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Fluorescence sensing and imaging techniques are being widely studied for detecting carbon monoxide (CO) in living organisms due to their speed, sensitivity, and ease of use to biological systems. Most fluorescent probes used for this purpose are based on heavy metal ions like Pd, with a few using elements like Ru, Rh, Ir, Os, Tb, and Eu. However, these metals can be expensive and toxic to cells. There is a need for more affordable and biologically safe fluorescent probes for CO detection. Drawing inspiration from the robust affinity exhibited by heme iron toward CO, in this work, a rhodamine derivative called RBF was developed for imaging CO in living cells by binding to Fe(III) and could be used for CO sensing. A Fe(III)-based fluorescent probe for CO imaging in living cells offers advantages of cost effectiveness, low toxicity, and ease of use. The fluorescence detection using the RBF-Fe system showed a direct correlation with increasing levels of CORM-3 (LOD = 146 nM) or the exposure time of CO gas, displaying reduced fluorescence. A CO test paper based on RBF-Fe was created for simple on-site CO detection, where fluorescence would diminish in response to CO exposure, allowing rapid (2 min) visual identification. Imaging of CO in living cells was successfully conducted using the probe system, showing a decrease in fluorescence intensity as CORM-3 concentrations increased, indicating its effectiveness in monitoring CO levels accurately within living cells.
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Monóxido de Carbono , Compuestos Férricos , Colorantes Fluorescentes , Monóxido de Carbono/análisis , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Humanos , Compuestos Férricos/química , Compuestos Férricos/análisis , Imagen Óptica , Rodaminas/química , Células HeLaRESUMEN
Self-assembled lipid nanoparticles (LNPs), serving as essential nanocarriers in recent COVID-19 mRNA vaccines, provide a stable and versatile platform for delivering a wide range of biological materials. Notably, LNPs with unique inverse mesostructures, such as cubosomes and hexosomes, are recognized as fusogenic nanocarriers in the drug delivery field. This study delves into the physicochemical properties, including size, lyotropic liquid crystalline mesophase, and apparent pKa of LNPs with various lipid components, consisting of two ionizable lipids (ALC-0315 and SM-102) used in commercial COVID-19 mRNA vaccines and a well-known inverse mesophase structure-forming helper lipid, phytantriol (PT). Two partial mesophase diagrams are generated for both ALC-0315/PT LNPs and SM-102/PT LNPs as a function of two factors, ionizable lipid ratio (α, 0-100 mol%) and pH condition (pH 3-11). Furthermore, the impact of different LNP stabilizers (Pluronic F127, Pluronic F108, and Tween 80) on their pH-dependent phase behavior is evaluated. The findings offer insights into the self-assembled mesostructure and ionization state of the studied LNPs with potentially enhanced endosomal escape ability. This research is relevant to developing innovative next-generation LNP systems for delivering various therapeutics.
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Alcoholes Grasos , Lípidos , Cristales Líquidos , Nanopartículas , Nanopartículas/química , Alcoholes Grasos/química , Cristales Líquidos/química , Concentración de Iones de Hidrógeno , Lípidos/química , Iones/química , LiposomasRESUMEN
OBJECTIVE: Fatty acids play a critical role in the proper functioning of the brain. This study investigated the effects of a high-fat (HF) diet on brain fatty acid profiles of offspring exposed to maternal gestational diabetes mellitus (GDM). METHODS: Insulin receptor antagonist (S961) and HF diet were used to establish the GDM animal model. Brain fatty acid profiles of the offspring mice were measured by gas chromatography at weaning and adulthood. Protein expressions of the fatty acid transport pathway Wnt3/ß-catenin and the target protein major facilitator superfamily domain-containing 2a (MFSD2a) were measured in the offspring brain by Western blot. RESULTS: Maternal GDM increased the body weight of male offspring (P < 0.05). In weaning offspring, factorial analysis showed that maternal GDM increased the monounsaturated fatty acid (MUFA) percentage of the weaning offspring's brain (P < 0.05). Maternal GDM decreased offspring brain arachidonic acid (AA), but HF diet increased brain linoleic acid (LA) (P < 0.05). Maternal GDM and HF diet reduced offspring brain docosahexaenoic acid (DHA), and the male offspring had higher DHA than the female offspring (P < 0.05). In adult offspring, factorial analysis showed that HF diet increased brain MUFA in offspring, and male offspring had higher brain MUFA than female offspring (P < 0.05). The HF diet increased brain LA in the offspring. Male offspring had higher level of AA than female offspring (P < 0.05). HF diet reduced DHA in the brains of female offspring. The brain protein expression of ß-catenin and MFSD2a in both weaning and adult female offspring was lower in the HF + GDM group than in the CON group (P < 0.05). CONCLUSIONS: Maternal GDM increased the susceptibility of male offspring to HF diet-induced obesity. HF diet-induced adverse brain fatty acid profiles in both male and female offspring exposed to GDM.
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Encéfalo , Diabetes Gestacional , Dieta Alta en Grasa , Ácidos Grasos , Efectos Tardíos de la Exposición Prenatal , Animales , Embarazo , Femenino , Diabetes Gestacional/metabolismo , Ratones , Dieta Alta en Grasa/efectos adversos , Encéfalo/metabolismo , Efectos Tardíos de la Exposición Prenatal/metabolismo , Masculino , Ácidos Grasos/metabolismo , Modelos Animales de Enfermedad , Fenómenos Fisiologicos Nutricionales MaternosRESUMEN
BACKGROUND: Polyunsaturated fatty acids (PUFAs), especially docosahexaenoic acid (DHA), are critical for proper fetal brain growth and development. Gestational diabetes mellitus (GDM) could affect maternal-fetal fatty acid metabolism. OBJECTIVE: This study aimed to explore the effect of GDM and high-fat (HF) diet on the DHA transport signaling pathway in the placenta-brain axis and fatty acid concentrations in the fetal brain. METHODS: Insulin receptor antagonist (S961) and HF diet were used to establish an animal model of GDM. Eighty female C57BL/6J mice were randomly divided into control (CON), GDM, HF, and HF+GDM groups. The fatty acid profiles of the maternal liver and fetal brain were analyzed by gas chromatography. In addition, we analyzed the protein amounts of maternal liver fatty acid desaturase (FADS1/3), elongase (ELOVL2/5) and the regulatory factor sterol-regulatory element-binding protein (SREBP)-1c, and the DHA transport signaling pathway (Wnt3/ß-catenin/MFSD2a) of the placenta and fetal brain using western blotting. RESULTS: GDM promoted the decrease of maternal liver ELOVL2, ELOVL5, and SREBP-1c. Accordingly, we observed a significant decrease in the amount of maternal liver arachidonic acid (AA), DHA, and total n-3 PUFA and n-6 PUFA induced by GDM. GDM also significantly decreased the amount of DHA and n-3 PUFA in the fetal brain. GDM downregulated the Wnt3/ß-catenin/MFSD2a signaling pathway, which transfers n-3 PUFA in the placenta and fetal brain. The HF diet increased n-6 PUFA amounts in the maternal liver, correspondingly increasing linoleic acid, gamma-linolenic acid, AA, and total n-6 PUFA in the fetal brain, but decreased DHA amount in the fetal brain. However, HF diet only tended to decrease placental ß-catenin and MFSD2a amounts (P = 0.074 and P = 0.098, respectively). CONCLUSIONS: Maternal GDM could affect the fatty acid profile of the fetal brain both by downregulating the Wnt3/ß-catenin/MFSD2a pathway of the placental-fetal barrier and by affecting maternal fatty acid metabolism.
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Diabetes Gestacional , Ácidos Grasos Omega-3 , Humanos , Animales , Ratones , Femenino , Embarazo , Diabetes Gestacional/metabolismo , Ácidos Grasos/metabolismo , Placenta/metabolismo , beta Catenina/metabolismo , Ratones Endogámicos C57BL , Ácidos Grasos Omega-3/metabolismo , Ácidos Grasos Insaturados/metabolismo , Ácidos Docosahexaenoicos/metabolismo , Ácido Araquidónico , Encéfalo/metabolismoRESUMEN
The use of manure, mycelium dregs and other waste as organic fertilizer is the main source of antibiotic resistance genes (ARGs) and pathogens in farmland. Composting of waste may effectively remove ARGs and pathogens. However, the profiles and drivers of changes in metal resistance genes (MRGs), biocide resistance genes (BRGs), and virulence genes (VGs) in soil-crop rhizosphere systems after compost application remain largely unknown. Here, we prepared two kinds of microbial organic fertilizers (MOF) by using Trichoderma dregs (TDs) and organic fertilizer mixing method (MOF1) and TDs co-composting method (MOF2). The effects of different types and doses of MOF on resistance genes, VGs and pathogens in soil-rhizosphere system and their potential mechanisms were studied. The results showed that co-composting of TDs promoted the decomposition of organic carbon and decreased the absolute abundance of ARGs and mobile genetic elements (MGEs) by 53.4-65.0%. MOF1 application significantly increased the abundance and diversity of soil ARGs, BRGs, and VGs, while low and medium doses of MOF2 significantly decreased their abundance and diversity in soil and rhizosphere. Patterns of positive co-occurrence between MGEs and VGs/MRGs/BRGs/ARGs were observed through statistical analysis and gene arrangements. ARGs/MRGs reductions in MOF2 soil were directly driven by weakened horizontal gene transfer triggered by MGEs. Furthermore, MOF2 reduced soil BRGs/VGs levels by shifting bacterial communities (e.g., reduced bacterial host) or improving soil property. Our study provided new insights into the rational use of waste to minimize the spread of resistomes and VGs in soil.
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Compostaje , Trichoderma , Suelo , Fertilizantes/análisis , Trichoderma/genética , Genes Bacterianos , Rizosfera , Virulencia , Bacterias , Antibacterianos/farmacología , Estiércol/análisis , Estiércol/microbiología , Microbiología del SueloRESUMEN
The prevalence of cardiovascular diseases continues to be a challenge for global health, necessitating innovative solutions. The potential of high-density lipoprotein (HDL) mimetic nanotherapeutics in the context of cardiovascular disease and the intricate mechanisms underlying the interactions between monocyte-derived cells and HDL mimetic showing their impact on inflammation, cellular lipid metabolism, and the progression of atherosclerotic plaque. Preclinical studies have demonstrated that HDL mimetic nanotherapeutics can regulate monocyte recruitment and macrophage polarization towards an anti-inflammatory phenotype, suggesting their potential to impede the progression of atherosclerosis. The challenges and opportunities associated with the clinical application of HDL mimetic nanotherapeutics, emphasize the need for additional research to gain a better understanding of the precise molecular pathways and long-term effects of these nanotherapeutics on monocytes and macrophages to maximize their therapeutic efficacy. Furthermore, the use of nanotechnology in the treatment of cardiovascular diseases highlights the potential of nanoparticles for targeted treatments. Moreover, the concept of theranostics combines therapy and diagnosis to create a selective platform for the conversion of traditional therapeutic medications into specialized and customized treatments. The multifaceted contributions of HDL to cardiovascular and metabolic health via highlight its potential to improve plaque stability and avert atherosclerosis-related problems. There is a need for further research to maximize the therapeutic efficacy of HDL mimetic nanotherapeutics and to develop targeted treatment approaches to prevent atherosclerosis. This review provides a comprehensive overview of the potential of nanotherapeutics in the treatment of cardiovascular diseases, emphasizing the need for innovative solutions to address the challenges posed by cardiovascular diseases.
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Enfermedades Cardiovasculares , Lipoproteínas HDL , Macrófagos , Monocitos , Humanos , Lipoproteínas HDL/química , Lipoproteínas HDL/metabolismo , Lipoproteínas HDL/farmacología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Animales , Enfermedades Cardiovasculares/tratamiento farmacológico , Monocitos/efectos de los fármacos , Nanopartículas/química , Aterosclerosis/tratamiento farmacológico , Placa Aterosclerótica/tratamiento farmacológico , Nanomedicina/métodos , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacologíaRESUMEN
Acute sleep deprivation has aroused widespread concern and the relationship between acute sleep deprivation and cortisol levels is inconsistent. This study aimed to explore additional evidence and details. The PubMed, Web of Science, EMBASE, CLINAHL and Cochrane databases were searched for eligible studies published up to June 7, 2023. All analyses were performed using Review Manager 5.4 and Stata/SE 14.0. A total of 24 studies contributed to this meta-analysis. There was no significant difference in cortisol levels between participants with acute sleep deprivation and normal sleep in 21 crossover-designed studies (SMD = 0.18; 95% CI: -0.11, 0.45; p = 0.208) or 3 RCTs (SMD = 0.26; 95% CI: -0.22, 0.73; p = 0.286). Subgroup analysis revealed that the pooled effects were significant for studies using serum as the sample (SMD = 0.46; 95%CI: 0.11, 0.81; p = 0.011). Studies reporting cortisol levels in the morning, in the afternoon and in the evening did not show significant difference (p > 0.05). The pooled effects were statistically significant for studies with multiple measurements (SMD = 0.28; 95%CI: 0.03, 0.53; p = 0.027) but not for studies with single cortisol assessments (p = 0.777). When the serum was used as the test sample, the cortisol levels of individuals after acute sleep deprivation were higher than those with normal sleep.
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Hidrocortisona , Privación de Sueño , Privación de Sueño/sangre , Hidrocortisona/sangre , HumanosRESUMEN
Diabetic cardiomyopathy (DCM) is a cardiac complication resulting from long-term uncontrolled diabetes, characterized by myocardial fibrosis and abnormal cardiac function. This study aimed at investigating the potential of ginsenoside RG1 (RG1)-induced mesenchymal stem cells (MSCs) in alleviating DCM. A DCM mouse model was constructed, and the effects of RG1-induced MSCs on myocardial function and fibrosis in diabetic mice were evaluated. RG1-induced MSCs were cocultured with high glucose-treated fibroblasts for subsequent functional and mechanism assays. It was discovered that RG1-induced MSCs secrete exosomes that induce macrophage M2 polarization. Mechanistically, exosomes derived from RG1-induced MSCs transferred circNOTCH1 into macrophages, activating the NOTCH signaling pathway. A competing endogenous RNA (ceRNA) regulatory axis consisting of circNOTCH1, miR-495-3p, and NOTCH1 was found to contribute to DCM alleviation.. This study unveiled that exosomal circNOTCH1 secreted by RG1-induced MSCs can alleviate DCM by activating the NOTCH signaling pathway to induce macrophage M2 polarization. This finding may contribute to the development of new therapeutic approaches for DCM.
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Diabetes Mellitus Experimental , Cardiomiopatías Diabéticas , Ginsenósidos , Células Madre Mesenquimatosas , MicroARNs , Ratones , Animales , Cardiomiopatías Diabéticas/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Macrófagos/metabolismo , MicroARNs/genéticaRESUMEN
BACKGROUND: This meta-analysis aimed to assess the safety and efficacy of robotic-assisted natural orifice specimen extraction surgery (NOSE) compared to traditional robotic transabdominal wall specimen retrieval surgery (TWSR) for colorectal cancer. METHODS: A systematic search was conducted in three electronic databases (PubMed, Web of Science and Embase) from inception to August 2023. Primary outcomes included postoperative complications, the number of lymph nodes harvested, overall survival and disease-free survival. Secondary outcomes included the postoperative visual analog scale (VAS) score, the additional use of analgesics, the restoration of gastrointestinal function, blood loss, the mean operation time, and length of postoperative hospital stay. RESULTS: In this meta-analysis, a total of 717 patients from 6 observational studies met the inclusion criteria. Compared with the TWSR group, the NOSE group had greater benefits in terms of overall postoperative complications [odds ratios (OR) 0.55; 95% confidence intervals (CI) = 0.34 to 0.89; P = 0.01, I2 = 0%)], the number of lymph nodes harvested [weighted mean differences (WMD) = 1.18; 95% CI = 0.15 to 2.21; P = 0.02, I2 = 0%)], the rate of wound infection (OR 0.17; 95% CI = 0.04 to 0.80; P = 0.02, I2 = 0%), the passed flatus time (WMD = - 0.35 days; 95% CI = - 0.60 to - 0.10; P = 0.007, I2 = 73%), the additional use of analgesics (OR 0.25; 95% CI = 0.15 to 0.40; P < 0.001, I2 = 0%), the diet recovery time (WMD = - 0.56; 95% CI = - 1.00 to - 0.11; P = 0.01, I2 = 78%) and the postoperative VAS score (WMD = - 1.23; 95% CI = - 1.63 to - 0.83; P < 0.001, I2 = 65%). There were no significant differences in the blood loss (WMD = - 5.78 ml; 95% CI = - 17.57 to 6.00; P = 0.34, I2 = 90%), mean operation time (WMD = 14.10 min; 95% CI = - 3.76 to 31.96; P = 0.12) (I2 = 93%), length of postoperative hospital stay (WMD = - 0.47 day; 95% CI = - 0.98 to 0.03; P = 0.07, I2 = 51%), incidences of postoperative ileus (OR 1.0; 95% CI = 0.22 to 4.46; P = 1.00, I2 = 0%), anastomotic leakage (OR 0.73; 95% CI = 0.33 to 1.60; P = 0.43, I2 = 0%), and intra-abdominal abscess (OR 1.59; 95% CI = 0.47 to 5.40; P = 0.46, I2 = 0%), or 3-year overall survival [hazard ratio (HR) = 1.07, 95% CI = 0.60 to 1.94; P = 0.81)] or disease-free survival (HR = 0.94, 95% CI = 0.54 to 1.63; P = 0.82, I2 = 0%). CONCLUSION: This meta-analysis showed that the NOSE group had better postoperative outcomes than did the TWSR group and that NOSE was a safe and viable alternative to TWSR. More large-sample reviews and further randomized trials are warranted.
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Neoplasias Colorrectales , Complicaciones Posoperatorias , Procedimientos Quirúrgicos Robotizados , Humanos , Procedimientos Quirúrgicos Robotizados/métodos , Neoplasias Colorrectales/cirugía , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Resultado del Tratamiento , Cirugía Endoscópica por Orificios Naturales/métodos , Tiempo de Internación/estadística & datos numéricos , Tempo OperativoRESUMEN
Micromechanical resonators have aroused growing interest as biological and chemical sensors, and microcantilever beams are the main research focus. Recently, a resonant microcantilever with an integrated heater has been applied in on-chip thermogravimetric analysis (TGA). However, there is a strong relationship between the mass sensitivity of a resonant microcantilever and the location of adsorbed masses. Different sampling positions will cause sensitivity differences, which will result in an inaccurate calculation of mass change. Herein, an integrated H-shaped resonant beam with uniform mass sensitivity and temperature distribution is proposed and developed to improve the accuracy of bio/chemical sensing and TGA applications. Experiments verified that the presented resonant beam possesses much better uniformity of sensitivity and temperature distribution compared with resonant microcantilevers. Gas-sensing and TGA experiments utilizing the integrated resonant beam were also carried out and exhibited good measurement accuracy.
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In the postantibiotic era, the pathogenicity and resistance of pathogens have increased, leading to an increase in intestinal inflammatory disease. Bacterial infections remain the leading cause of animal mortality. With increasing resistance to antibiotics, there has been a significant decrease in resistance to both inflammation and disease in animals, thus decreasing production efficiency and increasing production costs. These side effects have serious consequences and have detracted from the development of China's pig industry. Microcin C7 (McC7) demonstrates potent antibacterial activity against a broad spectrum of pathogens, stable physicochemical properties, and low toxicity, reducing the likelihood of resistance development. Thus, McC7 has received increasing attention as a potential clinical antibacterial and immunomodulatory agent. McC7 has the potential to serve as a new generation of antibiotic substitutes; however, its commercial applications in the livestock and poultry industry have been limited. In this review, we summarize and discuss the biosynthesis, biochemical properties, structural characteristics, mechanism of action, and immune strategies of McC7. We also describe the ability of McC7 to improve intestinal health. Our aim in this study was to provide a theoretical basis for the application of McC7 as a new feed additive or new veterinary drug in the livestock and poultry breeding industry, thus providing a new strategy for alleviating resistance through feed and mitigating drug resistance. Furthermore, this review provides insight into the new functions and anti-infection mechanisms of bacteriocin peptides and proposes crucial ideas for the research, product development, and application of bacteriocin peptides in different fields, such as the food and medical industries.
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Antibacterianos , Bacteriocinas , Bacteriocinas/farmacología , Bacteriocinas/química , Bacteriocinas/uso terapéutico , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/uso terapéutico , Animales , Agentes Inmunomoduladores/farmacología , Agentes Inmunomoduladores/química , Agentes Inmunomoduladores/uso terapéutico , Porcinos , HumanosRESUMEN
Waterlogging stress is an important abiotic stress that adversely affects maize growth and yield. The mechanism regulating the early stage of the maize response to waterlogging stress is largely unknown. In this study, CM37 and cmh15 seedlings were treated with waterlogging stress and then examined in terms of their physiological changes. The results indicated that inbred line cmh15 is more tolerant to waterlogging stress and less susceptible to peroxide-based damages than CM37. The RNA sequencing analysis identified 1,359 down-regulated genes and 830 up-regulated genes in the waterlogging-treated cmh15 plants (relative to the corresponding control levels). According to the Gene Ontology analysis for the differentially expressed genes (DEGs), some important terms were identified which may play important roles in the response to waterlogging stress. Moreover, enriched Kyoto Encyclopedia of Genes and Genomes pathways were also identified for the DEGs. Furthermore, the substantial changes in the expression of 36 key transcription factors may be closely related to the maize in response to waterlogging stress. This study offers important insights into the mechanism in regulating maize tolerance to waterlogging stress, with important foundations for future research.
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mRNA lipid nanoparticle (LNP) technology presents enormous opportunities to prevent and treat various diseases. Here, we developed a novel series of LNPs containing ionizable amino-lipids showing a remarkable array of tunable and pH-sensitive lyotropic liquid crystalline mesophases including the inverse bicontinuous cubic and hexagonal phases characterized by high-throughput synchrotron radiation X-ray scattering. Furthermore, with an interest in developing mRNA therapeutics for lung macrophage targeting, we discovered that there is a strong correlation between the mesophase transition of the LNPs during acidification and the macrophage association/transfection efficiency of mRNAs. The slight molecular structural differences between the SM-102 and ALC-0315 ionizable lipids are linked to the LNP's ability to transform their internal structures from an amorphous state to the inverse micellar, hexagonal, and finally cubic structures during endosomal maturation. SM-102 LNPs showed exceptionally improved transfection efficiency due to their ability to form a cubic structure at a lower pH than the ALC-0315 analogues, which remained within the hexagonal structure, previously attributed to promoting endosomal escape of the ionizable LNPs. Overall, the new knowledge draws our attention to the important role of mesophase transition in endosomal escape, and the novel LNP libraries reported herein have broad prospects for advancing mRNA therapeutics.
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To investigate the potential of the gut microbiome as a biomarker for predicting the early recurrence of HBV-related hepatocellular carcinoma (HCC), we enrolled 124 patients diagnosed with HBV-associated HCC and 82 HBV-related hepatitis, and 86 healthy volunteers in our study, collecting 292 stool samples for 16S rRNA sequencing and 35 tumor tissue samples for targeted metabolomics. We performed an integrated bioinformatics analysis of gut microbiome and tissue metabolome data to explore the gut microbial-liver metabolite axis associated with the early recurrence of HCC. We constructed a predictive model based on the gut microbiota and validated its efficacy in the temporal validation cohort. Dialister, Veillonella, the Eubacterium coprostanoligenes group, and Lactobacillus genera, as well as the Streptococcus pneumoniae and Bifidobacterium faecale species, were associated with an early recurrence of HCC. We also found that 23 metabolites, including acetic acid, glutamate, and arachidonic acid, were associated with the early recurrence of HCC. A comprehensive analysis of the gut microbiome and tissue metabolome revealed that the entry of gut microbe-derived acetic acid into the liver to supply energy for tumor growth and proliferation may be a potential mechanism for the recurrence of HCC mediated by gut microbe. We constructed a nomogram to predict early recurrence by combining differential microbial species and clinical indicators, achieving an AUC of 78.0%. Our study suggested that gut microbes may serve as effective biomarkers for predicting early recurrence of HCC, and the gut microbial-tumor metabolite axis may explain the potential mechanism by which gut microbes promote the early recurrence of HCC.
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Carcinoma Hepatocelular , Microbioma Gastrointestinal , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patología , Microbioma Gastrointestinal/genética , Virus de la Hepatitis B/genética , Neoplasias Hepáticas/patología , ARN Ribosómico 16S/genética , Biomarcadores , AcetatosRESUMEN
Novel high-performance fluorescent approaches have always significant demand for room-temperature detection of carbon monoxide (CO), which is highly toxic even at low concentration levels and is not easy to recognize due to its colorless and odorless nature. In this paper, we constructed a palladium-mediated fluorescence turn-on sensing platform (TPANN-Pd) for the recognition of CO at room temperature, revealing simultaneously quick response speed (<30 s), excellent selectivity, superior sensitivity, and low detection limit (â¼160 nM for CORM-3, â¼1.7 ppb for CO vapor). Moreover, rapid detection and efficient removal (24%) from the air by naked-eye vision has been successfully realized based on TPANN-Pd supramolecular gels. Furthermore, the developed sensing platform was elucidated with low cytotoxicity and high cellular uptake, and it was successfully applied to CO imaging in living cells, providing real-time monitoring of potential CO-involved reactions in biological systems.
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Monóxido de Carbono , Paladio , Colorantes Fluorescentes/química , Colorantes Fluorescentes/toxicidadRESUMEN
BACKGROUND: Inflammation-related predisposition to cancer plays an essential role in cancer progression and is associated with poor prognosis. A hypoxic microenvironment and neutrophil infiltration are commonly present in solid tumours, including gastric cancer (GC). Neutrophil extracellular traps (NETs) have also been demonstrated in the tumour immune microenvironment (TIME), but how NETs affect GC progression remains unknown. Here, we investigated the role of NET formation in the TIME and further explored the underlying mechanism of NETs in GC tumour growth. METHODS: Hypoxia-induced factor-1α (HIF-1α), citrulline histone 3 (citH3) and CD66b expression in tumour and adjacent nontumor tissue samples was evaluated by western blotting, immunofluorescence and immunohistochemical staining. The expression of neutrophil-attracting chemokines in GC cells and their hypoxic-CM was measured by qRTâPCR and ELISA. Neutrophil migration under hypoxic conditions was evaluated by a Transwell assay. Pathway activation in neutrophils in a hypoxic microenvironment were analysed by western blotting. NET formation was measured in vitro by immunofluorescence staining. The protumour effect of NETs on GC cells was identified by Transwell, wound healing and cell proliferation assays. In vivo, an lipopolysaccharide (LPS)-induced NET model and subcutaneous tumour model were established in BALB/c nude mice to explore the mechanism of NETs in tumour growth. RESULTS: GC generates a hypoxic microenvironment that recruits neutrophils and induces NET formation. High mobility group box 1 (HMGB1) was translocated to the cytoplasm from the nucleus of GC cells in the hypoxic microenvironment and mediated the formation of NETs via the toll-like receptor 4 (TLR4)/p38 MAPK signalling pathway in neutrophils. HMGB1/TLR4/p38 MAPK pathway inhibition abrogated hypoxia-induced neutrophil activation and NET formation. NETs directly induced GC cell invasion and migration but not proliferation and accelerated the augmentation of GC growth by increasing angiogenesis. This rapid tumour growth was abolished by treatment with the NET inhibitor deoxyribonuclease I (DNase I) or a p38 MAPK signalling pathway inhibitor. CONCLUSIONS: Hypoxia triggers an inflammatory response and NET formation in the GC TIME to augment tumour growth. Targeting NETs with DNase I or HMGB1/TLR4/p38 MAPK pathway inhibitors is a potential therapeutic strategy to inhibit GC progression. Video Abstract.
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Trampas Extracelulares , Proteína HMGB1 , Neoplasias Gástricas , Animales , Ratones , Trampas Extracelulares/metabolismo , Proteína HMGB1/metabolismo , Receptor Toll-Like 4/metabolismo , Neoplasias Gástricas/metabolismo , Ratones Desnudos , Neutrófilos , Desoxirribonucleasa I/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Microambiente TumoralRESUMEN
Despite the high sensitivity of the STOP-Bang questionnaire [snoring, tiredness, observed apneas, high blood pressure, body mass index, age, neck size, gender] questionnaire (SBQ), which is widely used to screen individuals at high risk of obstructive sleep apnea (OSA), few studies have evaluated the discrimination related to sex in the SBQ. Therefore, our study aimed to assess whether SBQ performance is gender-related and modified by changing body mass index (BMI) and neck circumference (NC) cut-off values. A total of 470 patients attended the sleep centres. They were divided into moderate-to-severe OSA and non-moderate-to-severe OSA groups based on the apnea-hypopnea index (AHI) and the results of the SBQ screening. The predictive performance of the SBQ screening instrument was evaluated by 2 × 2 contingency tables and discriminatory ability, which was estimated from the area under the curve (AUC) obtained from receiver operating characteristic curve. Our results suggest that when screening for moderate-to-severe OSA, the original SBQ has higher sensitivity and lower specificity for men; however, women have higher specificity and lower sensitivity. The SBQ achieved the maximum AUC of 0.783 for men and 0.634 for women when the BMI cut-off value was established at 30 kg/m2 and the NC cut-off value was established at 38 cm in men, and the BMI cut-off value was established at 25 kg/m2 and the NC cut-off value at 36 cm in women. Balancing the optimal sensitivity and specificity, the cut-off value of the optimal modified SBQ total scores for men was determined to be ≥4 and ≥3 for women.
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Tamizaje Masivo , Apnea Obstructiva del Sueño , Masculino , Humanos , Femenino , Tamizaje Masivo/métodos , Polisomnografía , Encuestas y Cuestionarios , Apnea Obstructiva del Sueño/diagnóstico , Apnea Obstructiva del Sueño/epidemiología , China/epidemiologíaRESUMEN
BACKGROUND: Colorectal cancer is one of the most serious malignant tumors, and lymph node metastasis (LNM) from colorectal cancer is a major factor for patient management and prognosis. Accurate image detection of LNM is an important task to help clinicians diagnose cancer. Recently, the U-Net architecture based on convolutional neural networks (CNNs) has been widely used to segment image to accomplish more precise cancer diagnosis. However, the accurate segmentation of important regions with high diagnostic value is still a great challenge due to the insufficient capability of CNN and codec structure in aggregating the detailed and non-local contextual information. In this work, we propose a high performance and low computation solution. METHODS: Inspired by the working principle of Fovea in visual neuroscience, a novel network framework based on U-Net for cancer segmentation named Fovea-UNet is proposed to adaptively adjust the resolution according to the importance-aware of information and selectively focuses on the region most relevant to colorectal LNM. Specifically, we design an effective adaptively optimized pooling operation called Fovea Pooling (FP), which dynamically aggregate the detailed and non-local contextual information according to the pixel-level feature importance. In addition, the improved lightweight backbone network based on GhostNet is adopted to reduce the computational cost caused by FP. RESULTS: Experimental results show that our proposed framework can achieve higher performance than other state-of-the-art segmentation networks with 79.38% IoU, 88.51% DSC, 92.82% sensitivity and 84.57% precision on the LNM dataset, and the parameter amount is reduced to 23.23 MB. CONCLUSIONS: The proposed framework can provide a valid tool for cancer diagnosis, especially for LNM of colorectal cancer.
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Neoplasias Colorrectales , Aprendizaje Profundo , Humanos , Neoplasias Colorrectales/diagnóstico por imagen , Metástasis Linfática , Redes Neurales de la ComputaciónRESUMEN
We investigate and compare the difference in the dynamics of two arrested states: colloidal glass and colloidal gel. Real-space experiments reveal two distinct nonergodicity origins for their slow dynamics, namely, cage effects for the glass and attractive bondings for the gel. Such distinct origins lead to a faster decay of the correlation function and a smaller nonergodicity parameter of the glass than those of the gel. We also find that the gel exhibits stronger dynamical heterogeneity compared with the glass due to the greater correlated motions in the gel. Moreover, a logarithmic decay in the correlation function is observed as the two nonergodicity origins merge, consistent with the mode coupling theory.
RESUMEN
BACKGROUND: Research ethics provides the ethical standards for conducting sound and safe research. The field of medical research in China is rapidly growing and facing various ethical challenges. However, in China, little empirical research has been conducted on the knowledge and attitudes of medical postgraduates toward research ethics and RECs. It is critical for medical postgraduates to develop a proper knowledge of research ethics at the beginning of their careers. The purpose of this study was to assess the knowledge and attitudes of medical postgraduates toward research ethics and RECs. METHODS: This cross-sectional study was conducted from May to July 2021 at a medical school and two affiliated hospitals in south-central China. The instrument of the study was an online survey that was distributed via WeChat. RESULTS: We found that only 46.7% were familiar with the ethical guidelines for research with human subjects. In addition, 63.2% of participants were familiar with the RECs that reviewed their research, and 90.7% perceived RECs as helpful. However, only 36.8% were fully aware of the functions of RECs. In the meantime, 30.7% believed that review by an REC would delay research and make it more difficult for researchers. Furthermore, most participants (94.9%) believed that a course on research ethics should be mandatory for medical postgraduates. Finally, 27.4% of the respondents considered the fabrication of some data or results to be acceptable. CONCLUSION: This paper serves to suggest that research ethics education should be prioritized in medical ethics curriculum, and course syllabi or teaching methods should be revised to provide medical postgraduates with a deeper understanding of the principles, regulations, and specifics of research ethics. We also recommend that RECs provide diverse approaches in their review procedure to facilitate the understanding of medical postgraduates of the functions and processes of RECs and to enhance their awareness of research integrity.