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The molecular chaperone GroEL, commonly found in various bacterial species, exhibits heightened expression levels in response to high temperatures and increased levels of oxygen free radicals. Limited literature currently exists on the probiotic role of GroEL in invertebrates. This study sought to explore how the surface protein GroEL from Lactobacillus plantarum Ep-M17 impacts the intestinal barrier function of Penaeus vannamei. Through pull-down and immunofluorescence assays, the interaction between GroEL and Act1 in the gastrointestinal tract of P. vannamei was confirmed. Results from bacterial binding assays demonstrated that rGroEL can bind to pathogens like Vibrio parahaemolyticus E1 (V. p-E1). In vitro experiments revealed that the administration of rGroEL significantly decreased the levels of inflammatory cytokines induced by pathogens while preserving the integrity of tight junctions between intestinal epithelial cells and reducing bacteria-induced apoptosis. Additionally, rGroEL notably lessened the intestinal loading of V. p-E1 in P. vannamei, downregulated immune-related gene expression, and upregulated BCL/BAX expression in the intestines following V. p-E1 challenge. Mechanistic investigations further showed that rGroEL treatment effectively suppressed the expression and phosphorylation of proteins involved in the NF-κB and PI3K-AKT-mTOR signalling pathways in the intestines of bacteria-infected P. vannamei. Furthermore, GroEL reinforces protection against bacterial infections by enhancing the phagocytic and anti-apoptotic capabilities of P. vannamei hemocytes. These results suggest that GroEL may impede the interaction between pathogens and the intestinal mucosa through its competitive binding characteristics, ultimately reducing bacterial infections.
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Chronic prostatitis is one of the most common urologic diseases that troubles young men, with unclear etiology and ineffective treatment approach. Pyroptosis is a novel model of cell death, and its roles in chronic prostatitis are unknown. In this study, P2X7R, NEK7, and GSDMD-NT expression levels were detected in prostate tissues from benign prostate hyperplasia (BPH) patients and experiment autoimmune prostatitis (EAP) mice. P2X7R agonist, antagonist, NLRP3 inhibitor, and disulfiram were used to explore the roles of the P2X7R-NEK7-NLRP3 axis in prostate epithelial cell pyroptosis and chronic prostatitis development. We found that P2X7R, NEK7, and GSDMD-NT were highly expressed in the prostate epithelial cells of BPH patients with prostatic inflammation and EAP mice. Activation of P2X7R exacerbated prostatic inflammation and increased NLRP3 inflammasome component expressions and T helper 17 (Th17) cell proportion. Moreover, P2X7R-mediated potassium efflux promoted NEK7-NLRP3 interaction, and NLRP3 assembly and activation, which caused GSDMD-NT-mediated prostate epithelial cell pyroptosis to exacerbate EAP development. Disulfiram could effectively improve EAP by inhibiting GSDMD-NT-mediated prostate epithelial cell pyroptosis. In conclusion, the P2X7R-NEK7-NLRP3 axis could promote GSDMD-NT-mediated prostate epithelial cell pyroptosis and chronic prostatitis development, and disulfiram may be an effective drug to treat chronic prostatitis.
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Células Epiteliales , Quinasas Relacionadas con NIMA , Proteína con Dominio Pirina 3 de la Familia NLR , Proteínas de Unión a Fosfato , Próstata , Prostatitis , Piroptosis , Animales , Humanos , Masculino , Ratones , Enfermedades Autoinmunes/metabolismo , Células Epiteliales/metabolismo , Gasderminas , Ratones Endogámicos C57BL , Quinasas Relacionadas con NIMA/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteínas de Unión a Fosfato/metabolismo , Proteínas de Unión a Poli-ADP-Ribosa/metabolismo , Próstata/metabolismo , Prostatitis/metabolismo , Piroptosis/efectos de los fármacos , Receptores Purinérgicos P2X7/metabolismoRESUMEN
BACKGROUND: The main aim of this study was to examine the perioperative results of reoperations and suggest novel surgical approaches. Based on a substantial number of robotic and laparoscopic nephron-sparing surgery (NSS), we aim to propose novel surgical strategies that offer practical recommendations to surgeons. METHODS: Renal cell carcinoma patients with ipsilateral recurrent tumors, without evidence of metastasis, and who underwent primary NSS at our center between 2013 and 2023 were enrolled in this study, and all received the second time surgery. We conducted an analysis to evaluate perioperative outcomes and observed trends over a decade. Additionally, based on the findings from this study, we developed our surgical strategies. RESULTS: In the past decade, our center has successfully conducted a total of 2546 surgeries for renal cell carcinoma, out of which this study includes 15 patients who met the specified criteria. For reoperation, robotic-assisted surgery was applied in 5 cases (33.3%), laparoscopic surgery in 6 cases (40%), and open surgeries in 4 cases (26.7%). While 4 (26.7%) patients underwent NSS while radical nephrectomy was performed on 11 patients (73.3%). The median operative time was 215 minutes (IQR: 135-300), and the median estimated blood loss was 50 ml (IQR: 50-100). The median length of postoperative hospitalization was 6 days (IQR: 5-9). Furthermore, there has been a yearly increase in the application of robotic-assisted NSS at our institution. CONCLUSION: Reoperation following the pNSS is a secure and effective surgical approach. We introduce novel surgical strategies for primary surgery and reoperation, which offer valuable insights to surgeons in current study.
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Conductive hydrogels are widely used in flexible sensors owing to their adjustable structure, good conductivity, and flexibility. The performance of excellent mechanical properties, high sensitivity, and elastic modulus compatible with human tissues is of great interest in the field of flexible sensors. In this paper, the functional groups of trisodium citrate dihydrate (SC) and MXene form multiple hydrogen bonds in the polymer network to prepare a hydrogel with mechanical properties (Young's modulus (23.5-92 kPa) of similar human tissue (0-100 kPa)), sensitivity (stretched GF is 4.41 and compressed S1 is 5.15 MPa-1), and durability (1000 cycles). The hydrogel is able to sensitively detect deformations caused by strain and stress and can be used in flexible sensors to detect human movement in real time such as fingers, wrists, and walking. In addition, the combination of matrix sensing and machine learning was successfully used for handwriting recognition with an accuracy of 0.9744. The combination of machine learning and flexible sensors shows great potential in areas such as healthcare, information security, and smart homes.
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Escritura Manual , Hidrogeles , Aprendizaje Automático , Hidrogeles/química , Humanos , Módulo de Elasticidad , Dispositivos Electrónicos Vestibles , Piel/químicaRESUMEN
Precisely sensing and guiding cell-state transitions via the conditional genetic activation of appropriate differentiation factors is challenging. Here we show that desired cell-state transitions can be guided via genetically encoded sensors, whereby endogenous cell-state-specific miRNAs regulate the translation of a constitutively transcribed endoribonuclease, which, in turn, controls the translation of a gene of interest. We used this approach to monitor several cell-state transitions, to enrich specific cell types and to automatically guide the multistep differentiation of human induced pluripotent stem cells towards a haematopoietic lineage via endothelial cells as an intermediate state. Such conditional activation of gene expression is durable and resistant to epigenetic silencing and could facilitate the monitoring of cell-state transitions in physiological and pathological conditions and eventually the 'rewiring' of cell-state transitions for applications in organoid-based disease modelling, cellular therapies and regenerative medicine.
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Ground ozone (O3) pollution has emerged as a prominent environmental concern in eastern cities of China, particularly during the summer and autumn seasons. However, a comprehensive investigation into the three-dimensional (3-D) evolution characteristics of O3 within complicated urban environments, especially in lake-land environment, is notably scarce. To enhance our understanding of the mechanisms underlying elevated O3 concentrations within a 3-D scale, this study employed an ozone lidar to delineate vertical ozone profiles in Changzhou, a typical city in China with complicated anthropogenic and biogenic emissions and complex land cover. The process analysis tool integrated into the Weather Research and Forecasting with Chemistry (WRF-Chem) model was further utilized to analyze the formation processes of O3. The results unveil a persistent O3 pollution episode lasting over 15 days in Changzhou during the study period, with multiple peaks exceeding 200 µg m⻳. Notably, O3 predominantly accumulated within the boundary layer, confined below 1.2 km. Both ground and vertical contributions to this pollution were mainly due to local chemical reactions, with a maximum near-surface contribution reaching 19 ppb h-1 and a vertical contribution of 10 ppb h-1 at the height of 900 ± 200 m. Furthermore, episodes of the enhanced O3 concentrations on August 9 and August 26, 2021, were influenced by external advection process. Our study also found that local circulation plays an important role in the accumulation of surface O3 during certain periods. There was a temperature difference between the surface of Lake Tai and the adjacent land, resulting in the formation of lake-land breezes that facilitate the transport of O3 from the lake surface to the terrestrial environment during pollution events. Our study emphasizes the necessity of reducing local pollutant emissions and implementing joint emission controls as the primary strategies for mitigating O3 pollution in Changzhou and the surrounding region.
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Innovative solutions for rapid protection against broad-spectrum infections are very important in dealing with complex infection environments. We utilized a functionally inactive mutated endolysin protein of Streptococcus pneumoniae (ΔA146Ply) to immunize mice against pneumonic infections by multidrug-resistant bacteria, Candida albicans and influenza virus type A. ΔA146Ply protection relied on both immunized tissue-resident and monocyte-derived alveolar macrophages and inhibited infection induced ferroptosis that upregulated expression of GPX4 (glutathione peroxidase) in alveolar macrophages. Ferroptosis resistance endowed macrophages with enhanced phagocytosis by inhibiting lipid peroxidation during infection. Moreover, we demonstrated ΔA146Ply upregulated GPX4 through the TLR4/IRG1/NRF2 pathway. ΔA146Ply also induced ferroptosis inhibition and phagocytosis improvement in human monocytes. This mode of action is a novel and potentially prophylactic and rapid broad-spectrum anti-infection mechanism. Our study provides new insights into protective interventions that act by regulating ferroptosis to improve multiple pathogen resistance via GPX4 targeting.
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Ferroptosis , Macrófagos Alveolares , Factor 2 Relacionado con NF-E2 , Fosfolípido Hidroperóxido Glutatión Peroxidasa , Streptococcus pneumoniae , Receptor Toll-Like 4 , Animales , Fosfolípido Hidroperóxido Glutatión Peroxidasa/metabolismo , Fosfolípido Hidroperóxido Glutatión Peroxidasa/genética , Ratones , Streptococcus pneumoniae/patogenicidad , Ferroptosis/genética , Factor 2 Relacionado con NF-E2/metabolismo , Factor 2 Relacionado con NF-E2/genética , Receptor Toll-Like 4/metabolismo , Receptor Toll-Like 4/genética , Humanos , Macrófagos Alveolares/metabolismo , Macrófagos Alveolares/inmunología , Macrófagos Alveolares/microbiología , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Fagocitosis , Candida albicans/patogenicidad , Candidiasis/inmunología , Candidiasis/genética , Candidiasis/microbiología , Candidiasis/metabolismo , Regulación hacia Arriba , FemeninoRESUMEN
OBJECTIVES: To determine the usefulness of LINC00152 and LARS2-AS1 as potential biomarkers for latent tuberculosis (LTB) and active tuberculosis (ATB), as well as their effect on Mycobacterium (Mtb) infection. METHODS: The expression levels of LINC00152 and LARS2-AS1 in the health, patients with LTB and ATB were detected by qRT-PCR. The ROC curves were constructed to show their potential as biomarkers. The intracellular survival assays for Mtb and the levels of immune-related cytokines were determined to discover the effect of LINC00152 and LARS2-AS1 on Mtb infection. The relationships of miR-485-5p with LINC00152 and LARS2-AS1 were explored. RESULTS: LINC00152 and LARS2-AS1 levels were significantly elevated in patients with ATB and LTB, and Mtb-infected macrophages. LINC00152 and LARS2-AS1 can distinguish the LTB from the health and ATB from LTB. LARS2-AS1 and LINC00152 knock-down reduced the intracellular Mtb survival and induced cellular immune response after Mtb challenge. miR-485-5p was a targeting miRNA for LINC00152 and LARS2-AS1. CONCLUSIONS: LINC00152 and LARS2-AS1 can be considered as potential biomarkers for tuberculosis disease. LINC00152 and LARS2-AS1 have anti-Mtb effects.
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Clear cell renal cell carcinoma (ccRCC) is a common urological malignancy that is involved in tumor genesis and development. However, few studies have focused on the predictive role of the global histone modification status in ccRCC. A total of 621 patients with complete transcript information and corresponding clinical profiles were obtained from TCGA-KIRC, GSE22541, and EMTAB3267 cohorts. A total of 122 histone modification relevant pathways were derived from MSigDB, and their activation status was quantified using GSVA. Differentially expressed genes (DEGs) were identified and filtrated using univariate Cox regression analysis. The signature was built relied on the least absolute shrinkage and selection operator (LASSO) regression analysis, and evaluated from survival difference, chemotherapy response, and activated pathways. A novel nomogram was established to quantify the probability of death in different patients. Seven risky and fifty-eight protective genes were used in LASSO analysis, and six genes were used to build the histone modification gene (HiMG) signature, which showed significant independent prognostic potential in all three cohorts. The nomogram showed acceptable incremental predictions. CKS2 (p = 0.004) and PD1 (p = 0.002) expression were significantly higher in grade 3 ccRCC than in grades 1-2. CKS2 siRNA in renal cancer cells caused reductions in cellular proliferation, migration, and invasion. Patients with low HiMG may be potential responders to rapamycin, erlotinib and FH535, while AZD6482 and CHIR-99,021 may be more suitable for patients with high HiMG levels. ccRCC histone modification distribution and a clinical signature for prognosis prediction, clinical decision making, and molecular mechanism exploration, were established for risk stratification and personalized treatments.
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Currently, the development of hydrogels with excellent mechanical properties (elasticity, fatigue resistance, etc.) and conductive properties can better meet their needs in the field of flexible sensor device applications. Generally, hydrogels with a denser cross-linking density tend to have better mechanical properties, but the improvement in mechanical properties comes at the expense of reduced electrical conductivity. Directly generating CaCO3 in the hydrogel prepolymer can not only increase the cross-linking density of its network but also introduce additional ions to enhance its internal ionic strength, which is beneficial to improving the conductivity of the hydrogel. It is still a big challenge to directly generate CaCO3 in the static prepolymer solution and ensure its uniform dispersion in the hydrogel. Herein, we adopted an improved preparation method to ensure that the directly generated CaCO3 particles can be evenly dispersed in the static prepolymer solution until the polymerization is completed. Finally, a PAM/PVA/CaCO3 hydrogel with supertensile, compressive, toughness, and fatigue resistance properties was prepared. In addition, the presence of free Na+ and Cl- gives the hydrogel excellent conductivity and sensing performance to monitor daily human activities. On the basis of the application of hydrogels in information communication, we have further deepened this application by combining the characteristics of hydrogels themselves. Combined with ASCII code, the hydrogel can also be applied in information exchange and information encryption and decryption, achieving the antitheft function in smart locks. A variety of excellent performance integrated PAM/PVA/CaCO3 hydrogels have broad application prospects for flexible sensors, highlighting great potential in human-computer interaction and intelligent information protection.
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KEY MESSAGE: A large fragment deletion of CpAPRR2, encoding a two-component response regulator-like protein, which influences immature white rind color formation in zucchini (Cucurbita pepo). Fruit rind color is an important agronomic trait that affects commodity quality and consumer choice in zucchini (Cucurbita pepo). However, the molecular mechanism controlling rind color is unclear. We characterized two zucchini inbred lines: '19' (dark green rind) and '113' (white rind). Genetic analysis revealed white immature fruit rind color to be controlled by a dominant locus (CpW). Combining bulked segregant analysis sequencing (BSA-seq) and Kompetitive Allele-Specific PCR (KASP) markers, we mapped the CpW locus to a 100.4 kb region on chromosome 5 and then narrow down the candidate region to 37.5 kb using linkage analysis of 532 BC1 and 1613 F2 individuals, including 6 coding genes. Among them, Cp4.1LG05g02070 (CpAPRR2), encoding a two-component response regulator-like protein, was regarded to be a promising candidate gene. The expression level of CpAPRR2 in dark green rind was significantly higher than that in white rind and was induced by light. A deletion of 2227 bp at the 5' end of CpAPRR2 in '113' might explain the white phenotype. Further analysis of allelic diversity in zucchini germplasm resources revealed rind color to be associated with the deletion of CpAPRR2. Subcellular localization analysis indicated that CpAPRR2 was a nuclear protein. Transcriptome analysis using near-isogenic lines with dark green (DG) and white (W) rind indicated that genes involved in photosynthesis and porphyrin metabolism pathways were enriched in DG compared with W. Additionally, chlorophyll synthesis-related genes were upregulated in DG. These results identify mechanisms of zucchini rind color and provide genetic resources for breeding.
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Mapeo Cromosómico , Cucurbita , Frutas , Fenotipo , Pigmentación , Frutas/genética , Frutas/crecimiento & desarrollo , Pigmentación/genética , Cucurbita/genética , Cucurbita/crecimiento & desarrollo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Ligamiento Genético , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Alelos , Genes de Plantas , Color , TranscriptomaRESUMEN
Touch panels are deemed as a critical platform for the future of human--computer interaction. Recently, flexible touch panels have attracted much attention due to their superior adhesivity and integratability to the human body. However, hydrogel- or organogel-based devices suffer from instability due to liquid evaporation or low-conductivity substrates. It demands an alternative functional touch panel featuring temperature tolerance, high conductivity, and stretchability. Here, we introduce an eutectogel by immobilizing a novel deep eutectic solvent (DES) within 2-hydroxyethyl acrylate (HEA) covalently cross-linked polymer scaffolds. In this DES (ethylene carbonate(EC)-LiTFSI), the CâO group of EC is unique as an electron donor exhibiting strong coordination interactions with Li+, promoting the dissociation of Li+ from LiTFSI to achieve excellent conductivity. Benefiting from their traits, eutectogel presents high conductivity, transmittance, antifreezing, and mechanical strength. In addition, using the surface-capacitive sensing mechanism, the eutectogel can be designed as a 1D strip and 2D rectangular touch panel which can achieve high-resolution touching tracks, even in a low-temperature environment and pressure-then-recovered state. This eutectogel strategy is envisioned to facilitate the development of next-generation intelligent devices, especially in extreme stretching and low-temperature application scenarios.
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Catalyst deactivation by sintering and coking is a long-standing issue in metal-catalyzed harsh high-temperature hydrocarbon reactions. Ultrathin oxide coatings of metal nanocatalysts have recently appeared attractive to address this issue, while the porosity of the overlayer is difficult to control to preserve the accessibility of embedded metal nanoparticles, thus often leading to a large decrease in activity. Here, we report that a nanometer-thick alumina coating of MgAl2O4-supported metal catalysts followed by high-temperature reduction can transform a nonporous amorphous alumina overlayer into a porous Mg1-xAl2Oy crystalline spinel structure with a pore size of 2-3â nm and weakened acidity. The high porosity stems from the restrained Mg migration from the MgAl2O4 support to the alumina overlayer through solid-state reactions at high temperatures. The resulting Ni/MgAl2O4 and Pt/MgAl2O4 catalysts with a porous crystalline Mg1-xAl2Oy overlayer achieved remarkably high stability while preserving much higher activity than the corresponding alumina-coated Ni and Pt catalysts on MgO and Al2O3 supports in the reactions of dry reforming of methane and propane dehydrogenation, respectively.
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Intelligent devices, when subjected to multiple interactions, tend to generate electromagnetic pollution, which can disrupt the normal functioning of electronic components. Ferrite, which acts as a microwave-absorbing material (MAM), offers a promising strategy to overcome this issue. To further enhance the microwave absorption properties of ferrite MAM, numerous works have been conducted, including ion doping and combining with other materials. Notably, the microstructure is also key factor that affects the microwave absorption properties of ferrite-based MAM. Thus, this article provides a comprehensive overview of research progress on the influence of the microstructure on ferrite-based MAM. MAMs with sheet and layered structures are also current important research directions. For core-shell structure composites, the solid core-shell structure, hollow core-shell structure, yolk-eggshell structure, and non-spherical core-shell structure are introduced. For porous composites, the biomass porous structure and other porous structures are presented. Finally, the development trends are summarized, and prospects for the structure design and preparation of high-performance MAMs are predicted.
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Since the COVID-19, cough sounds have been widely used for screening purposes. Intelligent analysis techniques have proven to be effective in detecting respiratory diseases. In 2021, there were up to 10 million TB-infected patients worldwide, with an annual growth rate of 4.5%. Most of the patients were from economically underdeveloped regions and countries. The PPD test, a common screening method in the community, has a sensitivity of as low as 77%. Although IGRA and Xpert MTB/RIF offer high specificity and sensitivity, their cost makes them less accessible. In this study, we proposed a feature fusion model-based cough sound classification method for primary TB screening in communities. Data were collected from hospitals using smart phones, including 230 cough sounds from 70 patients with TB and 226 cough sounds from 74 healthy subjects. We employed Bi-LSTM and Bi-GRU recurrent neural networks to analyze five traditional feature sets including the Mel frequency cepstrum coefficient (MFCC), zero-crossing rate (ZCR), short-time energy, root mean square, and chroma_cens. The incorporation of features extracted from the speech spectrogram by 2D convolution training into the Bi-LSTM model enhanced the classification results. With traditional futures, the best TB patient detection result was achieved with the Bi-LSTM model, with 93.99% accuracy, 93.93% specificity, and 92.39% sensitivity. When combined with a speech spectrogram, the classification results showed 96.33% accuracy, 94.99% specificity, and 98.13% sensitivity. Our findings underscore that traditional features and deep features have good complementarity when fused using Bi LSTM modelling, which outperforms existing PPD detection methods in terms of both efficiency and accuracy.
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Tos , Redes Neurales de la Computación , Tuberculosis Pulmonar , Humanos , Tos/diagnóstico , Tuberculosis Pulmonar/diagnóstico , Masculino , Femenino , Adulto , Persona de Mediana Edad , COVID-19/diagnóstico , Anciano , Sensibilidad y EspecificidadRESUMEN
Na3V2(PO4)3 is considered as one of the most promising cathodes for sodium ion batteries owing to its fast Na+ diffusion, good structural stability and high working potential. However, its practical application is limited by its low intrinsic electronic conductivity. Herein, a carbon coated Cu2+-doped Na3V2(PO4)3 cathode was prepared. The carbon coating not only improve its apparent conductivity, but also inhibit crystal growth and prevent agglomeration of particles. Moreover, Cu2+ doping contributes to an enhanced intrinsic conductivity and decreased Na+ diffusion energy barrier, remarkably boosting its charge transfer kinetics. Based on the structure characterizations, electrochemical performances tests, charge transfer kinetics analyses and theoretical calculations, it's proved that such an elaborate design ensures the excellent rate performances (116.9 mA h g-1 at 0.1C; 92.6 mA h g-1 at 10C) and distinguished cycling lifespan (95.8 % retention after 300 cycles at 1C; 84.8 % retention after 3300 cycles at 10C). Besides, a two-phase reaction mechanism is also confirmed via in-situ XRD. This research is expected to promote the development of Na3V2(PO4)3-based sodium ion batteries with high energy/power density and excellent cycling lifespan.
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Salt stress severely limits the growth and yield of wheat in saline-alkali soil. While nanozymes have shown promise in mitigating abiotic stress by scavenging reactive oxygen species (ROS) in plants, their application in alleviating salt stress for wheat is still limited. This study synthesized a highly active nanozyme catalyst known as ZnPB (Zn-modified Prussian blue) to improve the yield and quality of wheat in saline soil. According to the Michaelis-Menten equation, ZnPB demonstrates exceptional peroxidase-like enzymatic activity, thereby mitigating oxidative damage caused by salt stress. Additionally, studies have shown that the ZnPB nanozyme is capable of regulating intracellular Na+ efflux and K+ retention in wheat, resulting in a decrease in proline and soluble protein levels while maintaining the integrity of macromolecules within the cell. Consequently, field experiments demonstrated that the ZnPB nanozyme increased winter wheat yield by 12.15â¯%, while also significantly enhancing its nutritional quality. This research offers a promising approach to improving the salinity tolerance of wheat, while also providing insights into its practical application.
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Ferrocianuros , Tolerancia a la Sal , Semillas , Triticum , Zinc , Triticum/efectos de los fármacos , Ferrocianuros/química , Zinc/química , Zinc/farmacología , Tolerancia a la Sal/efectos de los fármacos , Semillas/efectos de los fármacos , Peroxidasa/metabolismo , Sodio/metabolismo , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Antibiotic resistance and the surge of infectious diseases during the pandemic present significant threats to human health. Trained immunity emerges as a promising and innovative approach to address these infections. Synthetic or natural fungal, parasitic and viral components have been reported to induce trained immunity. However, it is not clear whether bacterial virulence proteins can induce protective trained immunity. Our research demonstrates Streptococcus pneumoniae virulence protein PepO, is a highly potent trained immunity inducer for combating broad-spectrum infection. Our findings showcase that rPepO training confers robust protection to mice against various pathogenic infections by enhancing macrophage functionality. rPepO effectively re-programs macrophages, re-configures their epigenetic modifications and bolsters their immunological responses, which is independent of T or B lymphocytes. In vivo and in vitro experiments confirm that trained macrophage-secreted complement C3 activates peritoneal B lymphocyte and enhances its bactericidal capacity. In addition, we provide the first evidence that granulocyte colony-stimulating factor (G-CSF) derived from trained macrophages plays a pivotal role in shaping central-trained immunity. In summation, our research demonstrates the capability of rPepO to induce both peripheral and central trained immunity in mice, underscoring its potential application in broad-spectrum anti-infection therapy. Our research provides a new molecule and some new target options for infectious disease prevention.
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Macrófagos , Ratones Endogámicos C57BL , Streptococcus pneumoniae , Animales , Streptococcus pneumoniae/inmunología , Ratones , Macrófagos/inmunología , Infecciones Neumocócicas/inmunología , Infecciones Neumocócicas/prevención & control , Proteínas Bacterianas/inmunología , Linfocitos B/inmunología , Femenino , Inmunidad EntrenadaRESUMEN
The mottled leaf is one of the agronomic traits of zucchini and can be applied as a marker trait in aggregation breeding. However, the genetic mechanism responsible for mottled leaf has yet to be elucidated. In the present study, we used two inbred lines (line '19': silver mottled leaf; line '113': normal leaf) as parents for the physiological and genetic analysis of mottled leaf. The synthesis and net photosynthetic rate of chlorophyll were not significantly affected in the mottled areas of leaves. However, we detected a large space between the palisade parenchyma in the leaf mottle area of line '19', which may have caused the mottled leaf phenotype. Light also plays an important role in the formation of mottled leaf, and receiving light during the early stages of leaf development is a necessary factor. Genetic analysis has previously demonstrated that mottled leaf is a quantitative trait that is controlled by multiple genes. Based on the strategy of quantitative trait locus sequencing (QTL-seq), two QTLs were identified on chromosomes 1 and 17, named CpML1.1 and CpML17.1, respectively. Two major loci were identified using R/qtl software version 1.66 under greenhouse conditions in April 2019 (2019A) and April 2020 (2020A) and under open cultivation conditions in May 2020 (2020M). The major QTL, CpML1.1, was located in a 925.2-kb interval on chromosome 1 and explained 10.51%-24.15% of the phenotypic variation. The CpML17.1 was located in a 719.7-kb interval on chromosome 17 and explained 16.25%-38.68% of the phenotypic variation. Based on gene annotation, gene sequence alignment, and qRT-PCR analysis, the Cp4.1LG01g23790 at the CpML1.1 locus encoding a protein of the TPX2 family (target protein of Xklp2) may be a candidate gene for mottled leaf in zucchini. Our findings may provide a theoretical basis for the formation of mottled leaf and provide a foundation for the fine mapping of genes associated with mottled leaf. Molecular markers closely linked to mottled leaf can be used in molecular-assisted selection for the zucchini mottled leaf breeding.
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Cucurbita , Cucurbita/genética , Fitomejoramiento , Mapeo Cromosómico , Sitios de Carácter Cuantitativo , Hojas de la Planta/genéticaRESUMEN
Background: Carotid arterial atherosclerotic stenosis is a well-recognized pathological basis of ischemic stroke; however, its underlying molecular mechanisms remain unknown. Vascular smooth muscle cells (VSMCs) play fundamental roles in the initiation and progression of atherosclerosis. Organelle dynamics have been reported to affect atherosclerosis development. However, the association between organelle dynamics and various cellular stresses in atherosclerotic progression remain ambiguous. Methods: In this study, we conducted transcriptomics and bioinformatics analyses of stable and vulnerable carotid plaques. Primary VSMCs were isolated from carotid plaques and subjected to histopathological staining to determine their expression profiles. Endoplasmic reticulum (ER), mitochondria, and lysosome dynamics were observed in primary VSMCs and VSMC cell lines using live-cell imaging. Moreover, the mechanisms underlying disordered organelle dynamics were investigated using comprehensive biological approaches. Results: ER whorls, a representative structural change under ER stress, are prominent dynamic reconstructions of VSMCs between vulnerable and stable plaques, followed by fragmented mitochondria and enlarged lysosomes, suggesting mitochondrial stress and lysosomal defects, respectively. Induction of mitochondrial stress alleviated ER stress and autophagy in an eukaryotic translation initiation factor (eIF)-2α-dependent manner. Furthermore, the effects of eIF2α on ER stress, mitochondrial stress, and lysosomal defects were validated using clinical samples. Conclusion: Our results indicate that morphological and functional changes in VSMC organelles, especially in ER whorls, can be used as reliable biomarkers for atherosclerotic progression. Moreover, eIF2α plays an important role in integrating multiple stress-signaling pathways to determine the behavior and fate of VSMCs.