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1.
Sci Total Environ ; 946: 174256, 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38936734

RESUMEN

Since 2012, the "Mountain Excavation and City Construction" (MECC) project has been implemented extensively on the Loess Plateau of China, transforming gullies into flat land for urban sprawl by leveling loess hilltops to fill in valleys. However, this unprecedented human activity has caused widespread controversy over its unknown potential ecological impacts. Quantitative assessment of the impacts of the MECC project on the vegetation is key to ecological management and restoration. Taking the largest MECC project area on the Loess Plateau, Yan'an New District (YND), as the study area, this study investigated the spatiotemporal pattern of vegetation dynamics before and after the implementation of the MECC project using a multitemporal normalized difference vegetation index (NDVI) time series from 2009 to 2023 and explored the response of vegetation dynamics to the large-scale MECC project. The results showed that the vegetation dynamics in the YND exhibited significant spatial and temporal heterogeneity due to the MECC project, with the vegetation in the project-affected areas showing rapid damage followed by slow recovery. Vegetation damage occurred only in the project-affected area, and 84 % of these areas began recovery within 10 years, indicating the limited impact of the large-scale MECC project on the regional vegetation. The strong correlation between vegetation dynamics and the MECC project suggested that the destruction and recovery of vegetation in the project-affected areas was mainly under anthropogenic control, which highlights the importance of targeted ecological policies. Specifically, the MECC project induced local anthropogenic damage to the plant population structure during the land creation period, but regeneration and rational allocation of the vegetation were achieved through urbanization, gradually forming a new balanced ecological environment. These findings will contribute to a full understanding of the response of vegetation to such large-scale engineering activities and help local governments adopt projects or policies that facilitate vegetation recovery.

2.
Sci Total Environ ; 946: 174064, 2024 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-38889812

RESUMEN

Microplastics (MPs) have drawn exponential attention as anthropogenic pollutants, which have invaded every corner of planet. Seamounts are prominent features of the deep-sea topography, acting as breeding ground for marine animal calves and hotspots of pelagic biodiversity, yet MPs pollution in seamounts is scarcely studied. We investigated the MPs load in the whole vertical profile of seamount ambient water in the Subtropical Northwest Pacific Ocean. Based on focal plane array Fourier Transform Infrared spectrometry, MPs were detected in all layers, and varied from 0.9 to 3.8 items L-1, PP and PE were dominant, PA and PET tended to gather at the seamount summit. With depth increasing, small MPs (20-50 µm) were dominant, and MPs surface roughness including crack, hole, and biofouling showed an increase. Three plastic-degrading bacteria were noted in the layers around the seamount, indicating that the seamount community may accelerate MPs aging and further migration. Our work first unveiled the MPs occurrence in the whole vertical profile of the seamount. It reveals that ocean MPs migration and degradation are significantly affected by the unique topography and biotopes of the seamount.

3.
RSC Adv ; 14(28): 20199-20209, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38919279

RESUMEN

Heterogeneous solvent-metal-free aerobic oxidation of alcohols under ambient conditions is interesting but remains a significant challenge. Herein, a series of porous TEMPO-functionalized poly(ionic liquid)s (TEMPO-PILs) featuring a pure polycationic framework were successfully developed through the free radical polymerization of the ionic liquid 3-(2-chloroacetic acid-2,2,6,6-tetramethyl-1-oxo-4-piperidyl)-1-vinylimidazolium chloride and bis-vinylimidazolium bromide salt. Characterizations revealed that the obtained TEMPO-PILs possessed a high TEMPO density, abundant bromide ions, and a tunable porous structure, which enabled them to serve as solvent-free heterogeneous organocatalysts for the metal-free aerobic oxidation of benzyl alcohol under ambient conditions, exhibiting high catalytic activity and stable recyclability. A high yield of 99% coupled with a turnover frequency (TOF) of 13.3 h-1 was obtainable, which is higher than most of the reported TEMPO-based heterogeneous catalysts, even superior to homogeneous TEMPO-functionalized ionic liquids. Furthermore, a broad range of alcohols were effectively converted into their corresponding ketones and aldehydes. A possible reaction mechanism is proposed for understanding the catalytic oxidation behavior, indicative of the synergistic effect of TEMPO moieties and bromide ions.

4.
Theranostics ; 14(8): 3300-3316, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38855182

RESUMEN

Patient-derived organoids (PDOs) have emerged as a promising platform for clinical and translational studies. A strong correlation exists between clinical outcomes and the use of PDOs to predict the efficacy of chemotherapy and/or radiotherapy. To standardize interpretation and enhance scientific communication in the field of cancer precision medicine, we revisit the concept of PDO-based drug sensitivity testing (DST). We present an expert consensus-driven approach for medication selection aimed at predicting patient responses. To further standardize PDO-based DST, we propose guidelines for clarification and characterization. Additionally, we identify several major challenges in clinical prediction when utilizing PDOs.


Asunto(s)
Antineoplásicos , Consenso , Desarrollo de Medicamentos , Neoplasias , Organoides , Medicina de Precisión , Organoides/efectos de los fármacos , Humanos , Medicina de Precisión/métodos , Neoplasias/tratamiento farmacológico , Desarrollo de Medicamentos/métodos , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Ensayos de Selección de Medicamentos Antitumorales/métodos
5.
Neurochem Int ; 178: 105787, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38830510

RESUMEN

OBJECTIVES: To investigate the possible roles of Interleukin 17A (IL-17A) and IL-17A neutralizing antibodies (IL-17Ab) in glaucoma and the potential mechanisms. METHODS: The two glaucoma animal models, chronic ocular hypertension (COH) and N-methyl-D-aspartate (NMDA)-induced retinal ganglion cell (RGC) damage, were established and treated with intravitreal injection of IL-17A or IL-17Ab. Intraocular pressure (IOP) was measured by a rebound tonometer. The retina and RGC injury were evaluated by HE staining, TUNLE assay and Brn3a immunofluorescence staining. The frequency of IL-17A+CD4+T cells in peripheral blood was detected by flow cytometry. The expression of glial fibrillary acidic protein (GFAP) was detected by immunofluorescence staining, Western Blot and qPCR in retina. The RNA and protein expression of Act1/TRAF6/NF-κB were detected by Western Blot and qPCR in retina. RESULTS: The expression of IL-17A increased in glaucoma models. After intravitreal injection of IL-17A, in the retina, the number of RGCs decreased, the apoptosis of RGCs increased, the Müller cell gliosis was more obvious. In addition, peripheral inflammation aggravated. Whereas the intravitreal injection of IL-17Ab alleviated the relevant manifestations and peripheral inflammation, reduced the gliosis of Müller cells. In the COH model, IOP increased after the injection of IL-17A, while the intravitreal injection of IL-17Ab led to a decrease in IOP. Furthermore, IL-17A promotes the apoptosis of RGCs by binding to IL-17A receptor, activating Act1/TRAF6/NF-κB pathways. CONCLUSION: IL-17A plays a role in and aggravates RGC damage in glaucoma. IL-17Ab can neutralize the pro-inflammatory effect of IL-17A and have a protective function in glaucoma. These findings reveal the importance of IL-17A in the pathogenesis of glaucoma, which will shed light on a novel direction for the prevention and treatment of glaucoma, and also provide a reference for further research on other retinal diseases.

6.
Int J Biol Macromol ; 273(Pt 2): 132685, 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38823749

RESUMEN

To overcome the trade-off challenge encountered in the engineering of alginate lyase AlyG2 from Seonamhaeicola algicola Gy8T and to expand its potential industrial applications, we devised a two-step strategy encompassing activity enhancement followed by thermal stability engineering. To enhance the specific activity of efficient AlyG2, we strategically substituted residues with bulky steric hindrance proximal to the active pocket with glycine or alanine. This led to the generation of three promising positive mutants, with particular emphasis on the T91S mutant, exhibiting a 1.91-fold specific activity compared to the wild type. To mitigate the poor thermal stability of T91S, mutants with negative ΔΔG values in the thermal flexibility region were screened out. Notably, the S72Ya mutant not only displayed 17.96 % further increase in specific activity but also exhibited improved stability compared to T91S, manifesting as a remarkable 30.97 % increase in relative activity following a 1-hour incubation at 42 °C. Furthermore, enhanced kinetic stability was observed. To gain deeper insights into the mechanism underlying the enhanced thermostability of the S72Ya mutant, we conducted molecular dynamics simulations, principal component analysis (PCA), dynamic cross-correlation map (DCCM), and free energy landscape (FEL) analysis. The results unveiled a reduction in the flexibility of the surface loop, a stronger correlation dynamic and a narrower motion subspace in S72Ya system, along with the formation of more stable hydrogen bonds. Collectively, our findings suggest amino acids substitutions resulting in smaller side chains proximate to the active site can positively impact enzyme activity, while reducing the flexibility of surface loops emerges as a pivotal factor in conferring thermal stability. These insights offer valuable guidance and a framework for the engineering of other enzyme types.

7.
J Ethnopharmacol ; 333: 118424, 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38844252

RESUMEN

ETHNIC PHARMACOLOGICAL RELEVANCE: Diabetic kidney disease (DKD) is the main cause of end-stage renal disease (ESRD), which is a public health problem with a significant economic burden. Serious adverse effects, such as hypotension, hyperkalemia, and genitourinary infections, as well as increasing adverse cardiovascular events, limit the clinical application of available drugs. Plenty of randomized controlled trials(RCTs), meta-analysis(MAs) and systematic reviews(SRs) have demonstrated that many therapies that have been used for a long time in medical practice including Chinese patent medicines(CPMs), Chinese medicine prescriptions, and extracts are effective in alleviating DKD, but the mechanisms by which they work are still unknown. Currently, targeting inflammation is a central strategy in DKD drug development. In addition, many experimental studies have identified many Chinese medicine prescriptions, medicinal herbs and extracts that have the potential to alleviate DKD. And part of the mechanisms by which they work have been uncovered. AIM OF THIS REVIEW: This review aims to summarize therapies that have been proven effective by RCTs, MAs and SRs, including CPMs, Chinese medicine prescriptions, and extracts. This review also focuses on the efficiency and potential targets of Chinese medicine prescriptions, medicinal herbs and extracts discovered in experimental studies in improving immune inflammation in DKD. METHODS: We searched for relevant scientific articles in the following databases: PubMed, Google Scholar, and Web of Science. We summarized effective CPMs, Chinese medicine prescriptions, and extracts from RCTs, MAs and SRs. We elaborated the signaling pathways and molecular mechanisms by which Chinese medicine prescriptions, medicinal herbs and extracts alleviate inflammation in DKD according to different experimental studies. RESULTS: After overviewing plenty of RCTs with the low hierarchy of evidence and MAs and SRs with strong heterogeneity, we still found that CPMs, Chinese medicine prescriptions, and extracts exerted promising protective effects against DKD. However, there is insufficient evidence to prove the safety of Chinese medicines. As for experimental studies, Experiments in vitro and in vivo jointly demonstrated the efficacy of Chinese medicines(Chinese medicine prescriptions, medicinal herbs and extracts) in DKD treatment. Chinese medicines were able to regulate signaling pathways to improve inflammation in DKD, such as toll-like receptors, NLRP3 inflammasome, Nrf2 signaling pathway, AMPK signaling pathway, MAPK signaling pathway, JAK-STAT, and AGE/RAGE. CONCLUSION: Chinese medicines (Chinese medicine prescriptions, medicinal herbs and extracts) can improve inflammation in DKD. For drugs that are effective in RCTs, the underlying bioactive components or extracts should be identified and isolated. Attention should be given to their safety and pharmacokinetics. Acute, subacute, and subchronic toxicity studies should be designed to determine the magnitude and tolerability of side effects in humans or animals. For drugs that have been proven effective in experimental studies, RCTs should be designed to provide reliable evidence for clinical translation. In a word, Chinese medicines targeting immune inflammation in DKD are a promising direction.

8.
Lab Chip ; 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38896021

RESUMEN

Liver cancer, characterized as a kind of malignant tumor within the digestive system, poses great health harm, and immune escape stands out as an important reason for its occurrence and development. Chemokines, pivotal in guiding immune cells' migration, is necessary to initiate and deliver an effective anti-tumor immune response. Therefore, understanding the chemotactic environment and identifying chemokines that regulate recruitment of immune cells to the tumor microenvironment (TME) are critical to improve current immunotherapy interventions. Herein, we report a well-defined inverse opal scaffold generated with a microfluidic emulsion template for the construction of a vascularized liver tumor model, offering insights into immune cells' recruitment. Due to the excellent 3D porous morphology of the inverse opal scaffold, human hepatocellular carcinoma cells can aggregate in the pores of the scaffold to form uniform multicellular tumor spheroids. More attractively, the vascularized liver tumor model can be achieved by constructing a 3D co-culture system involving endothelial cells and hepatocellular carcinoma cells. The results demonstrate that the 3D co-cultured tumor cells increase the neutrophil chemokines remarkably and recruit neutrophils to tumor tissues, then promote tumor progression. This approach opens a feasible avenue for realizing a vascularized liver tumor model with a reliable immune microenvironment close to that of a solid tumor of liver cancer.

9.
Proc Natl Acad Sci U S A ; 121(22): e2322479121, 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38771871

RESUMEN

The significance of biochemical cues in the tumor immune microenvironment in affecting cancer metastasis is well established, but the role of physical factors in the microenvironment remains largely unexplored. In this article, we investigated how the mechanical interaction between cancer cells and immune cells, mediated by extracellular matrix (ECM), influences immune escape of cancer cells. We focus on the mechanical regulation of macrophages' targeting ability on two distinct types of colorectal carcinoma (CRC) cells with different metastatic potentials. Our results show that macrophages can effectively target CRC cells with low metastatic potential, due to the strong contraction exhibited by the cancer cells on the ECM, and that cancer cells with high metastatic potential demonstrated weakened contractions on the ECM and can thus evade macrophage attack to achieve immune escape. Our findings regarding the intricate mechanical interactions between immune cells and cancer cells can serve as a crucial reference for further exploration of cancer immunotherapy strategies.


Asunto(s)
Neoplasias Colorrectales , Matriz Extracelular , Macrófagos , Escape del Tumor , Microambiente Tumoral , Neoplasias Colorrectales/inmunología , Neoplasias Colorrectales/patología , Macrófagos/inmunología , Humanos , Microambiente Tumoral/inmunología , Matriz Extracelular/metabolismo , Matriz Extracelular/inmunología , Línea Celular Tumoral , Metástasis de la Neoplasia , Animales , Ratones , Comunicación Celular/inmunología
10.
bioRxiv ; 2024 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-38746445

RESUMEN

Improvements in single-cell whole-genome sequencing (scWGS) assays have enabled detailed characterization of somatic copy number alterations (CNAs) at the single-cell level. Yet, current computational methods are mostly designed for detecting chromosome-scale changes in cancer samples with low sequencing coverage. Here, we introduce HiScanner (High-resolution Single-Cell Allelic copy Number callER), which combines read depth, B-allele frequency, and haplotype phasing to identify CNAs with high resolution. In simulated data, HiScanner consistently outperforms state-of-the-art methods across various CNA types and sizes. When applied to high-coverage scWGS data from human brain cells, HiScanner shows a superior ability to detect smaller CNAs, uncovering distinct CNA patterns between neurons and oligodendrocytes. For 179 cells we sequenced from longitudinal meningioma samples, integration of CNAs with point mutations revealed evolutionary trajectories of tumor cells. These findings show that HiScanner enables accurate characterization of frequency, clonality, and distribution of CNAs at the single-cell level in both non-neoplastic and neoplastic cells.

11.
Environ Sci Technol ; 58(19): 8251-8263, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38695612

RESUMEN

The novel brominated flame retardant, 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE), has increasingly been detected in environmental and biota samples. However, limited information is available regarding its toxicity, especially at environmentally relevant concentrations. In the present study, adult male zebrafish were exposed to varying concentrations of BTBPE (0, 0.01, 0.1, 1, and 10 µg/L) for 28 days. The results demonstrated underperformance in mating behavior and reproductive success of male zebrafish when paired with unexposed females. Additionally, a decline in sperm quality was confirmed in BTBPE-exposed male zebrafish, characterized by decreased total motility, decreased progressive motility, and increased morphological malformations. To elucidate the underlying mechanism, an integrated proteomic and phosphoproteomic analysis was performed, revealing a predominant impact on mitochondrial functions at the protein level and a universal response across different cellular compartments at the phosphorylation level. Ultrastructural damage, increased expression of apoptosis-inducing factor, and disordered respiratory chain confirmed the involvement of mitochondrial impairment in zebrafish testes. These findings not only provide valuable insights for future evaluations of the potential risks posed by BTBPE and similar chemicals but also underscore the need for further research into the impact of mitochondrial dysfunction on reproductive health.


Asunto(s)
Reproducción , Pez Cebra , Animales , Masculino , Reproducción/efectos de los fármacos , Espermatozoides/efectos de los fármacos , Testículo/efectos de los fármacos , Testículo/metabolismo , Retardadores de Llama/toxicidad , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Femenino
12.
Apoptosis ; 2024 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-38796567

RESUMEN

Podocyte apoptosis or loss is the pivotal pathological characteristic of diabetic kidney disease (DKD). Insulin-like growth factor-binding protein 2 (IGFBP2) have a proinflammatory and proapoptotic effect on diseases. Previous studies have shown that serum IGFBP2 level significantly increased in DKD patients, but the precise mechanisms remain unclear. Here, we found that IGFBP2 levels obviously increased under a diabetic state and high glucose stimuli. Deficiency of IGFBP2 attenuated the urine protein, renal pathological injury and glomeruli hypertrophy of DKD mice induced by STZ, and knockdown or deletion of IGFBP2 alleviated podocytes apoptosis induced by high concentration of glucose or in DKD mouse. Furthermore, IGFBP2 facilitated apoptosis, which was characterized by increase in inflammation and oxidative stress, by binding with integrin α5 (ITGA5) of podocytes, and then activating the phosphorylation of focal adhesion kinase (FAK)-mediated mitochondrial injury, including membrane potential decreasing, ROS production increasing. Moreover, ITGA5 knockdown or FAK inhibition attenuated the podocyte apoptosis caused by high glucose or IGFBP2 overexpression. Taken together, these findings unveiled the insight mechanism that IGFBP2 increased podocyte apoptosis by mitochondrial injury via ITGA5/FAK phosphorylation pathway in DKD progression, and provided the potential therapeutic strategies for diabetic kidney disease.

13.
Front Immunol ; 15: 1287415, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38707899

RESUMEN

Background: The dysregulated immune response to sepsis still remains unclear. Stratification of sepsis patients into endotypes based on immune indicators is important for the future development of personalized therapies. We aimed to evaluate the immune landscape of sepsis and the use of immune clusters for identifying sepsis endotypes. Methods: The indicators involved in innate, cellular, and humoral immune cells, inhibitory immune cells, and cytokines were simultaneously assessed in 90 sepsis patients and 40 healthy controls. Unsupervised k-means cluster analysis of immune indicator data were used to identify patient clusters, and a random forest approach was used to build a prediction model for classifying sepsis endotypes. Results: We depicted that the impairment of innate and adaptive immunity accompanying increased inflammation was the most prominent feature in patients with sepsis. However, using immune indicators for distinguishing sepsis from bacteremia was difficult, most likely due to the considerable heterogeneity in sepsis patients. Cluster analysis of sepsis patients identified three immune clusters with different survival rates. Cluster 1 (36.7%) could be distinguished from the other clusters as being an "effector-type" cluster, whereas cluster 2 (34.4%) was a "potential-type" cluster, and cluster 3 (28.9%) was a "dysregulation-type" cluster, which showed the lowest survival rate. In addition, we established a prediction model based on immune indicator data, which accurately classified sepsis patients into three immune endotypes. Conclusion: We depicted the immune landscape of patients with sepsis and identified three distinct immune endotypes with different survival rates. Cluster membership could be predicted with a model based on immune data.


Asunto(s)
Sepsis , Humanos , Sepsis/inmunología , Sepsis/diagnóstico , Sepsis/mortalidad , Masculino , Femenino , Persona de Mediana Edad , Anciano , Análisis por Conglomerados , Adulto , Citocinas/inmunología , Citocinas/metabolismo , Biomarcadores , Inmunidad Innata , Inmunidad Adaptativa
14.
Cell Commun Signal ; 22(1): 291, 2024 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-38802835

RESUMEN

A promising new therapy option for acute kidney injury (AKI) is mesenchymal stem cells (MSCs). However, there are several limitations to the use of MSCs, such as low rates of survival, limited homing capacity, and unclear differentiation. In search of better therapeutic strategies, we explored all-trans retinoic acid (ATRA) pretreatment of MSCs to observe whether it could improve the therapeutic efficacy of AKI. We established a renal ischemia/reperfusion injury model and treated mice with ATRA-pretreated MSCs via tail vein injection. We found that AKI mice treated with ATRA-MSCs significantly improved renal function compared with DMSO-MSCs treatment. RNA sequencing screened that hyaluronic acid (HA) production from MSCs promoted by ATRA. Further validation by chromatin immunoprecipitation experiments verified that retinoic acid receptor RARα/RXRγ was a potential transcription factor for hyaluronic acid synthase 2. Additionally, an in vitro hypoxia/reoxygenation model was established using human proximal tubular epithelial cells (HK-2). After co-culturing HK-2 cells with ATRA-pretreated MSCs, we observed that HA binds to cluster determinant 44 (CD44) and activates the PI3K/AKT pathway, which enhances the anti-inflammatory, anti-apoptotic, and proliferative repair effects of MSCs in AKI. Inhibition of the HA/CD44 axis effectively reverses the renal repair effect of ATRA-pretreated MSCs. Taken together, our study suggests that ATRA pretreatment promotes HA production by MSCs and activates the PI3K/AKT pathway in renal tubular epithelial cells, thereby enhancing the efficacy of MSCs against AKI.


Asunto(s)
Lesión Renal Aguda , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Tretinoina , Lesión Renal Aguda/terapia , Lesión Renal Aguda/patología , Lesión Renal Aguda/metabolismo , Lesión Renal Aguda/tratamiento farmacológico , Animales , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/citología , Tretinoina/farmacología , Tretinoina/uso terapéutico , Humanos , Ratones , Masculino , Ratones Endogámicos C57BL , Ácido Hialurónico/farmacología , Receptores de Hialuranos/metabolismo , Receptores de Hialuranos/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Línea Celular , Fosfatidilinositol 3-Quinasas/metabolismo , Transducción de Señal/efectos de los fármacos , Daño por Reperfusión/terapia , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/patología , Daño por Reperfusión/metabolismo , Modelos Animales de Enfermedad , Apoptosis/efectos de los fármacos
15.
Front Genet ; 15: 1366453, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38694874

RESUMEN

Introduction: Glaucoma, a principal cause of irreversible vision loss, is characterized by intricate optic neuropathy involving significant immune mechanisms. This study seeks to elucidate the molecular and immune complexities of glaucoma, aiming to improve our understanding of its pathogenesis. Methods: Gene expression profiles from glaucoma patients were analyzed to identify immune-related differentially expressed genes (DEGs). Techniques used were weighted gene co-expression network analysis (WGCNA) for network building, machine learning algorithms for biomarker identification, establishment of subclusters related to immune reactions, and single-sample gene set enrichment analysis (ssGSEA) to explore hub genes' relationships with immune cell infiltration and immune pathway activation. Validation was performed using an NMDA-induced excitotoxicity model and RT-qPCR for hub gene expression measurement. Results: The study identified 409 DEGs differentiating healthy individuals from glaucoma patients, highlighting the immune response's significance in disease progression. Immune cell infiltration analysis revealed elevated levels of activated dendritic cells, natural killer cells, monocytes, and immature dendritic cells in glaucoma samples. Three hub genes, CD40LG, TEK, and MDK, were validated as potential diagnostic biomarkers for high-risk glaucoma patients, showing increased expression in the NMDA-induced excitotoxicity model. Discussion: The findings propose the three identified immune-related genes (IRGs) as novel diagnostic markers for glaucoma, offering new insights into the disease's pathogenesis and potential therapeutic targets. The strong correlation between these IRGs and immune responses underscores the intricate role of immunity in glaucoma, suggesting a shift in the approach to its diagnosis and treatment.

16.
Materials (Basel) ; 17(7)2024 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-38612083

RESUMEN

In this paper, ordinary Portland cement, ultrafine cement, polyurethane, and epoxy resin were selected as typical grouting materials. Grouting simulation tests were first conducted to prepare the grouted concrete crack sample. The effect of concrete crack parameters (i.e., crack aperture and roughness), grout water-cement ratio, and grouting pressure on the water-plugging performance of different grouting materials was explored through the impermeability test. The microstructure of grouted concrete cracks was analyzed by means of scanning electron microscopy (SEM) and computed tomography (CT), and the difference in water-plugging performance of different grouting materials was explained at the micro level. The results show that the impermeability of the four grouting materials was ranked as follows: Epoxy resin > polyurethane > ultra-fine cement > ordinary Portland cement. The concrete cracks grouted by epoxy resin have the highest plugging failure water pressure and the lowest permeability, which is the optimal grouting material. The effectiveness of crack grouting in water-plugging was directly proportional to the grouting pressure, provided the pressure did not exceed a certain value. When the pressure surpassed the threshold, the increase in pressure did not have a significant impact on the water plugging performance. For the two cement-based materials, the threshold pressure was 1 MPa, while for the other two chemical grouts, it was 2 MPa. The two cement-based grouts with a water-cement ratio of 0.8 showed optimal water-plugging performance. The water-plugging performance of ordinary Portland cement paste, ultra-fine cement pastes, and polyurethane grout was negatively correlated with crack aperture and positively correlated with crack roughness. However, the water-plugging performance of epoxy resin grout was not affected by crack aperture or roughness.

17.
Am J Ophthalmol ; 265: 176-188, 2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38679355

RESUMEN

PURPOSE: To assess the incidence of secondary glaucoma in children following congenital cataract surgery. DESIGN: Systematic review and meta-analysis. METHODS: The PubMed, Embase, Cochrane Library, and Web of Science databases were searched from inception through March 16, 2023. Studies reporting congenital cataract surgery and glaucoma were enrolled. The quality of the selected studies was assessed using the Newcastle Ottawa Scale, and data analysis was executed utilizing R software. RESULTS: A total of 36 published studies with 3151 patients (4717 eyes) were included in the analysis. The incidence rate of glaucoma following congenital cataract surgery was 6.6% (95% CI: 3.9%, 9.9%). The incidence of secondary glaucoma in the primary intraocular lens (IOL) implantation group (3.3% [95% CI: 1.5%, 5.8%]) and the secondary IOL implantation group (3.5% [95% CI: 0%, 11.4%]) were lower compared to the aphakia group (13.5% [95% CI: 7.7%, 20.6%]). The incidence rate among children with congenital cataracts from Asia (6.9% [95% CI: 4.1%, 10.4%]) was higher than that in European children (0.9% [95% CI: 0%, 3.0%]; P < .01). A correlation was identified between the age at cataract surgery and the incidence of secondary glaucoma (P = .02). CONCLUSIONS: This meta-analysis found that the incidence of secondary glaucoma following congenital cataract surgery is approximately 6.6%. Children with IOL implantation exhibit a lower incidence of secondary glaucoma, with a lower incidence noted in European children compared to their Asian counterparts. The age at cataract surgery is an important risk factor to consider.

18.
Artif Intell Med ; 151: 102848, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38658132

RESUMEN

Medical Knowledge Graphs (MKGs) are vital in propelling big data technologies in healthcare and facilitating the realization of medical intelligence. However, large-scale MKGs often exhibit characteristics of data sparsity and missing facts. Following the latest advances, knowledge embedding addresses these problems by performing knowledge graph completion. Most knowledge embedding algorithms rely solely on triplet structural information, overlooking the rich information hidden within entity property sets, leading to bottlenecks in performance enhancement when dealing with the intricate relations of MKGs. Inspired by the semantic sensitivity and explicit type constraints unique to the medical domain, we propose BioBERT-based graph embedding model. This model represents an evolvable framework that integrates graph embedding, language embedding, and type information, thereby optimizing the utility of MKGs. Our study utilizes not only WordNet as a benchmark dataset but also incorporates MedicalKG to compare and corroborate the specificity of medical knowledge. Experimental results on these datasets indicate that the proposed fusion framework achieves state-of-art (SOTA) performance compared to other baselines. We believe that this incremental improvement provides promising insights for future medical knowledge graph completion endeavors.


Asunto(s)
Algoritmos , Humanos , Inteligencia Artificial , Semántica , Macrodatos
19.
Digit Health ; 10: 20552076241239246, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38577314

RESUMEN

Objectives: This study aims to investigate the impact of digital engagement on urban-rural disparities in depressive symptoms among Chinese women. Methods: Using a dataset from the China Family Panel Studies (CFPS) wave 2020, this study analyzes the impact of digital engagement on the urban-rural disparity in women's depressive symptoms using multiple linear regression and recentered influence function (RIF) models. Furthermore, the extent to which digital engagement affects the urban-rural disparity in women's depressive symptoms was calculated using the RIF decomposition method. Results: Analysis showed that rural women had significantly higher levels of depressive symptoms compared to urban women; digital engagement significantly reduced women's depressive symptoms levels and mitigated the urban-rural disparity for women with moderate to high levels of depressive symptoms, and the mitigating effect was stronger for the highly depressed sample, but still widened the urban-rural disparity in women's depressive symptoms overall. In addition, the results of the RIF decomposition showed that digital engagement explained 28.28% of the urban-rural disparity in women's depressive symptoms. Conclusion: There is a significant disparity in depressive symptoms levels between urban and rural women in China. Digital engagement reduces women's depressive symptoms, but it also widens the depressive symptoms disparity between urban and rural women overall. Digital engagement is potentially positive for reducing women's depressive symptoms.

20.
Nat Commun ; 15(1): 2818, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38561369

RESUMEN

Interplay between innate and adaptive immune cells is important for the antitumor immune response. However, the tumor microenvironment may turn immune suppressive, and tumor associated macrophages are playing a role in this transition. Here, we show that CD276, expressed on tumor-associated macrophages (TAM), play a role in diminishing the immune response against tumors. Using a model of tumors induced by N-butyl-N-(4-hydroxybutyl) nitrosamine in BLCA male mice we show that genetic ablation of CD276 in TAMs blocks efferocytosis and enhances the expression of the major histocompatibility complex class II (MHCII) of TAMs. This in turn increases CD4 + and cytotoxic CD8 + T cell infiltration of the tumor. Combined single cell RNA sequencing and functional experiments reveal that CD276 activates the lysosomal signaling pathway and the transcription factor JUN to regulate the expression of AXL and MerTK, resulting in enhanced efferocytosis in TAMs. Proving the principle, we show that simultaneous blockade of CD276 and PD-1 restrain tumor growth better than any of the components as a single intervention. Taken together, our study supports a role for CD276 in efferocytosis by TAMs, which is potentially targetable for combination immune therapy.


Asunto(s)
Macrófagos Asociados a Tumores , Neoplasias de la Vejiga Urinaria , Animales , Masculino , Ratones , Eferocitosis , Evasión Inmune , Macrófagos/metabolismo , Factores de Transcripción/metabolismo , Microambiente Tumoral , Neoplasias de la Vejiga Urinaria/metabolismo
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