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Africa carries a disproportionately high share of the global malaria burden, accounting for 94% of malaria cases and deaths worldwide in 2019. It is also a politically unstable region and the most vulnerable continent to climate change in recent decades. Knowledge about the modifying impacts of violent conflict on climate-malaria relationships remains limited. Here, we quantify the associations between violent conflict, climate variability, and malaria risk in sub-Saharan Africa using health surveys from 128,326 individuals, historical climate data, and 17,429 recorded violent conflicts from 2006 to 2017. We observe that spatial spillovers of violent conflict (SSVCs) have spatially distant effects on malaria risk. Malaria risk induced by SSVCs within 50 to 100 km from the households gradually increases from 0.1% (not significant, P>0.05) to 6.5% (95% CI: 0 to 13.0%). SSVCs significantly promote malaria risk within the average 20.1 to 26.9 °C range. At the 12-mo mean temperature of 22.5 °C, conflict deaths have the largest impact on malaria risk, with an approximately 5.8% increase (95% CI: 1.0 to 11.0%). Additionally, a pronounced association between SSVCs and malaria risk exists in the regions with 9.2 wet days per month. The results reveal that SSVCs increase population exposure to harsh environments, amplifying the effect of warm temperature and persistent precipitation on malaria transmission. Violent conflict therefore poses a substantial barrier to mosquito control and malaria elimination efforts in sub-Saharan Africa. Our findings support effective targeting of treatment programs and vector control activities in conflict-affected regions with a high malaria risk.
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Exposición a la Violencia , Malaria , Humanos , Malaria/epidemiología , África del Sur del Sahara/epidemiología , TemperaturaRESUMEN
Acute lung injury (ALI) and its most severe form, acute respiratory distress syndrome (ARDS), are pulmonary conditions that cause significant morbidity and mortality. The common etiologies of these conditions include pneumonia, pulmonary contusion, fat embolism, smoke inhalation, sepsis, shock, and acute pancreatitis. Inflammation, oxidative stress, apoptosis, and autophagy are key pathophysiological mechanisms underlying ALI. Hydrogen sulfide (H2S) and sulfur dioxide (SO2) are sulfur-containing gas signaling molecules that can mitigate these pathogenic processes by modulating various signaling pathways, such as toll-like receptor 4 (TLR4)/nod-like receptor protein 3 (NLRP3), extracellular signal-regulating protein kinase 1/2 (ERK1/2), mitogen-activated protein kinase (MAPK), phosphatidyl inositol 3 kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR), and nuclear factor kappa B (NF-κB), thereby conferring protection against ALI. Given the limited clinical effectiveness of prevailing ALI treatments, investigation of the modulation of sulfur-containing gas signaling molecules (H2S and SO2) in ALI is imperative. This article presents an overview of the regulatory pathways of sulfur-containing gas signaling molecules in ALI animal models induced by various stimuli, such as lipopolysaccharide, gas inhalation, oleic acid, and ischemia-reperfusion. Furthermore, this study explored the therapeutic prospects of diverse H2S and SO2 donors for ALI, stemming from diverse etiologies. The aim of the present study was to establish a theoretical framework, in order to promote the new treatment of ALI.
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BACKGROUND: Y-box binding protein 1 (YBX1) plays a variety of roles in progression of multiple tumors. However, the role of YBX1 in prognostic value and immune regulation for liver hepatocellular carcinoma (LIHC) remains unclear. The present study aimed to examine the effect of YBX1 on the regulation of tumor immunity and survival prediction in LIHC patients. METHODS: YBX1-related expression profiles and single-cell and bulk sequencing analysis were performed using online databases. YBX1 expression was validated by a quantitative real-time PCR (qRT-PCR), western blotting and immunohistochemistry. Univariate/multivariate Cox regression analysis was performed to determine independent predictors of overall survival (OS). The ESTIMATE (i.e., Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data) algorithm and Tumor Immune Dysfunction and Exclusion (TIDE) analysis were used to assess the relationships between YBX1 and LIHC immunity. RESULTS: YBX1 was over-expressed in LIHC tissues and cell lines. High YBX1 expression was significantly associated with poor OS. Univariate/multivariate Cox regression analysis revealed that YBX1 was an independent prognostic factor for LIHC. Gene set enrichment analysis revealed that YBX1 was associated with multiple signaling pathways correlated to LIHC. Additionally, YBX1 was expressed in multiple immune cells and was significantly correlated with immune cells, immune checkpoint markers and tumor immune microenvironment. The TIDE analysis demonstrated that LIHC patients with high YBX1 expression showed a higher T-cell dysfunction score and a higher exclusion score, as well as poorer immunotherapy response. CONCLUSIONS: YBX1 plays crucial oncogenic roles in LIHC and is closely associated with the immune defense system. YBX1 inhibition may serve as a potential treatment for LIHC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Pronóstico , Neoplasias Hepáticas/genética , Algoritmos , Microambiente Tumoral/genética , Proteína 1 de Unión a la Caja Y/genéticaRESUMEN
Acute myeloid leukemia (AML) is a common and catastrophic hematological neoplasm with high mortality rates. Conventional therapies, including chemotherapy, hematopoietic stem cell transplantation (HSCT), immune therapy, and targeted agents, have unsatisfactory outcomes for AML patients due to drug toxicity, off-target effects, drug resistance, drug side effects, and AML relapse and refractoriness. These intrinsic limitations of current treatments have promoted the development and application of nanomedicine for more effective and safer leukemia therapy. In this review, the classification of nanoparticles applied in AML therapy, including liposomes, polymersomes, micelles, dendrimers, and inorganic nanoparticles, is reviewed. In addition, various strategies for enhancing therapeutic targetability in nanomedicine, including the use of conjugating ligands, biomimetic-nanotechnology, and bone marrow targeting, which indicates the potential to reverse drug resistance, are discussed. The application of nanomedicine for assisting immunotherapy is also involved. Finally, the advantages and possible challenges of nanomedicine for the transition from the preclinical phase to the clinical phase are discussed.
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BACKGROUND: We analysed the COMparison Between All immunoTherapies for Multiple Sclerosis (NCT03193866), a Swedish nationwide observational study in relapsing-remitting multiple sclerosis (RRMS), to identify trajectories of fatigue and their association with physical disability following start of disease-modifying therapy (DMT). METHODS: Using a group-modelling approach, we assessed trajectories of fatigue with the Fatigue Scale for Motor and Cognitive Functions and physical disability with Expanded Disability Status Scale among 1587 and 1818 individuals who initiated a first DMT and had a first DMT switch, respectively, followed during 2011-2022. We investigated predictors of fatigue trajectories using group membership as a multinomial outcome and calculated conditional probabilities linking membership across the trajectories. RESULTS: We identified five trajectories of fatigue in participants who initiated their first DMT: no fatigue (mean starting values=23.7; 18.2% of population), low (35.5; 23.9%), mild (49.0; 21.6%), moderate (61.3; 20.1%) and severe (78.7; 16.1%). While no, low, mild and severe fatigue trajectories remained stable, the moderate trajectory increased to severe fatigue. Similarly, we identified six fatigue trajectories among participants who did a DMT switch, all indicating stable values over time. Women initiating a first DMT were more likely than men to display a severe fatigue trajectory, relative to the no fatigue one. There was a strong association between fatigue and physical disability trajectories. CONCLUSIONS: In this cohort of people with actively treated RRMS, self-reported fatigue remained stable or increased over the years following DMT start. There was a strong association between fatigue and disability after DMT start.
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Low temperature has been a major challenge for lithium-ion batteries to maintain satisfied electrochemical performance, as it leads to poor rechargeability and low capacity retention. Traditional carbonate solvents, vinyl carbonate and dimethyl carbonate are indispensable components of commercial electrolytes. However, the higher melting point of these carbonate solvents causes their electrical conductivity to be easily reduced when temperatures drop below zero, limiting their ability to facilitate lithium ion transport. In this work, we demonstrate that the use of methyl propionate (MP) carboxylate and fluorocarbonate vinyl (FEC) electrolytes can overcome the limitations of low temperature cycling. Compared with carbonate electrolyte, MP has the characteristics of low melting point, low viscosity and low binding energy with Li+, which is crucial to improve the low temperature performance of the battery, while FEC is an effective component to inhibit the side reaction between MP and lithium metal. The carefully formulated MP-based electrolyte can generate a solid electrolyte interface with low resistance and rich in inorganic substances, which is conducive to the smooth diffusion of Li+, allowing the battery to successfully cycle at a high rate of 0.5 C at -20 °C, and giving it a reversible capacity retention rate of 65.3% at -40oC. This work designs a promising advanced electrolyte and holds the potential to overcome limitations of lithium-ion batteries in harsh conditions.
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BACKGROUND AND AIM: Hydronidone (HDD) is a novel pirfenidone derivative developed initially to reduce hepatotoxicity. Our previous studies in animals and humans have demonstrated that HDD treatment effectively attenuates liver fibrosis, yet the underlying mechanism remains unclear. This study aimed to investigate whether HDD exerts its anti-fibrotic effect by inducing apoptosis in activated hepatic stellate cells (aHSCs) through the endoplasmic reticulum stress (ERS)-associated mitochondrial apoptotic pathway. METHODS: The carbon tetrachloride (CCl4)- and 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induced liver fibrosis models were used for in vivo studies. In vitro studies were conducted using the human hepatic stellate cell line LX-2. The apoptotic effect of HDD on aHSCs was examined using TUNEL and flow cytometry assays. The small interfering RNA (siRNA) technique was employed to downregulate the expression of interest genes. RESULTS: HDD treatment significantly promoted apoptosis in aHSCs in both the CCl4- and DDC-induced liver fibrosis in mice and LX-2 cells. Mechanistic studies revealed that HDD triggered ERS and subsequently activated the IRE1α-ASK1-JNK pathway. Furthermore, the influx of cytochrome c from the mitochondria into the cytoplasm was increased, leading to mitochondrial dysfunction and ultimately triggering apoptosis in aHSCs. Notably, inhibition of IRE1α or ASK1 by siRNA partially abrogated the pro-apoptotic effect of HDD in aHSCs. CONCLUSIONS: The findings of both in vivo and in vitro studies suggest that HDD induces apoptosis in aHSCs via the ERS-associated mitochondrial apoptotic pathway, potentially contributing to the amelioration of liver fibrosis.
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Apoptosis , Estrés del Retículo Endoplásmico , Células Estrelladas Hepáticas , Cirrosis Hepática , Células Estrelladas Hepáticas/efectos de los fármacos , Células Estrelladas Hepáticas/metabolismo , Células Estrelladas Hepáticas/patología , Apoptosis/efectos de los fármacos , Estrés del Retículo Endoplásmico/efectos de los fármacos , Animales , Humanos , Cirrosis Hepática/patología , Cirrosis Hepática/metabolismo , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/inducido químicamente , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Endorribonucleasas/metabolismo , Endorribonucleasas/genética , Tetracloruro de Carbono , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Masculino , Línea Celular , Piridonas/farmacología , Ratones , MAP Quinasa Quinasa Quinasa 5/metabolismo , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Transducción de Señal/efectos de los fármacosRESUMEN
This study reports a thermostable glucose-stimulated ß-glucosidase, BglY442, from hot-spring metagenomic data that was cloned and expressed in Escherichia coli BL21 (DE3). The molecular mass of recombinant BglY442 was 69.9 kDa and was used in the production of gardenia blue. The recombinant BglY442 showed its maximum activity at pH 6.0 and 75 °C, maintained 50 % activity at 70 °C for 36 h, presented over 90 % activity in a broad pH range and a wide range of pH stability. Moreover, BglY442 exhibited excellent tolerance toward methanol and ethanol. The specific activity of BglY442 was 235 U/mg at pH 6.0 and 75 °C with 10 mM pNPG as substrate. BglY442 activity increased by over fourfold with 2 M glucose or xylose. Specifically, the enzyme kinetics of BglY442 seem to be non-Michaelis-Menten kinetics or atypical kinetics because the Michaelis-Menten saturation kinetics were not observed with pNPG, oNPG or geniposide as substrates. Under optimum conditions, geniposide was dehydrated by BglY442 and reacted with nine amino acids respectively by the one-pot method. Only the Arg or Met derived pigments showed bright blue, and these two pigments had similar ultraviolet absorption spectra. The OD590 nm of GB was detected to be 1.06 after 24 h with the addition of Arg and 1.61 after 36 h with the addition of Met. The intermediate was elucidated and identified as ginipin. Molecular docking analysis indicated that the enzyme had a similar catalytic mechanism to the reported GH1 Bgls. BglY442 exhibited potential for gardenia blue production by the one-pot method. With outstanding thermostability and glucose tolerance, BglY442 should be considered a potential ß-glucosidase in biotechnology applications.
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Gardenia , Glucosa , Iridoides , Glucosa/farmacología , Proteínas Recombinantes/metabolismo , beta-Glucosidasa/metabolismo , Metagenoma , Simulación del Acoplamiento Molecular , Concentración de Iones de Hidrógeno , Estabilidad de Enzimas , Especificidad por Sustrato , Temperatura , CinéticaRESUMEN
Methanogens are the main participants in the carbon cycle, catalyzing five methanogenic pathways. Methanogens utilize different iron-containing functional enzymes in different methanogenic processes. Iron is a vital element in methanogens, which can serve as a carrier or reactant in electron transfer. Therefore, iron plays an important role in the growth and metabolism of methanogens. In this paper, we cast light on the types and functions of iron-containing functional enzymes involved in different methanogenic pathways, and the roles iron play in energy/substance metabolism of methanogenesis. Furthermore, this review provides certain guiding significance for lowering CH4 emissions, boosting the carbon sink capacity of ecosystems and promoting green and low-carbon development in the future.
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Hierro , Metano , Metano/metabolismo , Hierro/metabolismo , Archaea/metabolismoRESUMEN
BACKGROUND: Work-related musculoskeletal disorders (WMSDs) show a rapid growth trend. It has brought a huge economic burden to the society and become a serious occupational health problem that needs to be solved urgently. This study aimed to analyze the local muscle response under continuous ergonomic load, screen sensitive fatigue-related biomarkers and provide data support for the early prevention of local muscle damage and the exploration of early warning indicators. METHODS: Thirteen male college student volunteers were recruited to perform simulated repetitive manual lifting tasks in the laboratory. The lifting task was designed for 4 periods which lasted for 12 min in each, and then paused for 3 min for sampling. Local muscle fatigue is assesed by the Rating of perceived exertion (RPE) and the Joint analysis of sEMG spectrum and amplitude (JASA). Elbow venous blood was collected and 14 kinds of biomarkers were analyzed, which included Metabolic markers Ammonia (AMM), Lactic acid (LAC), Creatine kinase (CK), Lactate dehydrogenase (LDH), Cartilage oligomeric matrix protein (COMP), C-telopeptide of collagen I and II (CTX-I, CTX-II) and Calcium ion (Ca2+); Oxidative stress marker Glutathione (GSH); Inflammatory markers C-reaction protein (CRP), Prostaglandin E2 (PG-E2), Interleukin-6 (IL-6) and Tumor necrosis factor α (TNF-α); Pain marker Neuropeptide Y (NPY). Repeated measures analysis of variance (Repeated ANOVA), linear regression analysis, t-test and spearman correlation analysis were used to analyze the data. RESULTS: Both subjective and objective fatigue appeared at the same period. Serum AMM, LAC, CK, LDH, COMP, CTX-II, Ca2+ and NPY after fatigue were significantly higher than those before fatigue (p < 0.05). There was a certain degree of correlation between the markers with statistical differences before and after fatigue. CONCLUSIONS: Metabolic markers (serum AMM, LAC, CK, LDH, COMP, CTX-II, Ca2+) and pain markers (serum NPY) can reflect local muscle fatigue to a certain extent in repetitive manual lifting tasks. It is necessary to further expand the research on fatigue-related biomarkers in different types of subjects and jobs in the future.
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Biomarcadores , Elevación , Fatiga Muscular , Humanos , Masculino , Fatiga Muscular/fisiología , Biomarcadores/sangre , Adulto Joven , Elevación/efectos adversos , Trastornos de Traumas Acumulados/sangre , Trastornos de Traumas Acumulados/fisiopatología , Trastornos de Traumas Acumulados/diagnóstico , Adulto , Músculo Esquelético/metabolismoRESUMEN
The increasing volume of electronic waste (e-waste) poses significant challenges for efficient collection in China. Despite many measures were taken over the past two decades, the e-waste collection rate was still not high. To this end, the Chinese government issued a new policy, the collection target responsibility (CTR) policy. Under the CTR policy, however, it is essential for participants to know how to share the responsibility of collection and how much reasonable targets are set to ensure the efficiency of the collection models. Therefore, the purpose of this paper is to explore the determination of optimal collection targets and the corresponding performance from the perspective of responsibility sharing to support the successful implementation of the CTR. Firstly, the study focuses on participants including the government, manufacturers, and recyclers, and develops three CTR models, independent collection model, government cost-sharing model, and enterprise collaboration model. Secondly, collection target equations for each model are established by employing dynamic differential game analysis, and corresponding collection performances are derived. Thirdly, through practical case simulations, the evolution of collection performance is dynamically analyzed to determine reasonable collection targets for the three models, as 23.8%, 32.3%, and 34.4%, respectively. The findings highlight the effectiveness of CTR in improving e-waste collection targets and performance, with the highest levels attained when the collection responsibilities are shared by government cost-sharing and enterprise collaboration. This study provides theoretical support for setting reasonable collection targets under CTR, and assists decision-makers in developing targeted CTR implementation measures.
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Residuos Electrónicos , Administración de Residuos , Humanos , Reciclaje , ChinaRESUMEN
BACKGROUND & AIMS: Hepatitis B virus infection frequently leads to liver fibrosis and is the leading cause of hepatocellular carcinoma and cirrhosis in Asia Pacific. Pirfenidone is approved by the United States Food and Drug Administration for treatment of idiopathic pulmonary fibrosis, and hydronidone is a novel structural modification of pirfenidone with the aim of reducing hepatoxicity. We aimed to investigate the safety and efficacy of hydronidone in patients with chronic hepatitis B (CHB)-associated liver fibrosis. METHODS: This was a 52-week multicenter, randomized, double-blind, placebo-controlled, phase II study at 8 centers in China. Patients with CHB with biopsied documented liver fibrosis were eligible and were randomly assigned into receiving daily placebo or hydronidone orally (180 mg/day, 270 mg/day, or 360 mg/day). All enrolled subjects also received entecavir 0.5 mg/day. A second liver biopsy was performed at week 52. The primary endpoint was defined as fibrosis improvement (reduction of at least 1 Ishak score at week 52 of treatment). RESULTS: From June 25, 2015, to September 5, 2019, 168 patients with CHB and liver fibrosis met the inclusion/exclusion criteria and were subsequently randomized, 43 in the placebo group and 125 in the hydronidone groups (42 in the 180-mg group, 42 in the 270-mg group, and 41 in the 360-mg group). The fibrosis improvement endpoint was achieved by 11 patients (25.6%) in the placebo group and 17 patients (40.5%) in the 180-mg group (P = .12), 23 patients (54.8%) in the 270-mg group (P = .006), and 18 patients (43.90%) in the 360-mg group (P = .08). The improvement rate was 58 of 125 (46.4%) in the combined hydronidone group (P = .014). The overall safety profile and incidence of serious adverse events were similar among the groups. CONCLUSIONS: Hydronidone plus entecavir showed clinically significant histological improvement of liver fibrosis in patients with CHB, and the dose of 270 mg showed the best efficacy of fibrosis regression. Further studies are required to assess the long-term effectiveness of hydronidone in regression of hepatic fibrosis. CLINICALTRIALS: gov number, NCT02499562.
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Hepatitis B Crónica , Humanos , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/patología , Resultado del Tratamiento , Cirrosis Hepática/complicaciones , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/patología , Fibrosis , Método Doble Ciego , Antivirales/efectos adversosRESUMEN
BACKGROUND: Stress hyperglycemia ratio (SHR) is significantly related to adverse cardiovascular clinical outcomes and increased in-hospital mortality. However, the relationship between SHR and coronary artery disease (CAD) severity has hitherto not been reported. This study sought to clarify the relationship between the SHR and CAD severity of individuals with different glucose metabolic statuses. METHODS: A retrospective analysis was performed on 987 patients who underwent coronary angiography (CAG) from October 2020 to May 2022. Based on CAG results, patients were divided into single-vessel CAD and multi-vessel CAD groups. All subjects were stratified into three groups according to the tertiles of the SHR (T1 group: SHR < 0.930; T2 group: 0.930 ≤ SHR < 1.154; T3 group: 1.154 ≤ SHR). Moreover, according to glucose metabolism status, study subjects were divided into normal glucose regulation (NGR), pre-diabetes mellitus (pre-DM) and diabetes mellitus (DM) groups. Finally, the correlation between SHR and CAD severity was analyzed by logistic regression analysis and receiver operating characteristic (ROC) curve. RESULTS: The results showed significantly higher SHR in the multi-vessel CAD group than in the single-vessel group. Logistic regression analysis showed that SHR was an independent risk factor for multi-vessel CAD when used as a continuous variable (OR, 4.047; 95% CI 2.137-7.663; P < 0.001). After adjusting for risk factors, the risk of multi-vessel CAD in the T2 and T3 groups was 1.939-fold (95% CI 1.341-2.804; P < 0.001) and 1.860-fold (95% CI 1.272-2.719; P = 0.001) higher than in the T1 group, respectively. The area under the curve (AUC) of ROC plots was 0.613 for SHR. In addition, SHR was significantly correlated with an increased risk of multi-vessel CAD in the pre-DM and DM groups. CONCLUSIONS: Our study indicated that SHR was significantly correlated with the risk of multi-vessel CAD and predicted CAD severity, especially in pre-DM and DM patients.
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Enfermedad de la Arteria Coronaria , Diabetes Mellitus , Hiperglucemia , Humanos , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/etiología , Glucosa , Estudios Retrospectivos , Hiperglucemia/diagnóstico , Hiperglucemia/epidemiología , Hiperglucemia/complicaciones , Angiografía Coronaria/métodos , Factores de Riesgo , GemfibroziloRESUMEN
BACKGROUND AND PURPOSE: Liver fibrosis is a wound-healing reaction that eventually leads to cirrhosis. Hydronidone is a new pyridine derivative with the potential to treat liver fibrosis. In this study, we explored the antifibrotic effects of hydronidone and its potential mode of action. METHODS: The anti-hepatic fibrosis effects of hydronidone were studied in carbon tetrachloride (CCl4 )- and 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)- induced animal liver fibrosis. The antifibrotic mechanisms of hydronidone were investigated in hepatic stellate cells (HSCs). The antifibrotic effect of hydronidone was further tested after Smad7 knockdown in HSCs in mouse models of fibrosis. RESULTS: In animal models, hydronidone attenuated liver damage and collagen accumulation, and reduced the expression of fibrosis-related genes. Hydronidone decreased the expression of fibrotic genes in HSCs. Impressively, hydronidone significantly upregulated Smad7 expression and promoted the degradation of transforming growth factor ß receptor I (TGFßRI) in HSCs and thus inhibited the TGFß-Smad signalling pathway. Specific knockdown of Smad7 in HSCs in vivo blocked the antifibrotic effect of hydronidone. CONCLUSION: Hydronidone ameliorates liver fibrosis by inhibiting HSCs activation via Smad7-mediated TGFßRI degradation. Hydronidone is a potential drug candidate for the treatment of liver fibrosis.
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Cirrosis Hepática , Transducción de Señal , Factor de Crecimiento Transformador beta , Animales , Ratones , Tetracloruro de Carbono/toxicidad , Tetracloruro de Carbono/metabolismo , Células Estrelladas Hepáticas/efectos de los fármacos , Células Estrelladas Hepáticas/metabolismo , Hígado/patología , Cirrosis Hepática/tratamiento farmacológico , Receptor Tipo I de Factor de Crecimiento Transformador beta , Factor de Crecimiento Transformador beta/metabolismo , Proteína smad7/efectos de los fármacos , Proteína smad7/metabolismoRESUMEN
Exosomal miRNAs activates hepatic stellate cell (HSC) and promote fibrosis. miR-222 was found to be increased in hepatitis B virus (HBV)-infected hepatocytes, and ferroptosis was reported to ameliorate liver fibrosis (LF). Although miR-222 and ferroptosis have been implicated in LF, the association between miR-222 and ferroptosis and how they coordinate to regulate LF are still not explicit. This study investigates the roles of miR-222 and transferrin receptor (TFRC) in LF. Lipid reactive oxygen species (ROS) level was analyzed by flow cytometry. FerroOrange staining was used to measure intracellular iron level. Luciferase reporter assay was adopted to confirm the binding of miR-222 and TFRC. Real-time quantitative PCR and immunoblots were applied to analyze gene and protein expression. The results showed that supplementation of exosomes derived from HBV-infected LO2 cells remarkably enhanced LX-2 cell activation, evidenced by elevated hydroxyprolin (Hyp) secretion and α-SMA and COL1A2 expression. miR-222 was significantly increased in HBV-Exo. Overexpressing miR-222 upregulated cell viability, secretion of Hpy, and expression of α-SMA and COL1A2, which were all blocked by overexpression of TFRC. Further study showed that TFRC was a target of miR-222, and miR-222 promoted LX-2 cell activation through suppressing TFRC-induced ferroptosis in LX-2 cells. Exosomal miR-222 derived from HBV-infected hepatocytes promoted LF through inhibiting TFRC and TFRC-induced ferroptosis. This study emphasizes the significance of miR-222/TFRC axis in LF and suggests new insights in clinical decision making while treating LF. Exosomes derived from HBV-infected LO2 cells promote LX-2 cell activation and liver fibrosis in mouse Exosomal miR-222 derived from HBV-infected LO2 cells promotes LX-2 cell activation TFRC is a target of miR-222 and inhibits LX-2 cell activation induced by miR-222 miR-222 promotes LX-2 cell activation through inhibiting TFRC-induced ferroptosis.
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Exosomas , MicroARNs , Animales , Ratones , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/metabolismo , Exosomas/genética , Exosomas/metabolismo , Hepatocitos/metabolismo , Cirrosis Hepática/genética , Cirrosis Hepática/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Células Estrelladas Hepáticas/metabolismo , Células Estrelladas Hepáticas/patología , Receptores de Transferrina/metabolismoRESUMEN
Alkoxy-substituted enamides are often used as synthetic intermediates due to their special reactivity. To the best our knowledge, the biological activity of alkoxy-substituted amines has never been reported so far. We have synthesized a series of alkoxy-substituted enamides to study their anti-influenza A virus activity in vitro and in vivo. Among these compounds, compound E-2o had the best antiviral activity (EC50 = 2.76 ± 0.67 µM) and low cytotoxicity (CC50 = 662.87 ± 24.85 µM). The mechanism of action of this compound was preliminarily explored by us. It alleviated the cytopathic effects and cell death caused by different subtypes of influenza A virus. Different drug delivery methods and timed dosing experiments had shown that E-2o had the best therapeutic effect and mainly played a role in the early stages of virus replication. The expansion of influenza viruses in cells was inhibited by reducing ROS accumulation, cell apoptosis, and autophagy. Alkoxy-substituted enamide E-2o reduced the production of interferon and other pro-inflammatory factors in the RIG-â pathway and its downstream NF-κB was induced by influenza A virus in vitro and in vivo. It avoided damage in the mice which was caused by excessive inflammatory factors. In addition, the weight loss and lung lesion damage in mice caused by influenza virus were improved by compound E-2o. Therefore, Alkoxy-substituted enamide E-2o could inhibit the replication of influenza viruses in vivo and in vitro, and has the potential to be developed into a drug for treating influenza.
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Virus de la Influenza A , Gripe Humana , Animales , Ratones , Humanos , Antivirales/farmacología , Antivirales/uso terapéutico , Gripe Humana/tratamiento farmacológico , FN-kappa B/metabolismoRESUMEN
Red blood cells (RBCs) are the most abundant cells in the body, possessing unique biological and physical properties. RBCs have demonstrated outstanding potential as delivery vehicles due to their low immunogenicity, long-circulating cycle, and immune characteristics, exhibiting delivery abilities. There have been several developments in understanding the delivery system of RBCs and their derivatives, and they have been applied in various aspects of biomedicine. This article compared the various physiological and physical characteristics of RBCs, analyzed their potential advantages in delivery systems, and summarized their existing practices in biomedicine.
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Sistemas de Liberación de Medicamentos , EritrocitosRESUMEN
BACKGROUND Ablation has been developed as a radical surgical procedure for liver tumors. Local anesthesia in combination with general anesthesia or intravenous sedation is needed in ablative procedures. Although many studies have been published, a related bibliometric study is lacking. The present bibliometric analysis aimed to further understand the current situation of anesthesia for liver tumor ablation and discover candidate novel research directions. MATERIAL AND METHODS Web of Science Core Collection (WoSCC) was searched to identify studies associated with anesthesia for liver tumor ablation. Also, countries, journals, authors, and institutes contribution together with co-occurrence relations were analyzed by R, VOSviewer, and CiteSpace software; meanwhile, relevant research hotspots together with potential future trends were identified. RESULTS This work obtained 183 English-language documents during 1999-2022, and the annual growth rate was 8.83%. Most studies were conducted in the United States (24.04%, 44/183). The Oslo Univ Hosp contributed the most publications (n=11, 6.01%). Livraghi T (n=6), De Baere T (n=5), and Goldberg SN (n=4) ranked top in terms of cited authors and top authors. Keywords from that co-cited network were aggregated and identified, which revealed a shift in the liver tumor ablation anesthesia field. Initially, hotspots were predominantly "alcohol injection", "radiofrequency tissue ablation", and "metastases", but hotspots shifted to "efficacy", "ablation", "pain", "microwave ablation", "management", "analgesia", "safety", "irreversible electroporation", and "anesthesia" recently. CONCLUSIONS Anesthesia has received increased attention as liver tumor ablation advances. Bibliometric study findings provide insight into the current state and trends of anesthesia in liver tumor ablation research.
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Anestesiología , Neoplasias Hepáticas , Humanos , Anestesia General , Bibliometría , Neoplasias Hepáticas/cirugía , DolorRESUMEN
True natural environments are more complex, and light travels through non-spherical particle media, which can affect the transmission of light. The medium environment of non-spherical particles is more common than that of spherical particles, and some studies have shown that there are differences between spherical and non-spherical particles in polarized light transmission. Therefore, the use of spherical particles instead of non-spherical particles will result in great error. In view of this feature, this paper samples the scattering angle based on the Monte Carlo method, and then constructs a simulation model of a random sampling fitting phase function suitable for ellipsoidal particles. In this study, yeast spheroids and Ganoderma lucidum spores were prepared. The effects of different polarization states and optical thicknesses on the transmission of polarized light at three wavelengths were investigated using ellipsoidal particles with a ratio of 1.5 transverse to vertical axes. The results show that when the concentration of the medium environment increases, the polarized lights of different states all show obvious depolarization, but circularly polarized light has better polarization-preserving characteristics than linearly polarized light, and polarized light with larger wavelengths also shows more stable optical properties. When yeast and Ganoderma lucidum spores were used as the transport medium, the degree of polarization of polarized light had the same trend. However, the equal volume radius of yeast particles is smaller than that of Ganoderma lucidum spores, so when the laser is in the yeast particle medium, the polarization-maintaining property of polarized light is superior. This study provides an effective reference for the variation of polarized light transmission in an atmospheric transmission environment with heavy smoke.
RESUMEN
Since there are usually multiple layers present in a real-world sea fog environment, and because previous studies have tended to analyze sea fog as a single layer rather than as refined layered sea fog, this paper splits sea fog into two categories: water fog and salt fog double-layer environments. By adjusting the optical thickness of the two layers of media, we may investigate the issue of the law governing the transmission of polarized light. In this paper, the analysis is mainly carried out through a simulation and experimental tests. The simulation portion is based mostly on the improved layered Monte Carlo approach, which builds a simulation model more appropriate for multilayer non-spherical media by using the accumulation principle to determine the scattering and transmission properties between layers. The tests are conducted by altering the double-layer medium's optical thickness, incoming wavelength, and polarization state, and then getting the polarization information of visible light after transmission through the complicated environment. The findings demonstrate that the optical thickness of the sea fog double-layer media affects polarized light transmission in a non-negligible way. Longer wavelength polarized light may keep polarization information better as the optical thickness increases, and circularly polarized light has polarization-preserving properties that are superior to linearly polarized light. By contrasting the simulation findings with the experimental data, the consistency of the two conclusions is confirmed, and the study offers a helpful resource for the transmission of polarized light in the sea fog environment.