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Xenotropic and polytropic retrovirus receptor 1 (XPR1) is the only known transporter associated with Pi efflux in mammals, and its impact on tumor progression is gradually being revealed. However, the role of XPR1 in hepatocellular carcinoma (HCC) is unknown. A bioinformatics screen for the phosphate exporter XPR1 was performed in HCC patients. The expression of XPR1 in clinical specimens was analyzed using quantitative real-time PCR, Western blot analysis, and immunohistochemical assays. Knockdown of the phosphate exporter XPR1 was performed by shRNA transfection to investigate the cellular phenotype and phosphate-related cytotoxicity of the Huh7 and HLF cell lines. In vivo tests were conducted to investigate the tumorigenicity of HCC cells xenografted into immunocompromised mice after silencing XPR1. Compared with that in paracancerous tissue, XPR1 expression in HCC tissues was markedly upregulated. High XPR1 expression significantly correlated with poor patient survival. Silencing of XPR1 leads to decreased proliferation, migration, invasion, and colony formation in HCC cells. Mechanistically, knockdown of XPR1 causes an increase in intracellular phosphate levels; mitochondrial dysfunction characterized by reduced mitochondrial membrane potential and adenosine triphosphate levels; increased reactive oxygen species levels; abnormal mitochondrial morphology; and downregulation of key mitochondrial fusion, fission, and inner membrane genes. This ultimately results in mitochondria-dependent apoptosis. These findings reveal the prognostic value of XPR1 in HCC progression and, more importantly, suggest that XPR1 might be a potential therapeutic target.
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Extracellular clustering of amyloid-ß (Aß) and an impaired autophagy lysosomal pathway (ALP) are the hallmark features in the early stages of incurable Alzheimer's disease (AD). There is a pressing need to find or develop new small molecules for diagnostics and therapeutics for the early stages of AD. Herein, we report a small molecule, namely F-SLCOOH, which can bind and detect Aß1-42, Iowa mutation Aß, Dutch mutation Aß fibrils and oligomers exhibiting enhanced emission with high affinity. Importantly, F-SLCOOH can readily pass through the blood-brain barrier and shows highly selective binding toward the extracellular Aß aggregates in real-time in live animal imaging of a 5XFAD mice model. In addition, a high concentration of F-SLCOOH in both brain and plasma of wildtype mice after intraperitoneal administration was found. The ex vivo confocal imaging of hippocampal brain slices indicated excellent colocalization of F-SLCOOH with Aß positive NU1, 4G8, 6E10 A11 antibodies and THS staining dye, affirming its excellent Aß specificity and targetability. The molecular docking studies have provided insight into the unique and specific binding of F-SLCOOH with various Aß species. Importantly, F-SLCOOH exhibits remarkable anti-fibrillation properties against toxic Aß aggregate formation of Aß1-42, Iowa mutation Aß, and Dutch mutation Aß. F-SLCOOH treatment also exerts high neuroprotective functions and promotes autophagy lysosomal biogenesis in neuronal AD cell models. In summary, the present results suggest that F-SLCOOH is a highly promising theranostic agent for diagnosis and therapeutics of AD.
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Enfermedad de Alzheimer , Péptidos beta-Amiloides , Lisosomas , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Animales , Ratones , Péptidos beta-Amiloides/metabolismo , Lisosomas/metabolismo , Humanos , Mutación , Simulación del Acoplamiento Molecular , Placa Amiloide/metabolismo , Nanomedicina Teranóstica , Ratones TransgénicosRESUMEN
Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related deaths. With the development of screening, patient selection and treatment strategies, patients' survival outcomes and living quality significantly improved. However, some patients still have local recurrence or residual tumors after receiving definitive therapies. Salvage surgery has been regarded as an effective option for recurrent or residual NSCLC, but its effectiveness remains undetermined. Furthermore, conversion surgery is a special type of salvage surgery for tumors converted from "initially unresectable" to "potentially resectable" status due to a favorable response to systemic treatments. Although conversion surgery is a promising curative procedure for advanced NSCLC, its concept and clinical value remain unfamiliar to clinicians. In this narrative review, we provided an overview of the safety and efficacy of salvage surgery, especially salvage surgery after sublobar resection in early-stage NSCLC. More importantly, we highlighted the concept and value of conversion surgery after systemic treatment in advanced NSCLC to gain some insights into its role in the treatment of lung cancer.
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BACKGROUND: Lymph node metastasis is significantly associated with a worse prognosis in patients with localized early-stage esophageal squamous cell carcinoma. This study aimed to explore the prognostic factors and develop a nomogram for predicting survival in patients with pathologic T1-2N+ esophageal squamous cell carcinoma. METHODS: Between 2014 and 2022, patients with pT1-2N+ esophageal squamous cell carcinoma who underwent esophagectomy with lymphadenectomy at 2 institutes were reviewed and assigned to training and external validation cohorts. Independent prognostic factors were identified via univariate and multivariate Cox regression analyses. The nomogram model was developed and evaluated by the area under the receiver operating characteristic curve and calibration curve. RESULTS: In total, 268 patients with a median age of 65 years (range, 40-82) were included and assigned to training (n = 190) and external validation (n = 78) cohorts. The Cox proportional hazards model demonstrated that body mass index (P = .031), surgical approach (P < .001), T stage (P = .015), and Clavien-Dindo classification (P < .001) were independent prognostic factors in the training cohort. The nomogram showed good discrimination, with an area under the receiver operating characteristic curve for 1-year, 3-year, and 5-year of 0.810, 0.789, and 0.809 in the training cohort and 0.782, 0.679, and 0.698 in the validation cohort. The calibration curve showed that the predicted survival probability was in good agreement with the actual survival probability. CONCLUSION: Lower body mass index, left surgical approach, T2 stage, and Clavien-Dindo classification grade III to V were related to worse prognosis in patients with pT1-T2N+ esophageal squamous cell carcinoma. The developed nomogram may predict individual survival accurately.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Esofagectomía , Estadificación de Neoplasias , Nomogramas , Humanos , Persona de Mediana Edad , Masculino , Femenino , Estudios Retrospectivos , Anciano , Carcinoma de Células Escamosas de Esófago/cirugía , Carcinoma de Células Escamosas de Esófago/mortalidad , Carcinoma de Células Escamosas de Esófago/patología , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/cirugía , Pronóstico , Adulto , Anciano de 80 o más Años , Metástasis Linfática , Escisión del Ganglio Linfático , Curva ROC , Modelos de Riesgos ProporcionalesRESUMEN
How to address public health priorities after COVID-19 is becoming a critical task. To this end, we conducted wastewater surveillance for six leading pathogens, namely, SARS-CoV-2, norovirus, rotavirus, influenza A virus (IAV), enteroviruses and respiratory syncytial virus (RSV), in Nanchang city from January to April 2023. Metaviromic sequencing was conducted at the 1st, 4th, 7th, 9th, 12th and 14th weeks to reveal the dynamics of viral pathogens that were not covered by qPCR. Amplicon sequencing of the conserved region of norovirus GI and GII and the rotavirus and region encoding nonstructural protein of RSV was also conducted weekly. The results showed that after a rapid decrease in SARS-CoV-2 sewage concentrations occurred in January 2023, surges of norovirus, rotavirus, IAV and RSV started at the 6th, 7th, 8th and 11th weeks, respectively. The dynamics of the sewage concentrations of norovirus, rotavirus, IAV and RSV were consistent with the off-season resurgence of the above infectious diseases. Notably, peak sewage concentrations of norovirus GI, GII, rotavirus, IAV and RSV were found at the 6th, 3rd, 7th, 7th and 8th weeks, respectively. Astroviruses also resurge after the 7th week, as revealed by metaviromic data, suggesting that wastewater surveillance together with metaviromic data provides an essential early warning tool for revealing patterns of infectious disease resurgence.
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COVID-19 , Aguas Residuales , Humanos , Aguas Residuales/virología , COVID-19/epidemiología , COVID-19/virología , SARS-CoV-2/genética , SARS-CoV-2/aislamiento & purificación , China/epidemiología , Norovirus/genética , Norovirus/aislamiento & purificación , Aguas del Alcantarillado/virología , Rotavirus/genética , Rotavirus/aislamiento & purificación , Virus de la Influenza A/genética , Virus de la Influenza A/aislamiento & purificación , Brotes de Enfermedades , Monitoreo Epidemiológico Basado en Aguas ResidualesRESUMEN
BACKGROUND: Cervical lymph node metastasis (LNM) is an important prognostic factor for patients with non-small cell lung cancer (NSCLC). We aimed to develop and validate machine learning models that use ultrasound radiomic and descriptive semantic features to diagnose cervical LNM in patients with NSCLC. METHODS: This study included NSCLC patients who underwent neck ultrasound examination followed by cervical lymph node (LN) biopsy between January 2019 and January 2022 from three institutes. Radiomic features were extracted from the ultrasound images at the maximum cross-sectional areas of cervical LNs. Logistic regression (LR) and random forest (RF) models were developed. Model performance was assessed by the area under the curve (AUC) and accuracy, validated internally and externally by fivefold cross-validation and hold-out method, respectively. RESULTS: In total, 313 patients with a median age of 64 years were included, and 276 (88.18%) had cervical LNM. Three descriptive semantic features, including long diameter, shape, and corticomedullary boundary, were selected by multivariate analysis. Out of the 474 identified radiomic features, 9 were determined to fit the LR model, while 15 fit the RF model. The average AUCs of the semantic and radiomics models were 0.876 (range: 0.781-0.961) and 0.883 (range: 0.798-0.966), respectively. However, the average AUC was higher for the semantic-radiomics combined LR model (0.901; range: 0.862-0.927). When the RF algorithm was applied, the average AUCs of the radiomics and semantic-radiomics combined models were improved to 0.908 (range: 0.837-0.966) and 0.922 (range: 0.872-0.982), respectively. The models tested by the hold-out method had similar results, with the semantic-radiomics combined RF model achieving the highest AUC value of 0.901 (95% CI, 0.886-0.968). CONCLUSIONS: The ultrasound radiomic models showed potential for accurately diagnosing cervical LNM in patients with NSCLC when integrated with descriptive semantic features. The RF model outperformed the conventional LR model in diagnosing cervical LNM in NSCLC patients.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Metástasis Linfática , Aprendizaje Automático , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/patología , Ganglios Linfáticos/diagnóstico por imagen , Ganglios Linfáticos/patología , Metástasis Linfática/diagnóstico por imagen , Metástasis Linfática/patología , Cuello/diagnóstico por imagen , Radiómica , Estudios Retrospectivos , Ultrasonografía/métodosRESUMEN
BACKGROUND: Noninvasively and accurately predicting subcarinal lymph node metastasis (SLNM) for patients with non-small cell lung cancer (NSCLC) remains challenging. This study was designed to develop and validate a tumor and subcarinal lymph nodes (tumor-SLNs) dual-region computed tomography (CT) radiomics model for predicting SLNM in NSCLC. METHODS: This retrospective study included NSCLC patients who underwent lung resection and SLNs dissection between January 2017 and December 2020. The radiomic features of the tumor and SLNs were extracted from preoperative CT, respectively. Ninety machine learning (ML) models were developed based on tumor region, SLNs region, and tumor-SLNs dual-region. The model performance was assessed by the area under the curve (AUC) and validated internally by fivefold cross-validation. RESULTS: In total, 202 patients were included in this study. ML models based on dual-region radiomics showed good performance for SLNM prediction, with a median AUC of 0.794 (range, 0.686-0.880), which was superior to those of models based on tumor region (median AUC, 0.746; range, 0.630-0.811) and SLNs region (median AUC, 0.700; range, 0.610-0.842). The ML model, which is developed by using the naive Bayes algorithm and dual-region features, had the highest AUC of 0.880 (range of cross-validation, 0.825-0.937) among all ML models. The optimal logistic regression model was inferior to the optimal ML model for predicting SLNM, with an AUC of 0.727. CONCLUSIONS: The CT radiomics showed the potential for accurately predicting SLNM in NSCLC patients. The ML model with dual-region radiomic features has better performance than the logistic regression or single-region models.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Metástasis Linfática , Aprendizaje Automático , Tomografía Computarizada por Rayos X , Humanos , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Carcinoma de Pulmón de Células no Pequeñas/secundario , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/cirugía , Masculino , Femenino , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodos , Persona de Mediana Edad , Anciano , Estudios de Seguimiento , Pronóstico , Adulto , Ganglios Linfáticos/patología , Ganglios Linfáticos/diagnóstico por imagen , Ganglios Linfáticos/cirugía , Anciano de 80 o más Años , Escisión del Ganglio Linfático , Neumonectomía , RadiómicaRESUMEN
The poor film stability of Sn-Pb mixed perovskite film and the mismatched interface energy levels pose significant challenges in enhancing the efficiency of tin-lead (Sn-Pb) mixed perovskite solar cells. In this study, polyvinylpyrrolidone (PVP) is introduced into the PVK perovskite precursor solution, effectively enhancing the overall stability of the film. This improvement is achieved through the formation of robust coordination bonds between the carbonyl (C=O) in the pyrrole ring and the undercoordinated SnII and PbII, thereby facilitating the passivation of defects. Furthermore, the introduction of PVP inhibits the oxidation of tin (Sn), thereby enhancing the n-type characteristics of the perovskite film. This adjustment in the energy level of the PVK perovskite film proves instrumental in reducing interface energy loss, subsequently improving interface charge transfer and mitigating device recombination. Consequently, perovskite solar cells incorporating PVP achieve an outstanding champion power conversion efficiency (PCE) of 21.31%.
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Autophagy impairment is a key factor in Alzheimer's disease (AD) pathogenesis. TFEB (transcription factor EB) and TFE3 (transcription factor binding to IGHM enhancer 3) are nuclear transcription factors that regulate autophagy and lysosomal biogenesis. We previously showed that corynoxine (Cory), a Chinese medicine compound, protects neurons from Parkinson's disease (PD) by activating autophagy. In this study, we investigated the effect of Cory on AD models in vivo and in vitro. We found that Cory improved learning and memory function, increased neuronal autophagy and lysosomal biogenesis, and reduced pathogenic APP-CTFs levels in 5xFAD mice model. Cory activated TFEB/TFE3 by inhibiting AKT/mTOR signaling and stimulating lysosomal calcium release via transient receptor potential mucolipin 1 (TRPML1). Moreover, we demonstrated that TFEB/TFE3 knockdown abolished Cory-induced APP-CTFs degradation in N2aSwedAPP cells. Our findings suggest that Cory promotes TFEB/TFE3-mediated autophagy and alleviates Aß pathology in AD models.
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Enfermedad de Alzheimer , Autofagia , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice , Modelos Animales de Enfermedad , Canales de Potencial de Receptor Transitorio , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/metabolismo , Animales , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Autofagia/efectos de los fármacos , Ratones , Lisosomas/metabolismo , Lisosomas/efectos de los fármacos , Humanos , Ratones Transgénicos , Péptidos beta-Amiloides/metabolismo , Ratones Endogámicos C57BL , Serina-Treonina Quinasas TOR/metabolismo , Masculino , Proteínas Proto-Oncogénicas c-akt/metabolismo , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Neuronas/patología , Transducción de Señal/efectos de los fármacos , Precursor de Proteína beta-Amiloide/metabolismo , Precursor de Proteína beta-Amiloide/genéticaRESUMEN
Wastewater-based epidemiology (WBE) is a promising tool for monitoring the spread of SARS-CoV-2 and other pathogens, providing a novel public health strategy to combat disease. In this study, we first analysed nationwide reports of infectious diseases and selected Salmonella, norovirus, and influenza A virus (IAV) as prioritized targets apart from SARS-CoV-2 for wastewater surveillance. Next, the decay rates of Salmonella, norovirus, and IAV in wastewater at various temperatures were established to obtain corrected pathogen concentrations in sewage. We then monitored the concentrations of these pathogens in wastewater treatment plant (WWTP) influents in three cities, establishing a prediction model to estimate the number of infected individuals based on the mass balance between total viral load in sewage and individual viral shedding. From October 2022 to March 2023, we conducted multipathogen wastewater surveillance (MPWS) in a WWTP serving one million people in Xi'an City, monitoring the concentration dynamics of SARS-CoV-2, Salmonella, norovirus, and IAV in sewage. The infection peaks of each pathogen were different, with Salmonella cases and sewage concentration declining from October to December 2022 and only occasionally detected thereafter. The SARS-CoV-2 concentration rapidly increased from December 5th, peaked on December 26th, and then quickly decreased until the end of the study. Norovirus and IAV were detected in wastewater from January to March 2023, peaking in February and March, respectively. We used the prediction models to estimate the rate of SARS-CoV-2 infection in Xi'an city, with nearly 90 % of the population infected in urban regions. There was no significant difference between the predicted and actual number of hospital admissions for IAV. We also accurately predicted the number of norovirus cases relative to the reported cases. Our findings highlight the importance of wastewater surveillance in addressing public health priorities, underscoring the need for a novel workflow that links the prediction results of populations with public health interventions and allocation of medical resources at the community level. This approach would prevent medical resource panic squeezes, reduce the severity and mortality of patients, and enhance overall public health outcomes.
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COVID-19 , Norovirus , Humanos , Salud Pública , Aguas Residuales , Monitoreo Epidemiológico Basado en Aguas Residuales , COVID-19/epidemiología , Prueba de Estudio Conceptual , Prioridades en Salud , Aguas del Alcantarillado , SARS-CoV-2 , Brotes de Enfermedades , China/epidemiología , ARN ViralRESUMEN
This paper presents a new remote sensing (RS) algorithm for retrieving instantaneous sea surface solar irradiance (SR) by using the XGBoost (XGB) package in RStudio and available remote sensing data along with ground-truth solar irradiance data. By means of XGB, the new RS algorithm, called LSU model, was structurally built with nine key RS parameters, including photosynthetically available radiation (PAR); instantaneous PAR (iPAR); water leaving reflectance Rrs at wavelengths 412, 443, 469, and 488 nm; angstrom; aerosol optical thickness (aot_869); and latitude that represent major sources and sinks of solar irradiance, as model input variables. Among the nine parameters, the most important four parameters are PAR, iPAR, latitude, and aot_869. It was found that the sea surface SR is highly affected by conditions in both the atmosphere and the seawater. The aot_869 is by far the most important factor describing the effects of the atmospheric absorption and scattering of SR before reaching the sea surface. The most important factors describing the effects of seawater characteristics on solar irradiance are PAR, iPAR, and latitude. Comparisons with existing SR models indicate that LSU model is scientifically sound due to the use of major source and sink factors of SR as model input variables. LSU model is also technically accurate due to its fine resolution (1×1 km) and overall best performance in predicting instantaneous SR. More importantly, LSU model is globally applicable as it can be utilized to obtain global-scale SR data for any day, any time, and anywhere in the world.
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Monitoreo del Ambiente , Tecnología de Sensores Remotos , Luz Solar , Algoritmos , Agua de MarRESUMEN
The autophagy-lysosomal pathway (ALP) is a major cellular machinery involved in the clearance of aggregated proteins in Alzheimer disease (AD). However, ALP is dramatically impaired during AD pathogenesis via accumulation of toxic amyloid beta (Aß) and phosphorylated-Tau (phospho-Tau) proteins in the brain. Therefore, activation of ALP may prevent the increased production of Aß and phospho-Tau in AD. Peroxisome proliferator-activated receptor alpha (PPARα), a transcription factor that can activate autophagy, and transcriptionally regulate transcription factor EB (TFEB) which is a key regulator of ALP. This suggests that targeting PPARα, to reduce ALP impairment, could be a viable strategy for AD therapy. In this study, we investigated the anti-AD activity of Caudatin, an active constituent of Cynanchum otophyllum (a traditional Chinese medicinal herb, Qing Yang Shen; QYS). We found that Caudatin can bind to PPARα as a ligand and augment the expression of ALP in microglial cells and in the brain of 3XTg-AD mice model. Moreover, Caudatin could activate PPARα and transcriptionally regulates TFEB-augmented lysosomal degradation of Aß and phosphor-Tau aggregates in AD cell models. Oral administration of Caudatin decreased AD pathogenesis and ameliorated the cognitive dysfunction in 3XTg-AD mouse model. Conclusively, Caudatin can be a potential AD therapeutic agent via activation of PPARα-dependent ALP.
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Sorafenib is a tyrosine kinase inhibitor for the treatment of advanced-stage HCC; however, clinical trials of sorafenib failed to demonstrate long-term survival benefits due to drug resistance. Low Pi stress has been shown to inhibit tumor growth and the expression of multidrug resistance-associated proteins. In this study, we investigated the sensitivity of HCC to sorafenib under conditions of low Pi stress. As a result, we found that low Pi stress facilitated sorafenib-mediated suppression of migration and invasion of HepG-2 and Hepa1-6 cells by decreasing the phosphorylation or expression of AKT, Erk and MMP-9. Angiogenesis was inhibited due to decreased expression of PDGFR under low Pi stress. Low Pi stress also decreased the viability of sorafenib-resistant cells by directly regulating the expression of AKT, HIF-1a and P62. In vivo drug sensitivity analysis in the four animal models showed a similar tendency that low Pi stress enhances sorafenib sensitivity in both the normal and drug-resistant models. Altogether, low Pi stress enhances the sensitivity of hepatocellular carcinoma to sorafenib and expands the indications for sevelamer.
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Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Animales , Ratones , Sorafenib/farmacología , Sorafenib/uso terapéutico , Carcinoma Hepatocelular/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Neoplasias Hepáticas/metabolismo , Niacinamida/farmacología , Niacinamida/uso terapéutico , Compuestos de Fenilurea/farmacología , Línea Celular Tumoral , Ratones Endogámicos , Resistencia a Antineoplásicos , Antineoplásicos/farmacología , Antineoplásicos/uso terapéuticoRESUMEN
Esophageal cancer (EC) is one of the fatal malignant neoplasms worldwide. Neoadjuvant therapy (NAT) combined with surgery has become the standard treatment for locally advanced EC. However, the treatment efficacy for patients with EC who received NAT varies from patient to patient. Currently, the evaluation of efficacy after NAT for EC lacks accurate and uniform criteria. Radiomics is a multi-parameter quantitative approach for developing medical imaging in the era of precision medicine and has provided a novel view of medical images. As a non-invasive image analysis method, radiomics is an inevitable trend in NAT efficacy prediction and prognosis classification of EC by analyzing the high-throughput imaging features of lesions extracted from medical images. In this literature review, we discuss the definition and workflow of radiomics, the advances in efficacy prediction after NAT, and the current application of radiomics for predicting efficacy after NAT.
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Phenolic compounds are widely distributed in nature and industrial environment, and their detoxification or bioactive enhancement is of great value to environmental protection and industrial development. Laccases are multicopper oxidases that catalyse the oligo- or polymerisation of phenolic compounds. Identifying new laccase producers and investigating their application potential are of great importance. In this study, a white-rot fungus, Trametes hirsuta EZ1, with significantly high laccase productivity was isolated. The optimum conditions were studied for the maximum fermentation of extracellular laccase, which was achieved at 150 U/mL with a medium containing 10% strain EZ1, 7% maltodextrin, 1.5% peptone, and 0.5 mM Cu2+, and incubation at initial pH 6.0, 32 °C, and 180 rpm for nine days. Subsequently, a 70-kDa laccase was purified that showed activity over a wide range of temperature and pH, sensitivity to many metal ions and sodium dodecyl sulphate, and high tolerance to organic solvents. Purified laccase showed a significant unreported effect by catalysing catechol or ferulic acid into dimers, trimers, and tetramers or caffeic acid into dimers, trimers, tetramers, and pentamers. The oligomeric mixtures exhibited increased antioxidative capacity compared to that of each parent monomer, except for caffeic acid derivatives. Our study offers a novel strain source for laccase production and broadens its application in the enhancement of bioactive compounds.
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Polyporaceae , Trametes , LacasaRESUMEN
OBJECTIVE: Studies on extremely severe elbow stiffness after chronic dislocation in children are scarce. This study aims to investigate the choice of surgical treatment modalities and to analyze their treatment efficacy in children with chronic elbow dislocation with extremely severe periarticular stiffness. METHODS: Data of 21 children with chronic elbow dislocation with extremely severe periarticular stiffness diagnosed and treated in our department between February 2015 and February 2021 were retrospectively analyzed. Twenty boys and one girl were included in the study, their mean age was 11 ± 2.5 years, and they had concomitant distal humerus fractures. For the treatment protocol, all children with extremely severe elbow stiffness were treated with open arthrolysis, and elbow joint stability was intraoperatively assessed. All children performed passive functional exercises the day after surgery. The elbow flexion and extension angles, range of motion (ROM), and Mayo score were evaluated preoperatively and at the final follow-up. RESULTS: Of the 21 children, only one had recurrent severe stiffness of the elbow joint after surgery; nevertheless, the function was still improved compared with that before surgery. Preoperatively, the mean elbow extension and flexion angles were 72.2° ± 12.7° and 93.6° ± 11.1°, respectively, and the range of motion (ROM) of the elbow joint was 17.8° ± 8.3°. At the final follow-up, the mean elbow extension and flexion angles were 22.7° ± 18.6° and 118.8° ± 15.4°, respectively, and the elbow joint ROM was 96.1° ± 17.4°. The differences in the preoperative and postoperative ROMs, flexion angles, and extension angles of the elbow joint were significant (p < 0.01). The MEPS at the final follow-up was 78.57 ± 14.24, which was significantly higher than preoperative (29.76 ± 10.89), and the excellent rate was 81%. CONCLUSION: Open arthrolysis and open reduction and internal fixation of the elbow joint are effective in treating chronic elbow dislocation with extremely severe stiffness in children.
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Lesiones de Codo , Articulación del Codo , Artropatías , Luxaciones Articulares , Masculino , Femenino , Humanos , Niño , Adolescente , Codo , Articulación del Codo/cirugía , Estudios Retrospectivos , Artropatías/cirugía , Luxaciones Articulares/cirugía , Resultado del Tratamiento , Fijación Interna de Fracturas , Rango del Movimiento ArticularRESUMEN
Digital elevation models (DEMs) from different sources have been widely utilized in watershed modeling and environment management. Yet, little is known about how DEMs from different data sources affect modeling results and management decisions. This paper presents new insights into how the DEMs from three different sources affect model-simulated flow, nitrate (NO3), phosphorus (P), and sediment by using the BASINS/HSPF watershed modeling system. It was found that DEM source-induced uncertainties in simulation results are higher than the DEM resolution-induced uncertainties regardless of watershed slope or delineation method. Moreover, DEM source introduces higher uncertainties in simulation results for automatically delineated low-gradient watersheds than high gradient watersheds. Sediment and NO3 concentrations were the most and the least sensitive water quality parameters, respectively, to DEM sources. The uncertainties in simulation results may be reduced by using the manual method for watershed delineation but they cannot be completely eliminated. It is recommended that high precision (such as NED) DEMs be employed especially for flat watersheds. The findings provide guidelines for selection of DEM source based on available resources.
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Modelos Teóricos , Calidad del Agua , Monitoreo del Ambiente/métodos , Fuentes de Información , Simulación por ComputadorRESUMEN
This literature review presents major environmental indicators and their optimum variation ranges for the prevalence of Vibrio parahaemolyticus in the marine environment by critically reviewing and statistically analyzing more than one hundred studies from countries around the world. Results of this review indicated that the prevalence of Vibrio parahaemolyticus in the marine environment is primarily responsive to favorable environmental conditions that are described with environmental indicators. The importance of environmental indicators to the prevalence of Vibrio parahaemolyticus can be ranked from the highest to lowest as Sea Surface Temperature (SST), salinity, pH, chlorophyll a, and turbidity, respectively. It was also found in this study that each environmental indicator has an optimum variation range favoring the prevalence of Vibrio parahaemolyticus. Specifically, the SST range of 25.67 ± 2 °C, salinity range of 27.87 ± 3 ppt, and pH range of 7.96 ± 0.1 were found to be the optimum conditions for the prevalence of Vibrio parahaemolyticus. High vibrio concentrations were also observed in water samples with the chlorophyll a range of 16-25 µg/L. The findings provide new insights into the importance of environmental indicators and their optimum ranges, explaining not only the existence of both positive and negative associations reported in the literature but also the dynamic associations between the Vibrio presence and its environmental drivers.
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Vibrio parahaemolyticus , Clorofila A , Prevalencia , Salinidad , TemperaturaRESUMEN
Vibrio parahaemolyticus (V.p) is a marine pathogenic bacterium that poses a high risk to human health and shellfish industry, yet an effective regional-scale nowcasting model for managing the risk remains lacking. This study presents the first regional-scale model for nowcasting the level of V.p in oysters in the marine environment by developing an ensemble modeling approach. The ensemble modeling approach involves the integration of genetic programming (GP) and deep artificial neural networks (DNN)-based modeling. The new approach was demonstrated by developing three GP-DNN ensemble models for predicting the V.p level in North Carolina, New Hampshire, and the combined region. Specifically, GP was employed to establish nonlinear functions between the V.p level and antecedent conditions of environmental variables. The nonlinear GP functions and current conditions of individual environmental variables were then utilized as inputs into a DNN model, forming a GP-DNN ensemble model. Modeling results indicated that the GP-DNN ensemble models were capable of predicting the V.p level with the correlation coefficient of 0.91, 0.90, and 0.80 for North Carolina, New Hampshire, and the combined region, respectively, demonstrating the impact of distinct environmental conditions in the local areas on accuracy of the combined regional-scale model. Sensitivity analysis results showed that sea surface temperature and sea surface salinity are the two most important environmental predictors for the abundance of V.p in oysters, followed by water level, pH, chlorophyll-a, and turbidity. The findings suggested that the GP-DNN ensemble models could be utilized as effective predictive tools for mitigating the V.p risk.
Asunto(s)
Aprendizaje Profundo , Ostreidae , Vibrio parahaemolyticus , Animales , Humanos , Monitoreo del Ambiente , Ostreidae/microbiología , Mariscos/análisisRESUMEN
As the most efficient method to treat hepatocellular carcinoma in the immediate or advanced stage, transarterial chemoembolization (TACE) is coming into the era of microsphere (MP). Drug-eluting beads have shown their huge potential as an embolic agent and drug carrier for chemoembolization, but their sizes are strictly limited to be above 40 µm, which was considered to occlude vessels in a safe mode. microsphere smaller than 40 µm is easy to be washed out and transported to the normal liver lobe or other organs, causing severe adverse events and failed embolization. To determine whether sevelamer ultrafine particle (0.2-0.5 µm) is qualified as a safe and efficient embolic agent, we investigated the safety and therapeutic efficiency of transarterial sevelamer embolization (TASE) in the VX2 rabbit liver cancer model, aiming to challenge the "40 µm" rule on the selection criteria of the MP. In a four-arm study, blank bead (Callisphere, 100-300 µm), luminescent polystyrene microsphere (10, 100 µm), and sevelamer particle were transarterially administered to evaluate the threshold size of the MP size for intrahepatic or extrahepatic permeability. Another four-arm study was designed to clarify the safety and efficiency of preclinical transarterial sevelamer embolizationTASE tests over other techniques. Sham (saline), TASE, C-TACE, and D-TACE (n = 6) were compared in terms of serum chemistry, histopathology, and tumor necrosis ratio. In the first trials, the "40 µm" rule was detectable on the VX2 cancer model, but the regulation has no application to the new embolic agent as sevelamer ultrafine particles have not been found to leak out from the VX2 lesions, only found in the embolized vessels. Pathology proves that less viable tumor residue was found 2 weeks after the procedure, evidencing a better therapeutic outcome. No adverse events were found except for a short stress response. These results indicate that sevelamer is a safe and efficient embolic as an alternative to the current MP-based embolization therapy techniques.