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COVID-19 , Vacunas contra Papillomavirus , Humanos , COVID-19/prevención & control , COVID-19/epidemiología , Vacunas contra Papillomavirus/administración & dosificación , Estados Unidos/epidemiología , Estudios de Cohortes , Vacunación , Infecciones por Papillomavirus/prevención & control , SARS-CoV-2/inmunología , Bases de Datos Factuales , Femenino , Virus del Papiloma HumanoRESUMEN
Mercury, a neurotoxic substance, circulates globally, significantly stored in soils through atmospheric deposition and plant decay. Despite being deposited, mercury can be remobilized and released into the atmosphere and water, enhancing its global cycle. Recent research suggests that climate warming may amplify the remobilization of soil mercury, facilitating its incorporation into food webs that humans exploit. However, the potential geospatial feedback of soil mercury levels in response to warming remains unclear. By leveraging up-to-date soil measurements and observation-driven models, we determined the amount of mercury stored in global 0-100 cm soils to be 4.3 Tg (interquartile range: 2.5-6.3 Tg). Furthermore, our analysis indicates that warming likely aggravates global soil mercury levels, particularly in many temperate areas in East Asia, North Europe, and North America (>20 ng g-1 increase by 2100) due to warming-induced vegetation greening. Critically, observation-driven models raise the possibility that implementing ambitious mercury-emission-control schemes alone may be insufficient to counterbalance the positive feedback of soil mercury concentration, while process-based biogeochemical modeling demonstrates consistent patterns that reinforce this concern. These findings hold broad implications; for example, such feedback may catalyze mercury remobilization in land-ocean continuums and exacerbate human risks, stressing the necessity for continued reductions in greenhouse gas and mercury emissions.
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Central lymph node (CLN) status is considered to be an important risk factor in patients with papillary thyroid carcinoma (PTC). The aim of the present study was to identify risk factors associated with CLN metastasis (CLNM) for patients with PTC based on preoperative clinical, ultrasound (US) and contrast-enhanced computed tomography (CT) characteristics, and establish a prediction model for treatment plans. A total of 786 patients with a confirmed pathological diagnosis of PTC between January 2021 to December 2022 were included in the present retrospective study, with 550 patients included in the training group and 236 patients enrolled in the validation group (ratio of 7:3). Based on the preoperative clinical, US and contrast-enhanced CT features, univariate and multivariate logistic regression analyses were used to determine the independent predictive factors of CLNM, and a personalized nomogram was constructed. Calibration curve, receiver operating characteristic (ROC) curve and decision curve analyses were used to assess discrimination, calibration and clinical application of the prediction model. As a result, 38.9% (306/786) of patients with PTC and CLNM(-) status before surgery had confirmed CLNM using postoperative pathology. In multivariate analysis, a young age (≤45 years), the male sex, no presence of Hashimoto thyroiditis, isthmic location, microcalcification, inhomogeneous enhancement and capsule invasion were independent predictors of CLNM in patients with PTC. The nomogram integrating these 7 factors exhibited strong discrimination in both the training group [Area under the curve (AUC)=0.826] and the validation group (AUC=0.818). Furthermore, the area under the ROC curve for predicting CLNM based on clinical, US and contrast-enhanced CT features was higher than that without contrast-enhanced CT features (AUC=0.818 and AUC=0.712, respectively). In addition, the calibration curve was appropriately fitted and decision curve analysis confirmed the clinical utility of the nomogram. In conclusion, the present study developed a novel nomogram for preoperative prediction of CLNM, which could provide a basis for prophylactic central lymph node dissection in patients with PTC.
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Arsenate is a highly toxic element and excessive accumulation of arsenic in the aquatic environment easily triggers a problem threatening the ecological health. Phytoremediation has been widely explored as a method to alleviate As contamination. Here, the green algae, Chlamydomonas reinhardtii was investigated by profiling the accumulation of arsenate and phosphorus, which share the same uptake pathway, in response to arsenic stress. Both C. reinhardtii wild type C30 and the Crpht3 mutant were cultured under arsenic stress, and demonstrated a similar growth phenotype under limited phosphate supply. Sufficient phosphate obviously increased the uptake of polyphosphate and intercellular phosphate in the Crpht3 mutant, which increased the arsenic tolerance of the Crpht3 mutant under stress from 500 µmol L-1 As(V). Upregulation of the PHT3 gene in the Crpht3 mutant increased accumulation of phosphate in the cytoplasm under arsenate stress, which triggered a regulatory role for the differentially expressed genes that mediated improvement of the glutathione redox cycle, antioxidant activity and detoxification. While the wild type C30 showed weak arsenate tolerance because of little phosphate accumulation. These results suggest that the enhanced arsenic tolerance of the Crpht3 mutant is regulated by the PHT3 gene mediation. This study provides insight onto the responsive mechanisms of the PHT3 gene-mediated in alleviating arsenic toxicity in plants.
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Azaspiracids (AZAs) are lipid biotoxins produced by the marine dinoflagellates Azadinium and Amphidoma spp. that can accumulate in shellfish and cause food poisoning in humans. However, the mechanisms underlying the tolerance of shellfish to high levels of such toxins remain poorly understood. This study investigated the combined effects of detoxification metabolism and stress-related responses in scallops Chlamys farreri exposed to AZA. Scallops accumulated a maximum of 361.81 µg AZA1 eq/kg and 41.6 % AZA residue remained after 21 days of exposure. A range of AZA2 metabolites, including AZA19, AZA11, and AZA23, and trace levels of AZA2-GST, were detected. Total hemocyte counts significantly increased and ROS levels remained consistently high until gradually decreasing. Immune system activation mediated mitochondrial dysfunction and severe energy deficiency. DEGs increased over time, with key genes CYP2J6 and GPX6 contributing to AZA metabolism. These transcriptome and metabolic results identify the regulation of energy metabolism pathways, including inhibition of the TCA cycle and activation of carbohydrates, amino acids, and lipids. AZA also induced autophagy through the MAPK-AMPK signaling pathways, and primary inhibited PI3K/AKT to decrease mTOR pathway expression. Our results provide additional insights into the resistance of C. farreri to AZA, characterized by re-establishing redox homeostasis toward a more oxidative state.
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Toxinas Marinas , Pectinidae , Compuestos de Espiro , Animales , Toxinas Marinas/toxicidad , Compuestos de Espiro/toxicidad , Pectinidae/efectos de los fármacos , Pectinidae/metabolismo , Pectinidae/inmunología , Especies Reactivas de Oxígeno/metabolismo , Metabolismo Energético/efectos de los fármacos , Transcriptoma/efectos de los fármacos , Toxinas PoliéteresRESUMEN
As the utilization of high-resolution imaging modalities, such as ultrasound, becomes increasingly prevalent, there has been a swift rise in the detection rates of malignant thyroid nodules (MTC). Surgery remains the cornerstone of standard treatment for these nodules. However, the advent and evolution of thermal ablation (TA) techniques, encompassing radiofrequency ablation, laser ablation, and microwave ablation, have emerged as a novel therapeutic avenue for patients with MTC, particularly for those deemed unsuitable for surgery due to high risks or for those who refuse surgery. Presently, TA has been validated as an efficacious and safe intervention for both benign thyroid nodules and a subset of MTC. An expanding body of research has been dedicated to broadening the applicability of TA, initially from recurrent thyroid cancer and lymph nodes to now encompass isolated papillary thyroid microcarcinomas (PTMC) alongside a comprehensive exploration into the expanded parameters such as size, number, and location of PTMC, and its applicability in other types of thyroid cancer. This review provides a detailed synthesis of the clinical evidence about the use of TA in the management of MTC, as endorsed by current guidelines. It further delves into the ongoing research efforts aimed at extending its indications and discusses the prospective implications and challenges of integrating TA into the clinical management paradigms for MTC.
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Nódulo Tiroideo , Humanos , Nódulo Tiroideo/cirugía , Técnicas de Ablación/métodosRESUMEN
Globally, breast cancer (BC) has the highest prevalence among malignant diseases. BC is also the primary cause of death among women. Notably, BC morbidity has been increasing continuously at an approximate growth rate of 2.2% per year. Persistent BC is a major public health issue worldwide. Consequently, novel chemotherapeutic agents to combat this lethal disease should be developed urgently. Coumarins with interesting structural and mechanistic variations exhibit promising activity in several forms of BC, including BCs with multidrug resistance. In particular, coumarin hybrids composed of coumarin and one or more anti-BC pharmacophores can target different biological components in BC cells simultaneously. Thus, coumarin hybrids are useful scaffolds that can help improve the anti-BC efficacy of coumarins, reduce side effects, improve pharmacokinetics, minimize drug-drug interactions, and circumvent drug resistance. This review, in which articles published from 2020 to the present day have been evaluated, highlights the landscape of coumarin hybrids that exhibit therapeutic effects against breast cancer. These findings can aid further investigations on novel antibreast-cancer therapeutics.
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Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease mainly caused by insulin resistance, which can lead to a series of complications such as cardiovascular disease, retinopathy, and its typical clinical symptom is hyperglycaemia. Glucosidase inhibitors, including Acarbose, Miglitol, are commonly used in the clinical treatment of hypoglycaemia. In addition, Protein tyrosine phosphatase 1B (PTP1B) is also an important promising target for the treatment of T2DM. Gynostemma pentaphyllum is a well-known oriental traditional medicinal herbal plant, and has many beneficial effects on glucose and lipid metabolism. In the present study, three new and nine known dammarane triterpenoids isolated from G. pentaphyllum, and their structures were elucidated by spectroscopic methods including HR-ESI-MS,1H and 13C NMR and X-ray crystallography. All these compounds were evaluated for inhibitory activity against α-glucosidase, α-amylase and PTP1B. The results suggested that compounds 7â¼10 were potential antidiabetic agents with significantly inhibition activity against PTP1B in a dose-dependent manner.
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Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos , Gynostemma , Proteína Tirosina Fosfatasa no Receptora Tipo 1 , Proteína Tirosina Fosfatasa no Receptora Tipo 1/antagonistas & inhibidores , Proteína Tirosina Fosfatasa no Receptora Tipo 1/metabolismo , Gynostemma/química , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/aislamiento & purificación , Estructura Molecular , Relación Estructura-Actividad , alfa-Glucosidasas/metabolismo , Humanos , alfa-Amilasas/antagonistas & inhibidores , alfa-Amilasas/metabolismo , Hipoglucemiantes/farmacología , Hipoglucemiantes/química , Hipoglucemiantes/aislamiento & purificación , Modelos Moleculares , Cristalografía por Rayos X , Triterpenos/farmacología , Triterpenos/química , Triterpenos/aislamiento & purificación , Inhibidores de Glicósido Hidrolasas/farmacología , Inhibidores de Glicósido Hidrolasas/química , Inhibidores de Glicósido Hidrolasas/aislamiento & purificaciónRESUMEN
Organophosphate pesticides (OPs) are widely utilized in agricultural production, and the residues threaten public health and environmental safety due to their toxicity. Herein, a novel and simple DNA aptamer-based sensor has been fabricated for the rapid, visual, and quantitative detection of profenofos and isocarbophos. The proposed DNA aptamers with a G-quadruplex spatial structure could be recognized by SYBR Green I (SG-I), resulting in strong green fluorescence emitted by SG-I. The DNA aptamers exhibit a higher specific binding ability to target OP molecules through aromatic ring stacking, disrupting the interaction between SG-I and DNA aptamers to induce green fluorescence quenching. Meanwhile, the fluorescence wavelength of G-quadruplex fluorescence emission peaks changes, accompanied by an obvious fluorescence variation from green to blue. SG-I-modified aptasensor without any additive reference fluorescence units for use in multicolor fluorescence assay for selective monitoring of OPs was first developed. The developed aptasensor provides a favorable linear range from 0 to 200 nM, with a low detection limit of 2.48 and 3.01 nM for profenofos and isocarbophos, respectively. Moreover, it offers high selectivity and stability in real sample detection with high recoveries. Then, a self-designed portable smartphone sensing platform was successfully used for quantitative result outputs, demonstrating experience in designing a neotype sensing strategy for point-of-care pesticide monitoring.
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Aptámeros de Nucleótidos , Benzotiazoles , Diaminas , Colorantes Fluorescentes , Compuestos Orgánicos , Plaguicidas , Quinolinas , Espectrometría de Fluorescencia , Aptámeros de Nucleótidos/química , Quinolinas/química , Plaguicidas/análisis , Diaminas/química , Colorantes Fluorescentes/química , Benzotiazoles/química , Compuestos Orgánicos/química , Técnicas Biosensibles/métodos , Límite de Detección , G-Cuádruplex , Malatión/análogos & derivadosRESUMEN
Angiogenesis is crucial for blood flow recovery and ischemic tissue repair of peripheral artery disease (PAD). Exploration of new mechanisms underlying angiogenesis will shed light on the treatment of PAD. Ubiquitin-fold modifier 1 (UFM1), a newly identified ubiquitin-like molecule, has been discovered to be involved in various pathophysiological processes. However, the role of UFM1 in the pathogenesis of PAD, especially in endothelial angiogenesis remains obscure, and we aimed to clarify this issue in this study. We initially found UFM1 was significantly upregulated in gastrocnemius muscles of PAD patients and hind limb ischemia mice. And UFM1 was mainly colocalized with endothelial cells in ischemic muscle tissues. Further, elevated expression of UFM1 was observed in hypoxic endothelial cells. Subsequent genetic inhibition of UFM1 dramatically enhanced migration, invasion, adhesion, and tube formation of endothelial cells under hypoxia. Mechanistically, UFM1 reduced the stability of hypoxia-inducible factor-1α (HIF-1α) and promoted the von Hippel-Lindau-mediated K48-linked ubiquitin-proteasome degradation of HIF-1α, which in turn decreased angiogenic factor VEGFA expression and suppressed VEGFA related signaling pathway. Consistently, overexpression of UFM1 inhibited the angiogenesis of endothelial cells under hypoxic conditions, whereas overexpression of HIF-1α reversed this effect. Collectively, our data reveal that UFM1 inhibits the angiogenesis of endothelial cells under hypoxia through promoting ubiquitin-proteasome degradation of HIF-1α, suggesting UFM1 might serve as a potential therapeutic target for PAD.
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Subunidad alfa del Factor 1 Inducible por Hipoxia , Complejo de la Endopetidasa Proteasomal , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Animales , Humanos , Ratones , Complejo de la Endopetidasa Proteasomal/metabolismo , Neovascularización Fisiológica , Proteolisis , Hipoxia de la Célula , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Neovascularización Patológica/metabolismo , Neovascularización Patológica/patología , Masculino , Isquemia/metabolismo , Isquemia/patología , Angiogénesis , ProteínasRESUMEN
The innate immunity of bivalves serves as the initial defense mechanism against environmental pollutants, ultimately impacting genetic regulatory networks through synergistic interactions. Previous research has demonstrated variations in the accumulation and tolerance capacities of bivalves; however, the specific mechanism underlying the low accumulation of PSTs in M. unguiculatus remains unclear. This study examined the alterations in feeding behavior and transcriptional regulation of M. unguiculatus following exposure to two Alexandrium strains with distinct toxin profiles, specifically gonyautoxin (AM) and N-sulfocarbamoyl toxin (AC). The total accumulation rate of PSTs in M. unguiculatus was 43.64 % (AC) and 27.80 % (AM), with highest PSTs content in the AM group (455.39 µg STXeq/kg). There were significant variations (P < 0.05) in physiological parameters, such as total hemocyte count, antioxidant superoxide activity and tissue damage in both groups. The absorption rate was identified as the key factor influencing toxin accumulation. Transcriptomic analyses demonstrated that PSTs triggered upregulation of endocytosis, lysosome, and immune-related signaling pathways. Furthermore, PSTs induced a nucleotide imbalance in the AC group, with total PSTs content serving as the most toxic indicator. These results suggested that protein-like substances had a crucial role in the stress response of M. unguiculatus to PSTs. This study provided novel perspectives on the impacts of intricate regulatory mechanisms and varying immune responses to PSTs in bivalves.
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Dinoflagelados , Toxinas Marinas , Mytilus , Animales , Dinoflagelados/fisiología , Mytilus/fisiología , Inmunidad InnataRESUMEN
Preliminary pharmacological studies revealed that the EtOAc fraction (BGEA) might be the main active fraction with anti-inflammatory and antinociceptive effects in Beaumontia grandiflora Wall. Further assays on BGEA at doses of 200, 400, and 800 mg/kg using four animal models showed that it could inhibit the xylene-induced ear edema, carrageenan-induced paw edema, and acetic acid-induced writhing and prolong the latency time in the hot-plate test. ELISA analysis revealed that the anti-inflammatory activity of BGEA might be associated with the decrease of TNF-α, IL-1ß, and IL-6 levels and the increase of the IL-10 level. The acute toxicity test showed that except for the n-BuOH fraction, the LD50 values of the extract and other three fractions were higher than 2000 mg/kg bw. Finally, 14 compounds were identified from BGEA by LC-MS. This research provides some basis for the folk use of B. grandiflora in the treatment of inflammation and pain-related diseases.
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ETHNOPHARMACOLOGICAL RELEVANCE: Gynostemma pentaphyllum (Thunb.) Makino has traditional applications in Chinese medicine to treat lipid abnormalities. Gypenosides (GPs), the main bioactive components of Gynostemma pentaphyllum, have been reported to exert hypolipidemic effects through multiple mechanisms. The lipid-lowering effects of GPs may be attributed to the aglycone portion resulting from hydrolysis of GPs by the gut microbiota. However, to date, there have been no reports on whether gypenoside aglycones (Agl), the primary bioactive constituents, can ameliorate hyperlipidemia by modulating the gut microbiota. AIM OF THE STUDY: This study explored the potential therapeutic effects of gypenoside aglycone (Agl) in a rat model of high-fat diet (HFD)-induced hyperlipidemia. METHODS: A hyperlipidemic rat model was established by feeding rats with a high-fat diet. Agl was administered orally, and serum lipid levels were analyzed. Molecular techniques, including RT-polymerase chain reaction (PCR) and fecal microbiota sequencing, were used to investigate the effects of Agl on lipid metabolism and gut microbiota composition. RESULTS: Agl administration significantly reduced serum levels of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) and mitigated hepatic damage induced by HFD. Molecular investigations have revealed the modulation of key lipid metabolism genes and proteins by Agl. Notably, Agl treatment enriched the gut microbiota with beneficial genera, including Lactobacillus, Akkermansia, and Blautia and promoted specific shifts in Lactobacillus murinus, Firmicutes bacterium CAG:424, and Allobaculum stercoricanis. CONCLUSION: This comprehensive study established Agl as a promising candidate for the treatment of hyperlipidemia. It also exhibits remarkable hypolipidemic and hepatoprotective properties. The modulation of lipid metabolism-related genes, along with the restoration of gut microbiota balance, provides mechanistic insights. Thus, Agl has great potential for clinical applications in hyperlipidemia management.
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Microbioma Gastrointestinal , Hiperlipidemias , Ratas , Animales , Dieta Alta en Grasa/efectos adversos , Gynostemma , Hiperlipidemias/tratamiento farmacológico , Hiperlipidemias/metabolismo , Triglicéridos/metabolismo , Metabolismo de los Lípidos , LDL-Colesterol/metabolismo , Extractos VegetalesRESUMEN
Introduction: The purpose of this study is to examine the potential causal relationship between levels of circulating glycine and coronary artery disease (CAD) using a two-step Mendelian randomization (MR) analysis. Methods: We analyzed data from genome-wide association studies (GWAS) conducted on European and East Asian populations. To assess the causal effects of circulating glycine levels on the risk of CAD. We used the inverse-variance weighting (IVW), weighted median (WM), MR-Egger, and Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO) methods. Furthermore, we conducted mediation analysis to investigate the contribution of blood pressure and other cardiovascular disease-related traits. Results: The two-step Mendelian randomization analysis revealed that higher levels of glycine in the blood were associated with a reduced risk of CAD in Europeans [odds ratio ( OR)=0.84, 95% confidence interval ( CI): 0.72, -0.98; P=0.029] and East Asians: ( OR=0.76, 95% CI: 0.66, -0.89; P=3.57×10 -4). Sensitivity analysis confirmed the robustness of these findings. Additionally, our results suggest that about 6.06% of the observed causal effect is mediated through genetically predicted systolic blood pressure (SBP) in the European population. Discussion: Our results contribute to the current knowledge regarding the involvement of glycine in the progression of CAD, and provide valuable methodological insights for the prevention and treatment of this condition.
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Breast cancer, an epithelial malignant tumor that occurs in the terminal ducts of the breast, is the most common female malignancy. Currently, approximately 70%-80% of breast cancer with early-stage, nonmetastatic disorder is curable, but the emergency of drug resistance often leads to treatment failure. Moreover, advanced breast cancer with distant organ metastases is incurable with the available therapeutics, creating an urgent demand to explore novel antibreast cancer agents. Chalcones, the precursors for flavonoids and isoflavonoids, exhibit promising activity against various breast cancer hallmarks, inclusive of proliferation, angiogenesis, invasion, metastasis, inflammation, stemness, and regulation of cancer epigenetics, representing useful scaffolds for the discovery of novel antibreast cancer chemotherapeutic candidates. In particular, chalcone hybrids could act on two or more different biological targets simultaneously with more efficacy, lower toxicity, and less susceptibility to resistance. Accordingly, there is a huge scope for application of chalcone hybrids to tackle the present difficulties in breast cancer therapy. This review outlines the chalcone hybrids with antibreast cancer potential developed from 2018. The structure-activity relationships as well as mechanisms of action are also discussed to shed light on the development of more effective and multitargeted chalcone candidates.
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Antineoplásicos , Neoplasias de la Mama , Chalconas , Animales , Femenino , Humanos , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Proliferación Celular/efectos de los fármacos , Chalconas/farmacología , Chalconas/química , Estructura Molecular , Relación Estructura-ActividadRESUMEN
This study was set to investigate the effects of rice husk biochar (RHB) on soil characteristics and growth of lettuce (Lactuca sativa). A comprehensive research approach was employed to examine the effect of different RHB concentrations (i.e., 0-1.5%) on soil pH, soil enzyme activities (i.e., alkaline phosphatase, beta-glucosidase, and dehydrogenase), soil microbial community, lettuce growth, and earthworm toxicity. The results showed that, within the studied RHB concentration range, the RHB application did not have significant effects on the soil pH. However, the enzyme activities were increased with increasing RHB concentration after the 28 d-lettuce growth period. The RHB application also increased the abundances of the bacterial genera Massilia and Bacillus and fungal genus Trichocladium having the plant growth promoting abilities. Furthermore, the study revealed that the root weight and number of lettuce leaves were significantly increased in the presence of the RHB, and the growth was dependent on the RHB concentration. The improved lettuce growth can be explained by the changes in the enzyme and microbial dynamics, which have resulted from the increased nutrient availability with the RHB application. Additionally, the earthworm toxicity test indicated that the tested RHB concentrations can be safely applied to soil without any significant ecotoxicity. In conclusion, this study underscores the potential of RHB as a soil amendment with positive effects on crop growth, highlighting the utilization of agricultural byproducts to enhance soil biological quality and plant growth through biochar application.
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Oryza , Contaminantes del Suelo , Suelo , Lactuca , Agricultura , Carbón Orgánico/farmacología , Contaminantes del Suelo/toxicidad , Contaminantes del Suelo/análisisRESUMEN
Objectives: The purpose of this study is to evaluate the potential of the flattening filter free (FFF) mode of a linear accelerator for patients with hippocampal avoidance whole-brain radiotherapy (HA-WBRT) by comparison with flattened beams (FF) technique in the application of volumetric modulated arc therapy (VMAT) and intensity modulated radiation therapy (IMRT) using dosimetric and radiobiological indexes based on the volume of hippocampus and target. Methods: 2 VMAT- and 2 IMRT- plans were optimized in Eclipse planning system with 2 different delivery modes (6 MV standard vs. 6 MV FFF) for each of 25 patients. Dose distributions of the target and organs at risk (OARs), normal tissue complication probability (NTCP) of the hippocampus, monitor units, treatment time and quality assurance results were evaluated to compare the normal and FFF beam characteristics by Wilcoxon matched-pair signed-rank test with a significance level of 0.05. Results: VMAT-FFF provided the significantly best homogeneity and conformity of the target, delivered the lowest dose to hippocampus and the other OARs, and led to the lowest NTCP of the hippocampus among all modalities, which has the potential to alleviate neurocognitive decline after WBRT. IMRT-FFF reduced the dose to the lens with similar dose distributions of the target compared with IMRT-FF, whereas the lower dose to the hippocampus was achieved using the conventional beams. The monitor units were obviously increased by 19.2% for VMAT and 33.8% for IMRT, when FFF beams w ere used. The removal of flattening filter for IMRT resulted in a 26% reduction in treatment time, but VMAT had the similar treatment time for the two modes owing to the limitation of gantry rotation speed. Gamma analysis showed an excellent agreement for all plans at 3%/2 mm, and no statistical differences were found between FF and FFF. Conclusion: In conclusion, this study suggests that FFF mode is feasible and advantageous in HA-WBRT and VMAT-FFF is the optimal solution in terms of dose distribution of the target, OARs sparing, NTCP of the hippocampus and delivery efficiency compared to the other three techniques. Additionally, the advantages of the FFF technique for VMAT are more prominent in cases with small hippocampal volumes.
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Outdoor air pollution causes millions of premature deaths annually worldwide. Sulfate is a major component of particulate pollution. Winter sulfate observations in China show both high concentrations and an accumulation mode with a modal size >1 µm. However, we find that this observed size distribution cannot be simulated using classical gaseous and aqueous phase formation (CSF) or proposed aerosol-processing formation (APF) mechanisms. Specifically, the CSF simulation underestimates sulfate concentrations by 76% over megacities in China and predicts particle size distributions with a modal size of â¼0.35 µm, significantly smaller than observations. Although incorporating the APF mechanism in the atmospheric chemical model notably improves sulfate concentration simulation with reasonable parameters, the simulated sulfate particle size distribution remains similar to that using the CSF mechanism. We further conduct theoretical analyses and show that particles with diameters <0.3 µm grow rapidly (2-3 s) to 1 µm through the condensation of sulfuric acid in fresh high-temperature exhaust plumes, referred to as in-source formation (ISF). An ISF sulfate source equivalent to 15% of sulfur emissions from fossil fuel combustion largely explains both observed size distributions and mass concentrations of sulfate particles. The findings imply that ISF is a major source of wintertime micron-sized sulfate in China and underscore the importance of considering the size distribution of aerosols for accurately assessing the impacts of inorganic aerosols on radiative forcing and human health.
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Contaminantes Atmosféricos , Humanos , Contaminantes Atmosféricos/análisis , Material Particulado/análisis , Sulfatos/análisis , Estaciones del Año , China , Aerosoles/análisis , Monitoreo del Ambiente , Tamaño de la PartículaRESUMEN
Mercury, a pervasive global pollutant, primarily enters the atmosphere through human activities and legacy emissions from the land and oceans. A significant portion of this mercury subsequently settles on land through vegetation uptake. Characterizing mercury storage and distribution within vegetation is essential for comprehending regional and global mercury cycles. We conducted an unprecedented large-scale aboveground vegetation mercury survey across the expansive Tibetan Plateau. We find that mosses (31.1 ± 0.5 ng/g) and cushion plants (15.2 ± 0.7 ng/g) outstood high mercury concentrations. Despite exceptionally low anthropogenic mercury emissions, mercury concentrations of all biomes exceeded at least one-third of their respective global averages. While acknowledging the role of plant physiological factors, statistical models emphasize the predominant impact of atmospheric mercury on driving variations in mercury concentrations. Our estimations indicate that aboveground vegetation on the plateau accumulates 32-12+21 Mg (interquartile range) mercury. Forests occupy the highest biomass and store 82% of mercury, while mosses, representing only 3% of the biomass, disproportionally contribute 13% to mercury storage and account for 43% (2.5-1.4+3.0 Mg/year) of annual mercury assimilation by vegetation. Additionally, our study underscores that extrapolating aboveground vegetation mercury storage from lower-altitude regions to the Tibetan Plateau can lead to substantial overestimation, inspiring further exploration in alpine ecosystems worldwide.
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Mercurio , Humanos , Mercurio/análisis , Ecosistema , Tibet , Monitoreo del Ambiente , PlantasRESUMEN
Protein tyrosine phosphatase 1B (PTP1B) is a key factor and regulator of glucose, lipid metabolism throughout the body, and a promising target for treatment of type 2 diabetes mellitus (T2DM). Gynostemma pentaphyllum is a famous oriental traditional medicinal herbal plant and functional food, which has shown many beneficial effects on glucose and lipid metabolism. The aim of the present study is to assess the inhibitory activity of five new and four known dammarane triterpenoids isolated from the hydrolysate product of total G. pentaphyllum saponins. The bioassay data showed that all the compounds exhibited significant inhibitory activity against PTP1B. The structure-activity relationship showed that the strength of PTP1B inhibitory activity was mainly related to the electron-donating group on its side chain. Molecular docking analysis suggested that its mechanism may be due to the formation of competitive hydrogen bonding between the electron-donating moiety and the Asp48 amino acid residues on the PTP1B protein.