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To unravel the effects of environmental factors on fishery resources in the bay, we conducted six biological and environmental surveys in the Laizhou Bay between 2013 and 2020. The findings of our study illuminated several key aspects: (1) The annual discharge of water and sediment from the Yellow River to Laizhou Bay exhibited notable variations, while concurrently, environmental factors including temperature, salinity, and suspended particle matter underwent fluctuations, yet remained within a relatively stable range overall. (2) A total of 8318 eggs and larvae belonging to 10 orders, 16 families, and 19 genera were collected. Significant interannual fluctuations had been documented in the species composition, abundance, and biodiversity of ichthyoplankton. Notably, both Shannon-Wiener diversity index and Pielou evenness index were significantly negatively correlated with suspended particle matter concentration. (3) The water and sediment discharge significantly positively correlated with the number of cold-temperature species. However, the sediment input negatively correlated with the number of continental shelf benthopelagic fish. (4) Redundancy and correlation analyses confirmed the strong link between spatial and temporal distribution of fish communities and environmental factors, with salinity and dissolved oxygen key for ichthyoplankton abundance. Our research offers a scientific foundation for targeted fishery protection and management, which is crucial for preserving the ecological functions of spawning grounds in the bay.
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The effect of 7-day subfreezing storage on the physicochemical properties, nutritional composition, and microstructure of pork was investigated. After 7 days of chilling at 4°C, the meat exhibited color deterioration and the development of off-flavors. In contrast, the -12°C treatment significantly reduced the deterioration in water-holding capacity and color of samples (p < 0.05) and prevented changes in pH value. Similarly, the treatments at -12 and -18°C effectively preserved the meat's tenderness, thiobarbituric acid-reactive substances, protein solubility, and textural properties, maintaining these qualities close to those of fresh meat (p > 0.05). The nutrient content of samples stored at -12°C was comparable to those stored at -18°C (p > 0.05). Furthermore, subfreezing at -12°C was found to protect muscle integrity, promoting the formation of an elastic gel network and a homogenous muscle fiber structure. Therefore, the study concludes that 7-day subfreezing storage at -12°C can reduce protein denaturation and maintain thequality of pork, a result that is typically achieved under more extreme freezing conditions at -18°C.
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Accurate forecast of fine particulate matter (PM2.5) is crucial for city air pollution control, yet remains challenging due to the complex urban atmospheric chemical and physical processes. Recently deep learning has been routinely applied for better urban PM2.5 forecasts. However, their capacity to represent the spatiotemporal urban atmospheric processes remains underexplored, especially compared with traditional approaches such as chemistry-transport models (CTMs) and shallow statistical methods other than deep learning. Here we probe such urban-scale representation capacity of a spatiotemporal deep learning (STDL) model for 24-hour short-term PM2.5 forecasts at six urban stations in Rizhao, a coastal city in China. Compared with two operational CTMs and three statistical models, the STDL model shows its superiority with improvements in all five evaluation metrics, notably in root mean square error (RMSE) for forecasts at lead times within 12 h with reductions of 49.8 % and 47.8 % respectively. This demonstrates the STDL model's capacity to represent nonlinear small-scale phenomena such as street-level emissions and urban meteorology that are in general not well represented in either CTMs or shallow statistical models. This gain of small-scale representation in forecast performance decreases at increasing lead times, leading to similar RMSEs to the statistical methods (linear shallow representations) at about 12 h and to the CTMs (mesoscale representations) at 24 h. The STDL model performs especially well in winter, when complex urban physical and chemical processes dominate the frequent severe air pollution, and in moisture conditions fostering hygroscopic growth of particles. The DL-based PM2.5 forecasts align with observed trends under various humidity and wind conditions. Such investigation into the potential and limitations of deep learning representation for urban PM2.5 forecasting could hopefully inspire further fusion of distinct representations from CTMs and deep networks to break the conventional limits of short-term PM2.5 forecasts.
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BACKGROUND: Recent studies have demonstrated the relevance of circulating factors in the occurrence and development of colorectal cancer (CRC); however, the causal relationship remains unclear. METHODS: Summary-level data for CRC were obtained from the UK Biobank (5,657 cases and 372,016 controls), FinnGen cohort (3,022 cases and 215,770 controls), and BioBank Japan Project (BBJ, 7,062 cases and 195,745 controls). Thirty-two peripheral markers with consistent definitions were collected from the three biobanks. Mendelian randomization (MR) was used to evaluate the causal effect of circulating factors on CRC. The effects from the three consortiums were combined using trans-ancestry meta-analysis methods. RESULTS: Our analysis provided compelling evidence for the causal association of higher genetically predicted eosinophil cell count (EOS, odds ratio [OR], 0.8639; 95% confidence interval [CI] 0.7922-0.9421) and red cell distribution width (RDW, OR, 0.9981; 95% CI, 0.9972-0.9989) levels with a decreased risk of CRC. Additionally, we found suggestive evidence indicating that higher levels of total cholesterol (TC, OR, 1.0022; 95% CI, 1.0002-1.0042) may increase the risk of CRC. Conversely, higher levels of platelet count (PLT, OR, 0.9984; 95% CI, 0.9972-0.9996), total protein (TP, OR, 0.9445; 95% CI, 0.9037-0.9872), and C-reactive protein (CRP, OR, 0.9991; 95% CI, 0.9983-0.9999) may confer a protective effect against CRC. Moreover, we identified six ancestry-specific causal factors, indicating the necessity of considering patients' ancestry backgrounds before formulating prevention strategies. CONCLUSIONS: MR findings support the independent causal roles of circulating factors in CRC, which might provide a deeper insight into early detection of CRC and supply potential preventative strategies.
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Neoplasias Colorrectales , Análisis de la Aleatorización Mendeliana , Humanos , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/epidemiología , Predisposición Genética a la Enfermedad , Masculino , Femenino , Polimorfismo de Nucleótido Simple , Estudios de Casos y Controles , Japón/epidemiología , Factores de RiesgoRESUMEN
OBJECTIVE: To evaluate the effectiveness of low-level red light (LRL) in controlling the progression of myopia in children and adolescents. METHODS: A randomized controlled trial was conducted from March 2022 to June 2022 at the Xuzhou First People's Hospital. A total of 73 children and adolescents with myopia, between the ages of 6 and 14, and meeting the inclusion criteria, were randomly divided into two groups. The experimental group wore single vision spectacles with LRL intervention, while the control group wore single vision spectacles alone. Spherical equivalent refraction (SER), axial length (AL), subfoveal choroidal thickness (SFCT), and best-corrected visual acuity (BCVA) were measured for the participants. Data analysis was performed using chi-square test, independent samples t-test, and Mann-Whitney U test. To compare the changes in SER and AL between groups, we utilized the Generalized Estimating Equations (GEE) model. RESULTS: The experimental group was composed of 36 individuals, while the control group had 37. The mean age of the participants was 8.9 ± 2.0 years. No statistically significant distinctions in SER, AL and SFCT were observed between the two groups at baseline (P > 0.05). After 6 months of intervention, the experimental group's increase in SER (-0.01D; 95% CI: -0.09, 0.06) was higher than that of the control group (-0.41D; 95% CI: -0.51, -0.32), with a significance level of P < 0.001. Furthermore, the changes over time revealed significant differences between the two groups (Wald χ2group×time: 31.576, P < 0.001). The experimental group's AL increase (-0.02mm; 95% CI: -0.07, 0.03) was less than the control group's (0.22mm; 95% CI: 0.19, 0.25) (P < 0.001), with a significant difference over time between them (wald χ2group×time: 62.305, P < 0.001). SFCT change after 6 months in the experimental group was significantly greater (29.19µm; 95% CI: 18.48, 39.91) compared to that of the control group (-6.59µm; 95% CI: -14.28, 1.09) (P < 0.001). No adverse events were observed, and there was no evidence of fundus structural damage on OCT imaging. CONCLUSIONS: The findings suggest that low-level red light can effectively control myopia progression in children and adolescents within 6 months. No adverse reactions were observed.
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Natural killer (NK) cell-based immunotherapy holds promise for cancer treatment; however, its efficacy remains limited, necessitating the development of alternative strategies. Here, we report that venetoclax, an FDA-approved BCL-2 inhibitor, directly activates NK cells, enhancing their cytotoxicity against acute myeloid leukemia (AML) both in vitro and in vivo, likely independent of BCL-2 inhibition. Through comprehensive approaches, including bulk and single-cell RNA sequencing, avidity measurement, and functional assays, we demonstrate that venetoclax increases the avidity of NK cells to AML cells and promotes lytic granule polarization during immunological synapse (IS) formation. Notably, we identify a distinct CD161lowCD218b+ NK cell subpopulation that exhibits remarkable sensitivity to venetoclax treatment. Furthermore, venetoclax promotes mitochondrial respiration and ATP synthesis via the NF-κB pathway, thereby facilitating IS formation in NK cells. Collectively, our findings establish venetoclax as a multifaceted immunometabolic modulator of NK cell function and provide a promising strategy for augmenting NK cell-based cancer immunotherapy.
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Compuestos Bicíclicos Heterocíclicos con Puentes , Inmunoterapia Adoptiva , Células Asesinas Naturales , Leucemia Mieloide Aguda , Sulfonamidas , Compuestos Bicíclicos Heterocíclicos con Puentes/farmacología , Compuestos Bicíclicos Heterocíclicos con Puentes/uso terapéutico , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/efectos de los fármacos , Humanos , Sulfonamidas/farmacología , Animales , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/inmunología , Leucemia Mieloide Aguda/patología , Ratones , Inmunoterapia Adoptiva/métodos , Línea Celular Tumoral , FN-kappa B/metabolismo , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Ratones Endogámicos NODRESUMEN
Knowledge of protein function is essential for elucidating disease mechanisms and discovering new drug targets. However, there is a widening gap between the exponential growth of protein sequences and their limited function annotations. In our prior studies, we have developed a series of methods including GraphPPIS, GraphSite, LMetalSite and SPROF-GO for protein function annotations at residue or protein level. To further enhance their applicability and performance, we now present GPSFun, a versatile web server for Geometry-aware Protein Sequence Function annotations, which equips our previous tools with language models and geometric deep learning. Specifically, GPSFun employs large language models to efficiently predict 3D conformations of the input protein sequences and extract informative sequence embeddings. Subsequently, geometric graph neural networks are utilized to capture the sequence and structure patterns in the protein graphs, facilitating various downstream predictions including protein-ligand binding sites, gene ontologies, subcellular locations and protein solubility. Notably, GPSFun achieves superior performance to state-of-the-art methods across diverse tasks without requiring multiple sequence alignments or experimental protein structures. GPSFun is freely available to all users at https://bio-web1.nscc-gz.cn/app/GPSFun with user-friendly interfaces and rich visualizations.
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Proteínas , Programas Informáticos , Proteínas/química , Proteínas/metabolismo , Conformación Proteica , Análisis de Secuencia de Proteína , Aprendizaje Profundo , Sitios de Unión , Anotación de Secuencia Molecular , Redes Neurales de la Computación , Secuencia de Aminoácidos , Humanos , InternetRESUMEN
Sulforaphane (SFN) exerts anticancer effect on various cancers including gastric cancer. However, the regulatory effect of SFN on programmed death-ligand 1 (PD-L1) and checkpoint blockade therapy in gastric cancer have not been elucidated. Here we demonstrated that SFN suppressed gastric cancer cell growth both in vitro and in vivo study. SFN upregulated PD-L1 expression through activating ΔNP63α in gastric cancer cells. Further, we found that SFN impaired the anticancer effect of anti-PD-L1 monoclonal antibody (α-PD-L1 mab) on gastric cancer cells. These results uncover a novel PD-L1 regulatory mechanism and the double-edged role of SFN in gastric cancer intervention.
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Antígeno B7-H1 , Inhibidores de Puntos de Control Inmunológico , Isotiocianatos , Neoplasias Gástricas , Sulfóxidos , Factores de Transcripción , Isotiocianatos/farmacología , Humanos , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patología , Neoplasias Gástricas/genética , Antígeno B7-H1/metabolismo , Sulfóxidos/farmacología , Inhibidores de Puntos de Control Inmunológico/farmacología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Animales , Ratones , Línea Celular Tumoral , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Proteínas Supresoras de Tumor/metabolismo , Proteínas Supresoras de Tumor/genética , Proliferación Celular/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto , Ratones DesnudosRESUMEN
In this study, the improvement mechanism of low-frequency alternating magnetic field (LF-AMF, 5 mT, 3 h) combined with calcium chloride (CaCl2, 0-100 mM) on the gel characteristics of low-salt myofibrillar protein (MP) was investigated. LF-AMF combined with 80 mM CaCl2 treatment increased solubility (32.71%), surface hydrophobicity (40.86 µg), active sulfhydryl content (22.57%), water-holding capacity (7.15%). Besides, the combined treatment decreased turbidity, particle size and intrinsic fluorescence strength of MP. Fourier transform infrared spectroscopy (FT-IR) results indicated that the combined treatment altered the secondary structure of MP by increasing ß-sheet and ß-turn, and reducing α-helix and random coil. The combined treatment also induced a high G' value and shortened T2 relaxation time for forming a homogeneous and compact gel structure. These results revealed that LF-AMF combined CaCl2 treatment could as a potential approach for modifying the gel characteristics of low-salt MP.
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Background: Ropivacaine (Ropi) is a widely utilized anesthetic in cesarean sections (CS), however its optimal dosage remains controversial. Objective: To assess the efficacy and safety of varying doses (10mg, 5mg, 4mg, and 3mg) of Ropi in subarachnoid block (SA) for CS. Methods: A prospective cohort study was conducted, and a total of 74 pregnant women undergoing CS at Nantong Maternal and Child Health Care Hospital between January and June 2023 were selected as the study population. Participants were stratified into groups based on Ropivacaine dosage: Group A (10 mg, n=18), Group B (5 mg, n=26), Group C (4 mg, n=15), and Group D (3 mg, n=15). The total Ropivacaine dosage administered via SA was consistently 10 mg across all groups. We measured anesthetic efficacy, safety profiles, abdominal wall muscle relaxation, pre- and post-anesthesia stress and inflammatory responses before and after anesthesia and compared among the four groups. Results: Group A exhibited the shortest onset time for block initiation and longest recovery duration (P < .05). Group D displayed the highest incidence of patients requiring additional anesthetics and experiencing adverse reactions, whereas the utilization rate of vasopressors was most pronounced in Group A (P < .05). Notably, Group D reported the lowest satisfaction rate regarding abdominal wall muscle relaxation (P < .05). Stress responses were significantly lower in Groups A, B, and C compared to Group D, while the levels of inflammatory factors in Groups B and C were higher than those in Group A but lower than those in Group D (P < .05). Conclusions: Administration of 4 mg hyperbaric Ropi in SA can achieve an optimal anesthesia effect in CS with a high level of safety, along with inducing mild abdominal wall muscle relaxation and attenuating stress and inflammatory responses pre- and post-anesthesia. Thus, it is recommended for clinical application.
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Acute myeloid leukaemia (AML) is a prevalent haematological malignancy in which various immune and stromal cells in the bone marrow microenvironment have instrumental roles and substantially influence its progression. KIR2DL is a member of the immunoglobulin-like receptor family and a natural killer (NK) cell surface-specific receptor. However, its impact on immune infiltration regarding AML has not been addressed. We aimed to explore molecular markers associated with the immune microenvironment and prognosis of AML with a particular focus on KIR2DL family members. Analysis of data from The Cancer Genome Atlas and Genotype-Tissue Expression databases revealed that KIR2DL1, KIR2DL3 and KIR2DL4 expression were significantly upregulated in AML and associated with decreased overall survival (OS). Moreover, univariate Cox analysis implicated KIR2DL genes as independent prognostic markers of OS. Functional enrichment analysis revealed that KIR2DL genes were associated with immune cells, the immune microenvironment and NK cell-mediated cytotoxicity. Additionally, immune infiltration analyses revealed that KIR2DL upregulation was associated with stronger immune infiltration. Finally, we performed drug sensitivity profiling of KIR2DL genes using the Cellminer database. Collectively, our findings suggest that KIR2DL1, KIR2DL3 and KIR2DL4 have critical roles in AML and may represent novel biomarker genes for disease prognosis and immune infiltration.
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Leucemia Mieloide Aguda , Humanos , Pronóstico , Leucemia Mieloide Aguda/patología , Médula Ósea/patología , Microambiente Tumoral/genéticaRESUMEN
The Yellow River, renowned as the most sediment-laden river globally, grapples with sediment deposition issues compromising reservoir functionality and elevating downstream riverbeds, posing threats to human life and property safety. In response, the Water-Sediment Regulation Scheme (WSRS) has been innovatively implemented to address these challenges. While effectively mitigating sediment deposition, WSRS has concurrently disrupted the equilibrium of the estuarine ecosystem. This paper addresses the understudied but crucial topic of the interannual impact of WSRS on the estuarine ecosystem. Drawing upon physical, chemical, and biological data gathered through field surveys conducted before, during, and after WSRS from 2011 to 2022, the analysis delves into the interannual changes in the estuarine environment, fish eggs and larvae abundance, and species diversity under the influence of WSRS. The findings reveal an interannual decreasing trend in terrestrial material input due to WSRS, juxtaposed with an interannual increasing trend in fish eggs and larvae around the estuary, as well as the species diversity index. Notably, these trends became more pronounced post-2014. Compared to pre-2014, nutrient concentrations experienced a ~20 % decrease, chlorophyll-a concentration increased by 44 %, fish eggs proliferated approximately 1 time, and the species diversity index transitioned from a declining trend to an ascending trajectory. After 12 years of continuous WSRS implementation, the impact on the estuarine ecosystem has demonstrably diminished. This research aims to furnish reference experience and scientific basis for water and sediment regulation in major rivers around the world in terms of estuarine ecology.
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Ecosistema , Monitoreo del Ambiente , Estuarios , Sedimentos Geológicos , Ríos , Ríos/química , Sedimentos Geológicos/química , Animales , Peces , China , BiodiversidadRESUMEN
Three undescribed isosteroidal alkaloids, przewalskines A-C (1-3), as well as seven known alkaloids (4-10) were obtained from Fritillaria przewalskii bulbs. Their structures were deduced by extensive HRESIMS, 1D NMR, and 2D NMR analyses, and their bioactivities were evaluated involving the anti-inflammatory and inhibitory potencies on AChE, BChE, and Aß aggregation. Compound 4 revealed the potent effect on inhibiting Aß aggregation activity with IC50 value of 33.1â µM, AChE activity with IC50 value of 6.9â µM, and also showed NO release inhibitory acitivity with IC50 value of 32.6â µM. These findings contribute new multi-.target anti-AD agents and embody the chemical diversity of F. przewalskii.
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Alcaloides , Fritillaria , Fritillaria/química , Alcaloides/farmacología , Alcaloides/químicaRESUMEN
The frequent occurrence of extreme climate events has a significant impact on people's lives. Heavy rainfall can lead to an increase of regional Terrestrial Water Storage (TWS), which will cause land subsidence due to the influence of hydrological load. At present, regional TWS is mostly obtained from Gravity Recovery and Climate Experiment (GRACE) data, but the method has limitations for small areas. This paper used water level and flow data as hydrological signals to study the land subsidence caused by heavy rainfall in the Chaohu Lake area of East China (June 2016-August 2016). Pearson's correlation coefficient was used to study the interconnection between water resource changes and Global Navigation Satellites System (GNSS) vertical displacement. Meanwhile, to address the reliability of the research results, combined with the Coefficient of determination method, the research findings were validated by using different institutional models. The results showed that: (1) During heavy rainfall, the vertical displacement caused by atmospheric load was larger than non-tidal oceanic load, and the influence trends of the two were opposite. (2) The rapidly increasing hydrologic load in the Chaohu Lake area resulted in greater subsidence displacement at the closer CORS station (CHCH station) than the more distant CORS station (LALA station). The Pearson correlation coefficients between the vertical displacement and water level were as high as -0.80 and -0.64, respectively. The phenomenon confirmed the elastic deformation principle of disc load. (3) Although there was a systematic bias between the different environmental load deformation models, the deformation trends were generally consistent with the GNSS monitoring results. The average Coefficients of determination between the different models and the GNSS results were 0.63 and 0.77, respectively. The results demonstrated the effectiveness of GNSS in monitoring short-term hydrological load. This study reveals the spatial-temporal evolution of land deformation during heavy rainfall around Chaohu Lake, which is of reference significance for water resource management and infrastructure maintenance in this area.
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To explore the effect of feeding fermented distiller's grains (FDG) diets on spleen and mesenteric lymph nodes (MLN) immune status and metabolomics in finishing cattle, eighteen Guanling crossbred cattle (18 months old, 250.0 ± 25 kg) were randomly divided into 3 groups: a basal diet (Control) group, an FDG-15% group, and an FDG-30% group (containing 0%, 15% and 30% FDG to partially replace the concentrates, respectively). After 75 days, the spleens and MLN were collected for detection of relative spleen weight, immune parameters, and metabolomic analysis. Compared with the Control group, FDG-30% group significantly increased (P<0.05) the relative spleen weight. In addition, the level of IL-17A in the spleen of the FDG-30% group was significantly higher than that of the FDG-15% group. Metabolomic analysis showed that differential metabolites (VIPï¼1, Pï¼0.05) of spleen and MLN in FDG-15% and FDG-30% groups are mostly lipids and lipid molecules. KEGG analysis illustrated that choline metabolism in cancer, glycerophospholipid metabolism, biosynthesis of unsaturated fatty acids and insulin resistance were metabolic pathways in spleen shared by FDG-15% group vs.Control group and FDG-30% group vs.Control group, and choline metabolism in cancer was a metabolic pathway in MLN shared by FDG-15% group vs.Control group and FDG-30% group vs.Control group. These results suggest that feeding FDG may promote spleen development by regulating choline metabolism in cancer, glycerophospholipid metabolism, biosynthesis of unsaturated fatty acids and insulin resistance. Additionally, it may affect MLN development by regulating choline metabolism in cancer. SIGNIFICANCE: Fermented distiller's grains (FDG) is a high quality alternative to feed because it is rich in beneficial microorganisms and nutrients. The spleen and mesenteric lymph nodes (MLN) are important peripheral immune organs in animals, whose status reflects the health of the animal. However, there are few reports on the effect of feeding FDG diets on spleen and MLN immune status and metabolomics in domestic animals. In this study, we found that feeding FDG may promote spleen development by regulating choline metabolism in cancer, glycerophospholipid metabolism, biosynthesis of unsaturated fatty acids and insulin resistance metabolic pathways, and may affect MLN development by regulating choline metabolism in cancer. This study extends our understanding of the metabolomics of the spleen and MLN in FDG and helps to further understand of the immunomodulatory effects of the FDG diet.
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Resistencia a la Insulina , Neoplasias , Bovinos , Animales , Bazo , Fluorodesoxiglucosa F18 , Alimentación Animal/análisis , Dieta/veterinaria , Ácidos Grasos Insaturados , Ganglios Linfáticos , Glicerofosfolípidos , ColinaRESUMEN
Inflammatory bowel disease (IBD) is a gastrointestinal immune disease that requires clear diagnosis, timely treatment, and lifelong monitoring. The diagnosis and monitoring methods of IBD mainly include endoscopy, imaging examination, and laboratory examination, which are constantly developed to achieve early definite diagnosis and accurate monitoring. In recent years, with the development of nanotechnology, the diagnosis and monitoring methods of IBD have been remarkably enriched. Nanomaterials, characterized by their minuscule dimensions that can be tailored, along with their distinctive optical, magnetic, and biodistribution properties, have emerged as valuable contrast agents for imaging and targeted agents for endoscopy. Through both active and passive targeting mechanisms, nanoparticles accumulate at the site of inflammation, thereby enhancing IBD detection. This review comprehensively outlines the existing IBD detection techniques, expounds upon the utilization of nanoparticles in IBD detection and diagnosis, and offers insights into the future potential of in vitro diagnostics. STATEMENT OF SIGNIFICANCE: Due to their small size and unique physical and chemical properties, nanomaterials are widely used in the biological and medical fields. In the area of oncology and inflammatory disease, an increasing number of nanomaterials are being developed for diagnostics and drug delivery. Here, we focus on inflammatory bowel disease, an autoimmune inflammatory disease that requires early diagnosis and lifelong monitoring. Nanomaterials can be used as contrast agents to visualize areas of inflammation by actively or passively targeting them through the intestinal mucosal epithelium where gaps exist due to inflammation stimulation. In this article, we summarize the utilization of nanoparticles in inflammatory bowel disease detection and diagnosis, and offers insights into the future potential of in vitro diagnostics.
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Medios de Contraste , Enfermedades Inflamatorias del Intestino , Humanos , Distribución Tisular , Enfermedades Inflamatorias del Intestino/diagnóstico , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Mucosa Intestinal , InflamaciónRESUMEN
Transboundary water pollution induced by inter-regional trade is a complex and challenging issue due to the multiple jurisdictions involved. This study combined water pollution discharge inventory, multi-regional input-output analysis, discharge responsibility-sharing, and ecological compensation model to advance the collaborative control of water pollution embodied in China's inter-provincial trade. Over a fifth of China's water pollution discharges in 2017, equivalent to 1376 Kt, were a result of inter-provincial trade, which primarily flowed from wealthier coastal provinces to less developed ones. Moreover, the analysis demonstrates a mismatch between economic gains and environmental costs. In particular, Jiangxi and Guangxi bear the greatest environmental impact (64 and 58 Kt, respectively) while only receiving meager economic returns (131 and 80 billion Yuan). The economic benefit shared responsibility results for the great majority of provinces fell between production- and consumption-based discharges, and this compromise-based allocation of responsibility is more likely to gain acceptance across various regions. Provinces such as Shanghai, Jiangsu, and Beijing necessitate the highest compensation volumes to others, with 31 Kt, 25 Kt, and 20 Kt, respectively, while provinces including Guangxi, Jiangxi, and Ningxia require the largest inflows of compensation, totaling 26 Kt, 23 Kt, and 18 Kt, respectively. The compensation outcomes ensure that less developed regions, bearing a greater pollution burden, receive compensation from more developed regions with lower pollution burdens. The compensation values aligned with compensation volumes, with a few exceptions driven by variations in shadow prices of water pollution. Our study sheds light on the inter-provincial water pollution burdens and benefits and provides a quantitative basis for optimizing the responsibility-sharing and compensation strategies in China, thereby promoting regional cooperation on water pollution control.
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Conservación de los Recursos Naturales , Contaminación del Agua , China , Beijing , Modelos TeóricosRESUMEN
Hepatocellular carcinoma (HCC) stands as the fifth most prevalent malignant tumor on a global scale and presents as the second leading cause of cancer-related mortality. DNA damage-based radiotherapy (RT) plays a pivotal role in the treatment of HCC. Nevertheless, radioresistance remains a primary factor contributing to the failure of radiation therapy in HCC patients. In this study, we investigated the functional role of transketolase (TKT) in the repair of DNA double-strand breaks (DSBs) in HCC. Our research unveiled that TKT is involved in DSB repair, and its depletion significantly reduces both non-homologous end joining (NHEJ) and homologous recombination (HR)-mediated DSB repair. Mechanistically, TKT interacts with PARP1 in a DNA damage-dependent manner. Furthermore, TKT undergoes PARylation by PARP1, resulting in the inhibition of its enzymatic activity, and TKT can enhance the auto-PARylation of PARP1 in response to DSBs in HCC. The depletion of TKT effectively mitigates the radioresistance of HCC, both in vitro and in mouse xenograft models. Moreover, high TKT expression confers resistance of RT in clinical HCC patients, establishing TKT as a marker for assessing the response of HCC patients who received cancer RT. In summary, our findings reveal a novel mechanism by which TKT contributes to the radioresistance of HCC. Overall, we identify the TKT-PARP1 axis as a promising potential therapeutic target for improving RT outcomes in HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Animales , Ratones , Roturas del ADN de Doble Cadena , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/radioterapia , Carcinoma Hepatocelular/patología , Transcetolasa/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/patología , Reparación del ADN , ADN , Reparación del ADN por Unión de Extremidades , Reparación del ADN por Recombinación , Poli(ADP-Ribosa) Polimerasa-1/genéticaRESUMEN
INTRODUCTION: Dent disease type I is a rare X-linked recessive renal tubular disease resulting from pathogenic variants in the CLCN5 gene. Due to the rarity of Dent disease type I and the diversity of its phenotypes, its clinical diagnosis is complex and poses a challenge to clinicians. METHODS: A foetus and a child from a 36-year-old pregnant woman with a birth history of abnormal children were enrolled in this study. Pregnant women undergo amniocentesis for prenatal diagnosis at the gestational age of 12+ 3 weeks. Chromosomal microarray (CMA) analysis and whole-exome sequencing (WES) were employed to investigate the chromosomal copy number and single gene variants. Literature retrieval and data analysis were performed for genotype and phenotype collection analysis. RESULTS: No chromosomal abnormalities or CNVs were detected in the entire family through karyotype and familial CMA analyses. WES identified a nonsense pathogenic variant in CLCN5 of the X chromosome, c.1942 C > T (exon 11, NM_000084), which was inherited from his mother, who exhibited regular clinical features. CONCLUSION: This study suggests that children with low-molecular-weight proteinuria and hypercalciuria should undergo prompt genetic testing to exclude Dent disease.
Asunto(s)
Enfermedad de Dent , Adulto , Femenino , Humanos , Embarazo , Aberraciones Cromosómicas , Cromosomas Humanos X , Pruebas Genéticas , Diagnóstico PrenatalRESUMEN
A total of 30 Simmental crossbred cattle (6.50 months old, 265.0 ± 22.48 kg) were randomly divided into three groups, with 10 heads per group, and fed for 45 days. The diet treatments consisted of the Control group without PFDG supplementation, the PFDG-15% group with 15% PFDG substituting for 15% concentrate, and PFDG-30% group with 30% PFDG substituting for 30% concentrate. The results showed that compared with the Control group, the average daily gain (ADG) of the cattle in the PFDG-30% group decreased significantly (0.890 vs. 0.768 kg/d, p = 0.005). The serum malondialdehyde content of cattle in the PFDG-15% and PFDG-30% groups decreased significantly (p = 0.047) compared to that of the Control group. However, the serum superoxide dismutase activity of cattle in the PFDG-30% group was significantly higher than that of the Control group (p = 0.047). Meanwhile, both the PFDG-15% and PFDG-30% groups (1758.47 vs. 2061.30 µg/mL) showed higher serum levels of immunoglobulin G, while the interleukin-10 concentration was lower in the PFDG-30% group (p = 0.027). In addition, the PFDG-15% and PFDG-30% groups shifted the rumen microbiota by improving the abundances of F082 (related to propionic acid production) and fiber-degrading bacteria (Lachnospiraceae_UGG-009 and Prevotellaceae_UCG-001) and reducing the abundance of the disease-associated bacteria Selenomonas. A Kyoto encyclopedia of genes and genomes (KEGG) analysis illustrated that three key metabolic pathways, including phenylalanine metabolism, pyrimidine metabolism, and tryptophan metabolism, were enriched in the PFDG-15% group, but eight key metabolic pathways, including arachidonic acid metabolism, were enriched in the PFDG-30% group. Importantly, both the PFDG-15% and PFDG-30% groups increased (p < 0.01) the activities of cellulase, lipase, and protease in the rumen. Finally, the different bacterial abundance in the rumen was associated with changes in the ADG, serum antioxidant capacity, immune status, rumen enzyme activity, and metabolites. These results suggest that PFDG alters rumen microbiome abundance, metabolome, and enzyme activity for enhancing serum antioxidant capacity and the immune status, but when the supplemental level reaches 30%, it has a negative effect on ADG and the anti-inflammatory factors in finishing cattle.