RESUMEN

In eukaryotic cells, gene expression begins with transcription in the nucleus, followed by the maturation of messenger RNAs (mRNAs). These mRNA molecules are then exported to the cytoplasm through the nuclear pore complex (NPC), a process that serves as a critical regulatory phase of gene expression. The export of mRNA is intricately linked to precursor mRNA (pre-mRNA) processing, ensuring that only properly processed mRNA reaches the cytoplasm. This coordination is essential, as recent studies have revealed that mRNA export factors not only assist in transport but also influence upstream processing steps, adding a layer of complexity to gene regulation. Furthermore, the export process competes with RNA processing and degradation pathways, maintaining a delicate balance vital for accurate gene expression. While these mechanisms are generally conserved across eukaryotes, significant differences exist between yeast and higher eukaryotic cells, particularly due to the more genome complexity of the latter. This review delves into the current research on mRNA export in higher eukaryotic cells, focusing on its role in the broader context of gene expression regulation and highlighting how it interacts with other gene expression processes to ensure precise and efficient gene functionality in complex organisms.

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Mental disorders are becoming increasingly prevalent worldwide, and accurate incidence forecasting is crucial for effective mental health strategies. This study developed a long short-term memory (LSTM)-based recurrent neural network model to predict schizophrenia in inpatients in Taiwan. Data was collected on individuals aged over 20 years and diagnosed with schizophrenia between 1998 and 2015 from the National Health Insurance Research Database (NHIRD). The study compared six models, including LSTM, exponential smoothing, autoregressive integrated moving average, particle swarm optimization (PSO), PSO-based support vector regression, and deep neural network models, in terms of their predictive performance. The results showed that the LSTM model had the best accuracy, with the lowest mean absolute percentage error (2.34), root mean square error (157.42), and mean average error (154,831.70). This finding highlights the reliability of the LSTM model for forecasting mental disorder incidence. The study's findings provide valuable insights that can help government administrators devise clinical strategies for schizophrenia, and policymakers can use these predictions to formulate healthcare education and financial planning initiatives, fostering support networks for patients, caregivers, and the public.

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Near-infrared (NIR) fluorescent probes with aggregation-induced emission (AIE) properties are of great significance in cell imaging and cancer therapy. However, the complexity of its synthesis, poor photostabilities, and expensive raw materials still pose some obstacles to their practical application. This study reported an AIE luminescent material with red emission and its application in in vitro imaging and photodynamic therapy (PDT) study. This material has the characteristics of simple synthesis, large Stokes shift, good photostabilities, and excellent lipid droplets-specific testing ability. Interestingly, this red-emitting material can effectively produce reactive oxygen species (ROS) under white light irradiation, further achieving PDT-mediated killing of cancer cells. In conclusion, this study demonstrates a simple approach to synthesize NIR AIE probes with both imaging and therapeutic effects, providing an ideal architecture for constructing long-wavelength emission AIE materials.

Asunto(s)

Colorantes Fluorescentes , Rayos Infrarrojos , Gotas Lipídicas , Fotoquimioterapia , Especies Reactivas de Oxígeno , Humanos , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Colorantes Fluorescentes/farmacología , Gotas Lipídicas/química , Especies Reactivas de Oxígeno/metabolismo , Especies Reactivas de Oxígeno/análisis , Especies Reactivas de Oxígeno/química , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/síntesis química , Supervivencia Celular/efectos de los fármacos , Imagen Óptica , Estructura Molecular , Células HeLa

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OBJECTIVE: The aim was to investigate the mediating role of inflammatory biomarkers in the causal effect of body composition on glycaemic traits and type 2 diabetes. METHODS: A retrospective observational study and a Mendelian randomization (MR) study were used. Observational analyses were performed using data from 4717 Chinese children and adolescents aged 6-18 years who underwent dual-energy X-ray absorptiometry for body composition. MR analyses were based on summary statistics from UK Biobank, deCODE2021, Meta-Analysis of Glucose and Insulin-Related Traits Consortium (MAGIC) and other large consortiums. Inflammatory biomarkers included leptin, adiponectin, osteocalcin, fibroblast growth factor 23 (FGF23) and parathyroid hormone (PTH). RESULTS: In a retrospective observational study, increased fat mass had a positive effect on homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment of pancreatic beta cell function (HOMA-ß) through FGF23, whereas fat-free mass produced the opposite effects. PTH and osteocalcin played significant roles in the association of fat mass and fat-free mass with fasting glucose, fasting insulin and HOMA-IR (all p < 0.05). Mediation MR results indicated that childhood body mass index affected glycaemic traits through leptin and adiponectin. There existed a causal effect of fat-free mass on type 2 diabetes via FGF23 (indirect effect: OR [odds ratio]: 1.14 [95% CI, confidence interval: 1.01-1.28]) and adiponectin (OR: 0.85 [95% CI: 0.77-0.93]). Leptin mediated the causal association of fat mass (indirect effect: ß: -0.05 [95% CI: -0.07, -0.02]) and fat-free mass (ß: 0.03 [95% CI: 0.01, 0.04]) with fasting glucose. CONCLUSIONS: Our findings suggest that different body compositions have differential influences on glycaemic traits and type 2 diabetes through distinct inflammatory biomarkers. The findings may be helpful in tailoring management of body composition based on inflammatory biomarkers with different glycaemic statuses.

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Dried yellow chili is highly appreciated by consumers due to its excellent quality and flavor. The quality of products is determined by the drying and storage methods. In this study, dried yellow chilis were processed by natural air drying and hot air drying methods and then stored under three conditions: ambient temperature, ambient temperature with light avoidance, and at 10 °C with light avoidance for 12 months. The changes in the bioactive compounds during this period were analyzed attempting to reveal correlations between the different treatments and these compounds, with the aim of providing references for maintaining the bioactive compounds of pepper products. The results showed that samples treated with hot air had higher levels of fatty acids, resulting in a more pronounced flavor. During storage, samples stored at 10 °C with light avoidance were more effective in preserving soluble solids, total protein content, total phenols, capsaicinoids and most fatty acids.

Asunto(s)

Capsicum , Manipulación de Alimentos , Capsicum/química , Manipulación de Alimentos/métodos , Ácidos Grasos/análisis , Fenoles/análisis , Desecación/métodos , Gusto , Valor Nutritivo , Capsaicina/análisis

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Protein methylation is a functionally important post-translational modification that occurs on diverse amino acid residues. The current proteomics approaches are inefficient to discover the methylation on residues other than Arg and Lys, which hinders the deep understanding of the functional role of rare protein methylation. Herein, we present a methyl-specific metabolic labeling approach for global methylome mapping, which enable the acquisition of methylome dataset covering diverse methylation types. Interestingly, of the identified methylation events, His methylation is found to be preferably occurred in C3H1 zinc fingers (ZFs). These His methylation events are determined to be Nπ specific and catalyzed by CARNMT1. The His methylation is found to stabilize the structure of ZFs. U2AF1 is used as a proof-of-concept to highlight the functional importance of His methylation in ZFs in RNA binding and RNA metabolism. The results of this study enable novel understanding of how protein methylation regulates cellular processes.

Asunto(s)

Histidina , Procesamiento Proteico-Postraduccional , Dedos de Zinc , Histidina/metabolismo , Metilación , Humanos , Epigenoma , Células HEK293 , Metiltransferasas/metabolismo , Metiltransferasas/genética

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The association between metal mixtures and kidney function has been reported. However, reports on the mechanism of metal toxicity were limited. Oxidative stress was reported as a possible cause. This study aimed to determine the association between of kidney function and metals, such as arsenic (As), cadmium (Cd), cobalt (Co), copper (Cu), lead (Pb), selenium (Se), and zinc (Zn), and to explore the possible mediating role of tumor necrosis factor alpha (TNF-α) between metal toxicity and kidney function. In this study, we recruited 421 adults from a health examination. The concentration of blood metals was analyzed using inductively coupled plasma mass spectrometry. We used linear regression models to assess the association between metals and TNF-α. Then, mediation analysis was applied to investigate the relationship between metal exposure, TNF-α, and kidney function. In univariate linear regression, blood As, Cd, Co, Cu, Pb, and Zn levels significantly increased TNF-α and decreased kidney function. Higher blood As and Pb levels significantly increased TNF-α in multivariable linear regressions after adjusting for covariates. We found that blood levels of As (coefficients = -0.021, p = 0.011), Pb (coefficients = -0.060, p < 0.001), and Zn (coefficients = -0.230, p < 0.001) showed a significant negative association with eGFR in the multiple-metal model. Furthermore, mediation analysis showed that TNF-α mediated 41.7 %, 38.8 %, and 20.8 % of blood Cd, As and Pb, respectively. Among the essential elements, TNF-α mediated 24.5 %, 21.5 % and 19.9 % in the effects of blood Co, Cu, and Zn on kidney function, respectively. TNF-α, acting as a mediator, accounted for 20.1 % of the contribution between the WQS score of metal mixtures and the eGFR (p < 0.001). This study suggested that TNF-α may be a persuasive pathway mediating the association between metals and kidney function. Inflammation and kidney injury could be the underlying mechanisms of metal exposure. However, there is still a need to clarify the biochemical mechanism in follow-up studies.

Asunto(s)

Riñón , Análisis de Mediación , Metales Pesados , Factor de Necrosis Tumoral alfa , Factor de Necrosis Tumoral alfa/sangre , Humanos , Masculino , Femenino , Riñón/efectos de los fármacos , Persona de Mediana Edad , Metales Pesados/sangre , Metales Pesados/toxicidad , Adulto , Contaminantes Ambientales/sangre , Contaminantes Ambientales/toxicidad , Exposición a Riesgos Ambientales/efectos adversos , Modelos Lineales , Arsénico/sangre , Arsénico/toxicidad , Metales/sangre , Metales/toxicidad

RESUMEN

A bioassay-guided isolation from Atractylodes lancea (Thunb.) DC. obtained 22 compounds, including eight previously undescribed sesquiterpenoids and polyacetylenes (1, 3 and 12-17), as well as fourteen known analogues, and their structures were confirmed by extensive spectroscopic methods. This study evaluated their antibacterial activity against methicillin resistant Staphylococcus aureus (MRSA) for the first time, as well as anti-inflammatory activity. Most of them, including new compounds, showed varying degrees of antibacterial activity against S. aureus and MRSA. Notably, compound 21 exhibited significant antibacterial activity against four different bacteria (MIC 6.25-20.00 µg/mL). This suggested that 21 may have the potential to be developed into a broad-spectrum antibacterial agent. Moreover, except for 9 and 11, most compounds exhibited great anti-inflammatory activity (IC50 1.92-37.91 µM), and iNOS might be a potential target of these compounds according to the molecular docking analysis.

Asunto(s)

Antibacterianos , Antiinflamatorios , Atractylodes , Staphylococcus aureus Resistente a Meticilina , Pruebas de Sensibilidad Microbiana , Atractylodes/química , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/aislamiento & purificación , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Antiinflamatorios/farmacología , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Estructura Molecular , Simulación del Acoplamiento Molecular , Animales , Relación Estructura-Actividad , Ratones , Relación Dosis-Respuesta a Droga , Antiinflamatorios no Esteroideos/farmacología , Antiinflamatorios no Esteroideos/química , Antiinflamatorios no Esteroideos/aislamiento & purificación , Óxido Nítrico Sintasa de Tipo II/antagonistas & inhibidores , Óxido Nítrico Sintasa de Tipo II/metabolismo , Bioensayo , Células RAW 264.7 , Staphylococcus aureus/efectos de los fármacos

RESUMEN

Environmental plastic fragments have been verified as byproducts of large plastic and its secondary pollutants including micro and nanoplastics. There are few quantitative studies available, but their contours have values for the weathering mechanisms. We used geometric descriptors, fractal dimensions, and Fourier descriptors to characterize field and artificial polyethylene and polypropylene samples as a means of investigating the contour characteristics. It provides a methodological framework for contour classification. Unsupervised classification was performed using self-organizing neural networks with size-invariance parameters. We revealed the isometric phenomenon of plastic fragments during fragmentation, i.e., that the degree of contour rounding and complexity increase and decrease, respectively, with decreasing fragment size. With an average error rate of 8.9 %, we can distinguish artificial samples from field samples. It was also validated by the difference in Carbonyl Index between groups. We propose a two-stage process for plastic fragmentation and give three types of contour features which were key in the description of fragmented contours, i.e., size, complexity, and rounding. Our work will improve the accuracy of characterizations regarding the weathering and fragmentation processes of certain kinds of plastic fragments. The contour parameters also have the potential to be applied in more realistic scenarios and varied polymers.

RESUMEN

PURPOSE: Sodium zirconium cyclosilicate (SZC) is an oral potassium (K+)-lowering therapy for adults with hyperkalemia. HARMONIZE Asia (ClinicalTrials.gov identifier: NCT03528681) evaluated the efficacy and safety of SZC in Chinese patients with hyperkalemia. METHODS: This Phase III, randomized, double-blind, placebo-controlled study recruited patients with serum K+ (sK+) ≥5.1 mmol/L at 35 sites in China. Patients received SZC 10 g three times daily (TID) for 24 or 48 hours during an open-label initial phase (OLP). Those patients achieving normokalemia (sK+ 3.5-5.0 mmol/L inclusive) entered a 28-day randomized (2:2:1) treatment phase (RTP) and received SZC 5 g, SZC 10 g, or placebo once daily. The primary endpoint was mean sK+ during RTP Days 8 to 29. Secondary endpoints included mean change in sK+ during the OLP, the proportion of patients who achieved normokalemia at the end of the OLP, the proportion that maintained normokalemia during the RTP, and time to recurrence of hyperkalemia. FINDINGS: In total, 270 patients received SZC 10 g TID during the OLP; 256 (94.8%) completed the OLP. During the OLP, mean sK+ decreased by 1.1 mmol/L from baseline (5.9 mmol/L; P < 0.001) and 87.4% of patients achieved normokalemia. During the RTP, SZC 5 g and 10 g reduced mean sK+ versus placebo in a dose-dependent manner (each P < 0.001); least-squares means (95% confidence interval [CI]) sK+ were 4.9 mmol/L (4.7, 5.0), 4.4 mmol/L (4.3, 4.6), and 5.2 mmol/L (5.1, 5.4) for SZC 5 g, 10 g, and placebo, respectively. At RTP end, the proportions of patients who maintained normokalemia were 58.8% (SZC 5 g; odds ratio vs placebo, 2.5 [95% CI: 1.1, 6.1; P = 0.035]), 76.5% (SZC 10 g; odds ratio vs placebo, 6.3 [95% CI: 2.6, 15.3; P < 0.001]), and 36.8% for placebo. Risk of recurrent hyperkalemia was reduced by 61.0% and 84.0% with SZC 5 g and SZC 10 g, respectively, versus placebo (each P < 0.001). During the RTP, the incidence of adverse events was numerically higher with SZC 5 g (50.0% of patients) and 10 g (44.0%) versus placebo (36.0%); driven primarily by peripheral edema and constipation. IMPLICATIONS: Both SZC doses demonstrated clinically relevant and statistically significant, dose-dependent efficacy in managing sK+ levels in Chinese patients with hyperkalemia, compared with placebo. SZC tolerability was broadly aligned with the known safety profile of SZC.

Asunto(s)

Hiperpotasemia , Silicatos , Humanos , Hiperpotasemia/tratamiento farmacológico , Silicatos/efectos adversos , Silicatos/uso terapéutico , Silicatos/administración & dosificación , Masculino , Femenino , Persona de Mediana Edad , Método Doble Ciego , China , Anciano , Adulto , Resultado del Tratamiento , Potasio/sangre

RESUMEN

Optimizing nitrogen removal is crucial for ensuring the efficient operation of wastewater treatment plants (WWTPs), but it is susceptible to variations in influent conditions and operational parameter constraints, and conflicts with the energy-saving and carbon emission reduction goals. To address these issues, this study proposes a hybrid framework integrating process simulation, machine learning, and multi-objective genetic algorithms for nitrogen removal diagnosis and optimization, aiming to predict the total nitrogen in effluent, diagnose nitrogen over-limit risks, and optimize the control strategies. Taking a full-scale WWTP as a case study, a process time-lag simulation-enhanced machine learning model (PTLS-ML) was developed, achieving R2 values of 0.94 and 0.79 for the training and testing sets, respectively. The proposed model successfully identified the potential reasons of nitrogen over-limit risks under different influent conditions and operational parameters, and accordingly provided optimization suggestions. In addition, the multi-objective optimization (MOO) algorithms analysis further demonstrated that maintaining 4-6 mg/L total nitrogen concentration in effluent by adjusting process operational parameters can effectively balance multiple objectives (i.e., effluent water quality, operating costs, and greenhouse gas emissions), achieving coordinated optimization. This framework can serve as a reference for stable operation, energy-saving, and emission reduction in the nitrogen removal of WWTPs.

RESUMEN

OBJECTIVE: In this study, we developed an exercise training protocol for assessing both blood pressure dynamics and mRNA expression levels of purine receptors in various vascular tissues during physical activity. The objective is to assess the impact of exercise training on blood pressure regulation in spontaneously hypertensive rats (SHR) and purine receptors in vascular tissues. METHODS: Wistar Kyoto (WKY) and SHR rats were randomly allocated into sedentary (Sed) and exercise training (ExT) groups. Rats in the Sed groups were allowed unrestricted movement, whereas those in the ExT groups underwent a 16-week regimen of low- to moderate-intensity treadmill exercise. Throughout the intervention period, blood pressure measurements and body weight recordings were conducted. Additionally, mRNA expressions of purine receptors P2X1, P2Y1, and P2Y2 in renal artery (RA), internal carotid artery (Int), thoracic aorta (Aor), and caudal artery (Cau) tissues were assessed. RESULTS: In the Sed group, body weight of SHR rats was observed to be lower compared to the three other groups. Over the course of the exercise regimen, blood pressure in the ExT group of SHR rats reduced gradually, converging towards levels similar to those observed in WKY rats by the conclusion of the exercise period. Regarding mRNA expression patterns of P2X1 receptors across the four blood vessels, WKY and SHR rats demonstrated similar sequences, consistently displaying the highest expression levels in the Cau. Conversely, mRNA expressions of P2Y1 and P2Y2 receptors exhibited distinct sequences across the four blood vessels in both WKY and SHR rats. Notably, compared to the Sed group of WKY rats, mRNA expression of P2X1 receptor in the Int of SHR rats revealed an increase, while expressions in the Aor of WKY rats and the Cau of SHR rats decreased following exercise. Expression of P2Y1 receptor mRNA decreased across all four types of blood vessels in SHR rats. Post-exercise, P2Y1 receptor mRNA expression increased in the Aor, decreased in the Cau of WKY rats, and increased in the Int and renal artery (RA) of SHR rats. Conversely, expressions of P2Y2 receptor mRNA decreased in the Int and Aor of SHR rats. Except for the Aor of WKY rats, expressions of P2Y2 receptor mRNA increased in the other arteries of both rat types following exercise. CONCLUSION: Differences in the distribution of purine receptor subtypes among distinct arterial segments in both WKY and SHR rats were observed. Exercise training was found to enhance mRNA expression levels of P2Y receptors in these rat models. This finding implies that exercise training might reduce hypertension in SHR rats by bolstering the purinergic relaxation response.

RESUMEN

Air pollution has become a major global threat to human health. Urbanization and industrialization over the past few decades have increased the air pollution. Plausible connections have been made between air pollutants and dementia. This study used machine learning algorithms (k-nearest neighbors, random forest, gradient-boosted decision trees, eXtreme gradient boosting, and CatBoost) to investigate the association between cognitive impairment and air pollution. Data from the Taiwan Biobank and 75 air-pollution-monitoring stations in Taiwan were analyzed to determine individual levels of exposure to air pollutants. The pollutants examined were particulate matter with a diameter of ≤ 2.5 µm (PM2.5), nitrogen dioxide, nitric oxide, carbon monoxide, and ozone. The results revealed that the most strongly correlated with cognitive impairment were ozone, PM2.5, and carbon monoxide levels with adjustment of educational level, age, and household income. The model based on these factors achieved accuracy as high as 0.97 for detecting cognitive impairment, indicating a positive association between air pollutions and cognitive impairment.

RESUMEN

Post-traumatic stress disorder (PTSD) is a complex psychological disorder provoked by distressing experiences, and it remains without highly effective intervention strategies. The exploration of PTSD's underlying mechanisms is crucial for advancing diagnostic and therapeutic approaches. Current studies primarily explore PTSD through the lens of the central nervous system, investigating concrete molecular alterations in the cerebral area and neural circuit irregularities. However, the body's response to external stressors, particularly the changes in cardiovascular function, is often pronounced, evidenced by notable cardiac dysfunction. Consequently, examining PTSD with a focus on cardiac function is vital for the early prevention and targeted management of the disorder. This review undertakes a comprehensive literature analysis to detail the alterations in brain and heart structures and functions associated with PTSD. It also synthesizes potential mechanisms of heart-brain axis interactions relevant to the development of PTSD. Ultimately, by considering cardiac function, this review proposes novel perspectives for PTSD's prophylaxis and therapy.

Asunto(s)

Encéfalo , Corazón , Trastornos por Estrés Postraumático , Trastornos por Estrés Postraumático/fisiopatología , Trastornos por Estrés Postraumático/metabolismo , Trastornos por Estrés Postraumático/terapia , Humanos , Corazón/fisiopatología , Encéfalo/metabolismo , Encéfalo/fisiopatología , Animales

RESUMEN

PURPOSE: This study aimed to evaluate the effectiveness and safety of iodine-125 brachytherapy as a treatment for right lower paratracheal lymph node metastasis following unsuccessful prior therapies. METHODS: A retrospective review of patients who underwent iodine-125 brachytherapy for right lower paratracheal lymph node metastasis was conducted. The study included 24 patients who met the predefined criteria. Iodine-125 seeds were implanted under CT guidance, and treatment planning was performed using a treatment planning system. The primary endpoint was the objective response rate (ORR), while overall survival (OS) and complications were secondary endpoints. RESULTS: The ORR was 87.5%, with 4 patients achieving complete response (CR) and 17 patients achieving partial response (PR). The mean diameter of metastatic lymph nodes significantly reduced from 40.21 ± 6.66 mm before treatment to 12.25 ± 9.27 mm at the last follow-up (p < 0.001). The median OS was 14.70 months, with 1-year and 2-year survival rates of 78.9% and 20.9%, respectively. Clinical symptoms significantly improved, as indicated by increased Karnofsky Performance Score (KPS) scores. Complications were manageable, with no procedure-related deaths. CONCLUSION: Iodine-125 brachytherapy demonstrated promising efficacy and safety as an alternative treatment for right lower paratracheal lymph node metastasis after unsuccessful prior therapies.

Asunto(s)

Braquiterapia , Radioisótopos de Yodo , Metástasis Linfática , Cuidados Paliativos , Tomografía Computarizada por Rayos X , Humanos , Braquiterapia/métodos , Radioisótopos de Yodo/uso terapéutico , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Metástasis Linfática/radioterapia , Anciano , Femenino , Cuidados Paliativos/métodos , Adulto , Insuficiencia del Tratamiento , Ganglios Linfáticos/patología , Anciano de 80 o más Años , Resultado del Tratamiento , Radioterapia Guiada por Imagen/métodos , Tasa de Supervivencia

RESUMEN

Photoimmunotherapy represents an innovative approach to enhancing the efficiency of immunotherapy in cancer treatment. This approach involves the fusion of immunotherapy and phototherapy (encompassing techniques like photodynamic therapy (PDT) and photothermal therapy (PTT)). Boron-dipyrromethene (BODIPY) has the potential to trigger immunotherapy owing to its excellent PD and PT efficiency. However, the improvements in water solubility, bioavailability, PD/PT combined efficiency, and tumor tissue targeting of BODIPY require introduction of suitable carriers for potential practical application. Herein, a disulfide bond-based hollow mesoporous organosilica (HMON) with excellent biocompatibility and GSH-responsive degradation properties was used as a carrier to load a bithiophene Aza-BODIPY dye (B5), constructing a sample chemotherapy reagent-free B5@HMON nanoplatform achieving triple-synergistic photoimmunotherapy. HMON, involving disulfide bond, is utilized to improve water solubility, tumor tissue targeting, and PD efficiency by depleting GSH and enhancing host-guest interaction between B5 and HMO. The study reveals that HMON's large specific surface area and porous properties significantly enhance the light collection and oxygen adsorption capacity. The HMON's rich mesoporous structure and internal cavity achieved a loading rate of B5 at 11 %. It was found that the triple-synergistic nanoplatform triggered a stronger anti-tumor immune response, including tumor invasion, cytokine production, calreticulin translocation, and dendritic cell maturation, eliciting specific tumor-specific immunological responses in vivo and in vitro. The BALB/c mouse model with 4T1 tumors was used to assess tumor suppression efficiency in vivo, showing that almost all tumors in the B5@HMON group disappeared after 14 days. Such a simple chemotherapy reagent-free B5@HMON nanoplatform achieved triple-synergistic photoimmunotherapy.

Asunto(s)

Compuestos de Boro , Glutatión , Inmunoterapia , Animales , Compuestos de Boro/química , Compuestos de Boro/farmacología , Ratones , Inmunoterapia/métodos , Glutatión/química , Glutatión/metabolismo , Compuestos de Organosilicio/química , Compuestos de Organosilicio/farmacología , Ratones Endogámicos BALB C , Humanos , Tamaño de la Partícula , Tiofenos/química , Tiofenos/farmacología , Propiedades de Superficie , Fotoquimioterapia , Nanopartículas/química , Fototerapia/métodos , Línea Celular Tumoral , Femenino , Proliferación Celular/efectos de los fármacos , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Supervivencia Celular/efectos de los fármacos , Porosidad

RESUMEN

Warfarin-related nephropathy (WRN) is defined as acute kidney injury subsequent to excessive anticoagulation with warfarin. Patients with mechanical prosthetic valves require long-term anticoagulant therapy. Nonetheless, warfarin remains the sole available option for anticoagulant therapy. Consequently, patients with mechanical prosthetic valves constitute a special group among the entire anticoagulant population. The present study recorded two cases of patients who had undergone mechanical prosthetic valve surgery and were receiving warfarin therapy. They presented to the hospital with gross hematuria and progressive creatinine levels. Notably, their international normalized ratio (INR) did not exceed three. Subsequent renal biopsies confirmed WRN with IgA nephropathy. The two patients continued to receive warfarin as anticoagulation therapy and were prescribed oral corticosteroids and cyclophosphamide, which resulted in improved renal function during the follow-up. Based on a review of all relevant literature and the present study, we proposed a new challenge: must elevated INR levels be one of the criteria for clinical diagnosis of WRN? Perhaps some inspiration can be drawn from the present article.

Asunto(s)

Anticoagulantes , Warfarina , Humanos , Warfarina/efectos adversos , Anticoagulantes/efectos adversos , Masculino , Persona de Mediana Edad , Femenino , Relación Normalizada Internacional , Anciano , Glomerulonefritis por IGA , Biopsia , Lesión Renal Aguda/inducido químicamente , Riñón/patología , Riñón/efectos de los fármacos , Ciclofosfamida/efectos adversos , Corticoesteroides/uso terapéutico , Corticoesteroides/efectos adversos , Corticoesteroides/administración & dosificación

RESUMEN

Evidence has demonstrated that exoskeleton robots can improve intestinal function in patients with spinal cord injury (SCI). However, the underlying mechanisms remain unelucidated. This study investigated the effects of exoskeleton-assisted walking (EAW) on intestinal function and intestinal flora structure in T2-L1 motor complete paraplegia patients. The results showed that five participants in the EAW group and three in the conventional group reported improvements in at least one bowel management index, including an increased frequency of bowel evacuations, less time spent on bowel management per day, and less external assistance (manual digital stimulation, medication, and enema usage). After 8 weeks of training, the amount of glycerol used in the EAW group decreased significantly (p <0.05). The EAW group showed an increasing trend in the neurogenic bowel dysfunction (NBD) score after 8 weeks of training, while the conventional group showed a worsening trend. Patients who received the EAW intervention exhibited a decreased abundance of Bacteroidetes and Verrucomicrobia, while Firmicutes, Proteobacteria, and Actinobacteria were upregulated. In addition, there were decreases in the abundances of Bacteroides, Prevotella, Parabacteroides, Akkermansia, Blautia, Ruminococcus 2, and Megamonas. In contrast, Ruminococcus 1, Ruminococcaceae UCG002, Faecalibacterium, Dialister, Ralstonia, Escherichia-Shigella, and Bifidobacterium showed upregulation among the top 15 genera. The abundance of Ralstonia was significantly higher in the EAW group than in the conventional group, and Dialister increased significantly in EAW individuals at 8 weeks. This study suggests that EAW can improve intestinal function of SCI patients in a limited way, and may be associated with changes in the abundance of intestinal flora, especially an increase in beneficial bacteria. In the future, we need to further understand the changes in microbial groups caused by EAW training and all related impact mechanisms, especially intestinal flora metabolites. Clinical trial registration: https://www.chictr.org.cn/.