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1.
Chem Sci ; 15(33): 13191-13200, 2024 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-39183934

RESUMEN

The accurate construction of mono-, bi- and multi-layer networks has been an important challenge, especially for bi- and multi-layer networks. Monolayer, bilayer, sandwich bilayer, four-layer, and multi-layer two-dimensional pillararene-type metal-organic coordination networks have been constructed from functionalized pillar[5]arene and pillar[6]arene by utilizing the coordination interaction of cobalt and copper ions and combining with temperature control and guest induction. These two-dimensional coordination networks exhibit the excellent plasticity of pillararenes and structural variety, which are characterized by X-ray single crystal diffraction and PXRD, confirming that pillararenes units can function as excellent tunable scaffolds for structural regulation. Two-dimensional chiral double-layer structure products are also constructed from R- and S-pillar[6]arene, which are obtained by high-performance liquid chromatography. Atomic force microscopic imaging confirms the thicknesses of these networks. Moreover, these networks also exhibit high iodine adsorption capacity in aqueous environments at ambient temperature. The monolayer, bilayer, sandwich bilayer, four-layer and multi-layer structures of the pillararene-type networks represent a new facile supramolecular self-assembly strategy and platform for designing more mono-, bi- and multi-layer two-dimensional nanomaterials and chiral two-dimensional double-layer structures provide a new method for the construction of more two-dimensional chiral polymers.

2.
PeerJ ; 12: e17838, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39157771

RESUMEN

Purpose: The aim of this study was to identify factors associated with difficult video laryngoscopy in obese patients. Methods: A total of 579 obese patients undergoing elective laparoscopic weight loss surgery were intubated with a single-lumen endotracheal tube using a video laryngoscopy under general anesthesia, and the patients were divided into two groups based on the Cormack-Lehane classification (difficult video laryngoscopy defined as ≥ 3): the easy video laryngoscopy group and the difficult video laryngoscopy group. Record the general condition of the patient, bedside testing indicators related to the airway, Cormack-Lehane classification during intubation, and intubation failure rate. Results: The findings of this study show that the incidence of difficult video laryngoscopy in obese patients is 4.8%. Multivariate logistic regression analysis indicated that body mass index was significantly associated with difficult video laryngoscopy (OR = 1.082, 95% CI [1.033-1.132], P < 0.001). Conclusion: For Chinese obese patients without known difficult airways, the incidence of difficult video laryngoscopy is 4.8%. Body mass index is associated factors for the occurrence of difficult video laryngoscopy, with an increased risk observed as body mass index rise.


Asunto(s)
Índice de Masa Corporal , Intubación Intratraqueal , Laringoscopía , Obesidad , Humanos , Laringoscopía/métodos , Laringoscopía/efectos adversos , Masculino , Femenino , Estudios Prospectivos , Obesidad/cirugía , Intubación Intratraqueal/métodos , Intubación Intratraqueal/efectos adversos , Persona de Mediana Edad , Adulto , China/epidemiología , Laparoscopía/métodos , Factores de Riesgo , Cuidados Preoperatorios/métodos , Grabación en Video , Anestesia General
5.
Orthop Surg ; 16(8): 1999-2010, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38952024

RESUMEN

OBJECTIVE: Multiple-level Intervertebral disc degeneration (IDD) in patients with lumbar disc herniation (LDH) is related to postoperative re-herniation and low back pain. Although many investigators believed that there is an interdependence between paraspinal muscles degeneration and IDD, few studies focused on the fatty infiltration of paraspinal muscles on single- and multiple-level IDD in patients with LDH. This study aims to investigate the difference on the fatty infiltration of paraspinal muscles between single- and multiple-levels IDD in patients with LDH. and to explore in patients with LDH whether fatty infiltration is a potential risk factor for multiple-level IDD. METHODS: This study was conducted as a retrospective observational analysis of 82 patients with LDH from January 1, 2020 to December 30, 2020 in our hospital were enrolled. Twenty-seven cases had single-level IDD (Group A), and 55 cases had multiple-level IDD (Group B). We measured the mean computed tomography (CT) density value of the paraspinal muscles, including multifidus (MF), erector spinae (ES) and psoas muscle (PM) at each disc from L1 to S1. Subgroups were set to further analyze the odds ratio (OR) of fatty infiltration of paraspinal muscles in different sex and BMI groups. We measured sagittal angles and analyzed the relationships between these angles and IDD. Finally, we use logistic regression, adjusted for other confounding factors, to investigate whether fatty infiltration is an independent risk factor for multi-level IDD. RESULTS: The average age in multi-level IDD (51.40 ± 15.47 years) was significantly higher than single-level IDD (33.37 ± 7.10 years). The mean CT density value of MF, ES and PM in single-level IDD was significantly higher than multi-level IDD (all ps < 0.001). There was no significant difference of the mean value of angles between the two groups. No matter being fat (body mass index [BMI] > 24.0 kg/m2) or normal, patients with low mean muscle CT density value of MF and ES are significantly easier to suffer from multiple-level IDD. In the pure model, the average CT density value of the MF, ES and PM is all significantly associated with the occurrence of multi-IDD. However, after adjusting for various confounding factors, only the OR of the average CT density value for MF and ES remains statistically significant (OR = 0.810, 0.834, respectively). CONCLUSIONS: In patients with LDH, patients with multiple-level IDD have more severe fatty infiltration of MF and ES than those with single-level IDD. Fatty infiltration of MF and ES are independent risk factors for multiple-level IDD in LDH patients.


Asunto(s)
Tejido Adiposo , Degeneración del Disco Intervertebral , Desplazamiento del Disco Intervertebral , Vértebras Lumbares , Músculos Paraespinales , Humanos , Músculos Paraespinales/diagnóstico por imagen , Músculos Paraespinales/patología , Desplazamiento del Disco Intervertebral/diagnóstico por imagen , Masculino , Femenino , Degeneración del Disco Intervertebral/diagnóstico por imagen , Degeneración del Disco Intervertebral/patología , Degeneración del Disco Intervertebral/etiología , Estudios Retrospectivos , Persona de Mediana Edad , Vértebras Lumbares/diagnóstico por imagen , Adulto , Tejido Adiposo/patología , Tejido Adiposo/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Factores de Riesgo , Anciano
6.
Chem Asian J ; : e202400554, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38956446

RESUMEN

A six-cyclic crown ether-type pillar[5]arene was synthesized, and the five ethylene oxide loops were located outside the cavity and not affected by temperature changes which was confirmed by variable-temperature NMR experiment in DMSO-d6 and CDCl3 and 2D 1H-1H NOESY experiment in CDCl3. The six-cyclic pillar[5]-crown also showed greater binding ability of host-guest with bis(pyridinium) derivatives than conventional alkoxy pillar[5]arenes that illustrated through 1H NMR titration spectroscopic experiment in acetone-d6/CDCl3 (1 : 1) and UV-vis titration experiments in CHCl3 at room temperature. The five benzocrown ethers at the periphery were able to bind metal cations by 1H NMR titration spectroscopic experiment in CD2Cl2/methanol-d4(9 : 1).

7.
Pharmacol Res ; 206: 107294, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38992851

RESUMEN

Liver fibrosis is a determinant-stage process of many chronic liver diseases and affected over 7.9 billion populations worldwide with increasing demands of ideal therapeutic agents. Discovery of active molecules with anti-hepatic fibrosis efficacies presents the most attacking filed. Here, we revealed that hepatic L-aspartate levels were decreased in CCl4-induced fibrotic mice. Instead, supplementation of L-aspartate orally alleviated typical manifestations of liver injury and fibrosis. These therapeutic efficacies were alongside improvements of mitochondrial adaptive oxidation. Notably, treatment with L-aspartate rebalanced hepatic cholesterol-steroid metabolism and reduced the levels of liver-impairing metabolites, including corticosterone (CORT). Mechanistically, L-aspartate treatment efficiently reversed CORT-mediated glucocorticoid receptor ß (GRß) signaling activation and subsequent transcriptional suppression of the mitochondrial genome by directly binding to the mitochondrial genome. Knockout of GRß ameliorated corticosterone-mediated mitochondrial dysfunction and hepatocyte damage which also weakened the improvements of L-aspartate in suppressing GRß signaling. These data suggest that L-aspartate ameliorates hepatic fibrosis by suppressing GRß signaling via rebalancing cholesterol-steroid metabolism, would be an ideal candidate for clinical liver fibrosis treatment.


Asunto(s)
Ácido Aspártico , Tetracloruro de Carbono , Cirrosis Hepática , Hígado , Ratones Endogámicos C57BL , Receptores de Glucocorticoides , Animales , Receptores de Glucocorticoides/metabolismo , Receptores de Glucocorticoides/genética , Masculino , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/inducido químicamente , Cirrosis Hepática/metabolismo , Cirrosis Hepática/patología , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Ácido Aspártico/metabolismo , Ratones , Corticosterona , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Colesterol/metabolismo , Transducción de Señal/efectos de los fármacos , Mitocondrias Hepáticas/metabolismo , Mitocondrias Hepáticas/efectos de los fármacos , Mitocondrias Hepáticas/patología , Ratones Noqueados
9.
Head Neck ; 46(9): 2132-2144, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38887926

RESUMEN

BACKGROUND: To establish and validate a machine learning model using pretreatment multiparametric magnetic resonance imaging-based radiomics data with clinical data to predict radiation-induced temporal lobe injury (RTLI) in patients with nasopharyngeal carcinoma (NPC) after intensity-modulated radiotherapy (IMRT). METHODS: Data from 230 patients with NPC who received IMRT (130 with RTLI and 130 without) were randomly divided into the training (n = 161) and validation cohort (n = 69) with a ratio of 7:3. Radiomics features were extracted from pretreatment apparent diffusion coefficient (ADC) map, T2-weighted imaging (T2WI), and CE-T1-weighted imaging (CE-T1WI). T-test, spearman rank correlation, and least absolute shrinkage and selection operator (LASSO) algorithm were employed to identify significant radiomics features. Clinical features were selected with univariate and multivariate analyses. Radiomics and clinical models were constructed using multiple machine learning classifiers, and a clinical-radiomics nomogram that combined clinical with radiomics features was developed. Receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) were drawn to compare and verify the predictive performances of the clinical model, radiomics model, and clinical-radiomics nomogram. RESULTS: A total of 5064 radiomics features were extracted, from which 52 radiomics features were selected to construct the radiomics signature. The AUC of the radiomics signature based on multiparametric MRI was 0.980 in the training cohort and 0.969 in the validation cohort, outperforming the radiomics signature only based on T2WI and CE-T1WI (p < 0.05), which highlighted the significance of the DWI sequence in the prediction of temporal lobe injury. The area under the curve (AUC) of the clinical model was 0.895 in the training cohort and 0.905 in the validation cohort. The nomogram, which integrated radiomics and clinical features, demonstrated an impressive AUC value of 0.984 in the validation set; however, no statistically significant difference was observed compared to the radiomics model. The calibration curve and decision curve analysis of the nomogram demonstrated excellent predictive performance and clinical feasibility. CONCLUSIONS: The clinical-radiomics nomogram, integrating clinical features with radiomics features derived from pretreatment multiparametric MRI, exhibits compelling predictive performance for RTLI in patients diagnosed with NPC.


Asunto(s)
Aprendizaje Automático , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Traumatismos por Radiación , Radiómica , Radioterapia de Intensidad Modulada , Lóbulo Temporal , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Imágenes de Resonancia Magnética Multiparamétrica , Carcinoma Nasofaríngeo/radioterapia , Carcinoma Nasofaríngeo/diagnóstico por imagen , Neoplasias Nasofaríngeas/radioterapia , Neoplasias Nasofaríngeas/diagnóstico por imagen , Nomogramas , Valor Predictivo de las Pruebas , Traumatismos por Radiación/diagnóstico por imagen , Traumatismos por Radiación/etiología , Radioterapia de Intensidad Modulada/efectos adversos , Estudios Retrospectivos , Curva ROC , Lóbulo Temporal/diagnóstico por imagen , Lóbulo Temporal/efectos de la radiación
10.
PeerJ ; 12: e17431, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38827293

RESUMEN

Purpose: To compare the impact of erector spinae plane block (ESPB) and paravertebral block (PVB) on the quality of postoperative recovery (QoR) of patients following laparoscopic sleeve gastrectomy (LSG). Methods: A total of 110 patients who underwent elective LSG under general anesthesia were randomly assigned to receive either ultrasound-guided bilateral ESPB or PVB at T8 levels. Before anesthesia induction, 40 mL of 0.33% ropivacaine was administered. The primary outcome was the QoR-15 score at 24 hours postoperatively. Results: At 24 hours postoperatively, the QoR-15 score was comparable between the ESPB and PVB groups (131 (112-140) vs. 124 (111-142.5), P = 0.525). Consistently, there was no significant difference in QoR-15 scores at 48 hours postoperatively, numerical rating scale (NRS) pain scores at any postoperative time points, time to first ambulation, time to first anal exhaust, postoperative cumulative oxycodone consumption, and incidence of postoperative nausea and vomiting (PONV) between the two groups (all P > 0.05). No nerve block-related complications were observed in either group. Conclusion: In patients undergoing LSG, preoperative bilateral ultrasound-guided ESPB yields comparable postoperative recovery to preoperative bilateral ultrasound-guided PVB.


Asunto(s)
Gastrectomía , Laparoscopía , Bloqueo Nervioso , Dolor Postoperatorio , Humanos , Femenino , Bloqueo Nervioso/métodos , Masculino , Gastrectomía/efectos adversos , Gastrectomía/métodos , Laparoscopía/efectos adversos , Adulto , Dolor Postoperatorio/prevención & control , Persona de Mediana Edad , Anestésicos Locales/administración & dosificación , Anestésicos Locales/uso terapéutico , Ropivacaína/administración & dosificación , Ropivacaína/uso terapéutico , Ultrasonografía Intervencional/métodos , Dimensión del Dolor , Músculos Paraespinales/inervación , Músculos Paraespinales/diagnóstico por imagen , Resultado del Tratamiento , Obesidad Mórbida/cirugía , Náusea y Vómito Posoperatorios/epidemiología , Anestesia General/efectos adversos
11.
Phys Med Biol ; 69(15)2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-38862003

RESUMEN

Objective.Magnetic particle imaging (MPI) is an emerging medical tomographic imaging modality that enables real-time imaging with high sensitivity and high spatial and temporal resolution. For the system matrix reconstruction method, the MPI reconstruction problem is an ill-posed inverse problem that is commonly solved using the Kaczmarz algorithm. However, the high computation time of the Kaczmarz algorithm, which restricts MPI reconstruction speed, has limited the development of potential clinical applications for real-time MPI. In order to achieve fast reconstruction in real-time MPI, we propose a greedy regularized block Kaczmarz method (GRBK) which accelerates MPI reconstruction.Approach.GRBK is composed of a greedy partition strategy for the system matrix, which enables preprocessing of the system matrix into well-conditioned blocks to facilitate the convergence of the block Kaczmarz algorithm, and a regularized block Kaczmarz algorithm, which enables fast and accurate MPI image reconstruction at the same time.Main results.We quantitatively evaluated our GRBK using simulation data from three phantoms at 20 dB, 30 dB, and 40 dB noise levels. The results showed that GRBK can improve reconstruction speed by single orders of magnitude compared to the prevalent regularized Kaczmarz algorithm including Tikhonov regularization, the non-negative Fused Lasso, and wavelet-based sparse model. We also evaluated our method on OpenMPIData, which is real MPI data. The results showed that our GRBK is better suited for real-time MPI reconstruction than current state-of-the-art reconstruction algorithms in terms of reconstruction speed as well as image quality.Significance.Our proposed method is expected to be the preferred choice for potential applications of real-time MPI.


Asunto(s)
Algoritmos , Procesamiento de Imagen Asistido por Computador , Fantasmas de Imagen , Procesamiento de Imagen Asistido por Computador/métodos , Factores de Tiempo , Tomografía/métodos , Imagen Molecular/métodos
12.
BMC Cardiovasc Disord ; 24(1): 300, 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38867152

RESUMEN

BACKGROUND: Diabetes is a common chronic metabolic disease. The progression of the disease promotes vascular inflammation and the formation of atherosclerosis, leading to cardiovascular disease. The coronary artery perivascular adipose tissue attenuation index based on CCTA is a new noninvasive imaging biomarker that reflects the spatial changes in perivascular adipose tissue attenuation in CCTA images and the inflammation around the coronary arteries. In this study, a radiomics approach is proposed to extract a large number of image features from CCTA in a high-throughput manner and combined with clinical diagnostic data to explore the predictive ability of vascular perivascular adipose imaging data based on CCTA for coronary heart disease in diabetic patients. METHODS: R language was used for statistical analysis to screen the variables with significant differences. A presegmentation model was used for CCTA vessel segmentation, and the pericoronary adipose region was screened out. PyRadiomics was used to calculate the radiomics features of pericoronary adipose tissue, and SVM, DT and RF were used to model and analyze the clinical data and radiomics data. Model performance was evaluated using indicators such as PPV, FPR, AAC, and ROC. RESULTS: The results indicate that there are significant differences in age, blood pressure, and some biochemical indicators between diabetes patients with and without coronary heart disease. Among 1037 calculated radiomic parameters, 18.3% showed significant differences in imaging omics features. Three modeling methods were used to analyze different combinations of clinical information, internal vascular radiomics information and pericoronary vascular fat radiomics information. The results showed that the dataset of full data had the highest ACC values under different machine learning models. The support vector machine method showed the best specificity, sensitivity, and accuracy for this dataset. CONCLUSIONS: In this study, the clinical data and pericoronary radiomics data of CCTA were fused to predict the occurrence of coronary heart disease in diabetic patients. This provides information for the early detection of coronary heart disease in patients with diabetes and allows for timely intervention and treatment.


Asunto(s)
Tejido Adiposo , Angiografía por Tomografía Computarizada , Angiografía Coronaria , Enfermedad de la Arteria Coronaria , Vasos Coronarios , Diabetes Mellitus Tipo 2 , Valor Predictivo de las Pruebas , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Persona de Mediana Edad , Tejido Adiposo/diagnóstico por imagen , Masculino , Femenino , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Anciano , Vasos Coronarios/diagnóstico por imagen , Interpretación de Imagen Radiográfica Asistida por Computador , Máquina de Vectores de Soporte , Adiposidad , Pronóstico , Tejido Adiposo Epicárdico , Radiómica
13.
Comput Methods Programs Biomed ; 252: 108250, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38815547

RESUMEN

BACKGROUND AND OBJECTIVE: Magnetic particle imaging (MPI) is an emerging imaging technology in medical tomography that utilizes the nonlinear magnetization response of superparamagnetic iron oxide (SPIO) particles to determine the in vivo spatial distribution of nanoparticle contrast agents. The reconstruction image quality of MPI is determined by the characteristics of magnetic particles, the setting of the MPI scanner parameters, and the hardware interference of MPI systems. We explore a feasible method to systematically and quickly analyze the impact of these factors on MPI reconstruction image quality. METHODS: We propose a systematic 3-D MPI simulation model. The MPI simulation model has the capability of quickly producing the simulated reconstruction images of a scanned phantom, and quantitative analysis of MPI reconstruction image quality can be achieved by comparing the differences between the input image and output image. These factors are mainly classified as imaging parameters and interference parameters in our model. In order to reduce the computational time of the simulation model, we introduce GPU parallel programming to accelerate the processing of large complex matrix data. For ease of use, we also construct a reliable, high-performance, and open-source 3-D MPI simulation software tool based on our model. The efficiency of our model is evaluated by using OpenMPIData. To demonstrate the capabilities of our model, we conduct simulation experiments using parameters consistent with a real MPI scanner for improving MPI image quality. RESULTS: The experimental results show that our simulation model can systematically and quickly evaluate the impact of imaging parameters and interference parameters on MPI reconstruction image quality. CONCLUSIONS: We developed an easy-to-use and open-source 3-D MPI simulation software tool based on our simulation model incorporating all the stages of MPI formation, from signal acquisition to image reconstruction. In the future, our simulation model has potential guiding significance to practical MPI images.


Asunto(s)
Simulación por Computador , Imagenología Tridimensional , Fantasmas de Imagen , Imagenología Tridimensional/métodos , Programas Informáticos , Procesamiento de Imagen Asistido por Computador/métodos , Nanopartículas de Magnetita , Algoritmos , Medios de Contraste , Humanos
14.
Org Lett ; 26(16): 3338-3342, 2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38608176

RESUMEN

Isoquinolone is one of the most common heterocyclic core structures in countless natural products and many bioactive compounds. Here, a highly efficient approach to synthesize isoquinolone scaffolds on DNA via rhodium(III)-catalyzed C-H activation has been described. This chemistry transformation is robust and has shown good compatibility with DNA, which is suitable for DNA-encoded library synthesis.


Asunto(s)
ADN , Rodio , Rodio/química , Catálisis , Estructura Molecular , ADN/química , Isoquinolinas/química , Isoquinolinas/síntesis química
15.
J Org Chem ; 89(7): 4768-4773, 2024 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38503266

RESUMEN

The protocol of aerobic oxidative dehydroxycyclization installed in the synthesis of rarely studied 1-hydroxyphenothiazines from catechols and o-mercaptoanilines is presented. Utilizing a natural renewable low-toxicity gallic acid as an organocatalyst, this established transformation proceeded smoothly in an aqueous ethanol solution under mild conditions with good functional group compatibility and up to a 94% isolated yield. This protocol is also characterized by its operational simple workup involving only recrystallization, revealing its sustainability and synthetic practicability.

16.
Neural Comput ; 36(5): 936-962, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38457762

RESUMEN

Zero-shot learning (ZSL) refers to the design of predictive functions on new classes (unseen classes) of data that have never been seen during training. In a more practical scenario, generalized zero-shot learning (GZSL) requires predicting both seen and unseen classes accurately. In the absence of target samples, many GZSL models may overfit training data and are inclined to predict individuals as categories that have been seen in training. To alleviate this problem, we develop a parameter-wise adversarial training process that promotes robust recognition of seen classes while designing during the test a novel model perturbation mechanism to ensure sufficient sensitivity to unseen classes. Concretely, adversarial perturbation is conducted on the model to obtain instance-specific parameters so that predictions can be biased to unseen classes in the test. Meanwhile, the robust training encourages the model robustness, leading to nearly unaffected prediction for seen classes. Moreover, perturbations in the parameter space, computed from multiple individuals simultaneously, can be used to avoid the effect of perturbations that are too extreme and ruin the predictions. Comparison results on four benchmark ZSL data sets show the effective improvement that the proposed framework made on zero-shot methods with learned metrics.

17.
Front Pharmacol ; 15: 1320040, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38333010

RESUMEN

Background and aims: Obesity is one of the most prevalent diseases worldwide with less ideal approved agents in clinic. Activating the HSF1/PGC-1α axis in adipose tissues has been reported to induce thermogenesis in mice, which presents a promising therapeutic avenue for obesity treatment. The present study aimed to identified novel natural HSF1 activator and evaluated the therapeutic effects of the newly discovered compound on obesity-associated metabolic disorders and the molecular mechanisms of these effects. Methods: Our previous reported HSF1/PGC-1α activator screening system was used to identify novel natural HSF1 activator. The PGC-1α luciferase activity, immunoblot, protein nuclear-translocation, immunofluorescence, chromatin immunoprecipitation assays were used to evaluate the activity of compound HN-001 in activating HSF1. The experiments of mitochondrial number measurement, TG assay and imaging, cellular metabolic assay, gene assays, and CRISPR/Cas 9 were applied for investigating the metabolic effect of HN-001 in C3H10-T1/2 adipocytes. The in vivo anti-obesity efficacies and beneficial metabolic effects of HN-001 were evaluated by performing body and fat mass quantification, plasma chemical analysis, GTT, ITT, cold tolerance test, thermogenesis analysis. Results: HN-001 dose- and time-dependently activated HSF1 and induced HSF1 nuclear translocation, resulting in an enhancement in binding with the gene Pgc-1α. This improvement induced activation of adipose thermogenesis and enhancement of mitochondrial oxidation capacity, thus inhibiting adipocyte maturation. Deletion of HSF1 in adipocytes impaired mitochondrial oxidation and abolished the above beneficial metabolic effects of HN-001, including adipocyte browning induction, improvements in mitogenesis and oxidation capacity, and lipid-lowering ability. In mice, HN-001 treatment efficiently alleviated diet-induced obesity and metabolic disorders. These changes were associated with increased body temperature in mice and activation of the HSF1/PGC-1α axis in adipose tissues. UCP1 expression and mitochondrial biogenesis were increased in both white and brown adipose tissues of HN-001-treated mice. Conclusion: These data indicate that HN-001 may have therapeutic potential for obesity-related metabolic diseases by increasing the capacity of energy expenditure in adipose tissues through a mechanism involving the HSF1/PGC-1α axis, which shed new light on the development of novel anti-obesity agents derived from marine sources.

18.
Angew Chem Int Ed Engl ; 63(8): e202315599, 2024 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-38169100

RESUMEN

Polypeptides, as natural polyelectrolytes, are assembled into tailored proteins to integrate chromophores and catalytic sites for photosynthesis. Mimicking nature to create the water-soluble nanoassemblies from synthetic polyelectrolytes and photocatalytic molecular species for artificial photosynthesis is still rare. Here, we report the enhancement of the full-spectrum solar-light-driven H2 production within a supramolecular system built by the co-assembly of anionic metalloporphyrins with cationic polyelectrolytes in water. This supramolecular photocatalytic system achieves a H2 production rate of 793 and 685 µmol h-1 g-1 over 24 h with a combination of Mg or Zn porphyrin as photosensitizers and Cu porphyrin as a catalyst, which is more than 23 times higher than that of free molecular controls. With a photosensitizer to catalyst ratio of 10000 : 1, the highest H2 production rate of >51,700 µmol h-1 g-1 with a turnover number (TON) of >1,290 per molecular catalyst was achieved over 24 h irradiation. The hierarchical self-assembly not only enhances photostability through forming ordered stackings of the metalloporphyrins but also facilitates both energy and electron transfer from antenna molecules to catalysts, and therefore promotes the photocatalysis. This study provides structural and mechanistic insights into the self-assembly enhanced photostability and catalytic performance of supramolecular photocatalytic systems.

19.
Sci Prog ; 107(1): 368504231225860, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38196238

RESUMEN

As shallow coal reserves continue to deplete rapidly, deep mining has become an unavoidable course of action. In the process of deep coal mining, affected by blasting, mining, and excavation, the coal-rock interface often encounters the action of compression-shear composite load. The interface crack directly affects the stability of the coal-rock structure. Uniaxial compression experiments have been conducted on rock and coal-like material with pre-existing interfacial oblique cracks to study the crack propagation criterion of the rock and coal-like material interface. An image acquisition system is used to record the surface speckle field of the whole process of specimen failure. The strain fields and stress intensity factor of the sample at different times are obtained by digital image correlation. At the same time, the stress field near the crack tip is calculated. The results show that with the increase of loading, two strains of localization bands are formed on the surface of the specimen. One of the strain-localized bands starts at the lower tip of the prefabricated crack and propagates along the vertical interface. The other starts at the upper tip of the prefabricated damage and propagates along the interface direction. It can be seen that the lower tip of the prefabricated crack enters into the crack fracture process zone earlier than the upper tip. The strain localization band narrows gradually with the load increase, and then macro cracks appear. The initiation of two tips is suitable for different fracture criteria. The lower tip is dominated by the maximum circumferential tensile stress, and the upper tip is dominated by shear stress. The specimens eventually fracture along the interface. The evolution of the strain field during the failure process of rock and coal-like material can reflect the generation and propagation of the crack.

20.
Acta Pharm Sin B ; 14(1): 304-318, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38261820

RESUMEN

Lipotoxicity is a pivotal factor that initiates and exacerbates liver injury and is involved in the development of metabolic-associated fatty liver disease (MAFLD). However, there are few reported lipotoxicity inhibitors. Here, we identified a natural anti-lipotoxicity candidate, HN-001, from the marine fungus Aspergillus sp. C1. HN-001 dose- and time- dependently reversed palmitic acid (PA)-induced hepatocyte death. This protection was associated with IRE-1α-mediated XBP-1 splicing inhibition, which resulted in suppression of XBP-1s nuclear translocation and transcriptional regulation. Knockdown of XBP-1s attenuated lipotoxicity, but no additional ameliorative effect of HN-001 on lipotoxicity was observed in XBP-1s knockdown hepatocytes. Notably, the ER stress and lipotoxicity amelioration was associated with PLA2. Both HN-001 and the PLA2 inhibitor MAFP inhibited PLA2 activity, reduced lysophosphatidylcholine (LPC) level, subsequently ameliorated lipotoxicity. In contrast, overexpression of PLA2 caused exacerbation of lipotoxicity and weakened the anti-lipotoxic effects of HN-001. Additionally, HN-001 treatment suppressed the downstream pro-apoptotic JNK pathway. In vivo, chronic administration of HN-001 (i.p.) in mice alleviated all manifestations of MAFLD, including hepatic steatosis, liver injury, inflammation, and fibrogenesis. These effects were correlated with PLA2/IRE-1α/XBP-1s axis and JNK signaling suppression. These data indicate that HN-001 has therapeutic potential for MAFLD because it suppresses lipotoxicity, and provide a natural structural basis for developing anti-MAFLD candidates.

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