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It is a significant challenge to develop a fast carbon fiber (CF) surface modification method, especially for the high strength electromagnetic wave (EMW) absorption materials. Herein, magnetic CoOx nanoparticles are successfully synthesized and uniformly assembled on CF surface with high oxygen-containing groups by rapid ambient microwave carbon thermal shock (MCTS). The presence of oxygen defect sites on CF surface promotes CoOx nanoparticles nucleation. The number of oxygen defects and the types of magnetic nanoparticles on the CF surface effectively adjust the surface chemical activity and the electromagnetic properties of CF, which is conducive to improving the EMW absorption performance and interface compatibility of the CoOx nanoparticles modified CF reinforced polyamide 6 (CO@CF/PA6) composites. Compared with CO@CF-0 s/PA6, the tensile strength and modulus of CO@CF-3.5 s/PA6 composite are increased by 18.1 % and 18.6 %, respectively. It also displays a minimum reflection loss value (-59.9 dB) at a thinner thickness of 1.9 mm while the maximum effective absorption bandwidth reaches 5.02 GHz with a thickness of 1.8 mm. Its radar cross-section values exhibit less than -10 dBm2 at all tested detection angles. This rapid MCTS shows great potential for large-scale production of CF modification with low-cost, efficient and environmentally friendly process.
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Due to the high-intensity pressure that the shoulder cuff endures, it is prone to traumas and tears. The main critical function of the shoulder cuff muscles is to effectively facilitate shoulder movement and securely maintain the humeral head in the precise center of the joint cavity to prevent superior migration during abduction processes. Shoulder cuff injuries typically involve the muscle-tendon-bone interface, but existing repair techniques do not always guarantee complete and secure healing, leading to retears. Hyperbaric oxygen therapy, as an auxiliary treatment, can significantly promote the muscle-tendon-bone healing process. To explore the impact of hyperbaric oxygen therapy on the bone-tendon interface healing process in a rabbit model specifically designed for shoulder cuff tears, an experiment was conducted on New Zealand white rabbits by performing a full-thickness tear of the supraspinatus tendon in the left shoulder, followed by 2 hours per day of 100% oxygen treatment at 2 absolute atmospheres for 5 days. The results indicate that hyperbaric oxygen therapy significantly enhances vascularization at the interface between the shoulder cuff and tendon-bone, promotes collagen fiber regeneration in the tendon, improves the tensile strength of the tendon-bone complex, and does not have a significant effect on biomechanical stability. This suggests that hyperbaric oxygen therapy has a significant positive impact on the histological and biomechanical healing of shoulder cuff tears in rabbits, expediting the healing process of the tendon-bone interface.
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Modelos Animais de Doenças , Oxigenoterapia Hiperbárica , Lesões do Manguito Rotador , Cicatrização , Animais , Coelhos , Lesões do Manguito Rotador/terapia , Lesões do Manguito Rotador/patologia , Manguito Rotador/patologia , Osso e Ossos/fisiologia , Osso e Ossos/patologia , Tendões/patologia , MasculinoRESUMO
Advances in mRNA technology have enabled mRNA-based therapies to enter a new era of medicine. Such therapies benefit from a single, standardized in vitro transcription (IVT) manufacturing process applicable to a wide range of targets. This process includes several downstream purification steps, which aim to eliminate impurities that potentially affect safety and efficacy. However, it is not fully understood which impurities are the most critical; hence, some efforts are still needed to establish the correlation between RNA impurities and their role in limiting therapeutic efficacy. To study this relationship, we produced in vitro-transcribed mRNAs using several bacteriophage T7 RNA polymerases, including one wild-type and four engineered variants. Important attributes of the mRNA such as integrity, purity, and functional activity were then measured using advanced physicochemical and cellular assays. For impurities including abortive transcripts, mRNAs containing partial poly(A) tails, and double-stranded (ds)RNA byproducts, structure-function relationships have been established by tracking cellular responses (i.e., protein expression, reactogenicity) in multiple cell models. By varying the T7 RNA polymerase, different levels of sense-antisense dsRNA byproducts were measured by mass photometry, contributing directly to immunological reactogenicity in bone marrow-derived dendritic cells. T7 RNA polymerase differences with regard to short (<20 nucleotides) 3'-loopback dsRNA byproducts were also further investigated using native mass spectrometry by precisely resolving these impurities at the nucleotide level. Overall, this study highlights the importance of developing sensitive and advanced analytical methods to characterize IVT mRNA impurities and understand their interaction with cellular machinery in order to ensure quality control of RNA-based therapies.
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To effectively inhibit the growth and metastasis of triple-negative breast cancer (TNBC), we developed a high-efficiency and low-toxicity arene ruthenium (Ru) complex based on apoferritin (AFt). To achieve this, we optimized a series of Ru(II) 1,10-phenanthroline-2,9-diformaldehyde thiosemicarbazone complexes by studying their structure-activity relationships to obtain an arene binuclear Ru(II) complex (C5) with significant cytotoxicity and high accumulation in the mitochondria of tumor cells. Subsequently, a C5-AFt nanoparticle (NPs) delivery system was constructed. We found that the C5/C5-AFt NPs effectively inhibited TNBC growth and metastasis with few side effects. The C5-AFt NPs improved the anticancer and targeting abilities of C5 in vivo. Moreover, we confirmed the mechanism by which C5/C5-AFt NPs inhibit tumor growth and metastasis via mitochondrial damage-mediated ferroptosis and activation of the cGAS-STING pathway.
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Plants such as herbs, vegetables, fruits, and cereals are closely related to human life. Developing effective testing methods to ensure their safety and quantify their active components are of significant importance. Recently, nanomaterials with enzyme-like activity (known as nanozymes) have been widely developed in various assays, including colorimetric, fluorescence, chemiluminescence, and electrochemical analysis. This review presents the latest advances in analyzing phytochemicals and hazardous substances in plant samples based on nanozymes, including some active ingredients, organophosphorus pesticides, heavy metal ions, and mycotoxins. Additionally, the current shortcomings and challenges of the actual sample analysis were discussed.
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Background: Despite the improved survival rates of children with tetralogy of Fallot (TOF), various degrees of neurodevelopmental disorders persist. Currently, there is a lack of quantitative and objective imaging markers to assess the neurodevelopment of individuals with TOF. This study aimed to noninvasively examine potential quantitative imaging markers of TOF neurodevelopment by combining radiomics signatures and morphological features and to further clarify the relationship between imaging markers and clinical neurodevelopment metrics. Methods: This study included 33 preschool children who had undergone surgical correction for TOF and 29 healthy controls (36 in the training cohort and 26 in the testing cohort), all of whom underwent three-dimensional T1-weighted high-resolution (T1-3D) head magnetic resonance imaging (MRI). Radiomics features were extracted by Pyradiomics to construct radiomics models, while surface morphometry (surface and volumetric) features were analyzed to build morphometry models. Merged models integrating radiomics and morphometry features were subsequently developed. The optimal discriminative radiomics signatures were identified via least absolute shrinkage and selection operator (LASSO). Machine learning classification models include support vector machine (SVM) with radial basis function (RBF) and multivariable logistic regression (MLR) models, both of which were used to evaluate the potential imaging biomarkers. Performances of models were evaluated based on their calibration and classification metrics. The area under the receiver operating characteristic curves (AUCs) of the models were evaluated using the Delong test. Neurodevelopmental assessments for children with corrected TOF were conducted with the Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition (WPPSI-IV). Furthermore, the correlation of the significant discriminative indicators with clinical metrics and neurodevelopmental scales was evaluated. Results: Twelve discriminative radiomics signatures, optimized for classification, were identified. The performance of the merged model (AUCs of 0.922 and 0.917 for the training set and test set with SVM, respectively) was superior to that of the single radiomics model (AUCs of 0.915 and 0.917 for the training set and test set with SVM, respectively) and that of the single morphometric models (AUCs of 0.803 and 0.756 for the training set and test set with SVM, respectively). The radiomics model demonstrated higher significance than did the morphometric models in training set with SVM (AUC: 0.915 vs. 0.803; P<0.001). Additionally, the significant indicators showed a correlation with clinical indicators and neurodevelopmental scales. Conclusions: MRI-based radiomics features combined with morphometry features can provide complementary information to identify neurodevelopmental abnormalities in children with corrected TOF, which will provide potential evidence for clinical diagnosis and treatment.
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The purpose of this study was to develop a novel reaction-based fluorescent sensor for the detection of Cu2+ and glutathione in real wine samples. The sensor, tris-(2-pyridyl)-methylamine rhodol derivative, was synthesized and validated for the tandem and selective detection of both Cu2+ and glutathione. The sensor exhibited a strong linear correlation between fluorescence intensity and Cu2+ concentration ranging from 100 to 900 nM, while the in situ generated Cu2+ ensemble selectively detected glutathione with a robust linear response from 3 to 30 µM. The detection limits for Cu2+ and glutathione were as low as 28 nM and 0.60 µM, respectively. Additionally, the sensor enabled quantitative detection of Cu2+ and glutathione in real wine samples. This work provides the first reaction-based fluorescence sensor with an "on-off-on" fluorescence response for the tandem detection of Cu2+ and glutathione in wine, offering potential applications in food and beverage quality control.
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Radiotherapy is recognized as the major treatment of nasopharyngeal carcinoma. Rapid and accurate dose prediction can improve the efficiency of the treatment planning process and the quality of radiotherapy plans. Currently, deep learning-based methods have been widely applied to dose prediction for radiotherapy treatment planning. However, it is important to note that existing models based on Convolutional Neural Networks (CNN) often overlook long-distance information. Although some studies try to use Transformer to solve the problem, it lacks the ability of CNN to process the spatial information inherent in images. Therefore, we propose a novel CNN and Transformer hybrid dose prediction model. To enhance the transmission ability of features between CNN and Transformer, we design a hierarchical dense recurrent encoder with a channel attention mechanism. Additionally, we propose a progressive decoder that preserves richer texture information through layer-wise reconstruction of high-dimensional feature maps. The proposed model also introduces object-driven skip connections, which facilitate the flow of information between the encoder and decoder. Experiments are conducted on in-house datasets, and the results show that the proposed model is superior to baseline methods in most dosimetric criteria. In addition, the image analysis metrics including PSNR, SSIM, and NRMSE demonstrate that the proposed model is consistent with ground truth and produces promising visual effects compared to other advanced methods. The proposed method could be taken as a powerful clinical guidance tool for physicists, significantly enhancing the efficiency of radiotherapy planning. The source code is available at https://github.com/CDUTJ102/THCN-Net .
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The liver is a primary target for distal metastasis of gastric cancer (GC). The hepatic pre-metastatic niche (PMN) facilitates crucial communications between primary tumor and liver, thereby playing an essential role in hepatic metastasis. Identification of the molecular mechanisms driving PMN formation in GC could facilitate development of strategies to prevent and treat liver metastasis. Here, we uncovered a role for ephrin A1 (EFNA1) signaling in development of the PMN. EFNA1 overexpression in GC cells significantly increased CCL2 secretion through the Hippo-YAP pathway. Secreted CCL2 activated hepatic stellate cells (HStCs) within the hepatic PMN via the WNT/ß-catenin pathway. Inhibition of CCL2 significantly suppressed HStC activation and reduced liver metastasis triggered by EFNA1 signaling in GC cells. Moreover, high CCL2 expression correlated with poor survival in GC patients. Overall, these findings reveal that EFNA1 signaling in GC cells upregulates CCL2, which activates HStCs to engender establishment of a hepatic pre-metastatic niche that supports liver metastasis.
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Accurate and efficient wildlife monitoring is essential for conservation efforts. Traditional image-based methods often struggle to detect small, occluded, or camouflaged animals due to the challenges posed by complex natural environments. To overcome these limitations, an innovative multimodal target detection framework is proposed in this study, which integrates textual information from an animal knowledge base as supplementary features to enhance detection performance. First, a concept enhancement module was developed, employing a cross-attention mechanism to fuse features based on the correlation between textual and image features, thereby obtaining enhanced image features. Secondly, a feature normalization module was developed, amplifying cosine similarity and introducing learnable parameters to continuously weight and transform image features, further enhancing their expressive power in the feature space. Rigorous experimental validation on a specialized dataset provided by the research team at Northwest A&F University demonstrates that our multimodal model achieved a 0.3% improvement in precision over single-modal methods. Compared to existing multimodal target detection algorithms, this model achieved at least a 25% improvement in AP and excelled in detecting small targets of certain species, significantly surpassing existing multimodal target detection model benchmarks. This study offers a multimodal target detection model integrating textual and image information for the conservation of rare and endangered wildlife, providing strong evidence and new perspectives for research in this field.
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This research aimed to investigate the effects of dietary fructooligosaccharides (FOS) on attenuating the Aeromonas hydrophila (A. hydrophila)-induced oxidative stress and apoptosis in blunt snout bream Megalobrama amblycephala. Fish were divided into three groups as follows: C1 (Control), T1 (A. hydrophila), and T2 (A. hydrophila + 4 g/kg FOS). The results showed that the activities of antioxidant enzymes increased, the liver morphology had disorderly arrangement, and extensive cell necrosis occurred because of A. hydrophila-infection. While the dietary FOS improved the above-mentioned liver damage. Additionaly, FOS elevated mRNA levels of pro-apoptotic molecules, including caspase-8 and 9, and down-regulated mRNA levels of the anti-apoptotic molecule Bcl-2, which is triggered by A. hydrophila-infection. The transcriptome analysis showed that the oxidative stress-related DEGs pathways were activated in intestine of blunt snout bream by A. hydrophila-infection. The FOS-added group led to the enrichment of more pathways to health. Further WGCNA co-expression network analysis showed that the screened single genes were clustered into 49 modules. The two modules with the highest association to the five traits (10 hub genes) were chosen to build the network by combining the physiological and biochemical characteristic. In summary, this research offers a foundation for the exploring of A. hydrophila-restoration genes in dietary FOS, and also lays a theoretical foundation for aquaculture in the future.
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Aeromonas hydrophila , Apoptose , Cyprinidae , Doenças dos Peixes , Infecções por Bactérias Gram-Negativas , Oligossacarídeos , Estresse Oxidativo , Animais , Estresse Oxidativo/efeitos dos fármacos , Oligossacarídeos/farmacologia , Cyprinidae/microbiologia , Cyprinidae/genética , Apoptose/efeitos dos fármacos , Doenças dos Peixes/microbiologia , Doenças dos Peixes/prevenção & controle , Fígado/metabolismo , Fígado/efeitos dos fármacos , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Perfilação da Expressão GênicaRESUMO
The prevalence of Fabry disease (FD) among males with chronic kidney disease (CKD) of unknown etiology in Taiwan is 0.6%. Despite this, FD is frequently overlooked in clinical settings. To address this issue, two consensus meetings were conducted in Taiwan-one in August 2022 and another in April 2023. The first meeting established screening criteria based on age, gender, family history, cardiac involvement, and symptoms. The second meeting, with a multidisciplinary team, developed treatment recommendations. The consensus emphasizes the importance of proactive data collection in dialysis units and outpatient follow-ups to enhance FD detection and management. The screening algorithm recommends incorporating FD screening into the diagnostic process for CKD patients, regardless of age. Priority is given to patients with a family history of FD, early stroke history, or classical FD symptoms. Comprehensive screening is also advised for CKD patients without obvious classical symptoms. Screening protocols for males include measuring α-galactosidase A enzyme activity, with reduced activity leading to further tests such as lyso-Gb3 level quantification and genetic analysis. For females, the protocol involves evaluating lyso-Gb3 plasma levels and genetic testing. FD, though often underestimated, is more prevalent than recognized and necessitates a multidisciplinary approach for timely diagnosis. Enhancing awareness and adopting a comprehensive approach are essential for improving patient outcomes.
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BACKGROUND: Stomach adenocarcinoma (STAD) is a major contributor to cancer-related mortality worldwide. Alterations in amino acid metabolism, which is integral to protein synthesis, have been observed across various tumor types. However, the prognostic significance of amino acid metabolism-related genes in STAD remains underexplored. METHODS: Transcriptomic gene expression and clinical data for STAD patients were obtained from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Amino acid metabolism-related gene sets were sourced from the Gene Set Enrichment Analysis (GSEA) database. A prognostic model was built using LASSO Cox regression based on the TCGA cohort and validated with GEO datasets (GSE84433, GSE84437, GSE84426). Kaplan-Meier analysis compared overall survival (OS) between high- and low-risk groups, and ROC curves assessed model accuracy. A nomogram predicted 1-, 3-, and 5-year survival. Copy number variations (CNVs) in model genes were visualized using data from the Xena platform, and mutation profiles were analyzed with "maftools" to create a waterfall plot. KEGG and GO enrichment analyses were performed to explore biological mechanisms. Immune infiltration and related functions were evaluated via ssGSEA, and Spearman correlation analyzed associations between risk scores and immune components. The TIDE database predicted immunotherapy efficacy, while FDA-approved drug sensitivity was assessed through CellMiner database. The role of MATN3 in STAD was further examined in vitro and in vivo, including amino acid-targeted metabolomic sequencing to assess its impact on metabolism. Finally, Mendelian randomization (MR) analysis evaluated the causal relationship between the model genes and gastric cancer. RESULTS: In this study, we developed a prognostic risk model for STAD based on three amino acid metabolism-related genes (SERPINE1, NRP1, MATN3) using LASSO regression analysis. CNV amplification was common in SERPINE1 and NRP1, while CNV deletion frequently occurred in MATN3. STAD patients were classified into high- and low-risk groups based on the median risk score, with the high-risk group showing worse prognosis. A nomogram incorporating the risk score and clinical factors was created to estimate 1-, 3-, and 5-year survival rates. Distinct mutation profiles were observed between risk groups, with KEGG pathway analysis showing immune-related pathways enriched in the high-risk group. High-risk scores were significantly associated with the C6 (TGF-ß dominant) subtype, while low-risk scores correlated with the C4 (lymphocyte-depleted) subtype. Higher risk scores also indicated increased immune infiltration, enhanced immune functions, lower tumor purity, and poorer immunotherapy response. Model genes were linked to anticancer drug sensitivity. Manipulating MATN3 expression showed that it promoted STAD cell proliferation and migration in vitro and tumor growth in vivo. Metabolomic sequencing revealed that MATN3 knockdown elevated levels of 30 amino acid metabolites, including alpha-aminobutyric acid, glycine, and aspartic acid, while reducing (S)-ß-Aminoisobutyric acid and argininosuccinic acid. MR analysis found a significant causal effect of NRP1 on gastric cancer, but no causal relationship for MATN3 or SERPINE1. CONCLUSION: In conclusion, the amino acid metabolism-related prognostic model shows promise as a valuable biomarker for predicting the clinical prognosis, selecting immunotherapy and drug treatment for STAD patients. Furthermore, our study has shed light on the potential value of the MATN3 as a promising strategy for combating the progression of STAD.
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Major depressive disorder (MDD) is a common disease affecting 300 million people worldwide. The existing drugs are ineffective for approximately 30% of patients, so it is urgent to develop new antidepressant drugs with novel mechanisms. Here, we found that norisoboldine (NOR) showed an antidepressant efficacy in the chronic social defeat stress (CSDS) depression model in the tail suspension, forced swimming, and sucrose consumption tests. We then utilized the drug-treated CSDS mice paradigm to segregate and gain differential protein groups of CSDS versus CON (CSDSCON), imipramine (IMI)-treated versus CSDS (IMICSDS), and NOR-treated versus CSDS (NORCSDS) from the prefrontal cortex. These protein expression alterations were first analyzed by ANOVA with p < 0.05. The protein cluster 1 and cluster 3, in which the pattern of protein levels similar to the mood pattern, showed enrichment in functions and localizations related to mitochondrion, ribosome and synapses. Further GO analysis of the common proteins for NORCSDS groups and NORIMI groups supported the findings from ANOVA analysis. We employed Protein-Protein interaction (PPI) analysis to examine the proteins of NORCSDS and NORIMI, revealing an enrichment of the proteins associated with the mitochondrial ribosomal and synaptic functions. Further independent analysis using parallel reaction monitoring (PRM) revealed that Cox7c, Mrp142, Naa30, Ighm, Apoa4, Ssu72, Mrps30, Apoh, Acbd5, and Cdv3, exhibited regulation in the NOR-treated group to support the homeostasis of mitochondrial functions. Additionally, Dcx, Arid1b, Rnf112, and Fam3c, were also observed to undergo modulation in the NOR-treated groups to support the synaptic formation and functions. These findings suggest that the proteins involved in depression treatment exert effects in strengthen the mitochondrial and synaptic functions in the mice PFC. Western blot analysis supported the data that the levels of Mrpl42, Cox7c, Naa30, Rnf112, Dcx Apoa4, Apoh and Fam3c were altered in the CSDS mice, and rescued by NOR treatment, supporting the PRM data. NOR treatment also rescued the NLRP3 inflammasome activation in CSDS mice. In summary, the current proteomic research conducted on the prefrontal cortex has provided valuable insights into the specific and shared molecular mechanisms underlying pathophysiology and treatment to CSDS-induced depression, shedding light on the therapeutic effects of Norisoboldine.
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Antidepressivos , Modelos Animais de Doenças , Mitocôndrias , Córtex Pré-Frontal , Proteômica , Estresse Psicológico , Animais , Camundongos , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Masculino , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Córtex Pré-Frontal/metabolismo , Córtex Pré-Frontal/efeitos dos fármacos , Estresse Psicológico/tratamento farmacológico , Estresse Psicológico/metabolismo , Sinapses/efeitos dos fármacos , Sinapses/metabolismo , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/metabolismo , Camundongos Endogâmicos C57BL , Proteína Duplacortina , Depressão/tratamento farmacológico , Depressão/metabolismo , Comportamento Animal/efeitos dos fármacos , Derrota SocialRESUMO
PURPOSE: To determine how low inorganic phosphate stress (LIPS) induced by sevelamer transartieral embolization (S-TAE) affects immune regulation and angiogenesis in hepatocellular carcinoma (HCC). MATERIAL AND METHODS: Transcatheter arterial embolization (TAE) using conventional lipiodol plus Poly (vinyl alcohol) (PVA) microsphere and S-TAE were conducted on a McA-RH7777 orthotopic liver tumor model in rats, followed by the assessment of alterations in immunity- and angiogenesis-related factors. The cells were cultured under hypoxic conditions and stimulated with LIPS to analyze the modulation of programmed cell death 1 ligand 1 (PD-L1), vascular endothelial growth factor (VEGFα), and transforming growth factor-ß1 (TGF-ß1) expression through Western blotting, qRTâPCR, and immunofluorescence assays. Cell migratory capacity and angiogenesis were also evaluated. RESULTS: TAE increased the expression of neoplastic PD-L1 and VEGFα, and S-TAE, which depletes intratumoral Pi, downregulated the expression of PD-L1, VEGFα and TGF-ß1, and augmented the infiltration of CD8+ T-cells, thereby inhibited angiogenesis and activated anticancer immunity. In vitro, the study demonstrated that LIPS inhibits hypoxia-induced upregulation of PD-L1 expression and the HIF-1α/VEGFα axis. Moreover, LIPS inhibited the tube formation ability of Human Umbilical Vein Endothelial Cells (HUVECs) and the migration ability and epithelial-mesenchymal transition (EMT) process of cancer cells under hypoxic conditions. CONCLUSIONS: S-TAE inhibited the expression of PD-L1 and VEGFα, thereby activated anti-tumor immunity and suppressing tumor angiogenesis. All the findings reveal the biology of tumors under low Pi stress and suggest the potential therapeutic value of S-TAE.
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Hemocytes are the primary immune cells of crustaceans. Few comparison studies have been done among different crustaceans and some key parameters of circulating hemocytes have not been investigated. Here, we compared the circulating hemocytes in six decapod crustaceans, Cherax quadrinatus, Procambarus clarkii, Penaeus vannamei, Penaeus monodon, Eriocheir sinensis, and Scylla paramamosain. Although the hemocytes of different species vary in size, they share common morphological characteristics. Based on their morphological features, circulating hemocytes can be basically classified into granular cells (GCs), semi-granular cells (SGCs), and hyaline cells (HCs). In the six decapods analyzed in this study, the proportion of GCs varied from 10 % to 30 %. P. vannamei, P. monodon, and P. clarkii had fewer GCs in circulation than the other three species. Correspondingly, proliferation was detected only in a small portion of cells in P. vannamei, P. monodon, and P. clarkii under physical conditions. The hemocyte renewal rates for P. clarkii, E. sinensis, and C. quadrinatus were 6.1 %, 5.1 %, and 1.5 % per day, while no steady new hemocyte production was found in S. paramamosain within six days. These data give a general picture of the similarities and differences of circulating hemocytes in decapods and provide a base for an in-depth study of their immune system.
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Deoxynivalenol (DON) is a secondary metabolite of Fusarium fungi and belonged to trichothecenes, and it widely presents in various food commodities. Previous studies have highlighted its potent toxicity, adversely affecting the growth, development, and reproductive in both humans and animals. However, the potential impact of DON on porcine oocyte organelles remains elusive. In present study, we delved into the toxic effects of DON on mitochondria, endoplasmic reticulum, Golgi during the porcine oocyte maturation. Our findings revealed that DON exposure significantly impeded granulosa cell diffusion and the expulsion of the first polar body. Additionally, mitochondrial fluorescence intensity and membrane potential underwent notable alterations under DON exposure. Notably, lysosomal fluorescence intensity decreased significantly, suggesting protein degradation and potential autophagy, which was further corroborated by the enhanced fluorescence intensity of LC3. Furthermore, endoplasmic reticulum fluorescence intensity declined, and DON exposure elevated endoplasmic reticulum stress levels, evident from the upregulated expression of GRP78. Concurrently, we observed disruption in the fusiform cortex distribution of the Golgi apparatus, characterized by reduced Golgi apparatus fluorescence intensity and GM130 expression. Collectively, our results indicate that DON exposure profoundly affects the fundamental functions of porcine oocyte organelles during meiosis and maturation.
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Retículo Endoplasmático , Oócitos , Tricotecenos , Animais , Tricotecenos/toxicidade , Oócitos/efeitos dos fármacos , Suínos , Feminino , Retículo Endoplasmático/efeitos dos fármacos , Retículo Endoplasmático/metabolismo , Mitocôndrias/efeitos dos fármacos , Chaperona BiP do Retículo Endoplasmático , Complexo de Golgi/efeitos dos fármacos , Complexo de Golgi/metabolismo , Autofagia/efeitos dos fármacos , Citoplasma/efeitos dos fármacos , Citoplasma/metabolismo , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Meiose/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacosRESUMO
INTRODUCTION: Sepsis-induced cardiac dysfunction is one of the most serious complications of sepsis. The mitochondrial translocator protein (TSPO), a mitochondrial outer membrane protein, is widely used as a diagnostic marker of inflammation-related diseases and can also lead to the release of inflammatory components. However, whether TSPO has a therapeutic effect on sepsis-induced cardiac dysfunction is unclear. OBJECTIVES: The aim of this study is to investigate the involvement of TSPO in the pathogenesis of sepsis-induced cardiac dysfunction and elucidate its underlying mechanism, as well as develop therapeutic strategies targeting TSPO for the prevention and treatment of sepsis-induced cardiac dysfunction. METHODS: The sepsis-induced cardiac dysfunction model was established by intraperitoneal injection of lipopolysaccharide (LPS) in C57BL/6 mice (LPS-induced cardiac dysfunction, LICD). TSPO knockout mice were constructed,and the effects of TSPO was detected by survival rate, echocardiography, HE staining, mitochondrial electron microscopy, TUNEL staining. TSPO-binding proteins were identified by co-immunoprecipitation and mass spectrometry. The mechanisms underlying between TSPO and voltage-dependent anion channel (VDAC) was studied through western blot and immunofluorescence. Proteolysis-Targeting Chimeras (PROTAC) technology was used to construct TSPO-PROTAC molecules that can degrade TSPO. RESULTS: Our present study found that LPS increased cardiac TSPO expression. Knockout of TSPO in C57BL/6 mice with LICD attenuated the cardiac pathology, mitochondrial dysfunction, and apoptosis of cardiomyocytes and significantly improved cardiac function and survival rate. Co-immunoprecipitation and mass spectrometry identified VDAC as a TSPO binding protein.Down-regulation of TSPO reduced PKA-mediated VDAC phosphorylation and VDAC oligomerization, ameliorated mitochondrial function, and reduced cardiomyocyte apoptosis. The study has clinical translational potential, because administration of TSPO-PROTAC to degrade TSPO improved cardiac function in mice with LICD. CONCLUSION: This study elucidated the effect of TSPO in LICD, providing a new therapeutic strategy to down-regulate TSPO by administration of TSPO-PROTAC for the prevention and treatment of LICD.
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It is a significant challenge to obtain hydrogels simultaneously with low tensile energy dissipation, high compressive resilience and long durability. Herein, the uniform dynamic nanospheres (Sil-4H0.75) derived from 4-Hydroxybutyl acrylate glycidyl ether grafted silk fibroin is designed to overcome this issue. Due to its uniform and dynamic characteristic, Sil-4H0.75 could endow hydrogel with homogeneous multiscale structure and produce unique framework effect. Thus, transparent Sil-4H0.75 crosslinked acrylamide hydrogel doped with Ag nanowires APS3.75%/AgNW0.1 exhibits a high stretchability (1260 %) and outstanding elastic resilience. The tensile energy dissipation ratio maintains a low value of 9 % across a wide 800 % strain range. A high compression resilience ratio of 92.2 % is kept after ten compression cycles under 90 % compressive strain. The orderly AgNWs motion guided by framework effect also make it be used as both tensile and compressive sensors and exhibits high gauge factor of 7.35, outstanding compression sensitivity of 30.379 kPa-1 and excellent durability (up to 2000 cycles). The detection or other applications based on both two sensing modes are also demonstrated. In a word, this work affords a general strategy to achieve high-performance hydrogel based on uniform dynamic nanospheres which exhibits great potential in the applications of flexible wearable strain sensors.
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As one of the main occupational hazards, welding fumes can cause oxidative damage and induce series of diseases, such as COPD or asthma. To clarify the effects of the metal fume ultrafine particulates (MF-UFPs) of welding fumes on oxidative damage, UFPs were collected by melt inert gas (MIG) and manual metal arc (MMA) welding, and the composition was confirmed. Human bronchial epithelial 16HBE cells were treated with 0-1000 µg/cm2 MF-UFPs to analyse the cytotoxicity, oxidative stress and cytokines. The protein and mRNA expression of Keap1-Nrf-2/antioxidant response elements (AREs) signalling pathway components were also analysed. After 4 h of treatment, the cell viability decreased 25% after 33.85 and 32.81 µg/cm2 MIG/MMA-UFPs treated. The intracellular ATP concentrations were also decreased significantly, while LDH leakage was increased. The decreased mitochondrial membrane potential and increased ROS suggested the occurrence of oxidative damage, and the results of proteome profiling arrays also showed a significant increase in IL-6 and IL-8. The expression of AREs which related to antioxidant and anti-inflammatory were also increased. These results indicate that the MF-UFPs can cause oxidative stress in 16HBE cells and activate the Nrf-2/ARE signalling pathway to against oxidative damage.