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1.
Artículo en Inglés | MEDLINE | ID: mdl-39401373

RESUMEN

During the utilization, blending, transportation, and storage, a significant amount of volatile organic compounds (VOCs) are released from inks, posing risks to both human health and the ecological environment. This study sought to identify the types and structures of VOCs released from four types of solvent-based inks (referred to as CAB, PVB, AKR, and Rs inks) in high-temperature settings and to assess the bioaccumulation factors, developmental toxicity, and acute toxicity of these released VOCs. The findings revealed that all tested inks released substantial amounts of VOCs in high-temperature environments. CAB and PVB inks released fewer types of VOCs with relatively smaller molecular weights, primarily with carboxylic acid groups and hydroxyl groups, while AKR and Rs inks released more types of VOCs with larger molecular weights, including polycyclic aromatic hydrocarbons. Toxicity analysis indicated that although the primary VOCs released from CAB and PVB ink displayed some developmental toxicity, their bioaccumulation factors were below 100. The principal VOCs from AKR ink did not exhibit developmental toxicity. Conversely, the predominant VOCs from Rs ink not only demonstrated developmental toxicity but also had bioaccumulation factors exceeding 100. Additionally, the VOCs released from CAB, PVB, and AKR inks exhibited stronger acute toxicity to luminescent bacteria, while those from Rs ink showed greater acute toxicity to fish. These results offer a scientific foundation for the safe usage of inks and environmental conservation.

2.
Artículo en Inglés | MEDLINE | ID: mdl-39412395

RESUMEN

The newly discovered two-dimensional (2D) ß-TeO2 possesses extraordinarily high p-type carrier mobility and demonstrates immense potential in the electronics field. However, current research on its p-type conductivity mechanisms and the modifications of element doping remains relatively insufficient. In this study, the intrinsic point defects and extrinsic element doping in monolayer ß-TeO2 are comprehensively analyzed to probe the potential sources of the intrinsic p-type conductivity and the extrinsic p-type doping possibility in 2D ß-TeO2 through hybrid density functional calculations. Our results reveal that the vacancy defects with low formation energies have deep transition levels and thus cannot be used as sources of unintentional p-type conductivity in 2D ß-TeO2. The investigations and discussions via Group V element doping modifications in 2D ß-TeO2 indicate that bismuth (Bi) doping can easily and significantly enhance the p-type conductivity of 2D ß-TeO2 under the presence of O-rich, which can be achieved experimentally. Furthermore, Bi doping can significantly increase carrier mobility without seriously affecting the electronic structure. The finding shows that the Bi element is an ideal dopant candidate for a p-type modification in 2D ß-TeO2. Our calculations pave an alternative strategy to achieve the realization of superior p-type conductivity in 2D ß-TeO2.

3.
Materials (Basel) ; 17(17)2024 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-39274673

RESUMEN

Ti-6Al-4V titanium alloy is known as one of the most difficult metallic materials to machine, and the machined surface residual stress distribution significantly affects properties such as static strength, fatigue strength, corrosion resistance, etc. This study utilized finite element software Abaqus 2020 to simulate the two-step cutting process of titanium alloy, incorporating stages of cooling, unloading, and de-constraining of the workpiece. The chip morphology and cutting force obtained from orthogonal cutting tests were used to validate the finite element model. Results from the orthogonal cutting simulations revealed that with increasing cutting speed and the tool rake angle, the residual stress undergoes a transition from compressive to tensile stress. To achieve greater residual compressive stress during machining, it is advisable to opt for a negative rake angle coupled with a lower cutting speed. Additionally, in two-step machining of titanium alloy, the initial cutting step exerts a profound influence on the subsequent cutting step, thereby shortening the evolution time of the Mises stress, equivalent plastic strain, and stiffness damage equivalent in the subsequent cutting step. These results contribute to optimizing titanium alloy machining processes by providing insights into controlling residual stress, ultimately enhancing product quality and performance of structural part of titanium alloy.

4.
Sci Rep ; 14(1): 22414, 2024 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-39341900

RESUMEN

Contemporary large-scale and systematic agricultural operations demand the collaborative efforts of multiple agricultural machines with distinct functionalities. However, the failure of a single agricultural machine during collaborative operations jeopardizes the entire undertaking. To address this challenge, this paper proposes a multi-machine collaborative dynamic job allocation method based on the improved ant colony algorithm. Initially, the improved ant colony algorithm is employed to determine the optimal solution for harvester scheduling. This solution is then fed into the data conversion algorithm to acquire the necessary unloading point information for transport vehicle scheduling. Subsequently, the improved ant colony algorithm is once again utilized to optimize the transport vehicle scheduling. In cases of agricultural machinery failure or changes in the operating environment, two distinct methods are employed based on the situation. The first involves double-layer rescheduling of both harvester and transport vehicles, while the second employs single-layer rescheduling exclusively for the transport vehicles, yielding the respective rescheduling results. The outcomes demonstrate that the proposed solution method effectively identifies the current optimal scheduling plan for both the harvester and transport vehicle in the event of malfunctions. Moreover, under the premise that the unproductive waiting time of the harvester is reduced to zero, and the number of transport vehicles is minimized, it achieves the minimization of operating time cost and transportation cost. This method exhibits significant potential for seamless integration into the practical application of unmanned farms, providing a foundation for addressing scheduling and management challenges in multi-agricultural machinery collaborative operations within complex farmland operating environments.

5.
Toxicol Sci ; 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39302723

RESUMEN

Bile acid (BA) signaling dysregulation is an important etiology for the development of Metabolic Dysfunction-associated Steatotic Liver Disease (MASLD). As diverse signaling molecules synthesized in the liver by pathways initiated with CYP7A1 and CYP27A1, BAs are endogenous modulators of farnesoid x receptor (FXR). FXR activation is crucial in maintaining BA homeostasis, regulating lipid metabolism, and suppressing inflammation. Additionally, BAs interact with membrane receptors and gut microbiota to regulate energy expenditure and intestinal health. Complex modulation of BAs in vivo and the lack of suitable animal models impede our understanding of the functions of individual BAs, especially during MASLD development. Previously, we determined that acute feeding of individual BAs differentially affects lipid, inflammation, and oxidative stress pathways in a low-BA mouse model, Cyp7a1/Cyp27a1 double knockout (DKO) mice. Currently, we investigated to what degree that cholic acid (CA), deoxycholic acid (DCA) or ursodeoxycholic acid (UDCA) at physiological concentrations impact MASLD development in DKO mice. The results showed that these three BAs varied in ability to activate hepatic and intestinal FXR, disrupt lipid homeostasis, and modulate inflammation and fibrosis. Additionally, UDCA activated intestinal FXR in these low-BA mice. Significant alterations in lipid uptake and metabolism in DKO mice following CA and DCA feeding indicate differences in cholesterol and lipid handling across genotypes. Overall, the DKO were less susceptible to weight gain, but more susceptible to MASH diet induced inflammation and fibrosis on CA and DCA supplement, while WT mice were more vulnerable to CA-induced fibrosis on control diet.

6.
Technol Cancer Res Treat ; 23: 15330338241273160, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39099463

RESUMEN

Introduction: The independent diagnostic value of inflammatory markers neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) and the diagnostic efficacy of NLR, derived neutrophil to lymphocyte ratio (dNLR), PLR, and lymphocyte-to-monocyte ratio (LMR) in glioma cases remain unclear. We investigated the correlation of preoperative peripheral blood inflammatory markers with pathological grade, Ki-67 Proliferation Index, and IDH-1 gene phenotype in patients with glioma, focusing on tumor grade and prognosis. Methods: We retrospectively analyzed the clinical, pathological, and laboratory data of 334 patients with glioma with varying grades and 345 with World Health Organization (WHO I) meningioma who underwent initial surgery at the Affiliated Hospital of Jining Medical University from December 2019 to December 2021. The diagnostic value of peripheral blood inflammatory markers for glioma was investigated. Results: The proportion of men smoking and drinking was significantly higher in the glioma group than in the meningioma group (P < .05); in contrast, the age and body mass index (Kg/m2) were significantly lower in the glioma group (P = .01). Significant differences were noted in the pathological grade (WHO II, III, and IV), Ki-67 Proliferation Index, and peripheral blood inflammatory markers such as lymphocyte median, NLR, dNLR, and PLR between the groups (P < .05). No significant correlation existed between peripheral blood inflammatory factors and IDH-1 gene mutation status or tumor location in patients with glioma (P > .05). LMR, NLR, dNLR, and PLR, varied significantly among different glioma types (P < .05). White blood cell (WBC) count, neutrophil, NLR, and dNLR correlated positively with glioma risk. Further, WBC, neutrophil, NLR, dNLR, and LMR had a high diagnostic efficiency. Conclusion: Peripheral blood inflammatory markers, serving as noninvasive biomarkers, offer high sensitivity and specificity for diagnosing glioma, differentiating it from meningioma, diagnosing GBM, and distinguishing GBM from low-grade glioma. These markers may be implemented as routine screening tools.


Asunto(s)
Biomarcadores de Tumor , Neoplasias Encefálicas , Glioma , Clasificación del Tumor , Neutrófilos , Humanos , Glioma/patología , Glioma/sangre , Glioma/cirugía , Glioma/diagnóstico , Masculino , Femenino , Pronóstico , Persona de Mediana Edad , Biomarcadores de Tumor/sangre , Neutrófilos/patología , Adulto , Estudios Retrospectivos , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/sangre , Neoplasias Encefálicas/cirugía , Neoplasias Encefálicas/diagnóstico , Anciano , Linfocitos/patología , Periodo Preoperatorio , Inflamación/patología , Inflamación/sangre , Plaquetas/patología , Curva ROC
7.
J Am Soc Echocardiogr ; 37(9): 894-905, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38761987

RESUMEN

BACKGROUND: The utility of radionuclide myocardial perfusion imaging including positron emission tomography (PET) for diagnosing mental stress-induced myocardial ischemia (MSIMI) is clinically restricted. This study aims to assess the diagnostic performance of novel echocardiographic techniques, including automated strain and quantitative myocardial contrast echocardiography (MCE) with dedicated software and deep neural network model, for MSIMI detection. The secondary objective was to explore the correlation between changes in myocardial blood flow and MSIMI. METHODS: Seventy-two female patients ages 18 to 75 with angina and nonobstructive coronary artery disease (ANOCA) and 23 healthy controls were prospectively recruited. Both echocardiography with contrast agent and PET imaging were performed during structured mental stress testing. Mental stress-induced myocardial ischemia was defined as a summed difference score ≥3 on PET. Echocardiographic parameters including left ventricular global longitudinal strain, ß, and A × ß were obtained, and their trends during mental stress testing were observed. ΔGLS was defined as the ratio of difference between global longitudinal strain values at stress and rest to the rest data. ß reserve and A×ß reserve were respectively calculated. RESULTS: Thirty-two ANOCA patients (44%) and 1 control (4%) were diagnosed with MSIMI (P < .01). For ANOCA patients with MSIMI, left ventricular GLS, ß, and A × ß declined to varied extents during mental stress testing compared with those without MSIMI and the controls (P < .05). Bland-Altman plots demonstrated good consistency between ß reserve and A × ß reserve output by the deep neural network model and iMCE software. Receiver operating characteristic curve analyses showed that ΔGLS, ß reserve, and A × ß reserve demonstrated favorable ability to predict MSIMI, especially the combination of A × ß reserve using iMCE analysis and ΔGLS (area under the curve, 0.94; sensitivity, 83%; specificity, 97%). CONCLUSIONS: Novel technologies in echocardiography exhibit the potential to be a clinical alternative to cardiac PET for effectively detecting MSIMI. Attenuated myocardial blood flow response during structured mental stress testing was correlated with MSIMI, providing a reasonable explanation for the chest discomfort persisting in ANOCA women.


Asunto(s)
Enfermedad de la Arteria Coronaria , Ecocardiografía , Isquemia Miocárdica , Estrés Psicológico , Humanos , Femenino , Persona de Mediana Edad , Estrés Psicológico/fisiopatología , Estrés Psicológico/complicaciones , Enfermedad de la Arteria Coronaria/fisiopatología , Enfermedad de la Arteria Coronaria/complicaciones , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/diagnóstico , Adulto , Ecocardiografía/métodos , Isquemia Miocárdica/fisiopatología , Isquemia Miocárdica/diagnóstico por imagen , Isquemia Miocárdica/complicaciones , Isquemia Miocárdica/diagnóstico , Anciano , Estudios Prospectivos , Adolescente , Adulto Joven , Imagen de Perfusión Miocárdica/métodos , Tomografía de Emisión de Positrones/métodos , Medios de Contraste , Tensión Longitudinal Global
8.
Hepatol Commun ; 8(6)2024 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-38780301

RESUMEN

BACKGROUND: Vertical sleeve gastrectomy (SGx) is a type of bariatric surgery to treat morbid obesity and metabolic dysfunction-associated steatotic liver disease (MASLD). The molecular mechanisms of SGx to improve MASLD are unclear, but increased bile acids (BAs) and FGF19 (mouse FGF15) were observed. FGF15/19 is expressed in the ileum in response to BAs and is critical in not only suppressing BA synthesis in the liver but also promoting energy expenditure. We hypothesized the reduction of obesity and resolution of MASLD by SGx may be mediated by FGF15/19. METHODS: First, we conducted hepatic gene expression analysis in obese patients undergoing SGx, with the results showing increased expression of FGF19 in obese patients' livers. Next, we used wild-type and intestine-specific Fgf15 knockout mice (Fgf15ile-/-) to determine the effects of FGF15 deficiency on improving the metabolic effects. RESULTS: SGx improved metabolic endpoints in both genotypes, evidenced by decreased obesity, improved glucose tolerance, and reduced MASLD progression. However, Fgf15ile-/- mice showed better improvement compared to wild-type mice after SGx, suggesting that other mediators than FGF15 are also responsible for the beneficial effects of FGF15 deficiency. Further gene expression analysis in brown adipose tissue suggests increased thermogenesis. CONCLUSIONS: FGF15 deficiency, the larger BA pool and higher levels of secondary BAs may increase energy expenditure in extrahepatic tissues, which may be responsible for improved metabolic functions following SGx.


Asunto(s)
Hígado Graso , Factores de Crecimiento de Fibroblastos , Gastrectomía , Obesidad Mórbida , Adulto , Animales , Femenino , Humanos , Masculino , Ratones , Persona de Mediana Edad , Cirugía Bariátrica , Ácidos y Sales Biliares/metabolismo , Hígado Graso/genética , Hígado Graso/metabolismo , Factores de Crecimiento de Fibroblastos/genética , Factores de Crecimiento de Fibroblastos/metabolismo , Gastrectomía/métodos , Hígado/metabolismo , Ratones Endogámicos C57BL , Ratones Noqueados , Obesidad Mórbida/cirugía , Obesidad Mórbida/genética , Obesidad Mórbida/metabolismo
9.
Sci Total Environ ; 932: 172878, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38697541

RESUMEN

Excessive phosphorus (P) in eutrophic water induces cyanobacterial blooms that aggravate the burden of in-situ remediation measures. In order to ensure better ecological recovery, Flock & Lock technique has been developed to simultaneously sink cyanobacteria and immobilize P but requires a combination of flocculent and P inactivation agent. Here we synthesized a novel lanthanum-modified pyroaurite (LMP), as an alternative for Flock & Lock of cyanobacteria and phosphorus at the background of rich humic acid and suspended solids. LMP shows a P adsorption capacity of 36.0 mg/g and nearly 100 % removal of chlorophyll-a (Chl-a), turbidity, UV254 and P at a dosage (0.3 g/L) much lower than the commercial analogue (0.5 g/L). The resultant sediment (98.2 % as immobile P) exhibits sound stability without observable release of P or re-growth of cyanobacteria over a 50-day incubation period. The use of LMP also constrains the release of toxic microcystins to 1.4 µg/L from the sunk cyanobacterial cells, outperforming the commonly used polyaluminum chloride (PAC). Similar Flock & Lock efficiency could also be achieved in real eutrophic water. The outstanding Flock & Lock performance of LMP is attributable to the designed La modification. During LMP treatment, La acts as not only a P binder by formation of LaPO4, but also a coagulant to create a synergistic effect with pyroaurite. The controlled hydrolysis of surface La(III) over pyroaurite aided the possible formation of La(III)-pyroaurite networking structure, which significantly enhanced the Flock & Lock process through adsorption, charge neutralization, sweep flocculation and entrapment. In the end, the preliminary economic analysis is performed. The results demonstrate that LMP is a versatile and cost-effective agent for in-situ remediation of eutrophic waters.


Asunto(s)
Eutrofización , Lantano , Microcystis , Fósforo , Lantano/química , Contaminantes Químicos del Agua/análisis , Hidróxido de Aluminio/química , Adsorción , Restauración y Remediación Ambiental/métodos
10.
Cell Rep ; 43(4): 114088, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38602878

RESUMEN

Pancreatic ductal adenocarcinoma (PDAC) features an immunosuppressive tumor microenvironment (TME) that resists immunotherapy. Tumor-associated macrophages, abundant in the TME, modulate T cell responses. Bone marrow stromal antigen 2-positive (BST2+) macrophages increase in KrasG12D/+; Trp53R172H/+; Pdx1-Cre mouse models during PDAC progression. However, their role in PDAC remains elusive. Our findings reveal a negative correlation between BST2+ macrophage levels and PDAC patient prognosis. Moreover, an increased ratio of exhausted CD8+ T cells is observed in tumors with up-regulated BST2+ macrophages. Mechanistically, BST2+ macrophages secrete CXCL7 through the ERK pathway and bind with CXCR2 to activate the AKT/mTOR pathway, promoting CD8+ T cell exhaustion. The combined blockade of CXCL7 and programmed death-ligand 1 successfully decelerates tumor growth. Additionally, cGAS-STING pathway activation in macrophages induces interferon (IFN)α synthesis leading to BST2 overexpression in the PDAC TME. This study provides insights into IFNα-induced BST2+ macrophages driving an immune-suppressive TME through ERK-CXCL7 signaling to regulate CD8+ T cell exhaustion in PDAC.


Asunto(s)
Antígeno 2 del Estroma de la Médula Ósea , Proteínas Ligadas a GPI , Interferón-alfa , Neoplasias Pancreáticas , Macrófagos Asociados a Tumores , Animales , Femenino , Humanos , Ratones , Antígenos CD/metabolismo , Carcinoma Ductal Pancreático/patología , Carcinoma Ductal Pancreático/inmunología , Carcinoma Ductal Pancreático/metabolismo , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Línea Celular Tumoral , Proteínas Ligadas a GPI/metabolismo , Tolerancia Inmunológica , Interferón-alfa/metabolismo , Ratones Endogámicos C57BL , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/inmunología , Neoplasias Pancreáticas/metabolismo , Transducción de Señal , Microambiente Tumoral/inmunología , Macrófagos Asociados a Tumores/metabolismo , Macrófagos Asociados a Tumores/inmunología , Macrófagos Asociados a Tumores/patología
11.
Nanotechnology ; 35(24)2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38471140

RESUMEN

The prevailing theoretical frameworks indicate that depending on the growth conditions, the Bi2WO6(001) surface can manifest in three distinct terminations-DL-O-Bi (DL: double layers), O-Bi, and O-W. In this study, we conduct a comprehensive examination of the interplay between these terminations on Bi2WO6(001) and the 1I-terminated BiOI(001) facet, especially focusing on their impact on the photocatalytic activity of Bi2WO6/BiOI heterostructure, applying hybrid functional calculations. The models formulated for this research are designated as Bi2WO6(O-Bi)/BiOI(1I), Bi2WO6(DL-O-Bi)/BiOI(1I), and Bi2WO6(O-W)/BiOI(1I). Our findings reveal that Bi2WO6(O-Bi)/BiOI(1I) shows a type II band alignment, which facilitates the spatial separation of photo-generated electrons and holes. Notably, the Bi2WO6(DL-O-Bi)/BiOI(1I) configuration has the lowest binding energy and results in an S-scheme (or Step-scheme) heterostructure. In contrast to the type II heterostructure, this particular configuration demonstrates enhanced photocatalytic efficiency due to improved photo-generated carrier separation, augmented oxidation capability, and better visible-light absorption. Conversely, Bi2WO6(O-W)/BiOI(1I) presents a type I projected band structure, which is less conducive for the separation of photo-generated electron-hole pairs. In summation, this investigation points out that one could significantly refine the photocatalytic efficacy of not only Bi2WO6/BiOI but also other heterostructure photocatalysts by modulating the coupling of different terminations via precise crystal synthesis or growth conditions.

13.
Phys Chem Chem Phys ; 26(14): 10723-10736, 2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38512329

RESUMEN

Given some current speculations and controversies regarding the type of BiOCl/Bi2S3-(001) heterostructure in experiments, it is of great importance to clarify these controversies and further explain the relevant experimental results. In this work, based on first-principles hybrid density functional calculations, it is verified that the BiOCl/Bi2S3-(001) heterostructure is a direct Z-scheme photocatalyst with high photo-generated carrier separation efficiency and strong redox ability that can react with O2 and OH- to produce photocatalytic active species of superoxide ions (˙O2-) and hydroxyl radicals (˙OH), respectively. This is consistent with the experimental findings and explains the excellent photocatalytic performance of the BiOCl/Bi2S3-(001) heterostructure in experiments. Besides, excitingly, it is found that the optical absorption, built-in electric field intensity, interlayer recombination probability, hydrogen evolution reaction ability, and the difference in electron-hole mobility are further enhanced via S vacancy introduction in BiOCl/Bi2S3-(001). Therefore, the significant roles of S vacancy in further improving the photocatalytic properties of the BiOCl/Bi2S3-(001) heterostructure are profoundly revealed. This work can provide valuable theoretical insights for designing the superior direct Z-scheme BiOCl/VS-Bi2S3-(001) heterostructure with promising photocatalytic properties.

14.
Toxicol Sci ; 199(2): 316-331, 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38526215

RESUMEN

Bile acids (BAs) are signaling molecules synthesized in the liver initially by CYP7A1 and CYP27A1 in the classical and alternative pathways, respectively. BAs are essential for cholesterol clearance, intestinal absorption of lipids, and endogenous modulators of farnesoid x receptor (FXR). FXR is critical in maintaining BA homeostasis and gut-liver crosstalk. Complex reactions in vivo and the lack of suitable animal models impede our understanding of the functions of individual BAs. In this study, we characterized the in vivo effects of three-day feeding of cholic acid (CA), deoxycholic acid (DCA), or ursodeoxycholic acid (UDCA) at physiological/non-hepatotoxic concentrations in a novel low-BA mouse model (Cyp7a1-/-/Cyp27a1-/-, DKO). Liver injury, BA levels and composition and BA signaling by the FXR-fibroblast growth factor 15 (FGF15) axis were determined. Overall, higher basal inflammation and altered lipid metabolism in DKO mice might be associated with low BAs. CA, DCA, and UDCA feeding activated FXR signals with tissue specificity. Dietary CA and DCA similarly altered tissue BA profiles to be less hydrophobic, while UDCA promoted a more hydrophobic tissue BA pool with the profiles shifted toward non-12α-OH BAs and secondary BAs. However, UDCA did not offer any overt protective effects as expected. These findings allow us to determine the precise effects of individual BAs in vivo on BA-FXR signaling and overall BA homeostasis in liver physiology and pathologies.


Asunto(s)
Ácidos y Sales Biliares , Ácido Cólico , Factores de Crecimiento de Fibroblastos , Hígado , Ratones Noqueados , Receptores Citoplasmáticos y Nucleares , Animales , Receptores Citoplasmáticos y Nucleares/metabolismo , Receptores Citoplasmáticos y Nucleares/genética , Ácidos y Sales Biliares/metabolismo , Hígado/metabolismo , Hígado/efectos de los fármacos , Factores de Crecimiento de Fibroblastos/metabolismo , Factores de Crecimiento de Fibroblastos/genética , Ácido Cólico/metabolismo , Masculino , Ratones Endogámicos C57BL , Ácido Desoxicólico/toxicidad , Colestanotriol 26-Monooxigenasa/genética , Colestanotriol 26-Monooxigenasa/metabolismo , Ratones , Ácido Ursodesoxicólico/farmacología , Transducción de Señal/efectos de los fármacos , Colesterol 7-alfa-Hidroxilasa
15.
Microsc Res Tech ; 87(5): 948-956, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38174664

RESUMEN

Agitated saline microbubbles (MBs) are a common contrast agent for determining right-to-left shunt (RLS) by the contrast transcranial Doppler (c-TCD). The size of the generated bubbles is not standardized in clinical practice. MBs were generated using the recommended manual method by reciprocating motion through two syringes. The bubble size distributions (BSD) were measured using the microscopic shadow imaging technique. The results show that the diameter of MBs is mainly distributed between 10 and 100 µm, the mean bubble size is between 21 and 34 µm, the Sauter mean diameter (D32) is primarily between 50 and 300 µm, and the standard deviation (SD) is between 6 and 17 µm in 80 experiments. It provides a more accurate basis for the recommended manual method instability. The high variance values of the BSD indicate that the manual method has low stability and repeatability. The results of this study can be useful for further improvement of the reliability of c-TCD in detecting RLS. RESEARCH HIGHLIGHTS: This study provided the first detailed descriptions of the MBs size distribution in a flowing contrast agent by the microscopic shadow imaging technique. It reveals significant differences in the bubble size of manual foaming during repeated manipulations for each individual and between individuals.


Asunto(s)
Medios de Contraste , Microburbujas , Humanos , Reproducibilidad de los Resultados , Ultrasonografía Doppler Transcraneal/métodos
16.
Mol Divers ; 28(1): 309-333, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36790583

RESUMEN

Targeted protein degradation (TPD) technology has gradually become widespread in the past 20 years, which greatly boosts the development of disease treatment. Contrary to small inhibitors that act on protein kinases, transcription factors, ion channels, and other targets they can bind to, targeted protein degraders could target "undruggable targets" and overcome drug resistance through ubiquitin-proteasome pathway (UPP) and lysosome pathway. Nowadays, some bivalent degraders such as proteolysis-targeting chimeras (PROTACs) have aroused great interest in drug discovery, and some of them have successfully advanced into clinical trials. In this review, to better understand the mechanism of degraders, we elucidate the targeted protein degraders according to their action process, relying on the ubiquitin-proteasome system or lysosome pathway. Then, we briefly summarize the study of PROTACs employing different E3 ligases. Subsequently, the effect of protein of interest (POI) ligands, linker, and E3 ligands on PROTAC degradation activity is also discussed in detail. Other novel technologies based on UPP and lysosome pathway have been discussed in this paper such as in-cell click-formed proteolysis-targeting chimeras (CLIPTACs), molecular glues, Antibody-PROTACs (Ab-PROTACs), autophagy-targeting chimeras, and lysosome-targeting chimeras. Based on the introduction of these degradation technologies, we can clearly understand the action process and degradation mechanism of these approaches. From this perspective, it will be convenient to obtain the development status of these drugs, choose appropriate degradation methods to achieve better disease treatment and provide basis for future research and simultaneously distinguish the direction of future research efforts.


Asunto(s)
Complejo de la Endopetidasa Proteasomal , Factores de Transcripción , Suplementos Dietéticos , Descubrimiento de Drogas , Ubiquitinas , Proteolisis
17.
J Chromatogr A ; 1714: 464560, 2024 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-38070304

RESUMEN

The Fourier deconvolution ion mobility spectrometer (FDIMS) offers multiplexing and improves the resolving power and signal-to-noise ratio. To evaluate the FDIMS as a detector for gas chromatography for the analysis of complex samples, we connected a drift tube ion mobility spectrometer to a commercial gas chromatograph and compared the performance including resolving power, sensitivity, and linear range using 2,6-di­tert-butylpyridine. Mixed standards were also injected into the tandem system to evaluate the performance under optimized conditions. A complex plant extract sample used as natural flavoring was investigated using the resulting system. The results show that the instrument implemented with the Fourier deconvolution multiplexing method demonstrated higher performance over the traditional signal averaging method including higher resolving power, better limit of detection, and wider linear range for a variety of compounds and natural plant extract flavorings.


Asunto(s)
Extractos Vegetales , Cromatografía de Gases/métodos
19.
Molecules ; 28(21)2023 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-37959799

RESUMEN

Nuclear magnetic resonance (NMR) is a crucial technique for analyzing mixtures consisting of small molecules, providing non-destructive, fast, reproducible, and unbiased benefits. However, it is challenging to perform mixture identification because of the offset of chemical shifts and peak overlaps that often exist in mixtures such as plant flavors. Here, we propose a deep-learning-based mixture identification method (DeepMID) that can be used to identify plant flavors (mixtures) in a formulated flavor (mixture consisting of several plant flavors) without the need to know the specific components in the plant flavors. A pseudo-Siamese convolutional neural network (pSCNN) and a spatial pyramid pooling (SPP) layer were used to solve the problems due to their high accuracy and robustness. The DeepMID model is trained, validated, and tested on an augmented data set containing 50,000 pairs of formulated and plant flavors. We demonstrate that DeepMID can achieve excellent prediction results in the augmented test set: ACC = 99.58%, TPR = 99.48%, FPR = 0.32%; and two experimentally obtained data sets: one shows ACC = 97.60%, TPR = 92.81%, FPR = 0.78% and the other shows ACC = 92.31%, TPR = 80.00%, FPR = 0.00%. In conclusion, DeepMID is a reliable method for identifying plant flavors in formulated flavors based on NMR spectroscopy, which can assist researchers in accelerating the design of flavor formulations.


Asunto(s)
Aprendizaje Profundo , Espectroscopía de Resonancia Magnética , Redes Neurales de la Computación , Imagen por Resonancia Magnética , Aromatizantes
20.
BMC Plant Biol ; 23(1): 557, 2023 Nov 13.
Artículo en Inglés | MEDLINE | ID: mdl-37957587

RESUMEN

BACKGROUND: Artificial induction of polyploidy is the most common and effective way to improve the biological properties of Populus and develop new varieties of this tree. In this study, in order to confirm and expand earlier findings, we established a protocol using colchicine and based on an efficient shoot regeneration system of leaf blades to induce tetraploidy in vitro in three genotypes from diploid Populus hopeiensis. The stomatal characteristics, leaf blade size, and growth were evaluated for diploids and tetraploids of three genotypes. RESULTS: We found that genotype, preculture duration, colchicine concentration, and colchicine exposure time had highly significant effects on the tetraploid induction rate. The optimal protocol for inducing tetraploidy in P. hopeiensis was to preculture leaf blades for 7 days and then treat them for 4 days with 40 mg/L colchicine. The tetraploid induction rates of genotypes BT1, BT3, and BT8 were 21.2, 11.4 and 16.7%, respectively. A total of 136 tetraploids were identified by flow cytometry analysis and somatic chromosome counting. The stomatal length, width, and density of leaf blades significantly differed between diploid and tetraploid plants. Compared with their diploid counterparts, the tetraploids produced larger leaf blades and had a slower growth rate. Our findings further document the modified morphological characteristics of P. hopeiensis following whole-genome duplication (e.g., induced tetraploidy). CONCLUSIONS: We established a protocol for in vitro induction of tetraploidy from diploid leaf blades treated with colchicine, which can be applied to different genotypes of P. hopeiensis.


Asunto(s)
Populus , Tetraploidía , Populus/genética , Poliploidía , Diploidia , Variación Biológica Poblacional , Colchicina/farmacología
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