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Exploring feasible and renewable alternatives to reduce dependency on traditional fossil-based plastics is critical for sustainable development. These alternatives can be produced from biomass, which may have large uncertainties and variabilities in the feedstock composition and system parameters. This study develops a modeling framework that integrates cradle-to-grave life cycle assessment (LCA) with a rigorous process model and artificial intelligence (AI) models to conduct uncertainty and variability analyses, which are highly time-consuming to conduct using only the process model. This modeling framework examines polylactic acid (PLA) produced from corn stover in the U.S. An analysis of uncertainty and variability was conducted by performing a Monte Carlo simulation to show the detailed result distributions. Our Monte Carlo simulation results show that the mean life-cycle Global Warming Potential (GWP) of 1 kg PLA is 4.3 kgCO2eq (P5-P95 4.1-4.4) for composting PLA with natural gas combusted for the biorefinery, 3.7 kgCO2eq (P5-P95 3.4-3.9) for incinerating PLA for electricity with natural gas combusted for the biorefinery, and 1.9 kgCO2eq (P5-P95 1.6-2.1) for incinerating PLA for electricity with wood pellets combusted for the biorefinery. Tradeoffs for different environmental impact categories were identified. Based on feedstock composition variations, two AI models were trained: random forest and artificial neural networks. Both AI models demonstrated high prediction accuracy; however, the random forest performed slightly better.
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Inteligencia Artificial , Plásticos , Zea mays , Plásticos/análisis , Incertidumbre , Calentamiento Global , Poliésteres , Método de MontecarloRESUMEN
Cellulose, hemicellulose, and lignin are the major bio-components in lignocellulosic biomass (BC-LB), which possess excellent biomechanical properties and biocompatibility to satisfy the demands of orthopedic applications. To understand the basis and trends in the development of major bio-components in BC-LB in orthopedics, the bibliometric technology was applied to get unique insights based on the published papers (741) in the Web of Science (WOS) database from January 1st, 2001, to February 14th, 2023. The analysis includes the annual distributions of publications, keywords co-linearity, research hotspots exploration, author collaboration networks, published journals, and clustering of co-cited literature. The results reveal a steady growth in publications focusing on the application of BC-LB in orthopedics, with China and the United States leading in research output. The "International Journal of Biological Macromolecules" was identified as the most cited journal for BC-LB research in orthopedics. The research hotspots encompassed bone tissue engineering, cartilage tissue engineering, and drug delivery systems, indicating the fundamental research and potential development in these areas. This study also highlights the challenges associated with the clinical application of BC-LB in orthopedics and provides valuable insights for future advancements in the field.
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Bibliometría , Biomasa , Celulosa , Lignina , Ortopedia , Polisacáridos , Lignina/química , Polisacáridos/química , Celulosa/química , Humanos , Ingeniería de Tejidos/métodosRESUMEN
The electrode interface determines the performance of an electrochemical energy storage system. Using traditional electrolyte organic additives and high-concentration electrolyte emerging recently are two generally strategies for improving the electrode interface. Here, a hybrid-salt electrolyte strategy is proposed for constructing the stable electrode interface. Through the solubilization effect of phosphate ester on LiNO3, a hybrid-salts-based non-flammable phosphate ester electrolyte system (HSPE) with LiPF6 and LiNO3 as Li salts has been developed. By the strong interaction between NO3 - and Li+, the Li+ solvation sheath and solvent behaviors have been modulated, thus the undesirable effects of phosphate ester are eliminated and a robust SEI is formed. Experimental results and theoretical calculations illustrate that NO3 - as a kind of strongly coordinating anion can reduce the number of TEP molecules and lower the reduction reactivity of TEP. The reconfigured Li+ solvation structure allows the formation of an inorganic-rich SEI on the electrode surface. As a result, in the designed HSPE, the average coulombic efficiency of lithium plating/stripping is increased to 99.12 %. This work explored a new approach to construct the electrode interface and addressing the poor interface performance issue of phosphate esters.
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Various technologies and strategies have been proposed to decarbonize the chemical industry. Assessing the decarbonization, environmental, and economic implications of these technologies and strategies is critical to identifying pathways to a more sustainable industrial future. This study reviews recent advancements and integration of systems analysis models, including process analysis, material flow analysis, life cycle assessment, techno-economic analysis, and machine learning. These models are categorized based on analytical methods and application scales (i.e., micro-, meso-, and macroscale) for promising decarbonization technologies (e.g., carbon capture, storage, and utilization, biomass feedstock, and electrification) and circular economy strategies. Incorporating forward-looking, data-driven approaches into existing models allows for optimizing complex industrial systems and assessing future impacts. Although advances in industrial ecology-, economic-, and planetary boundary-based modeling support a more holistic systems-level assessment, more efforts are needed to consider impacts on ecosystems. Effective applications of these advanced, integrated models require cross-disciplinary collaborations across chemical engineering, industrial ecology, and economics.
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Industria Química , Biomasa , Aprendizaje Automático , Modelos Teóricos , Dióxido de Carbono/químicaRESUMEN
Triple-negative breast cancer (TNBC) is characterized by highly proliferative cancer cells and is the only subtype of breast cancer that lacks a targeted therapy. Boron neutron capture therapy (BNCT) is an approach that combines chemotherapy with radiotherapy and can potentially offer beneficial targeted treatment for TNBC patients owing to its unique ability to eradicate cancer cells selectively while minimizing damage to the surrounding healthy cells. Since BNCT relies on specific delivery of a high loading of B10 to the tumor site, there is growing research interest to develop more potent boron-based drugs for BNCT that can overcome the limitations of small-molecule boron compounds. In this study, polyethylene-glycol-coated boron carbon oxynitride nanoparticles (PEG@BCNO) of size 134.2±23.6nm were prepared as a promising drug for BNCT owing to their high boron content and enhanced biocompatibility. The therapeutic efficiency of PEG@BCNO was compared with a state-of-the-art 10BPA boron drug in mice bearing MDA-MB-231 tumor. In the orthotopic mouse model, PEG@BCNO showed higher B10 accumulation in the tumor tissues (6 µg 10B/g tissue compared to 3 µg 10B/g tissue in mice administered B10-enriched 10BPA drug) despite using the naturally occurring 11B/10B boron precursor in the preparation of the BCNO nanoparticles. The in vivo biodistribution of PEG@BCNO in mice bearing MDA-MB-231 showed a tumor/blood ratio of ~3.5, which is comparable to that of the state-of-the-art 10BPA-fructose drug. We further demonstrated that upon neutron irradiation, the mice bearing MDA-MB-231 tumor cells treated with PEG@BCNO and 10BPA showed tumor growth delay times of 9 days and 1 day, respectively, compared to mice in the control group after BNCT. The doubling times (DTs) for mice treated with PEG@BCNO and 10BPA as well as mice in the control group were calculated to be 31.5, 19.8, and 17.7 days, respectively. Immunohistochemical staining for the p53 and caspase-3 antibodies revealed that mice treated with PEG@BCNO showed lower probability of cancer recurrence and greater level of cellular apoptosis than mice treated with 10BPA and mice in the control group. Our study thus demonstrates the potential of pegylated BCNO nanoparticles in effectively inhibiting the growth of TNBC tumors compared to the state-of-the-art boron drug 10BPA.
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Terapia por Captura de Neutrón de Boro , Nanopartículas , Neoplasias de la Mama Triple Negativas , Ratones , Humanos , Animales , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/radioterapia , Boro/farmacología , Distribución Tisular , Nanopartículas/uso terapéuticoRESUMEN
Background: Compared to antibiotic treatment, fecal microbiota transplantation (FMT) is a more effective treatment for refractory or recurrent CDI (rCDI). Patients with inflammatory bowel disease (IBD) have a higher incidence of CDI and worse outcomes. There has been no study from Asia to evaluate the cost-effectiveness of FMT for overall rCDI patients and rCDI patients with IBD. Methods: We applied a Markov model with deterministic and probabilistic sensitivity analyses to evaluate the cost and effectiveness of different treatments for rCDI patients with a time horizon of 1 year from the payer's perspective. We compared the cost and clinical outcomes of FMT through colonoscopy to two antibiotics (vancomycin and fidaxomicin) using data from Chang Gung Memorial Hospital, Taoyuan, Taiwan. Results: Compared to vancomycin, FMT was cost-effective in overall rCDI patients as well as IBD patients with rCDI [USD 39356 (NT$1,101,971.98)/quality-adjusted life year (QALY) gained in overall patients; USD65490 (NT$1,833,719.14)/QALY gained in IBD patients]. Compared to fidaxomicin, FMT was only cost-effective in overall rCDI patients [USD20255 (NT$567,133.45)/QALY gained] but slightly increased QALY (0.0018 QALY gained) in IBD patients with rCDI. Conclusion: FMT is cost-effective, compared to vancomycin or fidaxomicin, for the treatment of rCDI in most scenarios from the payers' perspective in Taiwan.
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The domestication of forest trees for a more sustainable fiber bioeconomy has long been hindered by the complexity and plasticity of lignin, a biopolymer in wood that is recalcitrant to chemical and enzymatic degradation. Here, we show that multiplex CRISPR editing enables precise woody feedstock design for combinatorial improvement of lignin composition and wood properties. By assessing every possible combination of 69,123 multigenic editing strategies for 21 lignin biosynthesis genes, we deduced seven different genome editing strategies targeting the concurrent alteration of up to six genes and produced 174 edited poplar variants. CRISPR editing increased the wood carbohydrate-to-lignin ratio up to 228% that of wild type, leading to more-efficient fiber pulping. The edited wood alleviates a major fiber-production bottleneck regardless of changes in tree growth rate and could bring unprecedented operational efficiencies, bioeconomic opportunities, and environmental benefits.
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Edición Génica , Lignina , Populus , Madera , Carbohidratos/análisis , Lignina/genética , Madera/genética , Sistemas CRISPR-Cas , Populus/genética , Papel , Crecimiento SostenibleRESUMEN
Afforestation and reforestation (AR) on marginal land are nature-based solutions to climate change. There is a gap in understanding the climate mitigation potential of protection and commercial AR with different combinations of forest plantation management and wood utilization pathways. Here, we fill the gap using a dynamic, multiscale life cycle assessment to estimate one-century greenhouse gas (GHG) mitigation delivered by (both traditional and innovative) commercial and protection AR with different planting density and thinning regimes on marginal land in the southeastern United States. We found that innovative commercial AR generally mitigates more GHGs across 100 y (3.73 to 4.15 Giga tonnes of CO2 equivalent (Gt CO2e)) through cross-laminated timber (CLT) and biochar than protection AR (3.35 to 3.69 Gt CO2e) and commercial AR with traditional lumber production (3.17 to 3.51 Gt CO2e), especially in moderately cooler and dryer regions in this study with higher forest carbon yield, soil clay content, and CLT substitution. In a shorter timeframe (≤50 y), protection AR is likely to deliver higher GHG mitigation. On average, for the same wood product, low-density plantations without thinning and high-density plantations with thinning mitigate more life cycle GHGs and result in higher carbon stock than that of low-density with thinning plantations. Commercial AR increases the carbon stock of standing plantations, wood products, and biochar, but the increases have uneven spatial distributions. Georgia (0.38 Gt C), Alabama (0.28 Gt C), and North Carolina (0.13 Gt C) have the largest carbon stock increases that can be prioritized for innovative commercial AR projects on marginal land.
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Gases de Efecto Invernadero , Madera , Madera/metabolismo , Agricultura Forestal , Suelo , Carbono/metabolismo , GeorgiaRESUMEN
RAB37 GTPase regulates cargo exocytosis by cycling between an inactive GDP-bound form and an active GTP-bound form. We reveal that RAB37 simultaneously regulates autophagy activation and tissue inhibitor of metalloproteinase 1 (TIMP1) secretion in lung cancer cells under starvation conditions. TIMP1, an inflammatory cytokine, is a known inhibitory molecule of matrix metalloproteinases matrix metalloproteinase 9 and suppresses the mobility of lung cancer cells both in vitro and in vivo through conventional exocytosis under serum-free conditions. Notably, we disclosed that secretory autophagy participates in TIMP1 secretion in a RAB37- and Sec22b-dependent manner. Sec22b, a SNARE family protein, participates in vesicle and membrane fusion of secretory autophagy. Knockdown of Sec22b decreased TIMP1 secretion and cell motility but did not affect cell proliferation under starvation conditions. We confirmed that starvation-activated RAB37 accompanied by Sec22b is essential for secretory autophagy to further enhance TIMP1 exocytosis. We further use an off-label drug amiodarone to demonstrate that autophagy induction facilitates TIMP1 secretion and suppresses the motility and metastasis of lung cancer cells in a RAB37-dependent manner in the lung-to-lung mouse model. In conclusion, we demonstrated that the RAB37 activation plays a pivotal regulatory role in secretory autophagy for TIMP1 secretion in lung cancer.Abbreviations: ATG: autophagy-related gene; GDP: guanosine diphosphate; GTP: guanosine triphosphate; LC3: microtubule-associated protein 1A/1B-light chain 3; SNARE: soluble N-ethylmaleimide-sensitive-factor attachment protein receptor; TIMP1: tissue inhibitor matrix metalloproteinase 1.
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OBJECTIVE: To observe the effect of preoperative, intraoperative and postoperative electroacupuncture (EA) intervention on postoperative urination function in patients with mixed hemorrhoid surgery. METHODS: A total of 240 patients with mixed hemorrhoid surgery under lumbar anesthesia were randomly divided into an EA preconditioning group (group A, 60 cases, 9 cases dropped off), an intraoperative EA group (group B, 60 cases, 4 cases dropped off), a postoperative EA group (group C, 60 cases, 6 cases dropped off), and a non-acupuncture group (group D, 60 cases, 3 cases dropped off). In the groups A, B and C, EA was exerted at Zhongliao (BL 33) and Huiyang (BL 35) , with disperse-dense wave, 4 Hz/20 Hz in frequency, and lasting 30 min, at 30 min before lumbar anesthesia, immediately after lumbar anesthesia and 6 h after surgery, respectively. No EA intervention was performed in the group D. The postoperative urination smoothness score in each group was observed 24 h after surgery. The first urination time, first urination volume, urine residual volume after first urination were recorded, and incidence of indwelling catheterization, postoperative visual analogue scale (VAS) score, number of remedial analgesia, and the incidence of postoperative nausea and vomiting were observed in each group. RESULTS: In the groups A, B and C, the postoperative urination smoothness scores were superior to the group D (P<0.05), and the time of first urination was earlier than the group D (P<0.05). In the group C, the time of first urination was earlier than the group A and the group B (P<0.05), the first urination volume was higher than the group D (P<0.05), and the urine residual volume after first urination was lower than the group D (P<0.05). There was no significant difference in the incidence of indwelling catheterization and postoperative nausea and vomiting among the 4 groups (P>0.05). The VAS scores of the group A, B and C were lower than that in the group D (P<0.05), and the number of remedial analgesia cases was lower than that in the group D (P<0.05). CONCLUSION: EA intervention could promote the recovery of urination function and relieve postoperative pain in patients with mixed hemorrhoids surgery. Early postoperative EA intervention is more conducive to the recovery of urination function.
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Electroacupuntura , Hemorroides , Humanos , Hemorroides/cirugía , Micción , Náusea y Vómito Posoperatorios , Puntos de AcupunturaRESUMEN
The thermal stability of (Mg0.95Ni0.05)2TiO4 dielectric ceramics has been improved by mixing with CaTiO3 phases owing to higher positive temperature coefficients. The pure (Mg0.95Ni0.05)2TiO4 and the mixture phase systems of CaTiO3-modified (Mg0.95Ni0.05)2TiO4 were verified by XRD diffraction patterns to ensure the crystallite of different phases. The microstructures of the CaTiO3-modified (Mg0.95Ni0.05)2TiO4 were observed by SEM and EDS to investigate the relation between element ratios and grains. As a result, it can be seen that the thermal stability of the CaTiO3-modified (Mg0.95Ni0.05)2TiO4 can be effectively enhanced, compared with the pure (Mg0.95Ni0.05)2TiO4. Moreover, the radio frequency dielectric performances of CaTiO3-modified (Mg0.95Ni0.05)2TiO4 dielectric ceramics are strongly dependent upon the density and the morphology of the specimens. The champion sample with the ratio of (Mg0.95Ni0.05)2TiO4 and CaTiO3 of 0.92:0.08 showed an εr value of 19.2, an Qf value of 108,200 GHz, and a τf value of -4.8 ppm/°C, which may encourage (Mg0.95Ni0.05)2TiO4 ceramics to broaden the range of novel applications and match the requirements of 5G or next-generation communication systems.
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OBJECTIVES: About 17.7-34.0 % of patients with recurrent or metastatic nasopharyngeal carcinoma (RM-NPC) responded well to anti-PD-1 monotherapy. We sought to establish a nomogram to estimate the progression-free survival (PFS) of RM-NPC patients receiving subsequent-line anti-PD-1 monotherapy. MATERIALS AND METHODS: This cohort study investigated consecutive RM-NPC patients undergoing anti-PD-1 monotherapy. A nomogram was developed in the training cohort (n = 161), using a Cox multivariate model with backward stepwise inclusion, and was validated in the validation cohort (n = 69). Its predictive accuracy was assessed using a concordance index (C-index) and calibration curve. The primary endpoint was PFS. Secondary endpoints included the objective response rate (ORR), disease control rate (DCR), and overall survival (OS). RESULTS: Liver metastasis, albumin, lactate dehydrogenase, monocyte-to-lymphocyte ratio, and plasma Epstein-Barr virus DNA were used to develop a nomogram that could separate patients into favourable- and unfavourable-prognosis groups. The C-index in the training and validation cohort were 0.70 and 0.68, respectively, which was confirmed by calibration curves. Median PFS (mPFS) was lower for the unfavourable-prognosis than for the favourable-prognosis group (1.80 vs 4.93; hazard ratio 2.49 [95 % confidence interval: 1.78-3.49]; p < 0.001), across all subgroups. OS exhibited the same pattern. The ORR and DCR were markedly lower in the unfavourable-prognosis than in the favourable-prognosis group. All results were confirmed in the validation cohort. CONCLUSION: Our model is a reliable prognostic indicator of PFS in RM-NPC patients undergoing anti-PD-1 monotherapy, allowing robust estimation of the immunotherapy benefit an individual might derive.
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Infecciones por Virus de Epstein-Barr , Neoplasias Nasofaríngeas , Humanos , Pronóstico , Carcinoma Nasofaríngeo/patología , Estudios de Cohortes , Estadificación de Neoplasias , Recurrencia Local de Neoplasia/patología , Herpesvirus Humano 4 , Neoplasias Nasofaríngeas/patologíaRESUMEN
High blood glucose is one of the risk factors for metabolic disease and INS (insulin) is the key regulatory hormone for glucose homeostasis. Hypoinsulinemia accompanied with hyperglycemia was diagnosed in mice with pancreatic ß-cells exhibiting autophagy deficiency; however, the underlying mechanism remains elusive. The role of secretory autophagy in the regulation of metabolic syndrome is gaining more attention. Our data demonstrated that increased macroautophagic/autophagic activity leads to induction of insulin secretion in ß-cells both in vivo and in vitro under high-glucose conditions. Moreover, proteomic analysis of purified autophagosomes from ß-cells identified a group of vesicular transport proteins participating in insulin secretion, implying that secretory autophagy regulates insulin exocytosis. RAB37, a small GTPase, regulates vesicle biogenesis, trafficking, and cargo release. We demonstrated that the active form of RAB37 increased MAP1LC3/LC3 lipidation (LC3-II) and is essential for the promotion of insulin secretion by autophagy, but these phenomena were not observed in rab37 knockout (rab37-/-) cells and mice. Unbalanced insulin and glucose concentration in the blood was improved by manipulating autophagic activity using a novel autophagy inducer niclosamide (an antihelminthic drug) in a high-fat diet (HFD)-obesity mouse model. In summary, we reveal that secretory autophagy promotes RAB37-mediated insulin secretion to maintain the homeostasis of insulin and glucose both in vitro and in vivo.
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Hiperglucemia , Células Secretoras de Insulina , Animales , Ratones , Autofagia/fisiología , Glucosa/metabolismo , Secreción de Insulina , Proteómica , Proteínas de Unión al GTP rab/metabolismo , Insulina/metabolismo , Hiperglucemia/metabolismo , Células Secretoras de Insulina/metabolismoRESUMEN
The building sector, including building operations and materials, was responsible for the emission of â¼11.9 gigatons of global energy-related CO2 in 2020, accounting for 37% of the total CO2 emissions, the largest share among different sectors. Lowering the carbon footprint of buildings requires the development of carbon-storage materials as well as novel designs that could enable multifunctional components to achieve widespread applications. Wood is one of the most abundant biomaterials on Earth and has been used for construction historically. Recent research breakthroughs on advanced engineered wood products epitomize this material's tremendous yet largely untapped potential for addressing global sustainability challenges. In this review, we explore recent developments in chemically modified wood that will produce a new generation of engineered wood products for building applications. Traditionally, engineered wood products have primarily had a structural purpose, but this review broadens the classification to encompass more aspects of building performance. We begin by providing multiscale design principles of wood products from a computational point of view, followed by discussion of the chemical modifications and structural engineering methods used to modify wood in terms of its mechanical, thermal, optical, and energy-related performance. Additionally, we explore life cycle assessment and techno-economic analysis tools for guiding future research toward environmentally friendly and economically feasible directions for engineered wood products. Finally, this review highlights the current challenges and perspectives on future directions in this research field. By leveraging these new wood-based technologies and analysis tools for the fabrication of carbon-storage materials, it is possible to design sustainable and carbon-negative buildings, which could have a significant impact on mitigating climate change.
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BACKGROUND AND PURPOSE: We sought to determine the prognostic value of a pre-treatment peripheral blood signature and the peripheral blood signature-based nomogram for patients with non-metastatic nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: We retrospectively collected 21 peripheral blood indicators from patients with NPC between 2004 and 2015. Data were randomly divided into a training and a validation set (ratio: 6:4). The peripheral blood signature was constructed based on candidate biomarkers using the least absolute shrinkage and selection operator Cox regression model. Multivariable logistic regression was applied to identify the independent risk factors of overall survival to build the nomogram. The predictive value of the peripheral blood nomogram was evaluated using time-dependent area under the curve, decision curve analysis, and calibration curve. RESULTS: In total, 6668 patients were enrolled with 4000 and 2668 in the training and validation cohorts, respectively. Four peripheral blood indicators, (white blood cell count, lymphocyte percentage, haemoglobin, and mean platelet volume), were included to construct the peripheral blood signature. Patients were divided into low- and high-risk groups using an optimal cut-off value of - 1.71142. Patients in the high-risk group had significantly lower overall, distant metastasis-free, and progression-free survival than patients in the low-risk group in both cohorts (P < 0.05). We constructed and validated a peripheral blood signature-based nomogram in combination with five vital clinical characteristics, (age, sex, tumour stage, nodal stage, and pre-treatment Epstein-Barr virus DNA), which showed favourable performance. CONCLUSION: Patients with NPC with different outcomes could be distinguished based on their peripheral blood signature score; the proposed peripheral blood signature-based nomogram offers individualised risk estimation.
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Infecciones por Virus de Epstein-Barr , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/patología , Estudios Retrospectivos , Herpesvirus Humano 4 , Pronóstico , Nomogramas , Factores de Riesgo , Pruebas Hematológicas , Neoplasias Nasofaríngeas/patologíaRESUMEN
BACKGROUND: The Global Registry of Acute Coronary Events (GRACE) score is a powerful tool used to predict in-hospital mortality after acute myocardial infarction (AMI) and does not include a glycometabolism-related index. We investigated whether the addition of the stress hyperglycemia ratio (SHR) provides incremental prognostic value in addition to the GRACE score. METHODS: A retrospective cohort of 613 AMI patients was enrolled in the present analyses. The patients were stratified according to the primary endpoint (in-hospital mortality) and the tertiles of the SHR. RESULTS: During hospitalization, 40 patients reached the primary endpoint, which was more frequently observed in patients with a higher SHR. The SHR, but not admission blood glucose (ABG), adjusted for the GRACE score independently predicted in-hospital mortality [odds ratio 2.5861; 95% confidence interval (CI), 1.3910-4.8080; P = 0.0027]. The adjustment of the GRACE score by the SHR improved the predictive ability for in-hospital death (an increase in the C-statistic value from 0.787 to 0.814; net reclassification improvement, 0.6717, 95% CI 0.3665-0.977, P < 0.01; integrated discrimination improvement, 0.028, 95% CI 0.0066-0.0493, P = 0.01028). The likelihood ratio test showed that the SHR significantly improved the prognostic models, including the GRACE score. Adding the SHR to the GRACE score presented a larger net benefit across the range of in-hospital mortality risk than the GRACE score alone. CONCLUSION: The SHR, but not the ABG, is an independent predictor of in-hospital mortality after AMI even after adjusting for the GRACE score. The SHR improves the predictability and clinical usefulness of prognostic models containing the GRACE score.
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Síndrome Coronario Agudo , Hiperglucemia , Infarto del Miocardio , Humanos , Mortalidad Hospitalaria , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Glucemia , Sistema de RegistrosRESUMEN
BACKGROUND: Rab37-mediated exocytosis of tissue inhibitor of metalloproteinase 1 (TIMP1), an inflammatory cytokine, under serum-depleted conditions which leads to suppression of lung cancer cell metastasis has been reported. Starvation is also a stimulus of autophagic activity. Herein, we reveal that starvation activates Rab37 and induces autophagy. METHODS: We used an overexpression/knockdown system to determine the relationship between autophagy and Rab37 in vitro and in vivo. The autophagy activity was detected by immunoblotting, transmission electron microscope, autophagosome purification, and immunofluorescence under the confocal microscope. Lung-to-lung metastasis mouse model was used to clarify the role of autophagy and Rab37 in lung cancer. Clinical lung cancer patient specimens and an online big database were analyzed. RESULTS: Initially, we demonstrated that active-form Rab37 increased LC3-II protein level (the marker of autophagosome) and TIMP1 secretion. Accordingly, silencing of Rab37 gene expression alleviated Rab37 and LC3-II levels as well as TIMP1 secretion, and induction of autophagy could not increase TIMP1 exocytosis under such conditions. Moreover, silencing the Atg5 or Atg7 gene of lung cancer cells harboring active-mutant Rab37 (Q89L) led to decreased autophagy activity and TIMP1 secretion. In the lung-to-lung metastasis mouse model, increased TIMP1 expression accompanied by amiodarone-induced autophagy led to decreased tumor nodules and cancer cell metastasis. These phenomena were reversed by silencing the Atg5 or Atg7 gene. Notably, increasing autophagy activity alone showed no effect on TIMP1 secretion under either Rab37 or Sec22b silencing conditions. We further detected colocalization of LC3 with either Rab37 or TIMP1, identified Rab37 and Sec22b proteins in the purified autophagosomes of the lung cancer cells harboring the active-form Rab37 gene, and confirmed that these proteins are involved in the secretion of TIMP1. We reveal that autophagic activity was significantly lower in the tumors compared to the non-tumor parts and was associated with the overall lung cancer patient survival rate. CONCLUSIONS: We are the first to report that autophagy plays a promoting role in TIMP1 secretion and metastasis in a Rab37-dependent manner in lung cancer cells and the lung-to-lung mouse model.
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Neoplasias Pulmonares , Inhibidor Tisular de Metaloproteinasa-1 , Proteínas de Unión al GTP rab , Animales , Ratones , Autofagosomas , Autofagia/genética , Modelos Animales de Enfermedad , Exocitosis , Neoplasias Pulmonares/genética , Inhibidor Tisular de Metaloproteinasa-1/genética , Proteínas de Unión al GTP rab/genéticaRESUMEN
BACKGROUND: Bruxism is a rhythmic masticatory muscle activity that occurs involuntarily in a non-physiologically functional state. There is a lack of research classifying the functional status of masticatory muscles in patients with different mandibular movement types (centric clenching or eccentric grinding) of bruxism. AIM: To assess the differences of the masticatory muscle activity in patients with different types of bruxism. METHODS: A total of 21 subjects with centric bruxism (CB) and 21 subjects with eccentric bruxism (ECB) were screened from college students according to a questionnaire and their tooth wear features. Sixteen subjects with no bruxism were also recruited. The surface electromyography (EMG) signals of the temporalis anterior (TA) and superficial masseter muscle (MM) were measured in different mandibular positions and during the chewing task. The EMG amplitude and chewing cycle duration parameters were then analyzed. RESULTS: The CB group showed fewer muscle maximal motor units, with the MM being more pronounced, a higher proportion of muscle contractions to be recruited for the same load of chewing activity, and a longer chewing cycle. The ECB group showed more TA maximal motor units and higher MM activity on the non-working side in unilateral chewing. CONCLUSION: CB mainly affects the MM, and patients with CB show reduced masticatory muscle contraction efficiency and chewing cycle efficiency. ECB mainly affects the TA, and patients with ECB show enhanced contraction of non-functional lateral muscle bundles.
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CONTEXT: Avermectin pesticides are widely used in agriculture, and are thought to have low toxicity in humans. However, information on their toxicity after accidental or deliberate ingestion is limited. OBJECTIVE: The aim of this study was to evaluate the clinical manifestations of avermectin pesticide ingestion and identify factors associated with severe outcomes (death, intubation, or sustained hypotension requiring inotrope therapy). MATERIALS AND METHODS: This multicenter retrospective study included patients who visited the emergency departments of six teaching hospitals due to acute avermectin pesticide ingestion between January 2012 and May 2020. Patients who reported ingestion of any other pesticides, drugs, or substances were excluded. RESULTS: In total, 64 patients (median age, 72 years) were included: 60 had ingested emamectin pesticides, and 4 had ingested abamectin. Almost all (98%) were cases of self-harm. The most common presentation was drowsiness (47%), with a median Glasgow Coma Scale (GCS) score of 14, followed by shortness of breath (SOB)/dyspnea (33%) and nausea/vomiting (22%). Concurrent methanol exposure (via the solvent) was confirmed or suspected in five patients. Seventeen patients (27%) were intubated. Three patients who developed respiratory failure were not intubated because of a "do-not-resuscitate" (DNR) order. Four patients developed sustained hypotension requiring inotrope therapy. Fifty patients (78%) were admitted, of whom 27 (42%) required intensive care unit (ICU) admission. Four patients died, three of whom had a DNR order. Based on our definition, 20 patients (31%) had severe outcomes. A multivariate logistic regression model showed that a GCS score < 13 (OR 68.1, 95% CI 3.8-999) and the presence of SOB/dyspnea (OR 50.2, 95% CI 3.0-849.9) were associated with severe outcomes. CONCLUSIONS: Most patients who intentionally ingested avermectin pesticides required inpatient treatment. Forty-two percent needed ICU care and 31% had severe outcomes. A GCS score < 13 and SOB/dyspnea were independently associated with severe outcomes.