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BACKGROUND: With the fast pace of modern life, people have less time for meals, but few studies have examined the association between the habit of fast eating and metabolic diseases. OBJECTIVE: Combining the results of the current study and the prior ones, we aimed to investigate the possible relationship between fast eating and the risk of metabolic dysfunction-associated steatotic liver disease (MASLD). METHODS: This is a sub-analysis of a multicenter cross-sectional study of 1965 participants investigated the association between fast eating and MASLD in Chinese. Fast eating was defined as meal time less than five minutes and participants were divided into three categories based on their self-reported frequency of fast eating: ≤1 time/month, ≤1 time/week and ≥2 times/week. We further conducted a literature search for available studies published before November, 2023 as well as a meta-analysis to investigate the association between fast eating and MASLD. RESULTS: The proportion of MASLD was 59.3%, 50.5%, and 46.2% in participants with fast eating ≥2 times/week, ≤1 time/week and ≤1 time/month, respectively (P for trend <0.001). The frequency of fast eating was independently associated with risk of MASLD after multiple adjustment for sex, age, demographics, smoking and drinking status, BMI and clinical metabolic parameters (OR, 1.29; 95%CI, 1.09-1.53). Participants who ate fast frequently (≥2 times/week) had 81% higher risk of MASLD (P = 0.011). A meta-analysis of five eligible studies confirmed that frequent fast eating was associated with increased risk of MASLD (pooled OR, 1.22; 95%CI, 1.07-1.39). CONCLUSIONS: Frequent fast eating was associated with an increased risk of MASLD.
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Conducta Alimentaria , Humanos , Estudios Transversales , Masculino , Femenino , Persona de Mediana Edad , Adulto , Factores de Riesgo , Factores de Tiempo , China/epidemiología , Enfermedades Metabólicas/epidemiología , Enfermedades Metabólicas/etiología , Comidas , Hígado Graso/epidemiologíaRESUMEN
In recent years, ultrasound has emerged as a widely used technology for modifying proteins/peptides. In this study, we focused on the intrinsic mechanism of ultrasound-induced modification of bovine liver peptides, which were treated with ultrasound power of 0, 100, 200, 300, 400, and 500 W, and their physicochemical and functional properties, as well as ultrastructures, were investigated. The results show that ultrasound mainly affects hydrogen bonding and hydrophobic interactions to change the conformation of proteins and unfolds proteins through a cavitation effect, leading to an increase in biological activity. Fourier infrared spectroscopy showed that ultrasound inhibited the formation of hydrogen bonds and reduced intermolecular cross-linking. Molecular weight distribution showed that the antioxidant components of bovine liver polypeptides were mainly concentrated in fractions of 500-1,000 Da. Maximum values of ABTS (82.66 %), DPPH (76.02 %), chelated iron (62.18 %), and reducing power (1.2447) were obtained by treating bovine liver polypeptides with 500 W ultrasound. Combined with the scanning electron microscopy results, with the intervention of ultrasound, the impact force generated by ultrasonication may lead to the loosening of the protein structure, which further promotes the release of antioxidant peptides, and these findings provide new insights into the application of ultrasound in the release of antioxidant peptides from bovine liver.
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The anaerobic biological treatment of landfill leachate frequently encounters the souring problems because of the high concentration of organic in landfill leachate. Nonetheless, the performance of anaerobic membrane bioreactor (AnMBR) is commendable in terms of removal of organic compounds. Hence, this study explored the effect of organic concentration and hydraulic retention time(HRT) on the removal performance of actual landfill leachate, additionally, carbon conversion through carbon mass balance analysis was analyzed, in order to determine the optimal treatment potential of AnMBR in treating landfill leachate. For HRT values between 14.5 h and 34.6 h, and the influent COD (Chemical Oxygen Demand) range of 12,773.33-15706.67 mg/L, AnMBR could efficiently treat landfill leachate. As HRT was fixed at 14.5 h and influent COD was around 12,206.7-15,373.33 mg/L, AnMBR achieved a maximum organic removal rate of 18.22 ± 0.51 kg COD/(m3âd) with methane yield of 0.24 ± 0.01 m3 CH4/kg COD and methane content of 88.26%. Based on carbon mass balance, increasing COD concentration in the influent (less than 16,000 mg/L) boosted the conversion of organic compounds (45.19 ± 4.24%) into CH4; while decreasing HRT (more than 27.0 h) also promoted the conversion of organic compounds into CH4 (38.36-60.93%) resulting in a decreased TOC (Total Organic Carbon) loss by 2.02-7.19% with outflow. AnMBR may efficiently produce methane while treating landfill leachate by assessing the random forest model (RF) and adjusting the balance between HRT and influent COD concentration.
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Análisis de la Demanda Biológica de Oxígeno , Reactores Biológicos , Metano , Contaminantes Químicos del Agua , Metano/metabolismo , Anaerobiosis , Eliminación de Residuos Líquidos/métodosRESUMEN
Introduction: Rumen acidosis is one of the most common diseases in beef cattle. It severely affects the normal development of calves and poses a significant threat to the farming industry. However, the influence of rumen acidosis on the gut microbiota and serum metabolites of calves is currently unclear. Objective: The aim of this study is to investigate the changes in the gut microbiota and serum metabolites in calves after rumen acidosis and analyse the correlation. Methods: Eight calves were selected as the rumen acidosis group, and eight health calves were selected as the healthy group. The faecal gut microbiota and serum metabolites of calves were detected respectively using 16S rDNA high-throughput sequencing and non-target metabolomics. The correlation between gut microbiota and serum metabolites was analyzed by Spearman correlation analysis. Results: Differential analysis of the diversity and composition of gut microbiota between eight male healthy (Health) and eight male rumen acidosis (Disease) calves revealed that rumen acidosis increased the abundance of the gut microbiota in calves. At the phylum level, compared to the Healthy group, the relative abundance of Proteobacteria in the Disease group significantly decreased (P<0.05), while the relative abundance of Desulfobacterota significantly increased in the Disease group (P<0.05). At the genus level, compared to the Disease group, the relative abundance of Alloprevotella, Muribaculaceae, Succinivibrio, Prevotella, Agathobacter and Parabacteroides significantly increased in the Healthy group (P<0.05), while the relative abundance of Christensenellaceae_R-7 and Monoglobus significantly decreased in the Healthy group (P<0.05). Differential analysis results showed the Healthy group had 23 genera with higher abundance, while the Disease group had 47 genera with higher abundance. Serum metabolomics results revealed the differential metabolites associated with rumen acidosis, including nicotinamide, niacin, L-glutamic acid and carnosine, were mainly enriched in the nicotinate and nicotinamide pathway and the histidine pathway. Conclusion: The occurrence of rumen acidosis can induce changes in the gut microbiota of calves, with a significant increase of the Christensenellaceae_R-7 genus and a significant decrease of Prevotella and Succinivibrio genera. In addition, the occurrence of rumen acidosis can also induce changes in serum metabolites including niacin, niacinamide, L-glutamine, and carnosine, which may serve as the diagnostic biomarkers of rumen acidosis of calves.
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Acidosis , Enfermedades de los Bovinos , Heces , Microbioma Gastrointestinal , Metabolómica , ARN Ribosómico 16S , Rumen , Animales , Bovinos , Rumen/microbiología , Acidosis/veterinaria , Acidosis/microbiología , Acidosis/sangre , ARN Ribosómico 16S/genética , Enfermedades de los Bovinos/microbiología , Enfermedades de los Bovinos/sangre , Masculino , Heces/microbiología , ADN Ribosómico/genética , Bacterias/clasificación , Bacterias/genética , Bacterias/aislamiento & purificación , Secuenciación de Nucleótidos de Alto Rendimiento , ADN Bacteriano/genéticaRESUMEN
In order to investigate the effect of glucono-δ-lactone (GDL) and different salt ions (Na+ and Ca2+) induction on the cold-set gels of bovine serum albumin (BSA)-arabinoxylan (AX), the gel properties and structure of BSA-AX cold-set gels were evaluated by analyzing the gel strength, water-holding capacity, thermal properties, and Fourier Transform Infrared (FTIR) spectra. It was shown that the best gel strength (109.15 g) was obtained when the ratio of BSA to AX was 15:1. The addition of 1 % GDL significantly improved the water-holding capacity, gel strength and thermal stability of the cold-set gels (p < 0.05), and the microstructure was smoother. Low concentrations of Na+ (3 mM) and Ca2+ (6 mM) significantly enhanced the hydrophobic interaction and hydrogen bonding between BSA and AX after acid induction, and the Na+-induced formation of a denser microstructure with a higher water-holding capacity (75.51 %). However, the excess salt ions disrupted the stable network structure of the cold-set gels and reduced their thermal stability and crystalline structure. The results of this study contribute to the understanding of the interactions between BSA and AX induced by GDL and salt ions, and provide a basis for designing hydrogels with different properties.
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Geles , Albúmina Sérica Bovina , Xilanos , Albúmina Sérica Bovina/química , Xilanos/química , Geles/química , Animales , Bovinos , Gluconatos/química , Lactonas/química , Agua/química , Sales (Química)/química , Iones/química , Calcio/química , Espectroscopía Infrarroja por Transformada de Fourier , TemperaturaRESUMEN
Targeting selective CO2 photoreduction into CH4 remains a challenge due to the sluggish reaction kinetics and poor hydrogenation ability of the unstable intermediate. Here, the active Pt2+ sites were photodeposited on the SrTiO3 photocatalyst, which was well demonstrated to manipulate the CH4 product selectivity. The results showed that SrTiO3 mainly yielded the CO (6.98 µmol g-1) product with poor CH4 (0.17 µmol g-1). With the Pt2+ modification, 100% CH4 selectivity could be obtained with an optimized yield rate of 8.07 µmol g-1. The prominent enhancement resulted from the following roles: (1) the strong electronic interaction between the Pt2+ cocatalyst and SrTiO3 could prompt efficient separation of the photoelectron-hole pairs. (2) The Pt2+ sites were active to capture and activate inert CO2 into HCO3- and CO32- species and allowed fast *COOH formation with the lowered reaction barrier. (3) Compared with SrTiO3, the formed *CO species could be captured tightly on the Pt2+ cocatalyst surface for generating the *CH2 intermediate by the following electron-proton coupling reaction, thus leading to the CH4 product with 100% selectivity.
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In contrast to the passive remote sensing of global CO2 column concentrations (XCO2), active remote sensing with a lidar enables continuous XCO2 measurements throughout the entire atmosphere in daytime and nighttime. The lidar could penetrate most cirrus and is almost unaffected by aerosols. Atmospheric environment monitoring satellite (AEMS, also named DQ-1) aerosol and carbon dioxide detection Lidar (ACDL) is a novel spaceborne lidar that implements a 1572â nm integrated path differential absorption (IPDA) method to measure the global XCO2 for the first time. In this study, special methods have been developed for ACDL data processing and XCO2 retrieval. The CO2 measurement data products of ACDL, including the differential absorption optical depth between the online and offline wavelengths, the integral weighting function, and XCO2, are presented. The results of XCO2 measurements over the period from 1st June 2022 to 30th June 2022 (first month data of ACDL) are analyzed to demonstrate the measurement capabilities of the spaceborne ACDL system.
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Voltage-gated sodium (NaV) channels are intimately involved in the generation and transmission of action potentials, and dysfunction of these channels may contribute to nervous system diseases, such as epilepsy, neuropathic pain, psychosis, autism, and cardiac arrhythmia. Many venom peptides selectively act on NaV channels. These include conotoxins, which are neurotoxins secreted by cone snails for prey capture or self-defense but which are also valuable pharmacological tools for the identification and/or treatment of human diseases. Typically, conotoxins contain two or three disulfide bonds, and these internal crossbraces contribute to conotoxins having compact, well defined structures and high stability. Of the conotoxins containing three disulfide bonds, some selectively target mammalian NaV channels and can block, stimulate, or modulate these channels. Such conotoxins have great potential to serve as pharmacological tools for studying the functions and characteristics of NaV channels or as drug leads for neurologic diseases related to NaV channels. Accordingly, discovering or designing conotoxins targeting NaV channels with high potency and selectivity is important. The amino acid sequences, disulfide bond connectivity, and three-dimensional structures are key factors that affect the biological activity of conotoxins, and targeted synthetic modifications of conotoxins can greatly improve their activity and selectivity. This review examines NaV channel-targeted conotoxins, focusing on their structures, activities, and designed modifications, with a view toward expanding their applications. SIGNIFICANCE STATEMENT: NaV channels are crucial in various neurologic diseases. Some conotoxins selectively target NaV channels, causing either blockade or activation, thus enabling their use as pharmacological tools for studying the channels' characteristics and functions. Conotoxins also have promising potential to be developed as drug leads. The disulfide bonds in these peptides are important for stabilizing their structures, thus leading to enhanced specificity and potency. Together, conotoxins targeting NaV channels have both immediate research value and promising future application prospects.
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Conotoxinas , Canales de Sodio Activados por Voltaje , Conotoxinas/farmacología , Conotoxinas/química , Humanos , Animales , Canales de Sodio Activados por Voltaje/metabolismo , Canales de Sodio Activados por Voltaje/química , Canales de Sodio Activados por Voltaje/efectos de los fármacos , Bloqueadores del Canal de Sodio Activado por Voltaje/farmacología , Bloqueadores del Canal de Sodio Activado por Voltaje/química , Bloqueadores del Canal de Sodio Activado por Voltaje/uso terapéutico , Secuencia de AminoácidosRESUMEN
α7 nicotinic acetylcholine receptors (nAChRs) are mainly distributed in the central nervous system (CNS), including the hippocampus, striatum, and cortex of the brain. The α7 nAChR has high Ca2+ permeability and can be quickly activated and desensitized, and is closely related to Alzheimer's disease (AD), epilepsy, schizophrenia, lung cancer, Parkinson's disease (PD), inflammation, and other diseases. α-conotoxins from marine cone snail venom are typically short, disulfide-rich neuropeptides targeting nAChRs and can distinguish various subtypes, providing vital pharmacological tools for the functional research of nAChRs. [Q1G, ΔR14]LvΙB is a rat α7 nAChRs selective antagonist, modified from α-conotoxin LvΙB. In this study, we utilized three types of fluorescein after N-Hydroxy succinimide (NHS) activation treatment: 6-TAMRA-SE, Cy3 NHS, and BODIPY-FL NHS, labeling the N-Terminal of [Q1G, ΔR14]LvΙB under weak alkaline conditions, obtaining three fluorescent analogs: LvIB-R, LvIB-C, and LvIB-B, respectively. The potency of [Q1G, ΔR14]LvΙB fluorescent analogs was evaluated at rat α7 nAChRs expressed in Xenopus laevis oocytes. Using a two-electrode voltage clamp (TEVC), the half-maximal inhibitory concentration (IC50) values of LvIB-R, LvIB-C, and LvIB-B were 643.3 nM, 298.0 nM, and 186.9 nM, respectively. The stability of cerebrospinal fluid analysis showed that after incubation for 12 h, the retention rates of the three fluorescent analogs were 52.2%, 22.1%, and 0%, respectively. [Q1G, ΔR14]LvΙB fluorescent analogs were applied to explore the distribution of α7 nAChRs in the hippocampus and striatum of rat brain tissue and it was found that Cy3- and BODIPY FL-labeled [Q1G, ΔR14]LvΙB exhibited better imaging characteristics than 6-TAMARA-. It was also found that α7 nAChRs are widely distributed in the cerebral cortex and cerebellar lobules. Taking into account potency, imaging, and stability, [Q1G, ΔR14]LvΙB -BODIPY FL is an ideal pharmacological tool to investigate the tissue distribution and function of α7 nAChRs. Our findings not only provide a foundation for the development of conotoxins as visual pharmacological probes, but also demonstrate the distribution of α7 nAChRs in the rat brain.
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Encéfalo , Conotoxinas , Xenopus laevis , Receptor Nicotínico de Acetilcolina alfa 7 , Animales , Receptor Nicotínico de Acetilcolina alfa 7/metabolismo , Conotoxinas/farmacología , Conotoxinas/química , Ratas , Encéfalo/metabolismo , Encéfalo/efectos de los fármacos , Oocitos/efectos de los fármacos , Oocitos/metabolismo , Antagonistas Nicotínicos/farmacología , Colorantes Fluorescentes , Ratas Sprague-Dawley , Masculino , FemeninoRESUMEN
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading cause of chronic liver disease that affects over 30% of the world's population. For decades, the heterogeneity of non-alcoholic fatty liver disease (NAFLD) has impeded our understanding of the disease mechanism and the development of effective medications. However, a recent change in the nomenclature from NAFLD to MASLD emphasizes the critical role of systemic metabolic dysfunction in the pathophysiology of this disease and therefore promotes the progress in the pharmaceutical treatment of MASLD. In this review, we focus on the mechanism underlying the abnormality of hepatic lipid metabolism in patients with MASLD, and summarize the latest progress in the therapeutic medications of MASLD that target metabolic disorders.
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Enfermedades Metabólicas , Enfermedad del Hígado Graso no Alcohólico , Humanos , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Metabolismo de los LípidosRESUMEN
An integrated path differential absorption (IPDA) lidar can accurately measure regional C O 2 weighted column average concentrations (X C O 2), which are crucial for understanding the carbon cycle in climate change studies. To verify the performance and data inversion methods of space-borne IPDA lidar, in July 2021, we conducted an airborne lidar validation experiment in Dunhuang, Gansu Province, China. An aircraft was equipped with a lidar system developed to measure X C O 2 and an in situ greenhouse gas analyzer (GGA). To minimize measurement errors, energy monitoring was optimized. The system bias error of the DAOD was determined by changing the laser output mode from the off/on to the on/on mode. The X C O 2 inversion results obtained through comparing the schemes of averaging signals before "log (logarithm)" and averaging after "log" indicate that the former performs better. The IPDA lidar measured X C O 2 over the validation site at 405.57 ppm, and both the IPDA lidar and GGA measured sudden changes in the C O 2 concentration. The assimilation data showed a similar trend according to the altitude to the data measured by the in situ instrument. A comparison of the mean X C O 2 derived from the GGA results and assimilation data with the IPDA lidar measurements showed biases of 0.80 and 1.12 ppm, respectively.
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Background: Diabetic peripheral neuropathy (DPN) contributes to disability and imposes heavy burdens, while subclinical DPN is lack of attention so far. We aimed to investigate the relationship between vitamin D and distinct subtypes of subclinical DPN in type 2 diabetes (T2DM) patients. Methods: This cross-sectional study included 3629 T2DM inpatients who undertook nerve conduction study to detect subclinical DPN in Zhongshan Hospital between March 2012 and December 2019. Vitamin D deficiency was defined as serum 25-hydroxyvitamin D (25(OH)D) level < 50 nmol/L. Results: 1620 (44.6%) patients had subclinical DPN and they were further divided into subgroups: distal symmetric polyneuropathy (DSPN) (n=685), mononeuropathy (n=679) and radiculopathy (n=256). Compared with non-DPN, DPN group had significantly lower level of 25(OH)D (P < 0.05). In DPN subtypes, only DSPN patients had significantly lower levels of 25(OH)D (36.18 ± 19.47 vs. 41.03 ± 18.47 nmol/L, P < 0.001) and higher proportion of vitamin D deficiency (78.54% vs. 72.18%, P < 0.001) than non-DPN. Vitamin D deficiency was associated with the increased prevalence of subclinical DPN [odds ratio (OR) 1.276, 95% confidence interval (CI) 1.086-1.501, P = 0.003] and DSPN [OR 1. 646, 95% CI 1.31-2.078, P < 0.001], independent of sex, age, weight, blood pressure, glycosylated hemoglobin, T2DM duration, calcium, phosphorus, parathyroid hormone, lipids and renal function. The association between vitamin D deficiency and mononeuropathy or radiculopathy was not statistically significant. A negative linear association was observed between 25(OH)D and subclinical DSPN. Vitamin D deficiency maintained its significant association with subclinical DSPN in all age groups. Conclusions: Vitamin D deficiency was independently associated with subclinical DSPN, rather than other DPN subtypes.
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Diabetes Mellitus Tipo 2 , Neuropatías Diabéticas , Mononeuropatías , Deficiencia de Vitamina D , Humanos , Factores de Riesgo , Neuropatías Diabéticas/epidemiología , Neuropatías Diabéticas/etiología , Estudios Transversales , Deficiencia de Vitamina D/complicaciones , Deficiencia de Vitamina D/epidemiología , Mononeuropatías/complicacionesRESUMEN
OBJECTIVES: To evaluate the effectiveness and safety of rivaroxaban anticoagulation in COVID-19 patients. METHODS: PubMed, Embase, Cochrane Library electronic databases, and ClinicalTrials.gov were searched to identify all relevant randomized controlled trial studies from December 2019 to July 2023. RESULTS: A total of 6 randomized controlled trials, which included a total of 3323 patients, were considered for evaluation. Overall, short-term all-cause mortality and hospitalization rates were not significantly different between the rivaroxaban and control groups. Thrombotic events were significantly reduced in the rivaroxaban prophylaxis group compared to the placebo control group. However, the reduction in thrombotic events was not significantly different between rivaroxaban therapy and heparin or low-molecular-weight heparin (LMWH). Rivaroxaban prophylaxis and the therapeutic dose may be associated with a higher rate of overall bleeding rate, but major bleeding rates did not differ substantially. CONCLUSION: Rivaroxaban may reduce thrombotic events in COVID-19 patients, but it does not appear to have an advantage over heparin or LMWH, and it may increase the risk of bleeding.INPLASY Reg. No.: INPLASY 202370097.
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Anticoagulantes , Tratamiento Farmacológico de COVID-19 , COVID-19 , Hemorragia , Ensayos Clínicos Controlados Aleatorios como Asunto , Rivaroxabán , Humanos , Rivaroxabán/uso terapéutico , Rivaroxabán/efectos adversos , Anticoagulantes/uso terapéutico , Anticoagulantes/efectos adversos , COVID-19/complicaciones , Hemorragia/inducido químicamente , Heparina de Bajo-Peso-Molecular/uso terapéutico , Heparina de Bajo-Peso-Molecular/efectos adversos , Inhibidores del Factor Xa/uso terapéutico , Inhibidores del Factor Xa/efectos adversos , Trombosis/prevención & control , Trombosis/etiología , Resultado del Tratamiento , Heparina/uso terapéutico , Heparina/efectos adversos , SARS-CoV-2RESUMEN
This study prepared and characterized sodium alginate and carrageenan (SAC) composite films incorporated with peanut shell flavonoids (PSFs). PSFs compound identification research was implemented. The physicochemical features of PSFs-SAC composite films and their ability to preserve chilled pork in a 4 °C refrigerator were determined. PSFs consist of luteolin, eriodictyol, 5,7-dihydroxychromone, and 8 other components. They significantly improved the mechanical properties, barrier properties, thermal stability, and antioxidant properties of SAC composite films (P < 0.05). PSFs were also responsible for increasing the density of the film structure between the sodium alginate and carrageenan molecules. During storage, compared with the control group, the prepared PSFs-SAC composite films did not allow the total viable count (TVC), pH and total volatile base nitrogen (TVB-N) of the chilled pork to increase rapidly. Further, they were able to inhibit lipid oxidation more effectively (P < 0.05). For these reasons, the use of the PSFs-SAC composite films prolonged shelf life of chilled pork from 6 days to the 12 days. Therefore, PSFs-SAC composite films are expected to be used as bioactive substances in food preservation.
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Alginatos , Antioxidantes , Arachis , Carragenina , Flavonoides , Conservación de Alimentos , Antioxidantes/química , Antioxidantes/farmacología , Alginatos/química , Flavonoides/química , Flavonoides/farmacología , Carragenina/química , Conservación de Alimentos/métodos , Animales , Arachis/química , Porcinos , Embalaje de Alimentos/métodos , Carne de Cerdo/análisis , FríoRESUMEN
Microplastics (MPs) pollution's impact on the marine ecosystem is widely recognized. This study compared the effects of polyethylene (PE) and polyethylene terephthalate (PET) on two bivalve species, Ruditapes philippinarum (clam) and Chlamys farreri (scallop), at two particle concentrations (10 and 1000 µg/L). MPs were found in the digestive glands and gills of both species. Although clearance rates showed no significant changes, exposure to different MPs caused oxidative stress, energy disruption, and lipid metabolism disorders in both clam and scallop. Histopathological damage was observed in gills and digestive glands. IBR values indicated increasing toxicity with concentration, with PET being more toxic than PE. WOE model suggested increasing hazard with concentration, highlighting higher PET toxicity on clam digestive glands. In contrast, PE hazard increased in gills, showing different species responses. R. philippinarum exhibited higher sensitivity to MPs than C. farreri, providing insights for assessing ecological risk under realistic conditions and stress conditions.
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Bivalvos , Pectinidae , Contaminantes Químicos del Agua , Animales , Microplásticos/toxicidad , Plásticos/metabolismo , Ecosistema , Tereftalatos Polietilenos , Polietileno/metabolismo , Contaminantes Químicos del Agua/análisisRESUMEN
Purpose: We aim to explore the predictive values of homeobox gene A-antisense transcript 3 (HOXA-AS3), cystatin 6 (CST6), and chromobox homolog 4 (CBX4) expressions in cancer tissues for the recurrence of early colon cancer after surgery. Patients and Methods: A total of 136 patients who received surgery from January 2020 to January 2021 were enrolled and followed up for 24 months to observe the recurrence after surgery, based on which they were assigned into recurrence and non-recurrence groups. All patients underwent a histopathological examination on admission. Results: The recurrence group had a lower degree of differentiation as well as a higher HOXA-AS3 level and CST6 and CBX4 expression scores than those of the non-recurrence group (P<0.05). HOXA-AS3 level, CST6 expression score, and CBX4 expression score were risk factors for the recurrence of early colon cancer after surgery [odds ratio (OR)>1, P<0.05]. The receiver operating characteristic curve analysis showed that the areas under the curves of HOXA-AS3 level, CST6 expression score, CBX4 expression score, and their combination for predicting recurrence were 0.909 [95% confidence interval (95% CI): 0.785-1.000], 0.819 (95% CI: 0.690-0.948), 0.794 (95% CI: 0.663-0.926), and 0.942 (95% CI: 0.882-1.000), respectively. Conclusion: The expressions of HOXA-AS3, CST6, and CBX4 in cancer tissues have close correlations with the recurrence of early colon cancer after surgery and are thus of high predictive values.
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Topologically associating domains (TADs) are critical structural units in three-dimensional genome organization of mammalian genome. Dynamic reorganizations of TADs between health and disease states are associated with essential genome functions. However, computational methods for identifying reorganized TADs are still in the early stages of development. Here, we present DiffDomain, an algorithm leveraging high-dimensional random matrix theory to identify structurally reorganized TADs using high-throughput chromosome conformation capture (Hi-C) contact maps. Method comparison using multiple real Hi-C datasets reveals that DiffDomain outperforms alternative methods for false positive rates, true positive rates, and identifying a new subtype of reorganized TADs. Applying DiffDomain to Hi-C data from different cell types and disease states demonstrates its biological relevance. Identified reorganized TADs are associated with structural variations and epigenomic changes such as changes in CTCF binding sites. By applying to a single-cell Hi-C data from mouse neuronal development, DiffDomain can identify reorganized TADs between cell types with reasonable reproducibility using pseudo-bulk Hi-C data from as few as 100 cells per condition. Moreover, DiffDomain reveals differential cell-to-population variability and heterogeneous cell-to-cell variability in TADs. Therefore, DiffDomain is a statistically sound method for better comparative analysis of TADs using both Hi-C and single-cell Hi-C data.
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Cromosomas , Genoma , Animales , Ratones , Reproducibilidad de los Resultados , Sitios de Unión , Conformación Molecular , Cromatina/genética , Mamíferos/genéticaRESUMEN
α6ß4* nicotinic acetylcholine receptor (nAChR) (* represents the possible presence of additional subunits) is mainly distributed in the central and peripheral nervous system and is associated with neurological diseases, such as neuropathic pain; however, the ability to explore its function and distribution is limited due to the lack of pharmacological tools. As one of the analogs of α-conotoxin (α-CTx) LvIC from Conus lividus, [D1G, Δ14Q]LvIC (Lv) selectively and potently blocks α6/α3ß4 nAChR (α6/α3 represents a chimera). Here, we synthesized three fluorescent analogs of Lv by connecting fluorescent molecules 6-carboxytetramethylrhodamine succinimidyl ester (6-TAMRA-SE, R), Cy3 NHS ester (Cy3, C) and BODIPY-FL NHS ester (BDP, B) to the N-terminus of the peptide and obtained Lv-R, Lv-C, and Lv-B, respectively. The potency and selectivity of three fluorescent peptides were evaluated using two-electrode voltage-clamp recording on nAChR subtypes expressed in Xenopus laevis oocytes, and the potency and selectivity of Lv-B were almost maintained with the half-maximal inhibition (IC50) of 64 nM. Then, we explored the stability of Lv-B in artificial cerebrospinal fluid and stained rat brain slices with Lv-B. The results indicated that the stability of Lv-B was slightly improved compared to that of native Lv. Additionally, we detected the distribution of the α6ß4* nAChR subtype in the cerebral cortex using green fluorescently labeled peptide and fluorescence microscopy. Our findings not only provide a visualized pharmacological tool for exploring the distribution of the α6ß4* nAChR subtype in various situ tissues and organs but also extend the application of α-CTx [D1G, Δ14Q]LvIC to demonstrate the involvement of α6ß4 nAChR function in pathophysiology and pharmacology.
Asunto(s)
Conotoxinas , Caracol Conus , Receptores Nicotínicos , Ratas , Animales , Receptores Nicotínicos/química , Conotoxinas/química , Conotoxinas/farmacología , Caracol Conus/química , Péptidos/química , ÉsteresRESUMEN
Inter-organ crosstalk has gained increasing attention in recent times; however, the underlying mechanisms remain unclear. In this study, we elucidate an endocrine pathway that is regulated by skeletal muscle interferon regulatory factor (IRF) 4, which manipulates liver pathology. Skeletal muscle specific IRF4 knockout (F4MKO) mice exhibited ameliorated hepatic steatosis, inflammation, and fibrosis, without changes in body weight, when put on a nonalcoholic steatohepatitis (NASH) diet. Proteomics analysis results suggested that follistatin-like protein 1 (FSTL1) may constitute a link between muscles and the liver. Dual luciferase assays showed that IRF4 can transcriptionally regulate FSTL1. Further, inducing FSTL1 expression in the muscles of F4MKO mice is sufficient to restore liver pathology. In addition, co-culture experiments confirmed that FSTL1 plays a distinct role in various liver cell types via different receptors. Finally, we observed that the serum FSTL1 level is positively correlated with NASH progression in humans. These data indicate a signaling pathway involving IRF4-FSTL1-DIP2A/CD14, that links skeletal muscle cells to the liver in the pathogenesis of NASH.