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PURPOSE: Chronic obstructive pulmonary disease (COPD), characterized by airflow limitation and breathing difficulty, is usually caused by prolonged inhalation of toxic substances or long-term smoking habits. Some abnormal features of COPD can be observed using medical imaging methods, such as magnetic resonance imaging (MRI) and computed tomography (CT). This study aimed to conduct a multi-modal analysis of COPD, focusing on assessing respiratory diaphragm motion using MRI series in conjunction with low attenuation volume (LAV) data derived from CT images. MATERIALS AND METHOD: This study utilized MRI series from 10 normal subjects and 24 COPD patients, along with thoracic CT images from the same patients. Diaphragm profiles in the sagittal thoracic MRI series were extracted using field segmentation, and diaphragm motion trajectories were generated from estimated diaphragm displacements via registration. Re-sliced sagittal CT images were used to calculate regional LAVs for four distinct lung regions. The similarities among diaphragm motion trajectories at various positions were assessed, and their correlations with regional LAVs were analyzed. RESULTS: Compared with the normal subjects, patients with COPD typically exhibited fewer similarities in diaphragm motion, as indicated by the mean normalized correlation coefficient of the vertical motion component (0.96 for normal subjects vs. 0.76 for severity COPD patients). This reduction was significantly correlated with the LAV% in the two lower lung regions with a regression coefficient of 0.81. CONCLUSION: Our proposed evaluation method may assist in the diagnosis and therapy planning for patients with COPD.
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Human-induced disturbances such as dam construction and regulation have led to widespread alterations in hydrological processes and thus substantially influence plant characteristics in the hydro-fluctuation zones (HFZs). To reveal utilization of limited resources and mechanisms of inter-specific competition and species co-existence of plant communities based on niche breadth and overlap under the different HFZs of the Three Gorges Reservoir (TGR) in China, we conducted a field investigation with 368 quadrats on the effects of hydrological alterations on plant diversity and niche characteristics. The results showed anti-seasonal flooding precipitated the gradual disappearance of the original diverse niches, resulting in the reduction of plant species richness and functional diversity and more obvious competition among plant species with similar resource requirements. Annuals, perennials and shrubs accounted for 71.23%, 27.39% and 1.37%, respectively, suggesting that annuals and flood-tolerant riparian herbs were favored under such novel flooding conditions. A consistent increase in species number, Shannon-Wiener diversity index and Simpson dominance index with altitude was inconsistent with hump-shaped diversity-disturbance relationship of the intermediate disturbance hypothesis, while the opposite trend was observed for the Pielou evenness index. This species distribution pattern might be caused by several synergetic attributes (e.g., the submergence depth, plant tolerant capacity to flooding, life form, dispersal mode and inter-specific competition). Vegetation types shifted from xerophytes to mesophytes and eventually to hygrophytes with the increasing flooding time in the HFZs. Hydrological alterations proved to be the paramount driver of vegetation distribution in the different HFZs. The niche analysis provided the first insights on the mechanisms of resource utilization and inter-specific competition, of which annuals could germinate quickly after soil drainage to achieve the greatest competitive advantages and occupy a larger niche space than other plants. Vegetation was still in the early stage of primary succession in the novel riparian forests. Therefore, vegetation restoration strategies should be biased towards herbaceous plants, due to annuals with better environmental adaptability, supplemented by shrubs and small trees. To establish a complete reference system for vegetation restoration, natural vegetation monitory plots in the different succession stages should be established in the different HFZs of the TGR, and their environmental conditions, community structures and inter-specific relationships further analyzed.
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Objective Respiratory motion, cardiac motion, and inherently low signal-to-noise ratio (SNR) are major limitations of in vivo cardiac diffusion tensor imaging (DTI). We propose a novel enhancement method that uses unsupervised learning based invertible wavelet scattering (IWS) to improve the quality of in vivo cardiac DTI. Approach Our method starts by extracting nearly transformation-invariant features from multiple cardiac diffusion-weighted (DW) image acquisitions using multi-scale wavelet scattering (WS). The relationship between the WS coefficients and DW images is learned through a multiscale encoder and a decoder network. Using the trained encoder, the deep features of WS coefficients of multiple DW image acquisitions are further extracted and then fused using an average rule. Finally, using the fused WS features and trained decoder, the enhanced DW images are derived. Main Results We evaluated the performance of the proposed method by comparing it with several methods on three in vivo cardiac DTI datasets in terms of SNR, contrast to noise ratio (CNR), fractional anisotropy (FA), mean diffusivity (MD), and helix angle (HA). Compared to the best comparison method, SNR/CNR of diastolic, gastric peristalsis influenced, and end systolic DW images were improved by 1%/16%, 5%/6%, and 56%/30%, respectively. The approach also yielded consistent FA and MD values and more coherent helical fiber structures than the comparison methods used in this work. Significance The ablation results verify that using the transformation-invariant and noise-robust wavelet scattering features enables effective exploration of useful information from limited data. This provides a potential means to alleviate the dependence of the fusion results on the number of repeated acquisitions, which is beneficial for dealing with noise and residual motion issues simultaneously, thereby improving the quality of in vivo cardiac DTI.
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A pathological hallmark of Alzheimer's disease (AD) is the region-specific accumulation of the amyloid-beta protein (Aß), which triggers aberrant neuronal excitability, synaptic impairment, and progressive cognitive decline. Previous works have demonstrated that Aß pathology induced aberrant elevation in the levels and excessive enzymatic hydrolysis of voltage-gated sodium channel type 2 beta subunit (Navß2) in the brain of AD models, accompanied by alteration in excitability of hippocampal neurons, synaptic deficits, and subsequently, cognitive dysfunction. However, the mechanism is unclear. In this research, by employing cell models treated with toxic Aß1-42 and AD mice, the possible effects and potential mechanisms induced by Navß2. The results reveal that Aß1-42 induces remarkable increases in Navß2 intracellular domain (Navß2-ICD) and decreases in both BDNF exons and protein levels, as well as phosphorylated tropomyosin-related kinase B (pTrkB) expression in cells and mice, coupled with cognitive impairments, synaptic deficits, and aberrant neuronal excitability. Administration with exogenous Navß2-ICD further enhances these effects induced by Aß1-42, while interfering the generation of Navß2-ICD and/or complementing BDNF neutralize the Navß2-ICD-conducted effects. Luciferase reporter assay verifies that Navß2-ICD regulates BDNF transcription and expression by targeting its promoter. Collectively, our findings partially elucidate that abnormal enzymatic hydrolysis of Navß2 induced by Aß1-42-associated AD pathology leads to intracellular Navß2-ICD overload, which may responsible to abnormal neuronal excitability, synaptic deficit, and cognition dysfunction, through its transcriptional suppression on BDNF. Therefore, this work supplies novel evidences that Navß2 plays crucial roles in the occurrence and progression of cognitive impairment of AD by transcriptional regulatory activity of its cleaved ICD.
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Background: One of the primary reasons for tumor invasion and metastasis is anoikis resistance. Biochemical recurrence (BCR) of prostate cancer (PCa) serves as a harbinger of its distant metastasis. However, the role of anoikis in PCa biochemical recurrence has not been fully elucidated. Methods: Differential expression analysis was used to identify anoikis-related genes based on the TCGA and GeneCards databases. Prognostic models were constructed utilizing LASSO regression, univariate and multivariate Cox regression analyses. Moreover, Gene Expression Omnibus datasets (GSE70770 and GSE46602) were applied as validation cohorts. Gene Ontology, KEGG and GSVA were utilized to explore biological pathways and molecular mechanisms. Further, immune profiles were assessed using CIBERSORT, ssGSEA, and TIDE, while anti-cancer drugs sensitivity was analyzed by GDSC database. In addition, gene expressions in the model were examined using online databases (Human Protein Atlas and Tumor Immune Single-Cell Hub). Results: 113 differentially expressed anoikis-related genes were found. Four genes (EEF1A2, RET, FOSL1, PCA3) were selected for constructing a prognostic model. Using the findings from the Cox regression analysis, we grouped patients into groups of high and low risk. The high-risk group exhibited a poorer prognosis, with a maximum AUC of 0.897. Moreover, larger percentage of immune infiltration of memory B cells, CD8 Tcells, neutrophils, and M1 macrophages were observed in the high-risk group than those in the low-risk group, whereas the percentage of activated mast cells and dendritic cells in the high-risk group were lower. An increased TIDE score was founded in the high-risk group, suggesting reduced effectiveness of ICI therapy. Additionally, the IC50 results for chemotherapy drugs indicated that the low-risk group was more sensitive to most of the drugs. Finally, the genes EEF1A2, RET, and FOSL1 were expressed in PCa cases based on HPA website. The TISCH database suggested that these four ARGs might contribute to the tumor microenvironment of PCa. Conclusion: We created a risk model utilizing four ARGs that effectively predicts the risk of BCR in PCa patients. This study lays the groundwork for risk stratification and predicting survival outcomes in PCa patients with BCR.
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Non-alcoholic fatty liver disease (NAFLD) has emerged as the leading cause of chronic liver disease worldwide. Caspase 8 and FADD-like apoptosis regulator (CFLAR) has been identified as a potent factor in mitigating non-alcoholic steatohepatitis (NASH) by inhibiting the N-terminal dimerization of apoptosis signal-regulating kinase 1 (ASK1). While arginine methyltransferase 1 (PRMT1) was previously reported to be associated with increased hepatic glucose production, its involvement in hepatic lipid metabolism remains largely unexplored. The interaction between PRMT1 and CFLAR and the methylation of CFLAR were verified by Co-IP and immunoblotting assays. Recombinant adenoviruses were generated for overexpression or knockdown of PRMT1 in hepatocytes. The role of PRMT1 in NAFLD was investigated in normal and high-fat diet-induced obese mice. In this study, we found a significant upregulation of PRMT1 and downregulation of CFLAR after 48h of fasting, while the latter significantly rebounded after 12h of refeeding. The expression of PRMT1 increased in the livers of mice fed a methionine choline-deficient (MCD) diet and in hepatocytes challenged with oleic acid (OA)/palmitic acid (PA). Overexpression of PRMT1 not only inhibited the expression of genes involved in fatty acid oxidation (FAO) and promoted the expression of genes involved in fatty acid synthesis (FAS), resulting in increased triglyceride accumulation in primary hepatocytes, but also enhanced the gluconeogenesis of primary hepatocytes. Conversely, knockdown of hepatic PRMT1 significantly alleviated MCD diet-induced hepatic lipid metabolism abnormalities and liver injury in vivo, possibly through the upregulation of CFLAR protein levels. Knockdown of PRMT1 suppressed the expression of genes related to FAS and enhanced the expression of genes involved in FAO, causing decreased triglyceride accumulation in OA/PA-treated primary hepatocytes in vitro. Although short-term overexpression of PRMT1 had no significant effect on hepatic triglyceride levels under physiological conditions, it resulted in increased serum triglyceride and fasting blood glucose levels in normal C57BL/6J mice. More importantly, PRMT1 was observed to interact with and methylate CFLAR, ultimately leading to its ubiquitination-mediated protein degradation. This process subsequently triggered the activation of c-Jun N-terminal kinase 1 (JNK1) and lipid deposition in primary hepatocytes. Together, these results suggested that PRMT1-mediated methylation of CFLAR plays a critical role in hepatic lipid metabolism. Targeting PRMT1 for drug design may represent a promising strategy for the treatment of NAFLD.
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Hepatocitos , Metabolismo de los Lípidos , Hígado , Enfermedad del Hígado Graso no Alcohólico , Proteína-Arginina N-Metiltransferasas , Animales , Proteína-Arginina N-Metiltransferasas/metabolismo , Proteína-Arginina N-Metiltransferasas/genética , Hígado/metabolismo , Ratones , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/genética , Hepatocitos/metabolismo , Metilación , Masculino , Dieta Alta en Grasa/efectos adversos , Humanos , Ratones Endogámicos C57BL , Proteínas Reguladoras de la Apoptosis/metabolismo , Proteínas Reguladoras de la Apoptosis/genéticaRESUMEN
Purpose: Retinal microvascular changes are associated with ischemic stroke, and optical coherence tomography angiography (OCTA) is a potential tool to reveal the retinal microvasculature. We investigated the feasibility of using the OCTA image to automatically identify ischemic stroke and its subtypes (i.e. lacunar and non-lacunar stroke), and exploited the association of retinal biomarkers with the subtypes of ischemic stroke. Methods: Two cohorts were included in this study and a total of 1730 eyes from 865 participants were studied. A deep learning model was developed to discriminate the subjects with ischemic stroke from healthy controls and to distinguish the subtypes of ischemic stroke. We also extracted geometric parameters of the retinal microvasculature at different retinal layers to investigate the correlations. Results: Superficial vascular plexus (SVP) yielded the highest areas under the receiver operating characteristic curve (AUCs) of 0.922 and 0.871 for the ischemic stroke detection and stroke subtypes classification, respectively. For external data validation, our model achieved an AUC of 0.822 and 0.766 for the ischemic stroke detection and stroke subtypes classification, respectively. When parameterizing the OCTA images, we showed individuals with ischemic strokes had increased SVP tortuosity (B = 0.085, 95% confidence interval [CI] = 0.005-0.166, P = 0.038) and reduced FAZ circularity (B = -0.212, 95% CI = -0.42 to -0.005, P = 0.045); non-lacunar stroke had reduced SVP FAZ circularity (P = 0.027) compared to lacunar stroke. Conclusions: Our study demonstrates the applicability of artificial intelligence (AI)-enhanced OCTA image analysis for ischemic stroke detection and its subtypes classification. Biomarkers from retinal OCTA images can provide useful information for clinical decision-making and diagnosis of ischemic stroke and its subtypes.
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Biomarcadores , Accidente Cerebrovascular Isquémico , Curva ROC , Vasos Retinianos , Tomografía de Coherencia Óptica , Humanos , Masculino , Femenino , Tomografía de Coherencia Óptica/métodos , Vasos Retinianos/diagnóstico por imagen , Vasos Retinianos/patología , Accidente Cerebrovascular Isquémico/clasificación , Accidente Cerebrovascular Isquémico/diagnóstico , Accidente Cerebrovascular Isquémico/diagnóstico por imagen , Persona de Mediana Edad , Biomarcadores/metabolismo , Anciano , Aprendizaje Profundo , Angiografía con Fluoresceína/métodos , Fondo de OjoRESUMEN
Bacterial exonuclease III (ExoIII), widely acknowledged for specifically targeting double-stranded DNA (dsDNA), has been documented as a DNA repair-associated nuclease with apurinic/apyrimidinic (AP)-endonuclease and 3'â5' exonuclease activities. Due to these enzymatic properties, ExoIII has been broadly applied in molecular biosensors. Here, we demonstrate that ExoIII (Escherichia coli) possesses highly active enzymatic activities on ssDNA. By using a range of ssDNA fluorescence-quenching reporters and fluorophore-labeled probes coupled with mass spectrometry analysis, we found ExoIII cleaved the ssDNA at 5'-bond of phosphodiester from 3' to 5' end by both exonuclease and endonuclease activities. Additional point mutation analysis identified the critical residues for the ssDNase action of ExoIII and suggested the activity shared the same active center with the dsDNA-targeted activities of ExoIII. Notably, ExoIII could also digest the dsDNA structures containing 3'-end ssDNA. Considering most ExoIII-assisted molecular biosensors require the involvement of single-stranded DNA (ssDNA) or nucleic acid aptamer containing ssDNA, the activity will lead to low efficiency or false positive outcome. Our study revealed the multi-enzymatic activity and the underlying molecular mechanism of ExoIII on ssDNA, illuminating novel insights for understanding its biological roles in DNA repair and the rational design of ExoIII-ssDNA involved diagnostics.
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ADN de Cadena Simple , Escherichia coli , Exodesoxirribonucleasas , Exodesoxirribonucleasas/metabolismo , Exodesoxirribonucleasas/genética , ADN de Cadena Simple/metabolismo , ADN de Cadena Simple/genética , Escherichia coli/genética , Escherichia coli/metabolismo , Escherichia coli/enzimología , Proteínas de Escherichia coli/metabolismo , Proteínas de Escherichia coli/genéticaRESUMEN
Introduction: Metastatic castration-resistant prostate cancer (mCRPC) patients face challenges due to limited treatment options. About 50% of patients with mCRPC have a functional loss of phosphatase and tensin homology deleted on chromosome 10 (PTEN), leading to tumor progression, metastasis, and immune suppression. Moreover, elevated IL-23 produced by myeloid-derived suppressor cells (MDSCs) is found in CRPC patients, driving tumor progression. Therefore, a combination strategy based on PTEN restoration and IL-23 inhibition may block CRPC progression and metastasis. Methods: The antitumor effect of restoring PTEN expression combined with the IL-23 inhibitor Apilimod was studied in a mouse model of bone metastasis CRPC and mouse prostate cancer RM-1 cells. To verify the targeting ability of PTEN DNA coated with lipid nanoparticles (LNP@PTEN) in vitro and in vivo. In addition, RT-qPCR and flow cytometry were used to investigate the related mechanisms of the antitumor effect of LNP@PTEN combined with Apilimod. Results: LNPs exhibited significant tumor-targeting and tumor accumulation capabilities both in vitro and in vivo, enhancing PTEN expression and therapeutic efficacy. Additionally, the combination of LNP@PTEN with the IL-23 inhibitor Apilimod demonstrated enhanced inhibition of tumor growth, invasion, and metastasis (particularly secondary organ metastasis) compared to other groups, and extended the survival of mice to 41 days, providing a degree of bone protection. These effects may be attributed to the PTEN function restoration combined with IL-23 inhibition, which help reverse immune suppression in the tumor microenvironment by reducing MDSCs recruitment and increasing the CD8+/CD4+ T cell ratio. Discussion: In summary, these findings highlight the potential of LNPs for delivering gene therapeutic agents. And the combination of LNP@PTEN with Apilimod could achieve anti-tumor effects and improve tumor microenvironment. This combinational strategy opens new avenues for the treatment of mCRPC.
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To promote the generalization ability of breast tumor segmentation models, as well as to improve the segmentation performance for breast tumors with smaller size, low-contrast and irregular shape, we propose a progressive dual priori network (PDPNet) to segment breast tumors from dynamic enhanced magnetic resonance images (DCE-MRI) acquired at different centers. The PDPNet first cropped tumor regions with a coarse-segmentation based localization module, then the breast tumor mask was progressively refined by using the weak semantic priori and cross-scale correlation prior knowledge. To validate the effectiveness of PDPNet, we compared it with several state-of-the-art methods on multi-center datasets. The results showed that, comparing against the suboptimal method, the DSC and HD95 of PDPNet were improved at least by 5.13% and 7.58% respectively on multi-center test sets. In addition, through ablations, we demonstrated that the proposed localization module can decrease the influence of normal tissues and therefore improve the generalization ability of the model. The weak semantic priors allow focusing on tumor regions to avoid missing small tumors and low-contrast tumors. The cross-scale correlation priors are beneficial for promoting the shape-aware ability for irregular tumors. Thus integrating them in a unified framework improved the multi-center breast tumor segmentation performance. The source code and open data can be accessed at https://github.com/wangli100209/PDPNet.
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LOXL2, an enzyme belonging to the LOX family, facilitates the cross-linking of extracellular matrix (ECM) elements. However, the roles of the LOXL2 gene in mechanisms of oncogenesis and tumor development have not been clearly defined. In this pan-cancer study, we examined the notable disparity in LOXL2 expression at the mRNA and protein levels among various cancer types and elucidated its interconnected roles in tumor progression, mutational profile, immune response, and cellular senescence. Apart from investigating the hyperexpression of LOXL2 being related to poorer prognosis in different types of tumors, this study also unveiled noteworthy connections between LOXL2 and genetic mutations, infiltration of tumor immune cells, and genes in immune checkpoint pathways. Further analysis revealed the participation of LOXL2 in multiple pathways related to cancer extracellular matrix remodeling and cellular senescence. Moreover, our investigation uncovered that the knockdown and inhibition of LOXL2 significantly attenuated the proliferation and migration of PC-9 and HCC-LM3 cells. The knock-down and inhibition of LOXL2 enhanced cellular senescence in lung and liver cancer cells, as confirmed by SA-ß-Gal staining and quantitative RT-PCR analyses. This comprehensive analysis offers valuable insights on the functions of LOXL2 in different types of cancer and its role in regulating the senescence of cancer cells.
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Traditional Chinese medicine, specifically the Jianpi Tiaoqi (JPTQ) decoction, has been explored for its role in treating breast cancer, particularly in inhibiting lung metastasis in affected mice. Our study evaluated the effects of JPTQ on several factors, including tumour growth, apoptosis, angiogenesis, epithelial-to-mesenchymal transition (EMT) and immune microenvironment regulation. We used bioluminescence imaging to observe in situ tumour growth and potential lung metastasis. Transcriptomic analysis provided insights into gene expression, whereas flow cytometry was used to examine changes in specific immune cells, such as CD4+ T cells and myeloid-derived suppressor cells. Several essential proteins and genes, including vascular endothelial growth factor (VEGF), matrix metalloprotein-9 (MMP-9) and B-cell lymphoma 2 (Bcl-2), were assessed through quantitative real-time polymerase chain reaction, western blotting and immunohistochemistry. Our findings showed that JPTQ treatment inhibited tumour proliferation in cancer-bearing mice. Bioluminescence imaging and pathological analysis indicated a reduction in lung metastasis. Transcriptome analysis of lung and tumour tissues indicated that the genes associated with EMT, angiogenesis, proliferation and apoptosis were regulated in the JPTQ-treated group. Kyoto Encyclopedia of Genes and Genomes analysis suggested enrichment of immune-related pathways. Flow cytometry indicated that JPTQ treatment reduced the proportion of monocyte-myeloid-derived suppressor cells in the lung and increased the number of CD4+ T cells in the peripheral blood and the number of T helper 1 (Th1) cells in the spleen (P < 0.05). E-cadherin and cleaved caspase 3 were upregulated, whereas Snail, Bcl-2, Ki67 and VEGF were downregulated in the lung and tumour tissues; moreover, the expression of MMP-9 was downregulated in the lung tissue (P < 0.05). In essence, JPTQ not only inhibits tumour growth in affected mice, but also promotes positive immune responses, reduces angiogenesis, boosts tumour cell apoptosis, reverses EMT and decreases breast cancer lung metastasis.
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Proliferación Celular , Medicamentos Herbarios Chinos , Transición Epitelial-Mesenquimal , Neoplasias Pulmonares , Neoplasias de la Mama Triple Negativas , Animales , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/secundario , Neoplasias Pulmonares/metabolismo , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Ratones , Proliferación Celular/efectos de los fármacos , Femenino , Neoplasias de la Mama Triple Negativas/patología , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Transición Epitelial-Mesenquimal/efectos de los fármacos , Línea Celular Tumoral , Apoptosis/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Microambiente Tumoral/efectos de los fármacos , Neovascularización Patológica/tratamiento farmacológico , Neovascularización Patológica/patologíaRESUMEN
Kidneys from donors with prolonged warm and cold ischemia are prone to posttransplant T cell-mediated rejection (TCMR) due to ischemia-reperfusion injury (IRI). However, the precise mechanisms still remain obscure. Renal tubular epithelial cells (TECs) are the main target during IRI. Meanwhile, we have previously reported that murine double minute 2 (MDM2) actively participates in TEC homeostasis during IRI. In this study, we established a murine model of renal IRI and a cell model of hypoxia-reoxygenation by culturing immortalized rat renal proximal tubule cells (NRK-52E) in a hypoxic environment for different time points followed by 24 h of reoxygenation and incubating NRK-52E cells in a chemical anoxia-recovery environment. We found that during renal IRI MDM2 expression increased on the membrane of TECs and aggregated mainly on the basolateral side. This process was accompanied by a reduction of a transmembrane protein, programmed death ligand 1 (PD-L1), a coinhibitory second signal for T cells in TECs. Using mutant plasmids of MDM2 to anchor MDM2 on the cell membrane or nuclei, we found that the upregulation of membrane MDM2 could promote the ubiquitination of PD-L1 and lead to its ubiquitination-proteasome degradation. Finally, we set up a coculture system of TECs and CD4+ T cells in vitro; our results revealed that the immunogenicity of TECs was enhanced during IRI. In conclusion, our findings suggest that the increased immunogenicity of TECs during IRI may be related to ubiquitinated degradation of PD-L1 by increased MDM2 on the cell membrane, which consequently results in T-cell activation and TCMR.NEW & NOTEWORTHY Ischemic acute kidney injury (AKI) donors can effectively shorten the waiting time for kidney transplantation but increase immune rejection, especially T cell-mediated rejection (TCMR), the mechanism of which remains to be elucidated. Our study demonstrates that during ischemia-reperfusion injury (IRI), the translocation of tubular murine double minute 2 leads to basolateral programmed death ligand 1 degradation, which ultimately results in the occurrence of TCMR, which may provide a new therapeutic strategy for preventing AKI donor-associated TCMR.
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Lesión Renal Aguda , Proteínas Proto-Oncogénicas c-mdm2 , Daño por Reperfusión , Animales , Daño por Reperfusión/metabolismo , Daño por Reperfusión/inmunología , Daño por Reperfusión/patología , Lesión Renal Aguda/metabolismo , Lesión Renal Aguda/inmunología , Lesión Renal Aguda/patología , Proteínas Proto-Oncogénicas c-mdm2/metabolismo , Proteínas Proto-Oncogénicas c-mdm2/genética , Masculino , Ratas , Ratones Endogámicos C57BL , Antígeno B7-H1/metabolismo , Ubiquitinación , Modelos Animales de Enfermedad , Células Epiteliales/metabolismo , Células Epiteliales/inmunología , Células Epiteliales/patología , Ratones , Transporte de Proteínas , Túbulos Renales Proximales/metabolismo , Túbulos Renales Proximales/inmunología , Túbulos Renales Proximales/patología , Línea Celular , Membrana Celular/metabolismo , Hipoxia de la Célula , Trasplante de RiñónRESUMEN
This paper proposes an alternative method for grating period measurement based on heterodyne grating interferometry. The optical configurations for measuring the period of reflection/transmission gratings were demonstrated, and four commercially available gratings were used to evaluate the effectiveness of the proposed method. Based on the phase-lock technique, the grating period could be obtained immediately through the phase wrapped/unwrapped process. Under precise measurement conditions, the grating period measurement error of the proposed method was better than 1 nm, and the grating period difference between product specifications was less than 1%. In addition, the measurement results of the proposed method also exhibited high similarity with optical microscopy measurements.
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Background: Nephrolithiasis seriously affects people's health with increasing prevalence and high recurrence rates. However, there is still a lack of effective interventions for the clinical prevention of kidney stones. Hyperoxaluria-induced renal tubular epithelial cell (TEC) injury is a known key factor in kidney stone formation. Thus, developing new drugs to inhibit the hyperoxaluria-induced TEC injury may be the best way. Methods: We synthesized the Se@SiO2 nanocomposites as described in Zhu's study. The size and morphology of the Se@SiO2 nanocomposites were captured by transmission electron microscopy. Cell viability was measured by a Cell Counting Kit-8 (CCK-8) assay. The mice were randomly divided into the following four groups: (I) the control group (n=6); (II) the Se@SiO2 group (n=6); (III) the glyoxylic acid monohydrate (GAM) group; and (IV) the GAM + Se@SiO2 group (n=6). The concentration of Se in the mice was quantified using inductively coupled plasma atomic emission spectroscopy. Results: The CCK-8 assays showed that Se@SiO2 nanocomposites had almost no obvious cytotoxicity on the Transformed C3H Mouse Kidney-1 (TCMK-1) cell. The mice kidney Se concentration levels in the Se@SiO2 groups (Se@SiO2 6.905±0.074 mg/kg; GAM + Se@SiO2 7.673±2.85 mg/kg) (n=6) were significantly higher than those in the control group (Control 0.727±0.072 mg/kg; GAM 0.747±0.074 mg/kg) (n=6). The Se@SiO2 nanocomposites reduced kidney injury, calcium oxalate crystal deposition, and the osteoblastic-associated proteins in the hyperoxaluria mice models. Conclusions: Se@SiO2 nanocomposites appear to protect renal TECs from hyperoxaluria by reducing reactive oxygen species production, suggesting the potential role of preventing kidney stone formation and recurrence.
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Represented herein is a simple thiol identified as an effective precursor to photochemically form a carbocation. Thanks to the thiyl radical rapid transformation to disulfide, which serves not only to stabilize the generated thiyl radical but also to allow the second electron transfer to form a carbocation. The resulting carbocations, including primary benzylic, secondary, and tertiary carbocations, can smoothly couple with nitrogen, oxygen, and carbon nucleophilic coupling partners as well as complex drug molecules, accompanied by elemental sulfur formation in air.
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BACKGROUND: Antibiotic-associated diarrhea (AAD) refers to symptoms of diarrhea that cannot be explained by other causes after the use of antibiotics. AAD is thought to be caused by a disruption of intestinal ecology due to antibiotics. Fecal Microbiota Transplantation (FMT) is a treatment method that involves transferring microbial communities from the feces of healthy individuals into the patient's gut. METHOD: We selected 23 AAD patients who received FMT treatment in our department. Before FMT, we documented patients' bowel movement frequency, abdominal symptoms, routine blood tests, and inflammatory markers, and collected fecal samples for 16S rRNA sequencing to observe changes in the intestinal microbiota. Patients' treatment outcomes were followed up 1 month and 3 months after FMT. RESULTS: Out of the 23 AAD patients, 19 showed a clinical response to FMT with alleviation of abdominal symptoms. Among them, 82.61% (19/23) experienced relief from diarrhea, 65% (13/20) from abdominal pain, 77.78% (14/18) from abdominal distension, and 57.14% (4/7) from bloody stools within 1 month after FMT. Inflammatory markers IL-8 and CRP significantly decreased after FMT, but there were no noticeable changes in WBC, IL-6, and TNF-α before and after transplantation. After FMT, the abundance of Bacteroides and Faecalibacterium increased in patients' fecal samples, while the abundance of Escherichia-Shigella and Veillonella decreased. CONCLUSION: FMT has a certain therapeutic effect on AAD, and can alleviate abdominal symptoms and change the intestinal microbiota of patients.
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Antibacterianos , Diarrea , Trasplante de Microbiota Fecal , Heces , Microbioma Gastrointestinal , ARN Ribosómico 16S , Humanos , Diarrea/microbiología , Diarrea/terapia , Trasplante de Microbiota Fecal/métodos , Femenino , Masculino , Persona de Mediana Edad , Antibacterianos/efectos adversos , Heces/microbiología , Adulto , ARN Ribosómico 16S/genética , Anciano , Resultado del Tratamiento , Bacterias/clasificación , Bacterias/aislamiento & purificación , Bacterias/genéticaRESUMEN
Background: With the aging of the population and the increasing incidence of neurological diseases, amnestic mild cognitive impairment (aMCI) has attracted attention. Hyperbaric oxygen (HBO) has gradually shown the potential in the treatment of aMCI as an emerging treatment method in recent times. This study is to observe the effect of HBO on the long-term learning memory of aMCI rats, and investigate the associated mechanisms. Methods: Seventy-two male rats (4-month-old) were randomly divided into control (CON) group, aMCI group, HBO group, 24 rats in each group. Each group was randomly divided into CON1, CON7, CON28; aMCI1, aMCI7, aMCI28; HBO1, HBO7, HBO28, 8 rats in each group. The aMCI model rats were established in aMCI and HBO groups. HBO group was treated with HBO for 7 days. The ethological and cytopathology which include Morris water maze (MWM) test, HE staining, TUNEL staining and the expression of Fas/FasL on neuron membrane were conducted to evaluate the effects of HBO on day 1, day 7 and day 28 after HBO treatment. Results: MWM test showed that the spatial learning and memory ability of the rats decreased in aMCI group, and recovered in HBO group; Compared with aMCI group, the pathological damage of hippocampal nerve cells was alleviated, the number of apoptotic cells was significantly reduced (P < 0.05), and the expression of Fas/FasL on the surface of nerve cell membrane was significantly weakened in HBO group (P < 0.05). There were no significant changes in the spatial learning and memory ability, pathological damage of hippocampal neurons, the number of apoptotic cells, and the changes of Fas/FasL on the surface of hippocampal neurons in HBO1, HBO7, and HBO28 groups (P > 0.05). However, in aMCI1, aMCI7, and aMCI28 groups gradually aggravated (P < 0.05). Conclusion: 1. HBO can improve the long-term learning and memory impairment by attenuating neuronal apoptosis in aMCI rats. 2. Fas/FasL mediated cell receptor death pathway is involved in the apoptosis of hippocampal neurons.
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Recent advancements in polymer-assisted layer-by-layer (LbL) fabrication have revolutionized the development of wearable sensors for health monitoring. LbL self-assembly has emerged as a powerful and versatile technique for creating conformal, flexible, and multi-functional films on various substrates, making it particularly suitable for fabricating wearable sensors. The incorporation of polymers, both natural and synthetic, has played a crucial role in enhancing the performance, stability, and biocompatibility of these sensors. This review provides a comprehensive overview of the principles of LbL self-assembly, the role of polymers in sensor fabrication, and the various types of LbL-fabricated wearable sensors for physical, chemical, and biological sensing. The applications of these sensors in continuous health monitoring, disease diagnosis, and management are discussed in detail, highlighting their potential to revolutionize personalized healthcare. Despite significant progress, challenges related to long-term stability, biocompatibility, data acquisition, and large-scale manufacturing are still to be addressed, providing insights into future research directions. With continued advancements in polymer-assisted LbL fabrication and related fields, wearable sensors are poised to improve the quality of life for individuals worldwide.