Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 764
Filtrar
1.
Food Chem ; 403: 134473, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36358083

RESUMO

Milk fat globule membrane (MFGM) protein is a complex milk protein system with antioxidant property, which can alleviate skeletal muscle dysfunction caused by oxidative stress. In this study, peptide products of MFGM protein obtained through in vitro digestion were isolated and purified, and the composition and antioxidant activities of MFGM peptides (MFGMP) were identified and assessed using LC-MS/MS combined with molecular docking and in vitro approach. Three novel antioxidant peptides TGIIT, YAR and YYK were identified from MFGMPF1, among which TGIIT and YAR exhibited excellent antioxidant effects and protected dexamethasone (Dex)-induced L6 cells by enhancing mitochondrial function and biogenesis involving modulating Sirt-1/PGC-1α signaling pathway. Furthermore, YAR and TGIIT also significantly decreased expression of pro-apoptotic factors such as cyt-c, cleaved caspase-3 and caspase-9. Therefore, YAR and TGIIT, two novel antioxidant peptides, are expected to be utilized in functional food or medicine, providing an emerging role of MFGMP in maintaining anti-oxidant/oxidant status.


Assuntos
Antioxidantes , Hidrolisados de Proteína , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Hidrolisados de Proteína/farmacologia , Hidrolisados de Proteína/metabolismo , Cromatografia Líquida , Simulação de Acoplamento Molecular , Espectrometria de Massas em Tandem , Glicolipídeos/química , Proteínas do Leite/metabolismo , Gotículas Lipídicas/metabolismo , Mitocôndrias/metabolismo , Dexametasona/farmacologia
2.
J Colloid Interface Sci ; 630(Pt B): 179-192, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36327721

RESUMO

As a kind of novel functional material, graphene-related nanomaterials (GRMs) have great potentials in industrial and biomedical applications. Meanwhile, the production and wide application of GRMs will increase the risk of unintended or intentional oral exposure to human beings, attracting safety concerns about their biological fates and toxicological effects. The normal enzymatic activity of digestive enzymes is essential for the proper functioning of the gastrointestinal tract system. However, whether and how orally entered GRMs and their surface groups affect digestive enzymes' activity are still scarce. In this paper, we systematically studied the effects of graphene oxide (GO), graphene modified with hydroxyl groups (OH-G), carboxyl groups (COOH-G), and amino groups (NH2-G) on enzymatic activity of three typical digestive enzymes (pepsin, trypsin, and α-pancreatic amylase). The results showed that the activity of trypsin and α-pancreatic amylase could be greatly changed after GRMs incubation in a surface chemistry dependent manner, while the activity of pepsin was not affected. To elucidate the mechanisms at the molecular level, the interactions between trypsin and GRMs were studied by spectrometry, thermophoresis, and computational simulation approaches, and the key roles of surface chemistry of GRMs in tailoring the activity of trypsin were finally figured out. GO allosterically inhibited trypsin's activity in the non-competitive manner because of the conformation transition induced by the intensive interactions. COOH-G could effectively hamper enzymatic activity of trypsin in the competitive manner by blocking the active catalytic pocket. As for NH2-G and OH-G, they had little impact on the activity of trypsin due to the weak binding affinity or limited conformational change. Our findings not only indicate surface chemistry plays an important role in tailoring the effects of GRMs on the activity of digestive enzymes but also provide new insights for understanding the oral safety of nanomaterials from daily products and the environment.


Assuntos
Grafite , Humanos , Grafite/química , Tripsina/química , Pepsina A/metabolismo , alfa-Amilases/metabolismo , Amilases
3.
Front Microbiol ; 13: 1046099, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36452922

RESUMO

Three new antibacterial spirooxindole alkaloids, spirobrefeldins A-C (1-3), together with four known analogs, spirotryprostatin M (4), spirotryprostatin G (5), 12ß-hydroxyverruculogen TR-2 (6), and 12α-hydroxyverruculogen TR-2 (7), were isolated from terrestrial fungus Penicillium brefeldianum. All the new compounds were elucidated extensively by the interpretation of their NMR (1D and 2D) spectra and high-resolution mass data, and their absolute configurations were determined by computational chemistry and CD spectra. The absolute configurations of spiro carbon C-2 in spirotryprostatin G (5) and spirotryprostatin C in literature were reported as S, which were revised to R based on experimental and calculated CD spectra. All the compounds were evaluated for their antimicrobial activities toward Pseudomonas aeruginosa PAO1, Dickeya zeae EC1, Staphylococcus epidermidis, Escherichia coli, and Sporisorium scitamineum. Compound 7 displayed moderate inhibitory activity toward dimorphic switch of pathogenic smut fungi Sporisorium scitamineum at 25 µM. Compounds 3 and 6 showed weak antibacterial activities against phytopathogenic bacterial Dickeya zeae EC1 at 100 µM.

4.
Pharmacol Res ; 187: 106559, 2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36403720

RESUMO

Retinal Müller glial dysfunction and intracellular edema are important mechanisms leading to diabetic macular edema (DME). Aquaporin 11 (AQP11) is primarily expressed in Müller glia with unclear functions. This study aims to explore the role of AQP11 in the pathogenesis of intracellular edema of Müller glia in diabetic retinopathy (DR). Here, we found that AQP11 expression, primarily located at the endfeet of Müller glia, was down-regulated with diabetes progression, accompanied by intracellular edema, which was alleviated by intravitreal injection of lentivirus-mediated AQP11 overexpression. Similarly, intracellular edema of hypoxia-treated rat Müller cell line (rMC-1) was aggravated by AQP11 inhibition, while attenuated by AQP11 overexpression, accompanied by enhanced function in glutamate metabolism and reduced cell death. The down-regulation of AQP11 was also verified in the Müller glia from the epiretinal membranes (ERMs) of proliferative DR (PDR) patients. Mechanistically, down-regulation of AQP11 in DR was mediated by the HIF-1α-dependent and independent miRNA-AQP11 axis. Overall, we deciphered the AQP11 down-regulation, mediated by miRNA-AQP11 axis, resulted in Müller drainage dysfunction and subsequent intracellular edema in DR, which was partially reversed by AQP11 overexpression. Our findings propose a novel mechanism for the pathogenesis of DME, thus targeting AQP11 regulation provides a new therapeutic strategy for DME.

5.
J Hematol Oncol ; 15(1): 167, 2022 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-36384978

RESUMO

A novel recombinant SIRPα-Fc fusion protein, IMM01, was constructed and produced using an in-house developed CHO-K1 cell expression system, and the anti-tumor mechanism of IMM01 targeting the CD47-SIRPα pathway was explored. The phagocytosis and in vitro anti-tumor activity of IMM01 were evaluated by antibody-dependent cellular phagocytosis (ADCP), antibody-dependent cell-mediated cytotoxicity (ADCC), and complement-dependent cytotoxicity (CDC) assays. In vivo mouse tumor model studies were used to explore therapeutic efficacy as well as the mechanism of action. An in vitro binding assay revealed that IMM01 has a strong binding affinity to CD47 with an EC50 of 0.4967 nM. IMM01 can induce strong ADCP and moderate ADCC, but not CDC. IMM01-induced strong phagocytosis against tumor cells was attributed to dual activities of blocking the "don't eat me" signal and activating the "eat me" signal, and IMM01 exhibits strong and robust in vivo anti-tumor activities either as monotherapy on hematological malignancies, or in combination therapy with PD-L1 monoclonal antibody (mAb), PD-1 mAb, and HER-2 mAb on solid tumors. Finally, IMM01 demonstrated a favorable safety profile with no human RBC binding activity or hemagglutination induction. IMM01 inhibits the growth of tumor cells by the following three possible mechanisms: (1) directly activating macrophages to phagocytize tumor cells; (2) activated macrophages degrade phagocytized tumor cells and present tumor antigens to T cells through MHC molecules to activate T cells; (3) activated macrophages can convert "cold tumors" into "hot tumors" and increase the infiltration of immune cells through chemotaxis by secreting some cytokines and chemokines.


Assuntos
Antígeno CD47 , Neoplasias , Fagocitose , Animais , Camundongos , Neoplasias/tratamento farmacológico , Transdução de Sinais , Proteínas Recombinantes de Fusão/farmacologia , Receptores Imunológicos
6.
Metabolites ; 12(11)2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36422270

RESUMO

Tripterygium glycoside tablet (TGT), as a common clinical drug, can easily cause liver damage due to the narrow therapeutic window. Glycyrrhizic acid (GA) has a hepatoprotective effect, but the characteristics and mechanism of GA's impact on TGT-induced acute liver injury by regulating oxidative stress remain unelucidated. In this study, TGT-induced acute liver injury models were established in vitro and in vivo. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AKP), superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), catalase (CAT), lactate dehydrogenase (LDH), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) were quantified. The anti-apoptotic effect of GA was tested using flow cytometry. Potential target proteins of GA were profiled via activity-based protein profiling (ABPP) using a cysteine-specific (IAA-yne) probe. The results demonstrate that GA markedly decreased the concentrations of ALT, AST, AKP, MDA, LDH, TNF-α, IL-1ß and IL-6, whereas those of SOD, GSH and CAT increased. GA could inhibit TGT-induced apoptosis in BRL-3A cells. GA bound directly to the cysteine residue of PKM2. The CETSA and enzyme activity results validate the specific targets identified. GA could mitigate TGT-induced acute liver injury by mediating PKM2, reducing oxidative stress and inflammation and reducing hepatocyte apoptosis.

7.
Vis Comput Ind Biomed Art ; 5(1): 28, 2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36434401

RESUMO

With the increasing requirements of precision mechanical systems in electronic packaging, ultra-precision machining, biomedicine and other high-tech fields, it is necessary to study a precision two-stage amplification micro-drive system that can safely provide high precision and a large amplification ratio. In view of the disadvantages of the current two-stage amplification and micro-drive system, such as poor security, low motion accuracy and limited amplification ratio, an optimization design of a precise symmetrical two-stage amplification micro-drive system was completed in this study, and its related performance was studied. Based on the guiding principle of the flexure hinge, a two-stage amplification micro-drive mechanism with no parasitic motion or non-motion direction force was designed. In addition, the structure optimization design of the mechanism was completed using the particle swarm optimization algorithm, which increased the amplification ratio of the mechanism from 5 to 18 times. A precise symmetrical two-stage amplification system was designed using a piezoelectric ceramic actuator and two-stage amplification micro-drive mechanism as the micro-driver and actuator, respectively. The driving, strength, and motion performances of the system were subsequently studied. The results showed that the driving linearity of the system was high, the strength satisfied the design requirements, the motion amplification ratio was high and the motion accuracy was high (relative error was 5.31%). The research in this study can promote the optimization of micro-drive systems.

8.
Development ; 2022 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-36440598

RESUMO

Spatiotemporal regulation of the mechanistic target of rapamycin (mTOR) pathway is pivotal for establishment of brain architecture. Dysregulation of mTOR signaling is associated with a variety of neurodevelopmental disorders (NDDs). Here, we discover that the UBE4B-KLHL22 E3 ubiquitin ligase cascade regulates mTOR activity in neurodevelopment. In a mouse model with UBE4B conditionally deleted in the nervous system, animals display severe growth defects, spontaneous seizures, and premature death. Loss of UBE4B in the brains of mutant mice results in depletion of neural precursor cells (NPCs) and impairment of neurogenesis. Mechanistically, UBE4B polyubiquitinates and degrades KLHL22, an E3 ligase previously shown to degrade the GATOR1 component DEPDC5. Deletion of UBE4B causes upregulation of KLHL22 and hyperactivation of mTOR, leading to defective proliferation and differentiation of NPCs. Suppression of KLHL22 expression reverses the elevated activity of mTOR caused by acute local deletion of UBE4B. Prenatal treatment with the mTOR inhibitor rapamycin rescues neurogenesis defects in Ube4b mutant mice. Taken together, these findings demonstrate that UBE4B and KLHL22 are essential for maintenance and differentiation of the precursor pool through fine-tuning of mTOR activity.

9.
Am J Clin Oncol ; 45(12): 501-505, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36413679

RESUMO

OBJECTIVES: The best fractionation for stereotactic body radiotherapy (SBRT) in renal cell carcinoma (RCC) metastases has not been well defined. In addition, the literature on outcomes using 5-fraction SBRT in the setting of osseous metastases has not been well reported. MATERIALS AND METHODS: Thirty-nine patients with 69 RCC osseous metastases were treated using 5-fraction SBRT at a single institution using 2 dose-fractionation schemes. Overall survival and local-control (LC) outcomes of the 2 fractionation schemes were studied using Kaplan-Meier curves. RESULTS: Of the 69 lesions included in the study, 20 were treated with 30 grays (Gy) in 5 fractions and 49 were treated with 40 Gy in 5 fractions. The median age of patients at diagnosis was 58.4 years. The 1-year LC rate for all treated lesions was 85.5% (59/69) with an LC of 90% (18/20) for lesions receiving 30 Gy and 83.7% (41/49) in lesions receiving 40 Gy. There was no statistically significant difference in 1-year LC rate between the 2 fractionation schemes (P-value, 0.553). CONCLUSIONS: Patients with osseous RCC metastases undergoing 5 fractions of SBRT had favorable LC outcomes. There was no difference in survival or LC between the 40 Gy and 30 Gy treatment arms.


Assuntos
Neoplasias Ósseas , Carcinoma de Células Renais , Neoplasias Renais , Radiocirurgia , Humanos , Pessoa de Meia-Idade , Carcinoma de Células Renais/secundário , Radiocirurgia/efeitos adversos , Fracionamento da Dose de Radiação , Neoplasias Ósseas/radioterapia , Neoplasias Renais/patologia
10.
Front Microbiol ; 13: 1029361, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36338048

RESUMO

Dextrose equivalent of glucose from starch hydrolysis is a critical index for starch-hydrolysis industry. Improving glucose yield and decreasing the non]-fermentable sugars which caused by transglycosylation activity of the enzymes during the starch saccharification is an important direction. In this study, we identified two key α-glucosidases responsible for producing non-fermentable sugars in an industrial glucoamylase-producing strain Aspergillus niger O1. The results showed the transglycosylation product panose was decreased by more than 88.0% in agdA/agdB double knock-out strains than strain O1. Additionally, the B-P1 domain of agdB was found accountable as starch hydrolysis activity only, and B-P1 overexpression in ΔAΔB-21 significantly increased glucoamylase activity whereas keeping the glucoamylase cocktail low transglycosylation activity. The total amounts of the transglycosylation products isomaltose and panose were significantly decreased in final strain B-P1-3 by 40.7% and 44.5%, respectively. The application of engineered strains will decrease the cost and add the value of product for starch biorefinery.

11.
Precis Clin Med ; 5(4): pbac023, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36349141

RESUMO

Background: Aristolochic acids (AAs), a class of carcinogenic and mutagenic natural products from Aristolochia and Asarum plants, are well-known to be responsible for inducing nephrotoxicity and urothelial carcinoma. Recently, accumulating evidence suggests that exposure to AAs could also induce hepatotoxicity and even hepatocellular carcinoma, though the mechanisms are poorly defined. Methods: Here, we aimed to dissect the underlying cellular and molecular mechanisms of aristolochic acid I (AAI)-induced hepatotoxicity by using advanced single-cell RNA sequencing (scRNA-seq) and proteomics techniques. We established the first single-cell atlas of mouse livers in response to AAI. Results: In hepatocytes, our results indicated that AAI activated NF-κB and STAT3 signaling pathways, which may contribute to the inflammatory response and apoptosis. In liver sinusoidal endothelial cells (LSECs), AAI activated multiple oxidative stress and inflammatory associated signaling pathways and induced apoptosis. Importantly, AAI induced infiltration of cytotoxic T cells and activation of proinflammatory macrophage and neutrophil cells in the liver to produce inflammatory cytokines to aggravate inflammation. Conclusions: Collectively, our study provides novel knowledge of AAs-induced molecular characteristics of hepatotoxicity at a single-cell level and suggests future treatment options for AAs associated hepatotoxicity.

12.
BMC Pediatr ; 22(1): 636, 2022 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-36333735

RESUMO

BACKGROUND: Branchio-Oto-Renal (BOR) Syndrome is a rare autosomal disorder with a wide variety of clinical manifestations and a high degree of heterogeneity. Typical clinical manifestations of BOR syndrome include deafness, preauricular fistula, abnormal gill slits, and renal malformations. However, atypical phenotypes such as congenital hip dysplasia, congenital heart anomaly or facial nerve paresis are rare in BOR syndrome, and this might be easily misdiagnosed with other congenital disorders. CASE PRESENTATION: We report a 5-month-old boy of BOR syndrome with "congenital heart defects and proteinuria" as clinical features. Initially, as this case mainly presented with symptoms of recurrent respiratory infections and was found to be with congenital heart disease and proteinuria at the local hospital, but he only was diagnosed with congenital heart disease combined with pulmonary infection and anti-infective and supportive treatment was given. Subsequently, during the physical examination at our hospital, left side preauricular pit and branchial fistulae on the right neck were found. Subsequent evaluation of auditory brainstem response and distortion product otoacoustic emission were revealed sensorineural hearing impairment. Results of renal ultrasonography showed small kidneys. Genetic analysis revealed a microdeletion at chromosome 8q13.2-q13.3 encompassing EYA1 gene, this patient was finally diagnosed with BOR syndrome. Then, this patient received transcatheter patent ductus arteriosus closure and hearing aid treatment. Proteinuria, renal function and hearing ability are monitoring by nephrologist and otologist. The patient is currently being followed up until 3 months after discharge and his condition is stable. CONCLUSION: Careful physical examination, detailed history and the implementation of diagnostic laboratory tests can reduce the incidence of misdiagnosis. Genetic sequencing analysis of patients is a key guide to the differential diagnosis of BOR syndrome.


Assuntos
Síndrome Brânquio-Otorrenal , Cardiopatias Congênitas , Masculino , Humanos , Síndrome Brânquio-Otorrenal/complicações , Síndrome Brânquio-Otorrenal/diagnóstico , Síndrome Brânquio-Otorrenal/genética , Linhagem , Fenótipo , Proteinúria , Cardiopatias Congênitas/complicações , Cardiopatias Congênitas/diagnóstico , Cardiopatias Congênitas/genética
13.
Mar Environ Res ; 183: 105825, 2022 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-36401955

RESUMO

With the rapid marine economic development, the problem of the marine ecological environment has become progressively prominent. Mariculture monitoring plays an essential role in sustaining ecological stability, rational planning, and green economic development of sea areas. Using the Landsat image, the raft-mariculture area information of Haizhou Bay and its adjacent southern waters were extracted by the object-oriented classification method based on remote sensing techniques. Landscape pattern index and principal component analysis were used to analyze the spatiotemporal expansion and structural changes of mariculture areas, and to quantify the effects of natural, socio-economic factors on the spatiotemporal variations of mariculture areas. This study discusses the correlation between the mariculture area and the outbreak scale of Enteromorpha Enteromorpha green tide. Results show that the object-oriented classification method has the highest accuracy, with total classification accuracy and Kappa coefficient of more than 90% and 0.79, respectively. The total area, patch density, and landscape shape index of mariculture areas in Haizhou Bay increase yearly, which demonstrates that the heterogeneity and fragmentation increase with the expansion of the mariculture area. The landscape pattern changes in the mariculture area are predominantly impacted by annual mean sea surface temperature (SST), annual average wind speed, social development level, and population density, etc. The larger the area of raft-aquaculture, the wider the outbreak scale of the Enteromorpha prolifera disaster. Study results can provide scientific references for the further development of mariculture in Haizhou Bay and marine environmental protection.

14.
Sci Rep ; 12(1): 20459, 2022 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-36443638

RESUMO

To investigate the differential expression of genes in whole transcripts of congenital pulmonary airway malformation (CPAM) using second-generation sequencing (also known as next-generation sequencing, NGS) technology. Children with CPAM were strictly screened after setting the criteria, and grouped by taking CPAM parietal tissue and CPAM lesion tissue respectively, and RNA-Seq libraries were established separately using second-generation sequencing technology, followed by differential expression analysis and GO (gene ontology) functional enrichment analysis, KEGG (Kyoto encyclopedia of genes and genomes, a database) pathway analysis and GSEA (Gene Set Enrichment Analysis) analysis. Five cases were screened from 36 children with CPAM, and high-throughput sequencing was performed to obtain 10 whole transcripts of samples with acceptable sequence quality and balanced gene coverage. One aberrantly expressed sample (3b) was found by analysis of principal components, which was excluded and then subjected to differential expression analysis, and 860 up-regulated genes and 203 down-regulated genes. GO functional enrichment analysis of differentially expressed genes demonstrates the functional class and cellular localization of target genes. The whole transcript of CPAM shows obvious gene up and down-regulation, differentially expressed genes are located in specific cells and belong to different functional categories, and NGS can provide an effective means to study the transcriptional regulation of CPAM from the overall transcriptional level.


Assuntos
Malformação Adenomatoide Cística Congênita do Pulmão , Sequenciamento de Nucleotídeos em Larga Escala , Criança , Humanos , Ontologia Genética , Bases de Dados Factuais , Expressão Gênica
15.
Neurobiol Aging ; 2022 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-36446680

RESUMO

Enlarged perivascular spaces (ePVS) are difficult to quantify, and their etiologies and consequences are poorly understood. Vanderbilt Memory and Aging Project participants (n = 327, 73 ± 7 years) completed 3T brain MRI to quantify ePVS volume and count, longitudinal neuropsychological assessment, and cardiac MRI to quantify aortic stiffness. Linear regressions related (1) PWV to ePVS burden and (2) ePVS burden to cross-sectional and longitudinal neuropsychological performance adjusting for key demographic and medical factors. Higher aortic stiffness related to greater basal ganglia ePVS volume (ß = 7.0×10-5, p = 0.04). Higher baseline ePVS volume was associated with worse baseline information processing (ß = -974, p = 0.003), executive function (ß = -81.9, p < 0.001), and visuospatial performances (ß = -192, p = 0.02) and worse longitudinal language (ß = -54.9, p = 0.05), information processing (ß = -147, p = 0.03), executive function (ß = -10.9, p = 0.03), and episodic memory performances (ß = -10.6, p = 0.02). Results were similar for ePVS count. Greater arterial stiffness relates to worse basal ganglia ePVS burden, suggesting cardiovascular aging as an etiology. ePVS burden is associated with adverse cognitive trajectory, emphasizing the clinical relevance of ePVS.

16.
Phytother Res ; 2022 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-36281060

RESUMO

The treatments currently used for prostate cancer (PC) do not meet clinical needs, and thus, new therapies with greater effectiveness are urgently required. Metabolic reprogramming of tumor cells is emerging as an exciting field for cancer therapy. Although the Warburg effect is a common feature of glucose metabolism in many cancers, PC cells have a unique metabolic phenotype. Non-neoplastic prostate cells show reduced oxidative phosphorylation (OXPHOS) because large, accumulated zinc inhibits citrate oxidation. During transformation, there are low levels of zinc in PC cells, and the tricarboxylic acid (TCA) cycle is reactivated. However, metastatic PC exhibits the Warburg effect. Due to metabolic differences in prostate tissue, targeting metabolic alterations in PC cells is an attractive therapeutic strategy. In this study, we investigated the effect of juglone on energy metabolism in PC cells. We found that juglone inhibited cell proliferation and induced apoptosis. Mechanistically, we demonstrated that juglone suppressed OXPHOS and glycolysis due to its inhibition of hexokinase (HK), phosphofructokinase (PFK), and pyruvate kinase (PK) activity. Furthermore, downregulation of PFK and PK, but not HK contributed to the inhibition of these enzyme activities. The current study indicates that further development of juglone for PC treatment would be beneficial.

17.
Scanning ; 2022: 5914344, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36247719

RESUMO

Objective: To study the value of pelvic floor ultrasonography in evaluating pelvic floor dysfunction (PFD) after total hysterectomy for cervical cancer. Methods: All the enrolled patients were given 4D pelvic floor ultrasound examination before and after surgery. The results of ultrasonic examination and the parameters of four-dimensional ultrasonic examination before and after surgery were analyzed, and the quality of life of the patients before and after surgery was evaluated. Results: Postoperatively, the posterior angle of bladder and urethra, the rotation angle of urethra, the decreased value of bladder neck, and the distance between bladder neck and pubic symphysis were (122.60 ± 9.53)°, (136.47 ± 14.67)°, (58.90 ± 18.19)°, (18.14 ± 7.32) mm, and (2.76 ± 0.46) cm, significantly greater than the preoperative (89.90 ± 9.59)°, (107.30 ± 9.96)°, (27.59 ± 10.96)°, (13.27 ± 5.69) mm, and (2.24 ± 0.21) cm (P < 0.05). Postoperative detrusor muscle thickness, bladder neck movement, residual urine volume, and bladder rotation angle (4.48 ± 0.82) mm, (0.64 ± 0.17) cm, (12.82 ± 2.69) ml, (12.11 ± 2.43)° were significantly higher than those of preoperative (3.70 ± 0.64) mm, (0.43 ± 0.18) cm, (4.83 ± 1.07) ml, (4.30 - 1.19)° (P < 0.05). The scores of emotional function, psychological function, social function, and physiological function were (2.35 ± 0.75) points, (2.45 ± 0.66) points, (2.30 ± 0.77) points, and (2.19 ± 0.71) points, significantly higher than those of (1.01 ± 0.50) points, (1.25 ± 0.54) points, and (1.00 ± 0.57) points before surgery, (1.05 ± 0.46) (P < 0.05). Conclusions: The application of pelvic floor ultrasonography to detect pelvic floor dysfunction after total hysterectomy can clearly display the anatomical structure of the pelvic floor, which is conducive to disease prevention and treatment. Four-dimensional pelvic floor ultrasound can clearly show the postoperative pelvic floor function, which is worthy of clinical promotion and reference.


Assuntos
Diafragma da Pelve , Neoplasias do Colo do Útero , Feminino , Humanos , Histerectomia/efeitos adversos , Diafragma da Pelve/diagnóstico por imagem , Diafragma da Pelve/fisiologia , Qualidade de Vida , Ultrassonografia/métodos , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/cirurgia
18.
Front Neurol ; 13: 999540, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36247784

RESUMO

Background: In intensive care unit (ICU), what thresholds of MAP variability are effective in distinguishing low- and high-risk patients for short-term mortality (in-hospital and 28-day) remains unclear. Methods: Fifteen thousand five hundred sixty adult subjects admitted to ICU at Beth Israel Deaconess Medical Center (Boston, USA) between 2001 and 2012 were included in this retrospective study from MIMIC-III database. MAP within the first 24 h after admission were collected. Quantiles of MAP variability from 10% to 90% with 10% increasement each were considered to divide study participants into two groups, either having coefficients of variation of MAP greater or less than the given threshold. The threshold of MAP variability was identified by maximizing the odds ratio associated with increased risk of short-term mortality (in-hospital and 28-day). Logistic regression and Cox regression models were further applied to evaluate the association between increased variability of MAP and short-term mortality (in-hospital and 28-day). Results: 90% quantile of MAP variability was determined as the threshold generating the largest odds ratio associated with the increased risk of short-term mortality. Increased MAP variability, especially over 90% of MAP variability, was associated with increased risk of in-hospital mortality (odds ratio: 2.351, 95% CI: 2.064-2.673), and 28-day mortality (hazard ratio: 2.064, 95% CI: 1.820-2.337). Conclusion: Increased MAP variability, especially over 90% of MAP variability, is associated with short-term mortality. Our proposed threshold of MAP variability may aid in the early identification of critically ill patients with a high risk of mortality.

19.
Opt Express ; 30(19): 34034-34042, 2022 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-36242425

RESUMO

Toroidal dipole resonance can significantly reduce radiation loss of materials, potentially improving sensor sensitivity. Generally, toroidal dipole response is suppressed by electric and magnetic dipoles in natural materials, making it difficult to observe experimentally. However, as 2D metamaterials, metasurfaces can weaken the electric and magnetic dipole, enhancing toroidal dipole response. Here, we propose a new graphene-integrated toroidal resonance metasurface as an ultra-sensitive chemical sensor, capable of qualitative detection of chlorothalonil in the terahertz region, down to a detection limit of 100 pg/mL. Our results demonstrate graphene-integrated toroidal resonance metasurfaces as a promising basis for ultra-sensitive, qualitative detection in chemical and biological sensing.


Assuntos
Grafite , Nitrilas
20.
Aerosp Med Hum Perform ; 93(10): 717-724, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-36243911

RESUMO

BACKGROUND: Teleoperation enables performing tasks in hazardous or inaccessible environments. The relationship between spatial ability and teleoperation performance has been extensively studied; however, relatively few studies have considered examples wherein the specific influence mechanism between the two is examined. This study aims to explore how individuals' spatial ability affects teleoperation performance.METHODS: Forty subjects completed teleoperated expedition and escape tasks in a virtual unfamiliar environment according to the assigned requirements. After each expedition task, subjects' mental model about the unfamiliar environment was evaluated. The escape task performance was measured in terms of path length, completion time, and the number of collisions. The impact of spatial ability on escape task performance wherein mental model as a mediator was examined. The Bootstrapping method was used to examine the hypothesis regarding the mediating role of mental model in the influence of spatial ability on teleoperation performance.RESULTS: Subjects with higher spatial ability exhibited significantly better mental models and had fewer collisions. In addition, subjects with better mental models had significantly shorter path lengths and spent marginally less time on escape. In general, the mental model appeared important for path length and completion time, but not collisions.CONCLUSIONS: The combined results of the two tasks preliminarily proved that spatial ability affected path length of the escape task through the mental model after the exploration task. The findings are expected to aid in astronaut selection and teleoperation training for space station missions.Pan D, Liu D, Tian Z, Zhang Y. Performance influence mechanism of individuals' spatial ability in teleoperation. Aerosp Med Hum Perform. 2022; 93(10):717-724.


Assuntos
Navegação Espacial , Humanos , Análise e Desempenho de Tarefas , Interface Usuário-Computador
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...