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Chronic obstructive pulmonary disease (COPD) stands as the prevailing chronic airway ailment, characterized by chronic bronchitis and emphysema. Current medications fall short in treatment of these diseases, underscoring the urgent need for effective therapy. Prior research indicated immunoproteasome inhibition alleviated various inflammatory diseases by modulating immune cell functions. However, its therapeutic potential in COPD remains largely unexplored. Here, an elevated expression of immunoproteasome subunits LMP2 and LMP7 in the macrophages isolated from mouse with LPS/Elastase-induced emphysema and polarized macrophages in vitro is observed. Subsequently, intranasal administration of the immunoproteasome-specific inhibitor ONX-0914 significantly mitigated COPD-associated airway inflammation and improved lung function in mice by suppressing macrophage polarization. Additionally, ONX-0914 capsulated in PLGA nanoparticles exhibited more pronounced therapeutic effect on COPD than naked ONX-0914 by targeting immunoproteasome in polarized macrophages. Mechanistically, ONX-0914 activated autophagy and endoplasmic reticulum (ER) stress are not attribute to the ONX-0914 mediated suppression of macrophage polarization. Intriguingly, ONX-0914 inhibited M1 polarization through the nuclear factor erythroid 2-related factor-1 (NRF1) and NRF2-P62 axis, while the suppression of M2 polarization is regulated by inhibiting the transcription of interferon regulatory factor 4 (IRF4). In summary, the findings suggest that targeting immunoproteasome in macrophages holds promise as a therapeutic strategy for COPD.

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BACKGROUND: N6-Methyladenosine (m6A) methylation, a common form of RNA modification, play an important role in the pathogenesis of various diseases and in the ontogeny of organisms. Nevertheless, the precise function of m6A methylation in photoaging remains unknown. OBJECTIVES: This study aims to investigate the biological role and underlying mechanism of m6A methylation in photoaging. METHODS: m6A dot blot, Real-time quantitative PCR (RT-qPCR), western blot and immunohistochemical (IHC) assays were employed to detect the m6A level and specific m6A methylase in ultraviolet ray (UVR)-induced photoaging tissue. The profile of m6A-tagged mRNA was identified by methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA-seq analysis. Finally, we investigated the regulatory mechanism of KIAA1429 by MeRIP-qPCR, RNA knockdown and immunofluorescence assay. RESULTS: m6A levels were increased in photoaging and were closely associated with the upregulation of KIAA1429 expression. 1331 differentially m6A methylated genes were identified in the UVR group compared with the control group, of which 1192 (90%) were hypermethylated. Gene ontology analysis showed that genes with m6A hypermethylation and mRNA downregulation were mainly involved in extracellular matrix metabolism and collagen metabolism-related processes. Furthermore, KIAA1429 knockdown abolished the downregulation of TGF-bRII and upregulation of MMP1 in UVR-irradiated human dermal fibroblasts (HDFs). Mechanically, we identified MFAP4 as a target of KIAA1429-mediated m6A modification and KIAA1429 might suppress collagen synthesis through an m6A-MFAP4-mediated process. CONCLUSIONS: The increased expression of KIAA1429 hinders collagen synthesis during UVR-induced photoaging, suggesting that KIAA1429 represents a potential candidate for targeted therapy to mitigate UVR-driven photoaging.

Assuntos

Colágeno , Envelhecimento da Pele , Envelhecimento da Pele/efeitos da radiação , Envelhecimento da Pele/genética , Colágeno/metabolismo , Animais , Adenosina/análogos & derivados , Adenosina/metabolismo , Camundongos , Humanos , Raios Ultravioleta , Metilação , Fibroblastos/metabolismo , Fibroblastos/efeitos da radiação

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Background: Glycoprotein non-metastatic melanoma B (GPNMB)/osteoactivin was first identified in the human melanoma cell lines. GPNMB plays a key role in the anti-inflammatory and antioxidative functions as well as osteoblast differentiation, cancer progression, and tissue regeneration. Recently, GPNMB was used as an anti-aging vaccine for mice. The present study aimed to investigate the potential of biofluid GPNMB as an aging biomarker in humans using serum and urine samples from an aging Chinese population. Methods: We analyzed RNA-sequencing data (GSE132040) from 17 murine organs across different ages to assess the gene expression of potential ageing biomarkers. Spearman's correlation coefficients were used to evaluate the relationship between gene expression and age. Meanwhile, a cross-sectional population study was conducted, which included 473 participants (aged 25-91 years), a representative subset of participants from the Peng Zu Study on Healthy Ageing in China (Peng Zu Cohort). Biofluid GPNMB levels were measured by ELISA. The associations of serum and urine GPNMB levels with various clinical and anthropometrical indices were assessed using ANOVA, Kruskal-Wallis H test, and univariate and multivariate linear regression analyses. Results: In mice, the Gpnmb mRNA expression levels showed a significant positive association with age in multiple organs in mice (P < 0.05). In Peng Zu Cohort, biofluid (both serum and urine) GPNMB levels showed a positive correlation with age (P < 0.05). Univariate linear regression analysis revealed that serum GPNMB levels were negatively associated with skeletal muscle mass index (SMI, P < 0.05) and insulin-like growth factor 1 (IGF-1, P < 0.05), and urine GPNMB levels showed a negative association with total bile acids (TBA, P < 0.05). Multivariate linear regression analysis further indicated that serum GPNMB levels negatively correlated with the systemic immune-inflammation index (SII, P < 0.05), and the urine GPNMB levels maintained a negative association with TBA (P < 0.05), additionally, urine GPNMB levels in men were significantly lower than in women (P < 0.05). Conclusions: The biofluid GPNMB was a strong clinical biomarker candidate for estimating biological aging.

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The transport, compartmentation and allocation of sugar are critical for plant growth and development, as well as for stress resistance, but sugar transporter genes have not been comprehensively characterized in soybean. Here, we performed a genome-wide identification and expression analyses of sugar transporter genes in soybean in order to reveal their putative functions. A total of 122 genes encoding sucrose transporters (SUTs) and monosaccharide transporters (MSTs) were identified in soybean. They were classified into 8 subfamilies according to their phylogenetic relationships and their conserved motifs. Comparative genomics analysis indicated that whole genome duplication/segmental duplication and tandem duplication contributed to the expansion of sugar transporter genes in soybean. Expression analysis by retrieving transcriptome datasets suggested that most of these sugar transporter genes were expressed in various tissues, and a number of genes exhibited tissue-specific expression patterns. Several genes including GmSTP21, GmSFP8, and GmPLT5/6/7/8/9 were predominantly expressed in nodules, and GmPLT8 was significantly induced by rhizobia inoculation in root hairs. Transcript profiling and qRT-PCR analyses suggested that half of these sugar transporter genes were significantly induced or repressed under stresses like salt, drought, and cold. In addition, GmSTP22 was found to be localized in the plasma membrane, and its overexpression promoted plant growth and salt tolerance in transgenic Arabidopsis under the supplement with glucose or sucrose. This study provides insights into the evolutionary expansion, expression pattern and functional divergence of sugar transporter gene family, and will enable further understanding of their biological functions in the regulation of growth, yield formation and stress resistance of soybean.

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OBJECTIVE: To analyze the influencing factors of postoperative thrombocytopenia in critically ill patients with heart disease and construct a nomogram prediction model. METHODS: From October 2022 to October 2023, 319 critically ill patients with heart disease who visited our hospital were collected and separated into postoperative thrombocytopenia group (n = 142) and no postoperative thrombocytopenia group (n = 177) based on their postoperative thrombocytopenia, Logistic regression analysis was applied to screen risk factors for postoperative thrombocytopenia in critically ill patients with heart disease; R software was applied to construct a nomogram for predicting postoperative thrombocytopenia in critically ill patients with heart disease, and ROC curves, calibration curves, and Hosmer-Lemeshow goodness of fit tests were applied to evaluate nomogram. RESULTS: A total of 142 out of 319 critically ill patients had postoperative thrombocytopenia, accounting for 44.51%. Logistic regression analysis showed that gender (95% CI 1.607-4.402, P = 0.000), age ≥ 60 years (95% CI 1.380-3.697, P = 0.001), preoperative antiplatelet therapy (95% CI 1.254-3.420, P = 0.004), and extracorporeal circulation time > 120 min (95% CI 1.681-4.652, P = 0.000) were independent risk factors for postoperative thrombocytopenia in critically ill patients with heart disease. The area under the ROC curve was 0.719 (95% CI: 0.663-0.774). The slope of the calibration curve was close to 1, and the Hosmer-Lemeshow goodness of fit test was χ2 = 6.422, P = 0.491. CONCLUSION: Postoperative thrombocytopenia in critically ill patients with heart disease is influenced by gender, age ≥ 60 years, preoperative antiplatelet therapy, and extracorporeal circulation time > 120 min. A nomogram established based on above multiple independent risk factors provides a method for clinical prediction of the risk of postoperative thrombocytopenia in critically ill patients with heart disease.

Assuntos

Estado Terminal , Cardiopatias , Nomogramas , Complicações Pós-Operatórias , Trombocitopenia , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Fatores de Risco , Cardiopatias/cirurgia , Medição de Risco/métodos , Idoso , Estudos Retrospectivos , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Curva ROC

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiologic agent of coronavirus disease 2019 (COVID-19). Severe and fatal COVID-19 cases often display cytokine storm i.e. significant elevation of pro-inflammatory cytokines and acute respiratory distress syndrome (ARDS) with systemic hypoxia. Understanding the mechanisms of these pathogenic manifestations would be essential for the prevention and especially treatment of COVID-19 patients. Here, using a dual luciferase reporter assay for hypoxia-response element (HRE), we initially identified SARS-CoV-2 nonstructural protein 5 (NSP5), NSP16, and open reading frame 3a (ORF3a) to upregulate hypoxia-inducible factor-1α (HIF-1α) signaling. Further experiments showed NSP16 to have the most prominent effect on HIF-1α, thus contributing to the induction of COVID-19 associated pro-inflammatory response. We demonstrate that NSP16 interrupts von Hippel-Lindau (VHL) protein interaction with HIF-1α, thereby inhibiting ubiquitin-dependent degradation of HIF-1α and allowing it to bind HRE region in the IL-6 promoter region. Taken together, the findings imply that SARS-CoV-2 NSP16 induces HIF-1α expression, which in turn exacerbates the production of IL-6.

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BACKGROUND: This study aimed to precisely predict the size and silicone oil injection of a foldable capsular vitreous body (FCVB) via computerized three-dimensional (3D) ocular reconstruction in the treatment of severe retinal detachment in China. METHODS: The 3D software Unigraphics NX was applied to determine the volume of the inner cavity with 16-30 mm axial length, assigning the anterior and posterior chambers, the FCVB sizes, and the silicone oil injection volume, and modeling the data between the axial length and the FCVB size. In clinical practice, IOL Master was applied to accurately measure the axial length of the contralateral healthy eye to anchor the anterior-posterior and horizontal diameters of the operated eye in horizontal position CT, and compared with the model to recommend the FCVB size and silicone oil amount, and the clinical effect was validated in cases across five hospitals in China. RESULTS: For the axial length of 16-30 mm, the volume of the inner cavity is 1.2 ml-8.4 ml. FCVB size and silicone oil volume were recommended based on this volume of the inner cavity. Of 253 cases, we noted 11 cases implanted with AV-10P and 1.05 ± 0.21 ml of silicone oil, 41 with AV-12P and 1.58 ± 0.18 ml of silicone oil, 163 with AV-13.5P and 2.48 ± 0.29 ml of silicone oil, 31 with AV-15P and 3.57 ± 0.39 ml of silicone oil, and 7 with AV-17P and 5.71 ± 0.81 ml of silicone oil. There was no significant difference in postoperative visual acuity scores compared with preoperative (P = 0.097), postoperative IOP(10.29 ± 0.57mmHg)was slightly higher than preoperative IOP (9.76 ± 0.48 mmHg), but there was still no statistically significant difference between the two comparisons (P = 0.405). CONCLUSION: Three-dimensional reconstruction prediction is a good solution for eyeballs with obvious individualized changes in severe retinal detachment, and this method helps doctors standardize FCVB size selection and the silicone oil amount for patients.

Assuntos

Imageamento Tridimensional , Descolamento Retiniano , Óleos de Silicone , Corpo Vítreo , Humanos , Descolamento Retiniano/cirurgia , Óleos de Silicone/administração & dosagem , Pessoa de Meia-Idade , Masculino , Feminino , Adulto , Corpo Vítreo/patologia , Corpo Vítreo/diagnóstico por imagem , Vitrectomia/métodos , Idoso , Adulto Jovem , Tamponamento Interno/métodos , Adolescente , Acuidade Visual/fisiologia

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This research investigates the impact of various concentrations of tea branch liquid smoke (TLS) on the protein structure of dry cured pork tenderloin using multispectral techniques, molecular docking, and 4D-DIA proteomics. The results reveal that TLS enhances the solubility of myofibrillar protein, with varying effects on tryptophan exposure based on the concentration. Notably, at 5 mL/kg, TLS inhibits myofibrillar protein unfolding. Raman spectroscopy demonstrates that higher TLS concentrations mitigate disruptions in hydrogen bonding and hydrophobicity. Guaiacol and furfural in TLS engage in π-stacking interactions with myosin, heightening myosin interaction with its carrier. 4D-DIA proteomics has revealed that TLS can down-regulate the expression of cytoplasmic and mitochondrial proteins, metabolic enzymes, and ligases, playing pivotal roles in metabolism and genetic information processing. These proteins, featuring membrane linkers and phosphatases, potentially impact peptide and amino acid biosynthesis, thereby affecting meat quality modifications.

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The increasing mortality rate of pancreatic cancer globally necessitates the urgent identification for novel therapeutic targets. This study investigated the expression, functions, and mechanistic insight of G protein inhibitory subunit 3 (Gαi3) in pancreatic cancer. Bioinformatics analyses reveal that Gαi3 is overexpressed in human pancreatic cancer, correlating with poor prognosis, higher tumor grade, and advanced classification. Elevated Gαi3 levels are also confirmed in human pancreatic cancer tissues and primary/immortalized cancer cells. Gαi3 shRNA or knockout (KO) significantly reduced cell viability, proliferation, cell cycle progression, and mobility in primary/immortalized pancreatic cancer cells. Conversely, Gαi3 overexpression enhanced pancreatic cancer cell growth. RNA-sequencing and bioinformatics analyses of Gαi3-depleted cells indicated Gαi3's role in modulating the Akt-mTOR and PKA-Hippo-YAP pathways. Akt-S6 phosphorylation was decreased in Gαi3-depleted cells, but was increased with Gαi3 overexpression. Additionally, Gαi3 depletion elevated PKA activity and activated the Hippo pathway kinase LATS1/2, leading to YAP/TAZ inactivation, while Gαi3 overexpression exerted the opposite effects. There is an increased binding between Gαi3 promoter and the transcription factor TCF7L2 in pancreatic cancer tissues and cells. Gαi3 expression was significantly decreased following TCF7L2 silencing, but increased with TCF7L2 overexpression. In vivo, intratumoral injection of Gαi3 shRNA-expressing adeno-associated virus significantly inhibited subcutaneous pancreatic cancer xenografts growth in nude mice. A significant growth reduction was also observed in xenografts from Gαi3 knockout pancreatic cancer cells. Akt-mTOR inactivation and increased PKA activity coupled with YAP/TAZ inactivation were also detected in xenograft tumors upon Gαi3 depletion. Furthermore, bioinformatic analysis and multiplex immunohistochemistry (mIHC) staining on pancreatic cancer tissue microarrays showed a reduced proportion of M1-type macrophages and an increase in PD-L1 positive cells in Gαi3-high pancreatic cancer tissues. Collectively, these findings highlight Gαi3's critical role in promoting pancreatic cancer cell growth, potentially through the modulation of the Akt-mTOR and PKA-Hippo-YAP pathways and its influence on the immune landscape.

Assuntos

Proliferação de Células , Neoplasias Pancreáticas , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/metabolismo , Humanos , Animais , Linhagem Celular Tumoral , Camundongos , Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/metabolismo , Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/genética , Camundongos Nus , Transdução de Sinais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Masculino , Regulação Neoplásica da Expressão Gênica , Feminino

RESUMO

Recently, diffusion models have shown considerable promise for MRI reconstruction. However, extensive experimentation has revealed that these models are prone to generating artifacts due to the inherent randomness involved in generating images from pure noise. To achieve more controlled image reconstruction, we reexamine the concept of interpolatable physical priors in k-space data, focusing specifically on the interpolation of high-frequency (HF) k-space data from low-frequency (LF) k-space data. Broadly, this insight drives a shift in the generation paradigm from random noise to a more deterministic approach grounded in the existing LF k-space data. Building on this, we first establish a relationship between the interpolation of HF k-space data from LF k-space data and the reverse heat diffusion process, providing a fundamental framework for designing diffusion models that generate missing HF data. To further improve reconstruction accuracy, we integrate a traditional physics-informed k-space interpolation model into our diffusion framework as a data fidelity term. Experimental validation using publicly available datasets demonstrates that our approach significantly surpasses traditional k-space interpolation methods, deep learning-based k-space interpolation techniques, and conventional diffusion models, particularly in HF regions. Finally, we assess the generalization performance of our model across various out-of-distribution datasets. Our code are available at https://github.com/ZhuoxuCui/Heat-Diffusion.

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Understanding the CO2 emission characteristics and key mitigation pathways of intercity passenger transport is crucial for achieving sustainable development in the transport system. Using origin-destination data on travel between city pairs by various transportation modes, we employ the life cycle assessment (LCA) method to estimate route-level CO2 emissions from intercity multimodal passenger transport corridors, considering infrastructure construction and vehicle operation phases. Subsequently, a sensitivity analysis is conducted to assess the impact of 39 parameters associated with the construction phase, operation phase, and transportation modes on CO2 emissions from corridors. Trend analysis is employed to explore the future emission mitigation potential for the parameters that have the most significant impact on corridor emissions. Four intercity multimodal passenger corridors in China are selected as case studies. Results indicate that the CO2 emissions per passenger-kilometer from these corridors exhibit an approximate negative linear relationship with corridor lengths. The proportion of construction-related CO2 emission intensity of various intercity passenger transport modes varies significantly, ranging from 2.5 to 32.9%. In the medium term, effective emission-mitigation strategies should focus on decreasing private car gasoline consumption in three corridors under 200 km in length, as well as decreasing private car gasoline consumption and promoting clean electricity in the Xi'an-Yan'an corridor. In the long term, efforts should be placed on increasing electric private car share and promoting clean electricity. This study lays a crucial foundation for the refined management of CO2 emissions from future intercity passenger transport.

Assuntos

Poluentes Atmosféricos , Dióxido de Carbono , Monitoramento Ambiental , Meios de Transporte , Emissões de Veículos , Dióxido de Carbono/análise , Poluentes Atmosféricos/análise , Monitoramento Ambiental/métodos , Emissões de Veículos/análise , China , Poluição do Ar/estatística & dados numéricos , Cidades

RESUMO

Metal organic frameworks (MOFs) are a class of potential superhydrophobic-oleophilic materials. The organic ligands in superhydrophobic MOFs usually contain long alkyl chains, fluorine groups or aromatic rings with large π conjugation, the preparation of which suffers from high cost, complex operation and so on. In addition, the topological structure of MOFs plays an important role in the hydrophobicity, which may be ignored previously. Here we report a superhydrophobic-oleophilic MOF (BiPPA2) obtained by a facile and fast method, which not only displays a large water contact angle of up to 163° and a small sliding angle of nearly equal to 0°, but also exhibits high sorption capacity for multiple oils and organic solvents, well reusability and high oil retention. In addition, BiPPA2 is stable in a wide pH range (0.5-11.0). Finally, the single crystal structure of BiPPA2 is resolved to reveal the intrinsic reason for the super-hydrophobicity. This work may inspire the further design of pristine superhydrophobic MOFs based on a simple method, which enriches the family of superhydrophobic MOFs and has great significance for practical applications.

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Solving the challenges faced during the measurement of the cross-interface transfer of perfluoroalkyl acids (PFAAs) in lakes is crucial for clarifying environmental behaviours of these chemicals and their efficient governance. This study developed a multimedia fugacity model based on the quantitative water-air-sediment interaction (QWASI) covering abiotic/biotic matrices to investigate the cross-interface transfer and fate of PFAAs in Luoma Lake, a typical PFAA-contaminated shallow lake in eastern China. The accuracy and reliability of the established model were confirmed using Percent bias and Monte Carlo simulation, respectively. Using the QWASI model, the multimedia transfer of the PFAAs and their accumulation and persistence in different sub-compartments were described and measured, and the differences among individual PFAAs were explored. The simulation results showed that the sedimentation and resuspension of PFAAs were the most intense cross-interfacial transfers, and the sediments served as a chemical sink in the long term. A significant negative correlation of NC-F (the number of CF bonds) with the relative outflow flux (TW·out-ct) but a positive correlation with the relative net transfer across the interface between water and aquatic plants (Tp-ct) was detected, indicating that the PFAA migration capacity decreased but the bioaccumulation potential increased with the CF bond number. The persistence in water (Pw) of individual PFAAs ranged from 19.65d (PFOA) to 32.22d (PFOS), with an average of 26.15d; their persistence in sediment (Ps) ranged from 432d (PFBA) to 3216d (PFOS), with an average of 1524d, increasing linearly with an increase in NC-F. The water advection flows into and out of the lake (QW·in and QW·out), the PFAA concentration of water inflow (CW·in), and bioconcentration factor of aquatic plants (BCFp) were the primary parameters sensitive to PFAAs in all sub-compartments, which are essential indexes for exploring promising remediation pathways for lacustrine PFAA contamination based on the fugacity model simulation.

Assuntos

Monitoramento Ambiental , Fluorocarbonos , Lagos , Poluentes Químicos da Água , Lagos/química , China , Poluentes Químicos da Água/análise , Fluorocarbonos/análise , Modelos Químicos , Sedimentos Geológicos/química , Modelos Teóricos

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Aim: This study investigated differences in gut flora between osteoporosis (OP) patients and healthy individuals using 16S rDNA sequencing. The correlation between differential flora abundance and bone mineral density (BMD) was analyzed, and key flora and potential mechanisms associated with OP were explored. Methods: Forty-three OP patients and twenty-four healthy volunteers were recruited. Gender, age, height, weight, and BMD data were collected. DNA from fecal samples was extracted for 16S rDNA sequencing. The Kruskal-Wallis test assessed differences in gut flora composition, while LEfSe analysis identified significant flora. Spearman correlation analysis examined the relationship between differential flora and BMD, and PICRUSt predicted pathways involved in OP. Results: Significant differences in microbial composition were found between the two groups. Klebsiella, Escherichia-Shigella, and Akkermansia were biomarkers in OP patients, with Faecalibacterium in the healthy group. Akkermansia abundance negatively correlated with lumbar BMD, while Klebsiella and Escherichia-Shigella negatively correlated with femoral neck and hip BMD. Faecalibacterium showed a positive correlation with BMD. Functional predictions indicated differences in metabolism-related pathways between the groups. Conclusion: Gut flora differed significantly between OP patients and healthy individuals. Akkermansia, Klebsiella, and Escherichia-Shigella could serve as diagnostic biomarkers for OP, highlighting the potential of gut flora in OP diagnosis and treatment.

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The fall armyworm (Spodoptera frugiperda) poses a substantial threat to many important crops worldwide, emphasizing the need to develop and implement advanced technologies for effective pest control. CRISPR/Cas9, derived from the bacterial adaptive immune system, is a prominent tool used for genome editing in living organisms. Due to its high specificity and adaptability, the CRISPR/Cas9 system has been used in various functional gene studies through gene knockout and applied in research to engineer phenotypes that may cause economical losses. The practical application of CRISPR/Cas9 in diverse insect orders has also provided opportunities for developing strategies for genetic pest control, such as gene drive and the precision-guided sterile insect technique (pgSIT). In this review, a comprehensive overview of the recent progress in the application of the CRISPR/Cas9 system for functional gene studies in S. frugiperda is presented. We outline the fundamental principles of applying CRISPR/Cas9 in S. frugiperda through embryonic microinjection and highlight the application of CRISPR/Cas9 in the study of genes associated with diverse biological aspects, including body color, insecticide resistance, olfactory behavior, sex determination, development, and RNAi. The ability of CRISPR/Cas9 technology to induce sterility, disrupt developmental stages, and influence mating behaviors illustrates its comprehensive roles in pest management strategies. Furthermore, this review addresses the limitations of the CRISPR/Cas9 system in studying gene function in S. frugiperda and explores its future potential as a promising tool for controlling this insect pest.

Assuntos

Sistemas CRISPR-Cas , Edição de Genes , Spodoptera , Sistemas CRISPR-Cas/genética , Edição de Genes/métodos , Animais , Spodoptera/genética

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Amauroderma rugosum (Blume and T. Nees) Torrend (Ganodermataceae) (A. rugosum) has been found to have anti-inflammatory ability in previous studies. The present study aimed to verify the therapeutic benefits of A. rugosum in the treatment of ulcerative colitis and to investigate its underlying mechanism of action. Acute experimental ulcerative colitis was induced by feeding the mice drinking water supplemented with dextran sodium sulfate (DSS). The findings indicated that the ethanolic extract of domesticated A. rugosum exhibited therapeutic efficacy comparable to Salazosulfapyridine (SASP) in mitigating clinical symptoms and the pathological score of the colon. Furthermore, A. rugosum exhibited the capacity to enhance the expression of tight junction (TJ) proteins, while concurrently decreasing the levels of TNF-ɑ and IL-6. A noteworthy finding is that it exhibited the capability to diminish the nuclear translocation of NF-κB p65. In conclusion, A. rugosum attenuates DSS-induced ulcerative colitis by enhancing intestinal barrier function and inhibiting mucosal inflammation. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-024-01565-5.

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Hematopoietic stem cells (HSCs) are vital for the differentiation of all mature blood cells, with their homeostasis being tightly regulated by intrinsic and extrinsic factors. Alternative splicing, mediated by the spliceosome complex, plays a crucial role in regulating HSC homeostasis by increasing protein diversity. This study focuses on the ATP-dependent RNA helicase DHX16, a key spliceosome component, and its role in HSC regulation. Using conditional knockout mice, we demonstrate that loss of Dhx16 in the hematopoietic system results in significant depletion of hematopoietic stem and progenitor cells, bone marrow failure, and rapid mortality. Dhx16-deficient HSCs exhibit impaired quiescence, G2-M phase cell cycle arrest, reduced protein synthesis, abnormal ribosome assembly, increased apoptosis, and decreased self-renewal capacity. Multi-omics analysis identified intron 4 retention in Emg1 mRNA in Dhx16 knockout HSCs, leading to reduced EMG1 protein expression, disrupted ribosome assembly, and nucleolar stress, activating the p53 pathway. Overexpression of Emg1 in Dhx16-deficient HSCs partially restored ribosome assembly and HSC function, suggesting Emg1 as a potential therapeutic target for ribosomopathies. Our findings reveal the critical role of Dhx16 in HSC homeostasis through the regulation of alternative splicing and ribosome assembly, providing insights into the molecular mechanisms underlying hematopoietic diseases and potential therapeutic strategies.

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BACKGROUND: Allergic rhinitis (AR) is a multifactorial disease triggered by interactions between genes and the environment. Clinical evidence has shown that trans-resveratrol, a widely used drug, significantly ameliorates AR pathology. However, the precise mechanisms underlying this effect remain unclear. PURPOSE: This study aimed to elucidate the pharmacological mechanisms of action of trans-resveratrol in patients with AR who exhibit hypoxic symptoms. This will be achieved through microRNA sequencing and signaling pathway screening combined with basic experiments to determine the effects of Trans-resveratrol intervention in this patient population. METHODS: Network pharmacology was used to determine the therapeutic value of trans-resveratrol in AR. The micro-RNA miR-204-3p was pinpointed by sequencing. Quantitative reverse transcription polymerase chain reaction was used to quantify the expression levels. Haematoxylin and eosin, alcian blue-periodic acid-Schiff, and Masson's trichrome staining were used to assess the effects of hypoxia on nasal mucosa immunohistochemistry and immunofluorescence-localised target proteins. Egl nine homolog 3 (EGLN3) was screened using bioinformatics software. Protein expression was detected by western blotting. Cell growth and death were gauged via Cell Counting Kit-8 and terminal deoxynucleotidyl transferase dUTP nick end labelling staining, respectively. Cell migration was observed using a transwell assay. Enzyme-linked immunosorbent assay was used to measure interleukin (IL)33 levels in the cell supernatants. Flow cytometry was used to verify cell cycle and antigen levels. Electron microscopy was used to visualise the status of the nasal mucosa prior to in vivo expression analysis. RESULTS: Patients with hypoxic AR demonstrated more pronounced nasal mucosal remodelling than that in patients with common AR. Sequencing results indicated that these patients had a reduced expression of miR-204-3p. Through a combination utilizing of bioinformatics analysis and experimental validation, EGLN3 has been identified as a direct target of HIF-1α. The low expression level of miR-204-3p represses EGLN3, resulting in the accumulation of HIF-1α and the activation of the IL33/ST2 signaling pathway. These stimulate the proliferation, survival, and migration of HNEpCs, ultimately contributing to mucosa remodeling and AR progression. Trans-resveratrol notably downregulated the levels of HIF-1α and IL33/ST2, while simultaneously increasing the expression of EGLN3. CONCLUSIONS: Downregulation of miR-204-3p initiated a vicious cycle of hypoxic AR via EGLN3/HIF-1α/IL33/ST2. Trans-resveratrol reversed the pathological process of nasal mucosa remodeling of hypoxic AR by exhibiting anti-inflammatory and anti-angiogenic functions via the above signaling pathway. Our study uncovers the underlying mechanism by which hypoxia drives the progression of AR. It presents innovative strategies for addressing inflammatory and hypoxia-related diseases, bridging traditional and modern medicine, and highlighting the potential of natural compounds in clinical practice.

Assuntos

Subunidade alfa do Fator 1 Induzível por Hipóxia , Interleucina-33 , MicroRNAs , Resveratrol , Rinite Alérgica , Transdução de Sinais , MicroRNAs/metabolismo , MicroRNAs/genética , Rinite Alérgica/tratamento farmacológico , Humanos , Resveratrol/farmacologia , Transdução de Sinais/efeitos dos fármacos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Interleucina-33/metabolismo , Proteína 1 Semelhante a Receptor de Interleucina-1/metabolismo , Prolina Dioxigenases do Fator Induzível por Hipóxia/metabolismo , Feminino , Masculino , Mucosa Nasal/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Adulto , Progressão da Doença

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Piezoelectric-assisted photocatalysis has a huge potential in solving the energy shortage and environmental pollution problems, and imaging their detailed charge-transfer process can provide in-depth understanding for the development of high-active piezo-photocatalysts; however, it is still challenging. Herein, topotactic heterostructures of TiO2@BaTiO3 (TO@BTO-S) were constructed by the epitaxial growth of ferroelectric BaTiO3 mesocrystals on TiO2-{001} facets, resulting in a ferroelectric photocatalyst with a polarization orientation on the surface. Notably, the photoinduced charge transfer in ferroelectric TiO2@BaTiO3 was accurately monitored and directly visualized at the single-particle level by the advanced photoluminescence (PL) imaging microscopy systems. The longer PL lifetime of TO@BTO-S demonstrated the efficient charge separation caused by a built-in electric field, which is constructed by the polarization orientation of BaTiO3 mesocrystals. Therefore, the TO@BTO-S heterostructure exhibits efficient piezoelectric-assisted photocatalytic pure water splitting, which is 290 times higher than photocatalysis. This work revealed time/spatial-resolved photoinduced charge transfer in piezoelectric assistance photocatalysts at the single-particle level and demonstrated the great role of polarization orientation in promoting charge transfer for photocatalysis.

RESUMO

GhPEL48_Dt, a Pectate lyase (PEL, EC4.2.2.2), is a crucial enzyme involved in cell-wall modification and pectin degradation. Studies have shown that the GhPEL48_Dt also plays a significant role in cotton-fiber development; however, the specific function and regulatory mechanism of GhPEL48_Dt in cotton-fiber development are still not fully understood. Here, we found that the histone deacetylase inhibitor-Trichostatin A significantly reduces the transcript levels of GhPEL48_Dt and its enzyme activity. Further, silencing of GhPEL48_Dt significantly inhibits the initiation and elongation of cotton fibers by promoting pectin degradation, and the heterologous expression of GhPEL48_Dt promotes the development of trichomes and root hairs in Arabidopsis, which suggests that GhPEL48_Dt plays a positive and conserved role in single cell i.e., fiber, root hair, and leaf trichome development. Collectively, this paper provides a comprehensive analysis of the fundamental characteristics and functions of GhPEL48_Dt in fiber development, including the regulatory role of histone acetylation on GhPEL48_Dt, which contributes to the understanding of pectin degradation pathways and establishes a theoretical foundation for elucidating its regulatory mechanism.