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In this study, we investigate the effect of neuregulin 4 (NRG4) on podocyte damage in a mouse model of diabetic nephropathy (DN) and we elucidate the underlying molecular mechanisms. In vivo experiments were conducted using a C57BL/6 mouse model of DN to determine the effect of NRG4 on proteinuria and podocyte injury, and in vitro experiments were performed with conditionally immortalized mouse podocytes treated with high glucose and NRG4 to assess the protective effects of NRG4 on podocyte injury. Autophagy-related protein levels and related signaling pathways were evaluated both in vivo and in vitro. The involvement of the adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway was detected using chloroquine or AMPK inhibitors. The results showed that the AMPK/mTOR pathway was involved in the protective roles of NRG4 against high glucose-mediated podocyte injury. Also, NRG4 significantly decreased albuminuria in DN mice. PAS staining indicated that NRG4 mitigated glomerular volume and mesangium expansion in DN mice. Consistently, western blot and RT-PCR analyses confirmed that NRG4 decreased the expression of pro-fibrotic molecules in the glomeruli of DN mice. The immunofluorescence results showed that NRG4 retained expression of podocin and nephrin, whereas transmission electron microscopy revealed that NRG4 alleviated podocyte injury. In DN mice, NRG4 decreased podocyte apoptosis and increased expression of nephrin and podocin, while decreasing the expression of desmin and HIF1α. Overall, NRG4 improved albuminuria, glomerulosclerosis, glomerulomegaly, and hypoxia in DN mice. The in vitro experiments showed that NRG4 inhibited HG-induced podocyte injury and apoptosis. Furthermore, autophagy of the glomeruli decreased in DN mice, but reactivated following NRG4 intervention. NRG4 intervention was found to partially activate autophagy via the AMPK/mTOR signaling pathway. Consequently, when the AMPK/mTOR pathway was suppressed or autophagy was inhibited, the beneficial effects of NRG4 intervention on podocyte injury were diminished. These results indicate that NRG4 intervention attenuates podocyte injury and apoptosis by promoting autophagy in the kidneys of DN mice, in part, by activating the AMPK/mTOR signaling pathway.
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Lignocellulosic nanofibrils (LCNFs) isolation is recognized as an efficient strategy for maximizing biomass utilization. Nevertheless, achieving a 100% yield presents a formidable challenge. Here, an esterification strategy mediated by the equilibrium moisture in biomass is proposed for LCNFs preparation without the use of catalysts, resulting in a yield exceeding 100%. Different from anhydrous chemical thermomechanical pulp (CTMP0%), the presence of moisture (moisture content of 7 wt%, denoted as CTMP7%) introduces a notably distinct process for the pretreatment of CTMP, comprising the initial disintegration and the post-esterification steps. The maleic acid, generated through maleic anhydride (MA) hydrolysis, degrades the recalcitrant lignin-carbohydrate complex (LCC) structures, resulting in esterified CTMP7% (E-CTMP7%). The highly grafted esters compensate for the mass loss resulting from the partial removal of hydrolyzed lignin and hemicellulose, ensuring a high yield. Following microfluidization, favorable LCNF7% with a high yield (114.4 ± 3.0%) and a high charge content (1.74 ± 0.09 mmol g-1) can be easily produced, surpassing most previous records for LCNFs. Additionally, LCNF7% presented highly processability for filaments, films, and 3D honeycomb structures preparation. These findings provide valuable insights and guidance for achieving a high yield in the isolation of LCNFs from biomass through the mediation of equilibrium moisture.
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The SWI/SNF complex is guided to the promoters of designated genes by its co-operator to activate transcription in a timely and appropriate manner to govern development, pathogenesis, and stress responses in fungi. Nevertheless, knowledge of the complexes and their co-operator in phytopathogenic fungi is still fragmented. We demonstrate that the heat shock transcription factor SsHsf1 guides the SWI/SNF complex to promoters of heat shock protein (hsp) genes and antioxidant enzyme genes using biochemistry and pharmacology. This is accomplished through direct interaction with the complex subunit SsSnf5 under heat shock and oxidative stress. This results in the activation of their transcription and mediates histone displacement to maintain reactive oxygen species (ROS) homeostasis. Genetic results demonstrate that the transcription module formed by SsSnf5 and SsHsf1 is responsible for regulating morphogenesis, stress tolerance, and pathogenicity in Sclerotinia sclerotiorum, especially by directly activating the transcription of hsp genes and antioxidant enzyme genes counteracting plant-derived ROS. Furthermore, we show that stress-induced phosphorylation of SsSnf5 is necessary for the formation of the transcription module. This study establishes that the SWI/SNF complex and its co-operator cooperatively regulate the transcription of hsp genes and antioxidant enzyme genes to respond to host and environmental stress in the devastating phytopathogenic fungi.
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Ascomicetos , Proteínas de Ligação a DNA , Fatores de Transcrição , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas de Ligação a DNA/metabolismo , Espécies Reativas de Oxigênio , Antioxidantes , Virulência , Proteínas de Choque Térmico/metabolismo , HomeostaseRESUMO
Single crystals of alkoxy-functionalized hydroxamate/zinc metal-organic frameworks (MOFs) were obtained by fixating the hydroxamate moiety via intramolecular hydrogen bonding. The resulting MOF structures depend on the steric demand of the alkoxy groups, whereby the incorporation of bulky isopropyl groups affords porous hydroxamate/zinc MOFs. The topological structures of the isopropyl-substituted MOFs could be controlled by adding acid.
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KEY MESSAGE: To establish a sterile culture system and protoplast regeneration system for Bryum argenteum, and to establish and apply CRISPR/Cas9 system in Bryum argenteum. Bryum argenteum is a fascinating, cosmopolitan, and versatile moss species that thrives in various disturbed environments. Because of its comprehensive tolerance to the desiccation, high UV and extreme temperatures, it is emerging as a model moss for studying the molecular mechanisms underlying plant responses to abiotic stresses. However, the lack of basic tools such as gene transformation and targeted genome modification has hindered the understanding of the molecular mechanisms underlying the survival of B. argenteum in different environments. Here, we reported the protonema of B. argenteum can survive up to 95.4% water loss. In addition, the genome size of B. argenteum is approximately 313 Mb by kmer analysis, which is smaller than the previously reported 700 Mb. We also developed a simple method for protonema induction and an efficient protoplast isolation and regeneration protocol for B. argenteum. Furthermore, we established a PEG-mediated protoplast transient transfection and stable transformation system for B. argenteum. Two homologues of ABI3(ABA-INSENSITIVE 3) gene were successfully cloned from B. argenteum. To further investigate the function of the ABI3 gene in B. argenteum, we used the CRISPR/Cas9 genetic editing system to target the BaABI3A and BaABI3B gene in B. argenteum protoplasts. This resulted in mutagenesis at the target in about 2-5% of the regenerated plants. The isolated abi3a and abi3b mutants exhibited increased sensitivity to desiccation, suggesting that BaABI3A and BaABI3B play redundant roles in desiccation stress. Overall, our results provide a rapid and simple approach for molecular genetics in B. argenteum. This study contributes to a better understanding of the molecular mechanisms of plant adaptation to extreme environmental.
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Briófitas , Bryopsida , Edição de Genes , Bryopsida/genética , Briófitas/genética , Estresse Fisiológico/genética , Transformação Genética , Sistemas CRISPR-Cas/genética , ProtoplastosRESUMO
To enrich the properties of polylactic acid (PLA)-based composite films and improve the base degradability, in this study, a certain amount of poly(propylene carbonate) (PPC) was added to PLA-based composite films, and PLA/PPC-based composite films were prepared by melt blending and hot-press molding. The effects of the introduction of PPC on the composite films were analyzed through in-depth studies on mechanical properties, water vapor and oxygen transmission rates, thermal analysis, compost degradability, and bacterial inhibition properties of the composite films. When the introduction ratio coefficient of PPC was 30%, the tensile strength of the composite film increased by 19.68%, the water vapor transmission coefficient decreased by 14.43%, and the oxygen transmission coefficient decreased by 18.31% compared to that of the composite film without PPC, the cold crystallization temperature of the composite film increased gradually from 96.9 °C to 104.8 °C, and PPC improved the crystallization ability of composite film. The degradation rate of the composite film with PPC increased significantly compared to the previous one, and the degradation rate increased with the increase in the PPC content. The degradation rate was 49.85% and 46.22% faster on average than that of the composite film without PPC when the degradation was carried out over 40 and 80 days; the composite film had certain inhibition, and the maximum diameter of the inhibition circle was 2.42 cm. This study provides a strategy for the development of PLA-based biodegradable laminates, which can promote the application of PLA-based laminates in food packaging.
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Poliésteres , Propano/análogos & derivados , Resistência à Tração , Poliésteres/química , Polipropilenos/química , Embalagem de Alimentos/métodos , Vapor , Polímeros/química , Antibacterianos/química , Antibacterianos/farmacologia , TemperaturaRESUMO
Porous α-Fe2O3 hollow rods/reduced graphene oxide (α-Fe2O3 HR/RGO) composites with unique morphological characteristics and a high surface area are prepared through a template strategy, which was systematically studied and found to have outstanding supercapacitive properties. When served as active material in a three-electrode setup, the optimized α-Fe2O3 HR/RGO-30, comprised 76.5 wt% α-Fe2O3 and 23.2 wt% RGO, was able to offer the largest specific capacitance of 426.3 F g-1, an excellent rate capability as well as satisfactory cycle life with capacitance retention of 87.7% and Coulombic efficiency of 98.9% after continuously charging/discharging at 10 A g-1 for beyond 10,000 cycles. Such electrochemical behaviors of the α-Fe2O3 HR/RGO-30 electrode can rival or even surpass those of many Fe2O3-based electrodes documented in the previous literature. Later, a symmetric supercapacitor cell of α-Fe2O3 HR/RGO-30//α-Fe2O3 HR/RGO-30 was fabricated. The assembled device offers the maximum energy density of 18.7 Wh kg-1, and also exhibits commendable rate capability, and features stable cycling durability (with capacitance retention of 83.2% together with a Coulombic efficiency of 99.3% after 10,000-cycle charge/discharge at 5 A g-1). These notable electrochemical performances enable the α-Fe2O3 HR/RGO-30 composite to be a high-potential material for advanced energy storage systems.
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BACKGROUND AND OBJECTIVE: Transformer, which is notable for its ability of global context modeling, has been used to remedy the shortcomings of Convolutional neural networks (CNN) and break its dominance in medical image segmentation. However, the self-attention module is both memory and computational inefficient, so many methods have to build their Transformer branch upon largely downsampled feature maps or adopt the tokenized image patches to fit their model into accessible GPUs. This patch-wise operation restricts the network in extracting pixel-level intrinsic structural or dependencies inside each patch, hurting the performance of pixel-level classification tasks. METHODS: To tackle these issues, we propose a memory- and computation-efficient self-attention module to enable reasoning on relatively high-resolution features, promoting the efficiency of learning global information while effective grasping fine spatial details. Furthermore, we design a novel Multi-Branch Transformer (MultiTrans) architecture to provide hierarchical features for handling objects with variable shapes and sizes in medical images. By building four parallel Transformer branches on different levels of CNN, our hybrid network aggregates both multi-scale global contexts and multi-scale local features. RESULTS: MultiTrans achieves the highest segmentation accuracy on three medical image datasets with different modalities: Synapse, ACDC and M&Ms. Compared to the Standard Self-Attention (SSA), the proposed Efficient Self-Attention (ESA) can largely reduce the training memory and computational complexity while even slightly improve the accuracy. Specifically, the training memory cost, FLOPs and Params of our ESA are 18.77%, 20.68% and 74.07% of the SSA. CONCLUSIONS: Experiments on three medical image datasets demonstrate the generality and robustness of the designed network. The ablation study shows the efficiency and effectiveness of our proposed ESA. Code is available at: https://github.com/Yanhua-Zhang/MultiTrans-extension.
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Processamento de Imagem Assistida por Computador , Redes Neurais de Computação , Humanos , Processamento de Imagem Assistida por Computador/métodos , Algoritmos , Diagnóstico por Imagem , Bases de Dados FactuaisRESUMO
Integrating lipid conjugation strategies into the design of nucleoside monophosphate and monophosphonate prodrugs is a well-established approach for discovering potential therapeutics. The unique prodrug design endows nucleoside analogues with strong lipophilicity and structures resembling lysoglycerophospholipids, which improve cellular uptake, oral bioavailability and pharmacological activity. In addition, the metabolic stability, pharmacological activity, pharmacokinetic profiles and biodistribution of lipid prodrugs can be finely optimized by adding biostable caps, incorporating transporter-targeted groups, inserting stimulus-responsive bonds, adjusting chain lengths, and applying proper isosteric replacements. This review summarizes recent advances in the structural features and application fields of lipid-conjugated nucleoside monophosphate and monophosphonate prodrugs. This collection provides deep insights into the increasing repertoire of lipid prodrug development strategies and offers design inspirations for medicinal chemists for the development of novel chemotherapeutic agents.
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Lipídeos , Nucleosídeos , Pró-Fármacos , Pró-Fármacos/química , Pró-Fármacos/farmacologia , Pró-Fármacos/síntese química , Humanos , Lipídeos/química , Nucleosídeos/química , Nucleosídeos/farmacologia , Nucleosídeos/síntese química , Animais , Sistemas de Liberação de Medicamentos , Antineoplásicos/química , Antineoplásicos/farmacologia , Estrutura Molecular , Organofosfonatos/química , Organofosfonatos/farmacologiaRESUMO
Background: Twin growth discordance is one of the leading causes of perinatal mortality in twin pregnancies. Whether prenatal exposure to heavy metals and trace elements is associated with twin growth discordance has not been studied yet. Objective: To evaluate the prenatal level of heavy metals and trace elements in twin pregnancy and its relationship with twin growth discordance. Methods: This study involving 60 twin pairs and their mothers was conducted in Zhejiang Province, China, in 2020-2021. The concentration of heavy metals and trace elements in maternal blood, umbilical cord, and placenta were collected at delivery and measured by inductively coupled plasma tandem mass spectrometer. The association of prenatal level with twin growth discordance was evaluated using conditional logistic regression. Results: High levels of heavy metal elements (thallium in maternal blood and umbilical cord blood of larger twins, vanadium in the placenta of larger twins) and trace elements (iodine in the placenta of larger twins) during pregnancy, as well as low levels of heavy metal elements (strontium in the umbilical cord blood of larger twins, strontium and chromium in the umbilical cord blood of smaller twins, strontium in the placenta of larger twins, molybdenum and lead in the placenta of smaller twins and difference of molybdenum in the placenta of twins), are associated with intertwin birthweight discordance. Univariate regression analyses showed a significant effect of gestational age at delivery and eleven trace element data on intertwin birthweight discordance. Multivariable logistic regression analysis with transformed variables as dichotomous risk factors combined with baseline demographic characteristics showed Tl in maternal blood as an independent risk factor. The model constructed by combining Tl in maternal blood (OR = 54.833, 95% CI, 3.839-83.156) with the gestational week (OR = 0.618, 95% CI, 0.463-0.824) had good predictive power for intertwin birthweight discordance (AUC = 0.871). The sensitivity analysis results indicate that the effect of maternal blood thallium on intertwin birthweight discordance is stable and reliable. Conclusion: To our knowledge, ours is the first case-control study to investigate the association between elevated maternal thallium levels before delivery and twin growth discordance.
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Metais Pesados , Oligoelementos , Feminino , Humanos , Gravidez , Peso ao Nascer , Estudos de Casos e Controles , Molibdênio , Mães , Gestantes , Estrôncio , TálioRESUMO
BACKGROUND: Linderae Radix (LR), the dried root of Lindera aggregata (Sims) Kosterm., is a traditional Chinese herbal medicine that has been used for thousands of years for promoting Qi circulation, soothing the liver, and treating diarrhea and dysentery. Previous studies have found that ethanol extract of LR plays an anti-ulcerative colitis (UC) role by regulating Th17/ Treg balance. Water extract is the classic clinical application form of LR, but the effect of water extract of LR (LRWE) on UC and its underlying mechanism is still unclear. PURPOSE: Purpose: UC is a gastrointestinal disease characterized by intestinal inflammation, mucosal injury, and fibrosis, and it is one of the high-risk factors for colon cancer. However, there is still a lack of remedies with satisfactory effects. This study aimed to investigate the efficacy and the potential mechanism of LRWE against UC. METHODS: LRWE samples were prepared using a reflux extraction method. Colitis in mice was induced by administering 2.5 % DSS water solution to evaluate the therapeutic effect of LRWE by assessing disease activity score, colon length, and fecal morphology. H&E staining, TEM, Masson staining, and AB-PAS staining were applied to observe histopathological changes in the colon tissues. Differentially expressed genes in colon tissues were analyzed by transcriptomics. Cell apoptosis was detected by TUNEL staining. The expression of inflammatory factors such as IL-6 and IL-1ß, as well as the expression of p-STAT1, p-JAK2, p-STAT3, Bax, and Bcl-2, were detected by immunofluorescence and immunohistochemistry. The expression of occludin, Bcl-2, Bax, and JAK/STAT signaling pathway-related vital proteins were quantified by Western blot (WB). RESULTS: LRWE alleviated body weight loss, colon shortening, DAI scores, pathological changes, and ultrastructural features of colon tissue in mice with colitis. It also inhibited the increase of pro-inflammatory cytokines (such as TNF-α, IL-6, and IL-1ß) and increased IL-10 levels. Additionally, it protected the intestinal barrier by upregulating the expression of Occludin and Mucin-2. Mechanistically, LRWE could inhibit the activation of JAK-STAT signaling pathway by reducing the protein expression of p-JAK2, p-STAT3, p-STAT1, Bcl2, and Bax, thus reducing the inflammatory responses and inhibiting cell apoptosis. CONCLUSION: LRWE has a protective effect on DSS-induced UC. This effect is related to the inhibition of the JAK-STAT signaling pathway, the improvement of intestinal inflammation, and the reduction of intestinal epithelial cell apoptosis.
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Colite Ulcerativa , Lindera , Raízes de Plantas , Transdução de Sinais , Animais , Colite Ulcerativa/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Camundongos , Raízes de Plantas/química , Masculino , Lindera/química , Medicamentos de Ervas Chinesas/farmacologia , Extratos Vegetais/farmacologia , Colo/efeitos dos fármacos , Colo/patologia , Colo/metabolismo , Sulfato de Dextrana , Fator de Transcrição STAT3/metabolismo , Apoptose/efeitos dos fármacos , Fator de Transcrição STAT1/metabolismo , Janus Quinase 2/metabolismo , Modelos Animais de Doenças , Fatores de Transcrição STAT/metabolismo , Janus Quinases/metabolismo , Citocinas/metabolismo , Camundongos Endogâmicos C57BLRESUMO
Patients with systemic lupus erythematosus (SLE), a heterogeneous and chronic autoimmune disease, exhibit unique changes in the complex composition and transcriptional signatures of peripheral blood mononuclear cells (PBMCs). While the mechanism of pathogenesis for both childhood-onset SLE (cSLE) and adult-onset SLE (aSLE) remains unclear, cSLE patients are considered more unpredictable and dangerous than aSLE patients. In this study, we analysed single-cell RNA sequencing data (scRNA-seq) to profile the PBMC clusters of cSLE/aSLE patients and matched healthy donors and compared the PBMC composition and transcriptional variations between the two groups. Our analysis revealed that the PBMC composition and transcriptional variations in cSLE patients were similar to those in aSLE patients. Comparative single-cell transcriptome analysis between healthy donors and SLE patients revealed IFITM3, ISG15, IFI16 and LY6E as potential therapeutic targets for both aSLE and cSLE patients. Additionally, we observed that the percentage of pre-B cells (CD34-) was increased in cSLE patients, while the percentage of neutrophil cells was upregulated in aSLE patients. Notably, we found decreased expression of TPM2 in cSLE patients, and similarly, TMEM150B, IQSEC2, CHN2, LRP8 and USP46 were significantly downregulated in neutrophil cells from aSLE patients. Overall, our study highlights the differences in complex PBMC composition and transcriptional profiles between cSLE and aSLE patients, providing potential biomarkers that could aid in diagnosing SLE.
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Leucócitos Mononucleares , Lúpus Eritematoso Sistêmico , Adulto , Humanos , Criança , Idade de Início , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Índice de Gravidade de Doença , Análise de Célula Única , Proteínas de Membrana , Proteínas de Ligação a RNA , Fatores de Troca do Nucleotídeo GuaninaRESUMO
Purpose: To evaluate the impact of surgical compliance on overall survival (OS) and cancer-specific survival (CSS) in ovarian cancer patients and identify factors influencing surgical compliance. Materials and methods: Data from patients with ovarian cancer in the SEER database (2004-2015) were analyzed to compare the characteristics of patients with high and low surgical compliance. Kaplan-Meier curves and Cox regression models were used to assess the impact of surgical compliance on survival outcomes. Nomograms incorporating surgical compliance and independent prognostic factors were constructed to predict OS and CSS and were validated using internal validation sets. Predictive accuracy was evaluated using Harrell's concordance index (C-index), decision curve analysis (DCA), receiver operating characteristic (ROC) curves, and calibration plots. Binary logistic regression analysis identified factors significantly affecting surgical compliance, and propensity score matching (PSM) was used to adjust for confounders. Results: Among the 41,859 patients, 783 (1.87 %) demonstrated poor surgical compliance, while 41,076 (98.13 %) exhibited good compliance. Surgical compliance has emerged as an independent prognostic indicator for ovarian cancer. Patients with high compliance had significantly better OS and CSS rates (P < 0.0001). The prognostic models were internally validated and showed strong discriminative and calibration capabilities. Factors affecting compliance included older age, advanced pathological stage, metastasis, elevated CA-125 levels, and lower income. After PSM, Kaplan-Meier analysis revealed significantly improved survival in patients with good compliance (P < 0.0001). Conclusion: Surgical compliance is a pivotal and independent predictor of overall and cancer-specific survival in patients undergoing OC. Factors contributing to lower surgical compliance include advanced age, later tumor stage, metastatic spread, elevated CA-125 levels, and reduced family income.
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To ensure the long-term performance of proton-exchange membrane fuel cells (PEMFCs), proton-exchange membranes (PEMs) have stringent requirements at high temperatures and humidities, as they may lose proton carriers. This issue poses a serious challenge to maintaining their proton conductivity and mechanical performance throughout their service life. Ionogels are ionic liquids (ILs) hybridized with another component (such as organic, inorganic, or organic-inorganic hybrid skeleton). This design is used to maintain the desirable properties of ILs (negligible vapor pressure, thermal stability, and non-flammability), as well as a high ionic conductivity and wide electrochemical stability window with low outflow. Ionogels have opened new routes for designing solid-electrolyte membranes, especially PEMs. This paper reviews recent research progress of ionogels in proton-exchange membranes, focusing on their electrochemical properties and proton transport mechanisms.
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Background: Cisplatin (DDP) is the principal agent used for chemotherapy in patients with non-small cell lung cancer (NSCLC). Nevertheless, DDP resistance is an essential cause for a worse prognosis of patient. Therefore, this study proposes to discover features of miR-424-5p in DDP resistance of NSCLC. Method: After exogenous modulation of miR-424-5p expression, A549 cell activity was measured using CCK-8 and flow cytometry. A549/DDP and A549/DDP-associated subcutaneous tumor model were constructed to investigate the effect of miR-424-5p on DDP resistance in NSCLC in vivo. TargetScan and JASPAR databases predicted the potential molecular mechanism of miR-424-5p. A549-and A549/DDP-derived exosomes were isolated and characterized using a transmission electron microscope and nanoparticle tracking analysis. Result: Overexpression of miR-424-5p facilitated proliferation and DDP resistance in A549 cells, and knockdown of miR-424-5p did the opposite. Knockdown of miR-424-5p enhanced DDP restriction on tumor weight and volume. Moreover, SOCS5 and SOCS56 (SOCS5/6) were downstream targets of miR-424-5p. miR-424-5p down-regulated SOCS5/6 expression to activate JAK2/STAT3 and PI3K/AKT pathways. Notably, tumor protein p53 (TP53) is a transcription factor for the miR-424-5p host gene, as confirmed by the dual-luciferase reporter gene. Cellular and animal experiments indicated that TP53 limited the regulatory function of miR-424-5p on NSCLC growth, DDP resistance, and related molecules. Interestingly, miR-424-5p was markedly enriched in A549/DDP cell-derived exosomes than in A549 cell-derived exosomes, and TP53 down-regulated miR-424-5p expression in A549/DDP cell-derived exosomes. Conclusion: DDP-resistant cell-derived exosome miR-424-5p contributes to NSCLC growth and DDP resistance by targeting SOCS5 and SOCS6 to activate JAK2/STAT3 and PI3K/AKT pathways, which are blocked by TP53.
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APSES (Asm1p, Phd1p, Sok2p, Efg1p, and StuAp) family transcription factors play crucial roles in various biological processes of fungi, however, their functional characterization in phytopathogenic fungi is limited. In this study, we explored the role of SsStuA, a typical APSES transcription factor, in the regulation of cell wall integrity (CWI), sclerotia formation and pathogenicity of Sclerotinia sclerotiorum, which is a globally important plant pathogenic fungus. A deficiency of SsStuA led to abnormal phosphorylation level of SsSmk3, the key gene SsAGM1 for UDP-GlcNAc synthesis was unable to respond to cell wall stress, and decreased tolerance to tebuconazole. In addition, ΔSsStuA was unable to form sclerotia but produced more compound appressoria. Nevertheless, the virulence of ΔSsStuA was significantly reduced due to the deficiency of the invasive hyphal growth and increased susceptibility to hydrogen peroxide. We also revealed that SsStuA could bind to the promoter of catalase family genes which regulate the expression of catalase genes. Furthermore, the level of reactive oxygen species (ROS) accumulation was found to be increased in ΔSsStuA. In summary, SsStuA, as a core transcription factor involved in the CWI pathway and ROS response, is required for vegetative growth, sclerotia formation, fungicide tolerance and the full virulence of S. sclerotiorum.
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Cellulose nanofibrils (CNF) isolation based on a catalyst-free maleic anhydride esterification has proven to be effective, however, the effects of pulp hornification on CNF isolation by this strategy have yet to be explored, which could present significant impacts for CNF isolation. Herein, dried northern bleached softwood Kraft pulp (D-NBSK) and never-dried northern bleached softwood Kraft pulp (ND-NBSK) were selected as the substrates. After esterification with maleic anhydride (MA), the esterified ND-NBSK pulp (E-ND) shows a significantly smaller size and more fragmented structure than the esterified D-NBSK pulp (E-D). Meanwhile, higher degree of esterification can be realized for the never dried pulp as compared to the dried pulp, which is corroborated by the significantly stronger characteristic peaks of CO (1720 cm-1) and -COO- (1575 cm-1) from the FTIR spectra and the higher surface charge content (0.86 ± 0.04 mmol/g vs. 0.55 ± 0.05 mmol/g). A comparison of the characteristics of the resulting CNF similarly demonstrated the negative impact of hornification. Overall, this work indicates that hornification tends to reduce the accessibility of chemical reagents to the pulp, leading to insufficient deconstruction. Such negative impact of hornification should be considered when performing nanocellulose isolation, especially when using pulp as feedstock.
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Herein, carvacrol (CRV) and modified cellulose nanocrystal-zinc oxide (CNC-ZnO) were incorporated into a poly (lactic acid) (PLA) matrix to prepare a PLA-based composite film using a simple solution casting method to achieve antimicrobial effects for application in antimicrobial food packaging. Compared with films obtained from neat PLA, the PLA@CRV20%@CNC-ZnO3% composite film shows better performance in terms of mechanical properties, ultraviolet (UV) blocking, and antimicrobial effects. The PLA composites containing CRV and 3 wt% CNC-ZnO blends exhibit improved tensile strength (21.8 MPa) and elongation at break (403.1 %) as well as excellent UV resistance. In particular, CRV and the CNC-ZnO hybrid endow the obtained PLA composite films with a synergistic antibacterial effect, resulting in good antibacterial properties for microbes, such as Escherichia coli, Staphylococcus aureus and Aspergillus niger. The diameters of the inhibition zone of the PLA@CRV20%@CNC-ZnO3% composite films against E. coli, S. aureus, and A. niger were 4.9, 5.0, and 3.4 cm, respectively. Appling the PLA@CRV20%@CNC-ZnO3% composite film as an antibacterial food packaging material, the storage period for strawberries was considerably extended. This study provides a theoretical basis for developing new organic/inorganic composite antimicrobial film materials from PLA.
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Antibacterianos , Celulose , Cimenos , Embalagem de Alimentos , Nanopartículas , Poliésteres , Óxido de Zinco , Óxido de Zinco/química , Óxido de Zinco/farmacologia , Poliésteres/química , Cimenos/química , Cimenos/farmacologia , Celulose/química , Antibacterianos/farmacologia , Antibacterianos/química , Nanopartículas/química , Embalagem de Alimentos/métodos , Staphylococcus aureus/efeitos dos fármacos , Nanocompostos/química , Escherichia coli/efeitos dos fármacos , Resistência à Tração , Testes de Sensibilidade Microbiana , Aspergillus niger/efeitos dos fármacosRESUMO
Pelvic masses frequently originate from the pelvic cavity and are often associated with uterine, ovarian, or intestinal disorders. This report describes the case of a patient with a pelvic mass diagnosed as a retroperitoneal dermoid cyst at our hospital. We analyzed this case and conducted a literature review, to mitigate the risk of misdiagnosis and enhance the treatment of retroperitoneal masses.
Assuntos
Adenomioma , Cisto Dermoide , Neoplasias Retroperitoneais , Neoplasias Uterinas , Humanos , Feminino , Cisto Dermoide/cirurgia , Cisto Dermoide/complicações , Cisto Dermoide/diagnóstico , Cisto Dermoide/patologia , Neoplasias Retroperitoneais/patologia , Neoplasias Retroperitoneais/complicações , Neoplasias Retroperitoneais/diagnóstico por imagem , Neoplasias Retroperitoneais/diagnóstico , Neoplasias Retroperitoneais/cirurgia , Neoplasias Uterinas/patologia , Neoplasias Uterinas/complicações , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/cirurgia , Neoplasias Uterinas/diagnóstico por imagem , Adenomioma/patologia , Adenomioma/cirurgia , Adenomioma/complicações , Adenomioma/diagnóstico , Adenomioma/diagnóstico por imagem , Tomografia Computadorizada por Raios X , AdultoRESUMO
BACKGROUND: Kidney renal clear cell carcinoma (KIRC) represents a significant proportion of renal cell carcinomas and is characterized by high aggressiveness and poor prognosis despite advancements in immunotherapy. Disulfidptosis, a novel cell death pathway, has emerged as a critical mechanism in various cellular processes, including cancer. This study leverages machine learning to identify disulfidptosis-related long noncoding RNAs (DRlncRNAs) as potential prognostic biomarkers in KIRC, offering new insights into tumor pathogenesis and treatment avenues. RESULTS: Our analysis of data from The Cancer Genome Atlas (TCGA) led to the identification of 431 DRlncRNAs correlated with disulfidptosis-related genes. Five key DRlncRNAs (SPINT1-AS1, AL161782.1, OVCH1-AS1, AC131009.3, and AC108673.3) were used to develop a prognostic model that effectively distinguished between low- and high-risk patients with significant differences in overall survival and progression-free survival. The low-risk group had a favorable prognosis associated with a protective immune microenvironment and a better response to targeted drugs. Conversely, the high-risk group displayed aggressive tumor features and poor immunotherapy outcomes. Validation through qRTâPCR confirmed the differential expression of these DRlncRNAs in KIRC cells compared to normal kidney cells, underscoring their potential functional significance in tumor biology. CONCLUSIONS: This study established a robust link between disulfidptosis-related lncRNAs and patient prognosis in KIRC, underscoring their potential as prognostic biomarkers and therapeutic targets. The differential expression of these lncRNAs in tumor versus normal tissue further highlights their relevance in KIRC pathogenesis. The predictive model not only enhances our understanding of KIRC biology but also provides a novel stratification tool for precision medicine approaches, improving treatment personalization and outcomes in KIRC patients.