which can activate T cell antitumor immunity in combination with ICD. Overall, ChiP-CeR possesses superior antitumor effects against primary and lung metastatic tumors, which provide an applicable nanomedicine and a feasible strategy for the systemic management of metastatic breast cancer.
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Deep learning technologies have enabled the development of a variety of deep learning models that can be used to detect plant leaf diseases. However, their use in the identification of soybean leaf diseases is currently limited and mostly based on machine learning methods. In this investigation an enhanced deep learning network model was developed to recognize soybean leaf diseases more accurately. The improved network model consists of three parts: feature extraction, attention calculation, and classification. The dataset used was first diversified through data augmentation operations such as random masking to enhance network robustness. An attention module was then used to generate feature maps at various depths. This increased the network's focus on discriminative features, reduced background noise, and enabled the use of the LeakyReLu activation function in the attention module to prevent situations in which neurons fail to learn when the input is negative. Finally, the extracted features were then integrated using a fully connected layer, and the predicted disease category inferred to improve the classification accuracy of soybean leaf diseases. The average recognition accuracy of the improved network model for soybean leaf diseases was 85.42% both higher than the six deep learning comparison models (ConvNeXt (66.41%), ResNet50 (72.22%), Swin Transformer (77.00%), MobileNetV3 (67.27%), ShuffleNetV2 (59.89%), and SqueezeNet (72.92%)), thus proving the effectiveness of the improved method.The model proposed in this paper was also tested on the grapevine leaf dataset, and the performance ability of the improved network model remained due to other common network models, and overall the proposed network model was very effective in leaf disease identification.
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Suministros de Energía Eléctrica , Glycine max , Aprendizaje Automático , Neuronas , Hojas de la PlantaRESUMEN
BACKGROUND: In Taiwan, Chinese herbal medicine (CHM) is used to treat female infertility. Evidence indicates that the absence of monotherapy efficacy assessment and comparison with mainstream interventions may lead to the improper use of CHM for female infertility. METHODS: A retrospective cohort study enrolled female patients at a hospital undergoing CHM intervention to treat infertility from 2012 to 2020 in order to determine the outcomes of CHM monotherapy for female infertility. Kaplan-Meier analysis under strict assumptions was used to estimate the cumulative probability of pregnancy and live births after CHM. Cox hazard regression analysis was used to estimate the hazard ratios of prognostic variables, namely, the woman's age and diagnostic category. RESULTS: 694 women met the inclusion criteria and accounted for 2,145 cycles. A total of 190 pregnancies resulted in 125 live births, all of which were singleton births of babies with 16 perinatal complications requiring hospitalization. The real cumulative pregnancy rate and cumulative live birth rate (CLBR) for the total population after 10 cycles were between 27.4% and 35.2% and between 18% and 22.1%, respectively. Compared with the live birth rate corresponding to patients aged under 35 years, that of older patients, particularly those aged 38-39 years, was significantly lower (hazard ratio: 0.19, 95% confidence interval: 0.11-0.33). Women with other diagnoses, namely, uterine problems or endometriosis, had a greater probability of a live birth than did women with tubal pathology (hazard ratio: 6.31, 95% confidence interval: 1.99-20.07). CONCLUSION: To the best of our knowledge, this is the first retrospective study to employ life table analysis to determine the CHM treatment outcomes in terms of female infertility. The study established a basis to compare in vitro fertilization (IVF) with CHM and identified the advantages and disadvantages of CHM for treating female infertility. Although the CLBR of present study is lower than those reported in IVF studies, CHM in treating female infertility can still be beneficial to women aged younger than 38 years or with diagnoses other than tubal pathology and worth recommendation by reproductive specialists according to the promising results gained from the strict criteria. However, in order to determine the optimal timing, possible mechanism, corresponding side effects, and the efficacy of CHM combined with IVF for treating female infertility, rigorous research is required.
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Medicamentos Herbarios Chinos , Infertilidad Femenina , Humanos , Femenino , Estudios Retrospectivos , Medicamentos Herbarios Chinos/uso terapéutico , Infertilidad Femenina/terapia , Resultado del Tratamiento , HospitalesRESUMEN
Lead (Pb), a hazardous heavy metal, can damage the health of organisms. However, it is not clear whether Pb can damage chicken cerebellums and thalami. Selenium (Se), an essential nutrient for organisms, has a palliative effect on Pb poisoning in chickens. In our experiment, a model of chickens treated with Pb and Se alone and in combination was established to investigate the molecular mechanism of Se alleviating Pb-caused damage in both chicken cerebellums and thalami. Our morphological results indicated that Pb caused apoptotic lesions, such as mitochondrial and nuclear damage. Further, the anti-apoptotic gene Bcl-2 decreased; on the contrary, four pro-apoptotic genes (p53, Bax, Cyt c, and Caspase-3) increased under Pb treatment, meaning that Pb caused apoptosis via the p53-Cyt c-Caspase-3 pathway. Furthermore, we further demonstrated that Pb elevated four HSPs (HSP27, HSP40, HSP70, and HSP90), as well as HSP70 took part in the molecular mechanism of Pb-caused apoptosis. In addition, we found that Pb exposure led to oxidative stress via up-regulating the oxidant H2O2 and down-regulating four antioxidants (CAT, SOD, GST, and GPx). Moreover, Pb decreased three Se-containing factors (Txnrd1, Txnrd2, and Txnrd3), further confirming that Pb caused oxidative stress. Interestingly, Se supplementation reversed the above changes caused by Pb and alleviated Pb-induced oxidative stress and apoptosis. A time dependency was demonstrated for Bcl-2, Bax, and Cyt c in the cerebellums, as well as CAT, GPx, and p53 in the thalami of Pb-exposed chickens. HSP70 in cerebellums and HSP27 in thalami were more sensitive than those in thalami and cerebellums, respectively, under Pb exposure. Pb-induced apoptosis of thalami was more severe than cerebellums. In conclusion, after Pb treatment, Txnrds mediated oxidative stress, oxidative stress up-regulated HSPs, and finally, HSP70 triggered apoptosis. Se supplementation antagonized Pb-induced oxidative stress and apoptosis via the mitochondrial pathway and selenoproteins in chicken cerebellums and thalami. This study provides new information for the mechanism of environmental pollutant poisoning and the detoxification of Se on abiotic stress.
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Background: To investigate the change in hypothalamic kisspeptin-1 (Kiss1) expression during the development of polycystic ovary syndrome (PCOS) and hypoglycemic drug intervention. Methods: Letrozole lavage was used to construct a polycystic ovary rat model. After successful modeling, we treated PCOS rats with metformin, pioglitazone, and acarbose, and we then observed changes in weight, estrus, glucose tolerance, insulin resistance, sex hormones, and hypothalamic kiss1 expression. Results: PCOS rats exhibited increased body weight, abnormal estrous cycle, impaired glucose tolerance, insulin resistance, increased testosterone level, increased luteinizing hormone level, and increased Kiss1 expression in the hypothalamus. However, intervention with metformin, pioglitazone, and acarbose improved the reproductive and metabolic disorders as well as reduced hypothalamic Kiss1 expression. Conclusion: The expression of hypothalamic Kiss1 may play an important role in the pathogenesis of PCOS. Metformin, pioglitazone, and acarbose may reduce the expression of hypothalamic Kiss1 by improving insulin resistance, thereby improving reproductive and metabolic disorders in PCOS rats.
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A series of pleuromutilin analogs containing substituted benzoxazole were designed, synthesised, and assessed for their antibacterial activity both in vivo and in vitro. The MIC of the synthesised derivatives was initially assessed using the broth dilution method against four strains of Staphylococcus aureus (MRSA ATCC 43300, S. aureus ATCC 29213, clinical isolation of S. aureus AD3 and S. aureus 144). Most of the synthesised derivatives displayed prominent in vitro activity (MIC ≤ 0.5 µg/mL). Compounds 50 and 57 exhibited the most effective antibacterial effect against MRSA (MIC = 0.125 µg/mL). Furthermore, the time-kill curves showed that compounds 50 and 57 had a certain inhibitory effect against MRSA in vitro. The in vivo antibacterial activity of compound 50 was evaluated further using a murine thigh model infected with MRSA (-1.24 log10CFU/mL). Compound 50 exhibited superior antibacterial efficacy to tiamulin. It was also found that compound 50 did not display significant inhibitory effect on the proliferation of RAW 264.7 cells. Molecular docking study revealed that compound 50 can effectively bind to the active site of the 50S ribosome (the binding free energy -7.50 kcal/mol).
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Antibacterianos , Staphylococcus aureus , Animales , Ratones , Simulación del Acoplamiento Molecular , Antibacterianos/farmacología , Benzoxazoles/farmacología , PleuromutilinasRESUMEN
Objective: The primary objective of this study was to evaluate the safety of 810 and 1064 nm laser treatment on dental implants. Background: Peri-implantitis is a challenge for clinicians and researchers. Methods: A pig mandible model was used to evaluate temperature increases during laser irradiation. Surface alterations on processed pure titanium discs were analyzed via scanning electron microscopy and measurement of surface contact angles. Processed titanium discs were cocultured in vitro with human gingival fibroblasts; subsequently, cell proliferation was measured. Results: The maximum temperature and time to reach each threshold were comparable. No surface alterations were detected after 810 nm laser irradiation, whereas surface cracks were observed after 1064 nm laser irradiation under the parameter setting of 31.84 W/cm2. Compared with unaltered processed pure titanium discs, the proliferation of human gingival fibroblasts was significantly greater on altered processed pure titanium discs. Conclusions: The use of either 810 or 1064 nm laser treatments may increase the risk of thermal damage in terms of increased temperature if the parameter setting is not warranted. In addition, the use of 1064 nm laser treatment could lead to changes in pure titanium discs that do not negatively affect cell proliferation. Further investigations of laser-assisted therapy are necessary to improve guidelines concerning the treatment of peri-implantitis. Clinical trial registration number: 2021-P2-098-01.
Asunto(s)
Implantes Dentales , Periimplantitis , Humanos , Animales , Porcinos , Temperatura , Titanio , Periimplantitis/radioterapia , Propiedades de Superficie , Rayos Láser , FibroblastosRESUMEN
Ginseng, a valuable Chinese medicinal herb, is renowned worldwide for its effectiveness in alleviating certain conditions and promoting overall health. In this study, we performed weighted gene co-expression network analysis (WGCNA) on the accumulation of essential saponins under the influence of 13 essential environmental factors (including air temperature, air bottom temperature, surface mean temperature, soil temperature, surface shortwave radiation, soil moisture, soil water content, rainfall, total precipitation, elevation, soil type, soil pH, and soil water potential). We identified a total of 40 transcript modules associated with typical environmental factors and the accumulation of essential saponins. Among these, 18 modules were closely related to the influence of typical environmental factors, whereas 22 modules were closely related to the accumulation of essential saponins. These results were verified by examining the transcriptome, saponin contents, environmental factor information and the published data and revealed the regulatory basis of saponin accumulation at the transcriptome level under the influence of essential environmental factors. We proposed a working model of saponin accumulation mediated by the transcriptional regulatory network that is affected by typical environmental factors. An isomorphic white-box neural network was constructed based on this model and the predicted results of the white-box neural network correlated with saponin accumulation. The effectiveness of our correlation-directed graph in predicting saponin contents was verified by bioinformatics analysis based on results obtained in this study and transcripts known to affect the biosynthesis of saponin Rb1. The directed graph represents a useful tool for manipulating saponin biosynthesis while considering the influence of essential environmental factors in ginseng and other medicinal plants.