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1.
J Environ Sci (China) ; 147: 74-82, 2025 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-39003085

RESUMEN

Endocrine disruptors such as bisphenol A (BPA) adversely affect the environment and human health. Laccases are used for the efficient biodegradation of various persistent organic pollutants in an environmentally safe manner. However, the direct application of free laccases is generally hindered by short enzyme lifetimes, non-reusability, and the high cost of a single use. In this study, laccases were immobilized on a novel magnetic three-dimensional poly(ethylene glycol) diacrylate (PEGDA)-chitosan (CS) inverse opal hydrogel (LAC@MPEGDA@CS@IOH). The immobilized laccase showed significant improvement in the BPA degradation performance and superior storage stability compared with the free laccase. 91.1% of 100 mg/L BPA was removed by the LAC@MPEGDA@CS@IOH in 3 hr, whereas only 50.6% of BPA was removed by the same amount of the free laccase. Compared with the laccase, the outstanding BPA degradation efficiency of the LAC@MPEGDA@CS@IOH was maintained over a wider range of pH values and temperatures. Moreover, its relative activity of was maintained at 70.4% after 10 cycles, and the system performed well in actual water matrices. This efficient method for preparing immobilized laccases is simple and green, and it can be used to further develop ecofriendly biocatalysts to remove organic pollutants from wastewater.


Asunto(s)
Compuestos de Bencidrilo , Enzimas Inmovilizadas , Lacasa , Fenoles , Polietilenglicoles , Contaminantes Químicos del Agua , Lacasa/química , Lacasa/metabolismo , Fenoles/química , Contaminantes Químicos del Agua/química , Enzimas Inmovilizadas/química , Enzimas Inmovilizadas/metabolismo , Polietilenglicoles/química , Quitosano/química , Hidrogeles/química , Biodegradación Ambiental , Disruptores Endocrinos/química
2.
Br J Pharmacol ; 2024 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-39374939

RESUMEN

BACKGROUND AND PURPOSE: Pathological retinal angiogenesis is a typical manifestation of vision-threatening ocular diseases. Many patients exhibit poor response or resistance to anti-vascular endothelial growth factor (VEGF) agents. Bruton's tyrosine kinase (BTK) controls the proliferation and function of immune cells. Therefore, we examined the anti-inflammatory and anti-angiogenic effects of BTK inhibition on retinal angiogenesis. EXPERIMENTAL APPROACH: Retinal neovascularisation and vascular leakage in oxygen-induced retinopathy in C57/BL6J mice were assessed by whole-mount retinal immunofluorescence. PLX5622 was used to deplete microglia and Rag1-knockout mice were used to test the contribution of lymphocytes to the effects of BTK inhibition. The cytokines, activation markers, inflammatory and immune-regulatory activities of retinal microglia/macrophages were detected using qRT-PCR and immunofluorescence. NLRP3 was detected by western blotting, and the effects of BTK inhibition on the co-culture of microglia and human retinal microvascular endothelial cells (HRMECs) were examined. KEY RESULTS: BTK inhibition suppressed pathological angiogenesis and vascular leakage, and significantly reduced retinal inflammation, which involved microglia/macrophages but not lymphocytes. BTK inhibition increased anti-inflammatory factors and reduced pro-inflammatory cytokines that resulted from NLRP3 inflammasome activation. BTK inhibition suppressed the inflammatory activity of microglia/macrophages, and acted synergistically with anti-VEGF without retinal toxicity. Moreover, the supernatant of microglia incubated with BTK-inhibitor reduced the proliferation, tube formation and sprouting of HRMECs. CONCLUSION AND IMPLICATIONS: BTK inhibition suppressed retinal neovascularisation and vascular leakage by modulating the inflammatory activity of microglia and macrophages. Our study suggests BTK inhibition as a novel and promising approach for alleviating pathological retinal angiogenesis.

3.
Regen Ther ; 26: 826-830, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-39329099

RESUMEN

Platelet rich plasma (PRP) is increasingly used in various fields of medicine, aiming to regeneration and repair damaged tissues, cells and organs. High concentration of bioactive molecules including growth factors, cytokines and chemokines are the rationale of using PRP. The aim of this study is to analyze the effect of frozen on the levels of growth factors. In our study, PRP samples were isolated from 50 healthy volunteers using the Trima Accel blood cell separator. The concentration of growth factors such as platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), insulin-like growth factor (IGF-1) and platelet factor 4 (PF-4) were assessed in fresh PRP and frozen PRP stored at -80 °C for one to twelve months. The study found that count of platelet in all fresh and frozen PRP samples was significantly increased compared to whole blood baseline. There was no significant difference in the concentrations of PDGF-BB, bFGF, VEGF, and PF-4 between fresh and frozen samples. The concentrations of EGF and IGF in Frozen-PRP group were significantly higher than those in Fresh-PRP group. And the storage condition of -80 °C is suitable for PRP, which will not lead to a decrease in growth factors concentration for at least 6 months.

4.
Conscious Cogn ; 124: 103734, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39096822

RESUMEN

The cognitive neural mechanisms by which sleep deprivation affects cognitive flexibility are poorly understood. Therefore, the study investigated the neuroelectrophysiological basis of the effect of 24 h sleep deprivation on cognitive flexibility in adolescents. 72 participants (36 females, mean age ± SD=20.46 ± 2.385 years old) participated in the study and were randomly assigned to the sleep deprivation group and control group. They were instructed to complete a task switch paradigm, during which participants' behavioral and electroencephalographic data were recorded. Behaviorally, there were significant between-group differences in accuracy. The results of event-related potential showed that the P2, N2 and P3 components had significant group effects or interaction effects. At the time-frequency level, there were statistically significant differences between the delta and theta bands. These results suggested that 24 h sleep deprivation affected problem-solving effectiveness rather than efficiency, mainly because it systematically impaired cognitive processing associated with cognitive flexibility.


Asunto(s)
Electroencefalografía , Potenciales Evocados , Privación de Sueño , Humanos , Privación de Sueño/fisiopatología , Femenino , Masculino , Adolescente , Potenciales Evocados/fisiología , Adulto Joven , Función Ejecutiva/fisiología , Adulto , Solución de Problemas/fisiología , Desempeño Psicomotor/fisiología
5.
Sci Transl Med ; 16(760): eadi6626, 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39141700

RESUMEN

Neovascular age-related macular degeneration (nvAMD) is the leading cause of blindness in the elderly population. Although it is known that nvAMD is associated with focal inflammation, understanding of the precise immune components governing this process remains limited. Here, we identified natural killer (NK) cells as a prominent lymphocyte population infiltrating the perivascular space of choroidal neovascularization (CNV) lesions in patients with nvAMD and in mouse models. Olink proteomic analysis and single-cell RNA sequencing combined with knockout studies demonstrated the involvement of C-C chemokine receptor 5 (CCR5) in NK cell recruitment and extravasation at the CNV sites of mice. Depletion of NK cells or inhibition of activating receptor NK group 2, member D (NKG2D) inhibited the formation of neutrophil extracellular traps, increased vascular leakage, and exacerbated pathological angiogenesis, indicating that NK cells restrain pathogenesis in this mouse model. Age is the strongest risk factor for AMD, and we show that NK cells from aged human donors exhibited a less cytotoxic phenotype. NK cells from old mice exhibited compromised protective effects in the CNV mouse model. In addition, interleukin-2 complex-mediated expansion of NK cells improved CNV formation in mice. Collectively, our study highlights NK cells as a potential therapeutic target for patients with nvAMD.


Asunto(s)
Trampas Extracelulares , Células Asesinas Naturales , Degeneración Macular , Animales , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/metabolismo , Degeneración Macular/patología , Humanos , Trampas Extracelulares/metabolismo , Neovascularización Coroidal/patología , Neovascularización Coroidal/metabolismo , Modelos Animales de Enfermedad , Ratones , Ratones Endogámicos C57BL , Neutrófilos/metabolismo , Neutrófilos/inmunología , Masculino , Anciano , Femenino
6.
J Nurs Care Qual ; 39(4): E47-E53, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39167924

RESUMEN

BACKGROUND: Diarrhea during enteral nutrition may induce various complications and increase the nursing workload. LOCAL PROBLEM: The diarrhea rate in our intensive care units (ICUs) was 37.14% from May to July 2021. Nurses reported a moderate to heavy burden regarding care for those with diarrhea. METHODS: A pre-post implementation design was used to evaluate the impact of evidence-based interventions for diarrhea screening and prevention. INTERVENTIONS: A diarrhea risk screening tool and countermeasures were developed through an extensive literature review. Tools were integrated into the electronic health record system. RESULTS: The rate of diarrhea decreased from 37.14% to 17.33% ( P = .000). Nurse's compliance with practice standards increased for diarrhea assessment, risk factor screening, agent choice, and countermeasures provision ( P < .05). CONCLUSIONS: The evidence-based tools developed for this project helped decrease the diarrhea rate in our ICUs.


Asunto(s)
Enfermedad Crítica , Diarrea , Nutrición Enteral , Unidades de Cuidados Intensivos , Mejoramiento de la Calidad , Humanos , Diarrea/prevención & control , Nutrición Enteral/normas , Factores de Riesgo , Femenino , Masculino , Persona de Mediana Edad
7.
Physiol Plant ; 176(4): e14465, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39126176

RESUMEN

Sugar is vital for plant growth and determines fruit quality via its content and composition. This study explores the differential sugar accumulation in two plum varieties, 'Fengtangli (FTL)' and 'Siyueli (SYL)'. The result showed that 'FTL' fruit displayed higher soluble solids and sugar content at various development stages. Metabolomic analysis indicated increased sorbitol in 'FTL', linked to elevated sorbitol-6-phosphate-dehydrogenase (S6PDH) activity. Transcriptome analysis identified a key gene for sorbitol synthesis, PsS6PDH4, which was significantly higher expressed in 'FTL' than in 'SYL'. The function of the PsS6PDH4 gene was verified in strawberry, apple, and plum fruits using transient overexpression and virus-induced gene silencing techniques. The results showed that overexpression of the PsS6PDH4 gene in strawberry, apple, and plum fruits promoted the accumulation of soluble solids content and sorbitol, while inhibition of the gene reduced soluble solids content and sorbitol content. Meanwhile, analysis of the relationship between PsS6PDH4 gene expression, sorbitol, and soluble solids content in four different plum varieties revealed a significant correlation between PsS6PDH4 gene expression and soluble solids content as well as sorbitol content. This research discovered PsS6PDH4 as a crucial regulator of sugar metabolism in plum, with potential applications in improving fruit sweetness and nutritional value in various fruit species. Understanding these molecular pathways can lead to innovative approaches for enhancing fruit quality, benefiting sustainable agriculture and consumer preferences in the global fruit industry.


Asunto(s)
Frutas , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas , Prunus domestica , Sorbitol , Sorbitol/metabolismo , Prunus domestica/genética , Prunus domestica/metabolismo , Frutas/genética , Frutas/metabolismo , Frutas/crecimiento & desarrollo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Fragaria/genética , Fragaria/metabolismo , Azúcares/metabolismo , Malus/genética , Malus/metabolismo
8.
Gene Ther ; 31(9-10): 511-523, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38961279

RESUMEN

Neovascular age-related macular degeneration (nAMD) causes severe visual impairment. Pigment epithelium-derived factor (PEDF), soluble CD59 (sCD59), and soluble fms-like tyrosine kinase-1 (sFLT-1) are potential therapeutic agents for nAMD, which target angiogenesis and the complement system. Using the AAV2/8 vector, two bi-target gene therapy agents, AAV2/8-PEDF-P2A-sCD59 and AAV2/8-sFLT-1-P2A-sCD59, were generated, and their therapeutic efficacy was investigated in laser-induced choroidal neovascularization (CNV) and Vldlr-/- mouse models. After a single injection, AAV2/8-mediated gene expression was maintained at high levels in the retina for two months. Both AAV2/8-PEDF-P2A-sCD59 and AAV2/8-sFLT-1-P2A-sCD59 significantly reduced CNV development for an extended period without side effects and provided efficacy similar to two injections of current anti-vascular endothelial growth factor monotherapy. Mechanistically, these agents suppressed the extracellular signal-regulated kinase and nuclear factor-κB pathways, resulting in anti-angiogenic activity. This study demonstrated the safety and long-lasting effects of AAV2/8-PEDF-P2A-sCD59 and AAV2/8-sFLT-1-P2A-sCD59 in CNV treatment, providing a promising therapeutic strategy for nAMD.


Asunto(s)
Neovascularización Coroidal , Dependovirus , Terapia Genética , Vectores Genéticos , Neovascularización Coroidal/terapia , Animales , Dependovirus/genética , Ratones , Terapia Genética/métodos , Vectores Genéticos/administración & dosificación , Vectores Genéticos/genética , Factores de Crecimiento Nervioso/genética , Factores de Crecimiento Nervioso/metabolismo , Proteínas del Ojo/genética , Proteínas del Ojo/metabolismo , Proteínas del Ojo/farmacología , Receptor 1 de Factores de Crecimiento Endotelial Vascular/genética , Receptor 1 de Factores de Crecimiento Endotelial Vascular/metabolismo , Antígenos CD59/genética , Antígenos CD59/metabolismo , Ratones Endogámicos C57BL , Humanos , Modelos Animales de Enfermedad , Parvovirinae/genética , Degeneración Macular/terapia , Serpinas
9.
Biomater Sci ; 12(15): 3905-3917, 2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-38916436

RESUMEN

Symblepharon is an adverse ocular disease resulting in ocular discomfort and impaired vision, severely dragging down a patient's quality of life. Due to the specificity of the ocular surface, the retention time of drugs on it is short, leading to limited therapeutic effects for ocular diseases. Therefore, it is imperative to design a novel drug delivery system, which can not only prolong the retention time of a drug but also play an anti-fibrosis role in symblepharon. Herein, an antifouling supramolecular polymer ophthalmic ointment consisting of poly(N-acryloyl alaninamide) (PNAAA), vitamin C (VitC) and levofloxacin (Levo) was developed (termed PNAVL ophthalmic ointment), which acted as a mucoadhesive and long-acting ocular delivery system. This antifouling PNAVL ophthalmic ointment improved the retention time of VitC and Levo, and simultaneously provided anti-inflammation and anti-fibrosis effects for mitigating symblepharon after ocular alkali burn injury.


Asunto(s)
Quemaduras Oculares , Pomadas , Animales , Ratas , Quemaduras Oculares/inducido químicamente , Quemaduras Oculares/tratamiento farmacológico , Quemaduras Oculares/patología , Quemaduras Químicas/tratamiento farmacológico , Ratas Sprague-Dawley , Polímeros/química , Polímeros/farmacología , Álcalis/química , Levofloxacino/administración & dosificación , Levofloxacino/farmacología , Levofloxacino/química , Masculino , Ácido Ascórbico/química , Ácido Ascórbico/farmacología , Ácido Ascórbico/administración & dosificación
10.
Nat Methods ; 21(7): 1349-1363, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38849569

RESUMEN

The Long-read RNA-Seq Genome Annotation Assessment Project Consortium was formed to evaluate the effectiveness of long-read approaches for transcriptome analysis. Using different protocols and sequencing platforms, the consortium generated over 427 million long-read sequences from complementary DNA and direct RNA datasets, encompassing human, mouse and manatee species. Developers utilized these data to address challenges in transcript isoform detection, quantification and de novo transcript detection. The study revealed that libraries with longer, more accurate sequences produce more accurate transcripts than those with increased read depth, whereas greater read depth improved quantification accuracy. In well-annotated genomes, tools based on reference sequences demonstrated the best performance. Incorporating additional orthogonal data and replicate samples is advised when aiming to detect rare and novel transcripts or using reference-free approaches. This collaborative study offers a benchmark for current practices and provides direction for future method development in transcriptome analysis.


Asunto(s)
Perfilación de la Expresión Génica , RNA-Seq , Humanos , Animales , Ratones , RNA-Seq/métodos , Perfilación de la Expresión Génica/métodos , Transcriptoma , Análisis de Secuencia de ARN/métodos , Anotación de Secuencia Molecular/métodos
11.
Curr Pharm Des ; 30(25): 2007-2026, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38867534

RESUMEN

BACKGROUND: Colorectal Cancer (CRC) is one of the top three malignancies with the highest incidence and mortality. OBJECTIVE: The study aimed to identify the effect of Traditional Chinese Medicine (TCM) on postoperative patients with stage II-III CRC and explore the core herb combination and its mechanism. METHODS: An observational cohort study was conducted on patients diagnosed with stage II-III CRC from January 2016 to January 2021. The primary outcome was disease-free survival, which was compared between the patients who received TCM or not, and the secondary outcome was the hazard ratio. The relevance principle was used to obtain the candidate herb combinations, and the core combination was evaluated through an assessment of efficacy and representativeness. Then, biological processes and signaling pathways associated with CRC were obtained by Gene Ontology function, Kyoto Encyclopedia of Gene and Genomes pathway, and Wikipathway. Furthermore, hub genes were screened by the Kaplan-Meier estimator, and molecular docking was employed to predict the binding sites of key ingredients to hub genes. The correlation analysis was employed for the correlations between the hub genes and tumor-infiltrating immune cells and hypoxiarelated genes. Ultimately, a quantitative polymerase chain reaction was performed to verify the regulation of hub genes by their major ingredients. RESULTS: A total of 707 patients were included. TCM could decrease the metastatic recurrence associated with stage II-III CRC (HR: 0.61, log-rank P < 0.05). Among those patients in the TCM group, the core combination was Baizhu → Yinchen, Chenpi, and Fuling (C combination), and its antitumor mechanism was most likely related to the regulation of BCL2L1, XIAP, and TOP1 by its key ingredients, quercetin and tangeretin. The expression of these genes was significantly correlated with both tumor-infiltrating immune cells and hypoxia- related genes. In addition, quercetin and tangeretin down-regulated the mRNA levels of BCL2L1, XIAP, and TOP1, thereby inhibiting the growth of HCT116 cells. CONCLUSION: Overall, a combination of four herbs, Baizhu → Yinchen, Chenpi, and Fuling, could reduce metastatic recurrence in postoperative patients with stage II-III CRC. The mechanism may be related to the regulation of BCL2L1, XIAP, and TOP1 by its key ingredients quercetin and tangeretin.


Asunto(s)
Neoplasias Colorrectales , Biología Computacional , Medicamentos Herbarios Chinos , Farmacología en Red , Humanos , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Estadificación de Neoplasias , Microambiente Tumoral/efectos de los fármacos , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia/prevención & control , Estudios de Cohortes , Medicina Tradicional China
12.
World J Gastrointest Oncol ; 16(5): 1849-1860, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38764830

RESUMEN

BACKGROUND: Lymph node (LN) staging in rectal cancer (RC) affects treatment decisions and patient prognosis. For radiologists, the traditional preoperative assessment of LN metastasis (LNM) using magnetic resonance imaging (MRI) poses a challenge. AIM: To explore the value of a nomogram model that combines Conventional MRI and radiomics features from the LNs of RC in assessing the preoperative metastasis of evaluable LNs. METHODS: In this retrospective study, 270 LNs (158 nonmetastatic, 112 metastatic) were randomly split into training (n = 189) and validation sets (n = 81). LNs were classified based on pathology-MRI matching. Conventional MRI features [size, shape, margin, T2-weighted imaging (T2WI) appearance, and CE-T1-weighted imaging (T1WI) enhancement] were evaluated. Three radiomics models used 3D features from T1WI and T2WI images. Additionally, a nomogram model combining conventional MRI and radiomics features was developed. The model used univariate analysis and multivariable logistic regression. Evaluation employed the receiver operating characteristic curve, with DeLong test for comparing diagnostic performance. Nomogram performance was assessed using calibration and decision curve analysis. RESULTS: The nomogram model outperformed conventional MRI and single radiomics models in evaluating LNM. In the training set, the nomogram model achieved an area under the curve (AUC) of 0.92, which was significantly higher than the AUCs of 0.82 (P < 0.001) and 0.89 (P < 0.001) of the conventional MRI and radiomics models, respectively. In the validation set, the nomogram model achieved an AUC of 0.91, significantly surpassing 0.80 (P < 0.001) and 0.86 (P < 0.001), respectively. CONCLUSION: The nomogram model showed the best performance in predicting metastasis of evaluable LNs.

13.
Environ Sci Technol ; 58(12): 5290-5298, 2024 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-38468128

RESUMEN

Hyperuricemia is characterized by elevated blood uric acid (UA) levels, which can lead to certain diseases. Epidemiological studies have explored the association between environmental contaminant exposure and hyperuricemia. However, few studies have investigated the role of chemical exposure in the development of hyperuricemia. Here, we sought to investigate the effects of bisphenol exposure on the occurrence of hyperuricemia. Fifteen bisphenol chemicals (BPs) were detected in human serum and urine samples collected from an area with a high incidence of hyperuricemia in China. Serum UA levels positively correlated with urinary bisphenol S (BPS), urinary bisphenol P (BPP), and serum bisphenol F (BPF). The effects of these three chemicals on UA levels in mice were explored at various exposure concentrations. An increase in serum UA levels was observed in BPS- and BPP-exposed mice. The results showed that BPS exposure increased serum UA levels by damaging the structure of the kidneys, whereas BPP exposure increased serum UA levels by disturbing purine metabolism in the liver. Moreover, BPF did not induce an increase in serum UA levels owing to the inhibition of guanine conversion to UA. In summary, we provide evidence of the mechanisms whereby exposure to three BPs disturbs UA homeostasis. These findings provide new insights into the risks of exposure to bisphenol chemicals.


Asunto(s)
Experimentación Animal , Hiperuricemia , Fenoles , Humanos , Animales , Ratones , Hiperuricemia/inducido químicamente , Exposición a Riesgos Ambientales , Compuestos de Bencidrilo/toxicidad
14.
Sci Total Environ ; 916: 170333, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38278269

RESUMEN

Recently intensified oil exploitation has resulted in the discharge of large amounts of wastewater containing high concentrations of organic matter and nutrients into the receiving aquatic and soil environments; however, the effects of oilfield-produced water on the soil microbiota are poorly understood. In this study, we conducted a comprehensive analysis to reveal the composition and diversity of the microbial community at horizontal and vertical scales in a typical arid soil receiving oilfield-produced water in Northwest China. Oilfield-produced water caused an increase in microbial diversity at the horizontal scale, and the communities in the topsoil were more variable than those in the subsoil. Additionally, the microbial taxonomic composition differed significantly between the near- and far-producing water soils, with Proteobacteria and Halobacterota dominating the water-affected and reference soil communities, respectively. Soil property analysis revealed that pH, salt, and total organic content influenced the bacterial communities. Furthermore, the oil-produced water promoted the complexity and modularity of distance-associated microbial networks, indicating positive interactions for soil ecosystem function, but not for irrigation or livestock watering. This is the first detailed examination of the microbial communities in soil receiving oilfield-produced water, providing new insights for understanding the microbial spatial distributions in receiving arid soils.


Asunto(s)
Microbiota , Suelo , Suelo/química , Agua , Yacimiento de Petróleo y Gas , Bacterias , Microbiología del Suelo
15.
Br J Ophthalmol ; 108(2): 285-293, 2024 01 29.
Artículo en Inglés | MEDLINE | ID: mdl-36596662

RESUMEN

BACKGROUND: The visual outcome of open globe injury (OGI)-no light perception (NLP) eyes is unpredictable traditionally. This study aimed to develop a model to predict the visual outcomes of vitrectomy surgery in OGI-NLP eyes using a machine learning algorithm and to provide an interpretable system for the prediction results. METHODS: Clinical data of 459 OGI-NLP eyes were retrospectively collected from 19 medical centres across China to establish a training data set for developing a model, called 'VisionGo', which can predict the visual outcome of the patients involved and compare with the Ocular Trauma Score (OTS). Another 72 cases were retrospectively collected and used for human-machine comparison, and an additional 27 cases were prospectively collected for real-world validation of the model. The SHapley Additive exPlanations method was applied to analyse feature contribution to the model. An online platform was built for real-world application. RESULTS: The area under the receiver operating characteristic curve (AUC) of VisionGo was 0.75 and 0.90 in previtrectomy and intravitrectomy application scenarios, which was much higher than the OTS (AUC=0.49). VisionGo showed better performance than ophthalmologists in both previtrectomy and intravitrectomy application scenarios (AUC=0.73 vs 0.57 and 0.87 vs 0.64). In real-world validation, VisionGo achieved an AUC of 0.60 and 0.91 in previtrectomy and intravitrectomy application scenarios. Feature contribution analysis indicated that wound length-related indicators, vitreous status and retina-related indicators contributed highly to visual outcomes. CONCLUSIONS: VisionGo has achieved an accurate and reliable prediction in visual outcome after vitrectomy for OGI-NLP eyes.


Asunto(s)
Lesiones Oculares Penetrantes , Lesiones Oculares , Humanos , Estudios Retrospectivos , Agudeza Visual , Retina , Vitrectomía , Pronóstico , Lesiones Oculares Penetrantes/diagnóstico , Lesiones Oculares Penetrantes/cirugía
16.
NAR Genom Bioinform ; 5(4): lqad105, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38046273

RESUMEN

scPipe is a flexible R/Bioconductor package originally developed to analyse platform-independent single-cell RNA-Seq data. To expand its preprocessing capability to accommodate new single-cell technologies, we further developed scPipe to handle single-cell ATAC-Seq and multi-modal (RNA-Seq and ATAC-Seq) data. After executing multiple data cleaning steps to remove duplicated reads, low abundance features and cells of poor quality, a SingleCellExperiment object is created that contains a sparse count matrix with features of interest in the rows and cells in the columns. Quality control information (e.g. counts per cell, features per cell, total number of fragments, fraction of fragments per peak) and any relevant feature annotations are stored as metadata. We demonstrate that scPipe can efficiently identify 'true' cells and provides flexibility for the user to fine-tune the quality control thresholds using various feature and cell-based metrics collected during data preprocessing. Researchers can then take advantage of various downstream single-cell tools available in Bioconductor for further analysis of scATAC-Seq data such as dimensionality reduction, clustering, motif enrichment, differential accessibility and cis-regulatory network analysis. The scPipe package enables a complete beginning-to-end pipeline for single-cell ATAC-Seq and RNA-Seq data analysis in R.

17.
Cell Host Microbe ; 31(11): 1792-1803.e7, 2023 11 08.
Artículo en Inglés | MEDLINE | ID: mdl-37944492

RESUMEN

Plants deploy intracellular receptors to counteract pathogen effectors that suppress cell-surface-receptor-mediated immunity. To what extent pathogens manipulate intracellular receptor-mediated immunity, and how plants tackle such manipulation, remains unknown. Arabidopsis thaliana encodes three similar ADR1 class helper nucleotide-binding domain leucine-rich repeat receptors (ADR1, ADR1-L1, and ADR1-L2), which are crucial in plant immunity initiated by intracellular receptors. Here, we report that Pseudomonas syringae effector AvrPtoB suppresses ADR1-L1- and ADR1-L2-mediated cell death. ADR1, however, evades such suppression by diversifying into two ubiquitination sites targeted by AvrPtoB. The intracellular sensor SNC1 interacts with and guards the CCR domains of ADR1-L1/L2. Removal of ADR1-L1/L2 or delivery of AvrPtoB activates SNC1, which then signals through ADR1 to trigger immunity. Our work elucidates the long-sought-after function of SNC1 in defense, and also how plants can use dual strategies, sequence diversification, and a multi-layered guard-guardee system, to counteract pathogen's attack on core immunity functions.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Proteínas de Arabidopsis/metabolismo , Inmunidad de la Planta , Ubiquitinación , Proteínas Portadoras/metabolismo , Enfermedades de las Plantas
18.
Nat Methods ; 20(11): 1810-1821, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37783886

RESUMEN

The lack of benchmark data sets with inbuilt ground-truth makes it challenging to compare the performance of existing long-read isoform detection and differential expression analysis workflows. Here, we present a benchmark experiment using two human lung adenocarcinoma cell lines that were each profiled in triplicate together with synthetic, spliced, spike-in RNAs (sequins). Samples were deeply sequenced on both Illumina short-read and Oxford Nanopore Technologies long-read platforms. Alongside the ground-truth available via the sequins, we created in silico mixture samples to allow performance assessment in the absence of true positives or true negatives. Our results show that StringTie2 and bambu outperformed other tools from the six isoform detection tools tested, DESeq2, edgeR and limma-voom were best among the five differential transcript expression tools tested and there was no clear front-runner for performing differential transcript usage analysis between the five tools compared, which suggests further methods development is needed for this application.


Asunto(s)
Perfilación de la Expresión Génica , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Perfilación de la Expresión Génica/métodos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Benchmarking/métodos , ARN , Isoformas de Proteínas
19.
Microbiol Spectr ; : e0078823, 2023 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-37707448

RESUMEN

Anaerobic fungi (AF) inhabit the gastrointestinal tract of ruminants and play an important role in the degradation of fiber feed. However, limited knowledge is available on seasonal dynamics and inter-species differences in rumen AF community in yak and cattle under natural grazing systems. Using the random forests model, the null model, and structural equation model, we investigated the seasonal dynamics and key driving factors of fiber-associated rumen AF in grazing yak and cattle throughout the year on the Qinghai-Tibet Plateau (QTP). We found that the richness and diversity of rumen AF of grazing yak and cattle in cold season were significantly higher than those in warm season (P < 0.05). We identified 12 rumen AF genera, among which , Cyllamyces, and Orpinomyces were predominant in the rumen of both grazing yak and cattle. LEfSe and random forest analysis showed that Feramyces, Tahromyces, and Buwchfawromyces were important seasonal indicator of rumen AF in grazing yak (P < 0.05), and Caecomyces, Cyllamyces, and Piromyces in grazing cattle (P < 0.05). Null model analysis revealed that the dynamic changes of rumen AF community structure were mainly affected by deterministic factors. Notably, mantel test and structural equation model revealed that forage physical-chemical properties, including dry matter (DM), neutral detergent fiber (NDF), and hemicellulose contents (HC) were the key factors driving the seasonal variations of the rumen AF community (P < 0.05). The results revealed that forage lignocellulose was probably an important factor affecting the seasonal dynamics and inter-species differences of the rumen AF community under natural grazing conditions. IMPORTANCE The seasonal dynamics of rumen anaerobic fungi in nature grazing yak and cattle were determined during cold and warm seasons based on pasture nutritional quality and environmental data sets. The main driving factors of anaerobic fungi in yak and cattle rumen were explored by combining random forest and structural equation models. In addition, the dynamic differences in the composition of the anaerobic fungi community in the yak and cattle in different seasons were characterized. It was found that some rumen anaerobic fungi have contributed to high fiber degradation rate in yak. These novel findings improve our understanding of the association of environmental and dietary seasonal variations with anaerobic fungal community, facilitating yak adaptation to high altitude.

20.
Sci Total Environ ; 901: 166429, 2023 Nov 25.
Artículo en Inglés | MEDLINE | ID: mdl-37619739

RESUMEN

Bisphenol A (BPA) and its analogs are endocrine-disrupting chemicals that are frequently detected in environmental and human samples. However, the effective removal of BPA and its analogs has not yet been extensively studied. Herein, we introduce a novel enzyme reactor for the degradation of BPA and its analogs in water. The influence of pore size on the degradation efficiency of immobilized laccase in the spatial nanopores of hydrogel was investigated using BPA as a representative compound. This showed that nanopores enhance the activity of immobilized laccases in a pore size-dependent manner and increase their stability. Compared with the same amount of free laccase, the 50 mg/L BPA degradation performance of laccase immobilized in 76 nm nanopores increased to 300 %. Taking advantage of magnetic separation, this immobilized laccase can be reused, and its degradation capacity was maintained at over 73.7 % after ten reactions. Moreover, the degradation of seven BPA analogs was 1.03-5.88 times higher using laccase immobilized in nanopores compared with free laccase. Also, the biocatalyst could efficiently degrade BPA analogs in real water matrix. This study opens up a new avenue for the removal of BPA and its analogs by immobilizing laccase in nanopores, overcoming the key limitations introduced by the short enzyme life span and non-reusability.

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