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1.
J Perinatol ; 2024 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-38734802

RESUMEN

OBJECTIVE: Test sustainability of Web-based Implementation for the Science of Enhancing Resilience (WISER) intervention efficacy in reducing healthcare worker (HCW) emotional exhaustion (EE), a key component of burnout. DESIGN: One-year follow-up of WISER RCT using two cohorts (one waitlist control with shortened intervention period) of HCWs of four NICUs each, to improve HCW well-being (primary outcome: EE). RESULTS: In Cohorts 1 and 2, 194 and 312 WISER initiators were identified by 1-year, and 99 and 80 completed 1-year follow-up, respectively. Combined cohort results showed that relative to baseline, at 1-year WISER decreased EE (-7.07 (95%CI: -10.22, -3.92), p < 0.001), depression (-4.49 (-6.81, -2.16), p = <0.001), and improved work-life integration (6.08 (4.25, 7.90), p = <0.001). EE continued to decline between 6-month and 1-year follow-up (p = 0.022). The percentage of HCWs reporting concerning outcomes was significantly decreased for EE (-10.9% (95%CI: -17.9%, -4.9%); p < 0.001), and secondary outcomes depression and work-life integration. CONCLUSION: WISER improves HCW well-being for at least 1 year. CLINICAL TRIALS NUMBER: NCT02603133; https://clinicaltrials.gov/ct2/show/NCT02603133.

2.
JCI Insight ; 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38713533

RESUMEN

Activation of brown adipose tissue (BAT) thermogenesis increases energy expenditure and alleviates obesity. Here we discover that histone methyltransferase suppressor of variegation 4-20 homolog 2 (Suv420h2) expression parallels that of Ucp1 in brown and beige adipocytes and that Suv420h2 knockdown significantly reduces, whereas Suv420h2 overexpression significantly increases Ucp1 levels in brown adipocytes. Suv420h2 knockout (H2KO) mice exhibit impaired cold-induced thermogenesis and are prone to diet-induced obesity. In contrast, mice with specific overexpression of Suv420h2 in adipocytes display enhanced cold-induced thermogenesis and are resistant to diet-induced obesity. Further study shows that Suv420h2 catalyzes H4K20 trimethylation at eukaryotic translation initiation factor 4E-binding protein 1 (4e-bp1) promoter, leading to down-regulated expression of 4e-bp1, a negative regulator of the translation initiation complex. This in turn up-regulates PGC1α protein levels, which is associated with increased expression of thermogenic program. We conclude that Suv420h2 is a key regulator of brown/beige adipocyte development and thermogenesis.

3.
World J Urol ; 42(1): 302, 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38720010

RESUMEN

PURPOSE: To evaluate the diagnostic performance of contrast-enhanced (CE) ultrasound using Sonazoid (SNZ-CEUS) by comparing with contrast-enhanced computed tomography (CE-CT) and contrast-enhanced magnetic resonance imaging (CE-MRI) for differentiating benign and malignant renal masses. MATERIALS AND METHODS: 306 consecutive patients (from 7 centers) with renal masses (40 benign tumors, 266 malignant tumors) diagnosed by both SNZ-CEUS, CE-CT or CE-MRI were enrolled between September 2020 and February 2021. The examinations were performed within 7 days, but the sequence was not fixed. Histologic results were available for 301 of 306 (98.37%) lesions and 5 lesions were considered benign after at least 2 year follow-up without change in size and image characteristics. The diagnostic performances were evaluated by sensitivity, specificity, positive predictive value, negative predictive value, and compared by McNemar's test. RESULTS: In the head-to-head comparison, SNZ-CEUS and CE-MRI had comparable sensitivity (95.60 vs. 94.51%, P = 0.997), specificity (65.22 vs. 73.91%, P = 0.752), positive predictive value (91.58 vs. 93.48%) and negative predictive value (78.95 vs. 77.27%); SNZ-CEUS and CE-CT showed similar sensitivity (97.31 vs. 96.24%, P = 0.724); however, SNZ-CEUS had relatively lower than specificity than CE-CT (59.09 vs. 68.18%, P = 0.683). For nodules > 4 cm, CE-MRI demonstrated higher specificity than SNZ-CEUS (90.91 vs. 72.73%, P = 0.617) without compromise the sensitivity. CONCLUSIONS: SNZ-CEUS, CE-CT, and CE-MRI demonstrate desirable and comparable sensitivity for the differentiation of renal mass. However, the specificity of all three imaging modalities is not satisfactory. SNZ-CEUS may be a suitable alternative modality for patients with renal dysfunction and those allergic to gadolinium or iodine-based agents.


Asunto(s)
Medios de Contraste , Compuestos Férricos , Hierro , Neoplasias Renales , Imagen por Resonancia Magnética , Óxidos , Tomografía Computarizada por Rayos X , Ultrasonografía , Humanos , Neoplasias Renales/diagnóstico por imagen , Neoplasias Renales/patología , Masculino , Femenino , Persona de Mediana Edad , Estudios Prospectivos , Ultrasonografía/métodos , Tomografía Computarizada por Rayos X/métodos , Imagen por Resonancia Magnética/métodos , Anciano , Diagnóstico Diferencial , Adulto , Anciano de 80 o más Años
4.
Sci Adv ; 10(19): eado1469, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38718113

RESUMEN

The underlying mechanism of the ongoing seismic swarm in the Noto Peninsula, Japan, which generates earthquakes at 10 times the average regional rate, remains elusive. We capture the evolution of the subsurface stress state by monitoring changes in seismic wave velocities over an 11-year period. A sustained long-term increase in seismic velocity that is seasonally modulated drops before the earthquake swarm. We use a three-dimensional hydromechanical model to quantify environmentally driven variations in excess pore pressure, revealing its crucial role in governing the seasonal modulation with a stress sensitivity of 6 × 10-9 per pascal. The decrease in seismic velocity aligns with vertical surface uplift, suggesting potential fluid migration from a high-pore pressure zone at depth. Stress changes induced by abnormally intense snow falls contribute to initiating the swarm through subsequent perturbations to crustal pore pressure.

5.
Comput Struct Biotechnol J ; 23: 1288-1297, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38560279

RESUMEN

Carbon materials are commonly used for soil carbon sequestration and fertilization, which can also affect crop growth by manipulating the rhizosphere bacterial community. However, the comparison of the differences between active carbon (e.g., organic fertilizers) and stable carbon (e.g., biochar) on rhizosphere microdomains is still unclear. Hence, a trial was implemented to explore the influence of control (CK, no fertilizer; NPK, chemical fertilizer), organic fertilizer (CF-O, organic fertilizer; CF-BO, biochar-based organic fertilizer) and biochar material (CF-B, perishable garbage biochar; CF-PMB, pig manure biochar) on the diversity, composition, and interaction of rice rhizosphere bacterial community through 16 S rRNA gene high-throughput sequencing. Our results demonstrate that organic fertilizer increases bacterial alpha-diversity compared to no-carbon supply treatment to the extend, whereas biochar has the opposite effect. The rhizosphere bacterial community composition showed pronounced variations among the various fertilization treatments. The relative abundance in Firmicutes decreased with organic fertilizer application, whereas that in Chloroflexi and Actinobacteria decreased with biochar application. Bacterial network analysis demonstrate that organic fertilizer enhances the complexity and key taxa of bacterial interactions, while biochar exhibits an opposing trend. The findings of our study indicate that organic fertilizer may contribute to a positive and advantageous impact on bacterial diversity and interaction in rice rhizosphere, whereas the influence of biochar is not as favorable and constructive. This study lays the foundation for elucidating the fate of the rhizosphere bacterial community following different carbon material inputs in the context of sustainable agricultural development.

6.
Zhongguo Zhong Yao Za Zhi ; 49(6): 1683-1689, 2024 Mar.
Artículo en Chino | MEDLINE | ID: mdl-38621952

RESUMEN

The purpose of this study was to evaluate the economics of Annao Pills combined with antihypertensive drugs in the treatment of primary hypertension in the Chinese medical setting. TreeAge pro 2018 was used for cost-effect analysis and sensitivity analysis of the two treatment regimens. The intervention time of the simulation model was 2 weeks. The cost parameters were derived from Yaozhi.com, and the effect parameters were based on Meta-analysis of randomized controlled trial(RCT) involving Annao Pills. The experimental group was treated with Annao Pills combined with anti-hypertensive drugs(nifedipine controlled-release tablets + losartan potassium tablets), and the control group was treated with anti-hypertensive drugs(nifedipine controlled-release tablets + losartan potassium tablets). The basic analysis showed that the incremental cost-effect ratio(ICER) of the two groups was 2 678.67 yuan, which was less than 7.26% of the per capita disposable income in 2022. That is, compared with anti-hypertensive drugs alone, Annao Pills combined with antihypertensive drugs cost 2 678.67 yuan more for each additional patient with primary hypertension. The results of sensitivity analysis verified the robustness of the basic analysis results. The probability sensitivity results showed that when the patient's personal willingness to pay the price was higher than 2 650 yuan, the probability of the regimen in the experimental group was higher, which was consistent with the results of the basic analysis. In conclusion, when the price was higher than 2 650 yuan, Annao Pills combined with anti-hypertensive drugs was more economical than anti-hypertensive drugs alone in terms of improving the response rate of the patients with primary hypertension.


Asunto(s)
Antihipertensivos , Nifedipino , Humanos , Antihipertensivos/uso terapéutico , Análisis Costo-Beneficio , Árboles de Decisión , Preparaciones de Acción Retardada , Hipertensión Esencial , Losartán/uso terapéutico
7.
World J Stem Cells ; 16(3): 267-286, 2024 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-38577236

RESUMEN

BACKGROUND: The bone remodeling during orthodontic treatment for malocclusion often requires a long duration of around two to three years, which also may lead to some complications such as alveolar bone resorption or tooth root resorption. Low-intensity pulsed ultrasound (LIPUS), a noninvasive physical therapy, has been shown to promote bone fracture healing. It is also reported that LIPUS could reduce the duration of orthodontic treatment; however, how LIPUS regulates the bone metabolism during the orthodontic treatment process is still unclear. AIM: To investigate the effects of LIPUS on bone remodeling in an orthodontic tooth movement (OTM) model and explore the underlying mechanisms. METHODS: A rat model of OTM was established, and alveolar bone remodeling and tooth movement rate were evaluated via micro-computed tomography and staining of tissue sections. In vitro, human bone marrow mesenchymal stem cells (hBMSCs) were isolated to detect their osteogenic differentiation potential under compression and LIPUS stimulation by quantitative reverse transcription-polymerase chain reaction, Western blot, alkaline phosphatase (ALP) staining, and Alizarin red staining. The expression of Yes-associated protein (YAP1), the actin cytoskeleton, and the Lamin A/C nucleoskeleton were detected with or without YAP1 small interfering RNA (siRNA) application via immunofluorescence. RESULTS: The force treatment inhibited the osteogenic differentiation potential of hBMSCs; moreover, the expression of osteogenesis markers, such as type 1 collagen (COL1), runt-related transcription factor 2, ALP, and osteocalcin (OCN), decreased. LIPUS could rescue the osteogenic differentiation of hBMSCs with increased expression of osteogenic marker inhibited by force. Mechanically, the expression of LaminA/C, F-actin, and YAP1 was downregulated after force treatment, which could be rescued by LIPUS. Moreover, the osteogenic differentiation of hBMSCs increased by LIPUS could be attenuated by YAP siRNA treatment. Consistently, LIPUS increased alveolar bone density and decreased vertical bone absorption in vivo. The decreased expression of COL1, OCN, and YAP1 on the compression side of the alveolar bone was partially rescued by LIPUS. CONCLUSION: LIPUS can accelerate tooth movement and reduce alveolar bone resorption by modulating the cytoskeleton-Lamin A/C-YAP axis, which may be a promising strategy to reduce the orthodontic treatment process.

8.
Stroke ; 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38591222

RESUMEN

BACKGROUND: Ischemic stroke (IS) is a major cause of disability and mortality worldwide. Increasing evidence suggests a strong association between blood pressure, blood glucose, circulating lipids, and IS. Nonetheless, the genetic association of these 3 risk factors with IS remains elusive. METHODS: We screened genetic instruments related to blood pressure, blood glucose, and circulating lipids and paired them with IS genome-wide association study data to conduct Mendelian randomization analysis. Positive Mendelian randomization findings were then subjected to colocalization analysis. Subsequently, we utilized the Gene Expression Omnibus data set to perform differential expression analysis, aiming to identify differentially expressed associated genes. We determined the importance scores of these differentially expressed associated genes through 4 machine learning models and constructed a nomogram based on these findings. RESULTS: The combined results of the Mendelian randomization analysis indicate that blood pressure (systolic blood pressure: odds ratio [OR], 1.02 [95% CI, 1.01-1.02]; diastolic blood pressure: OR, 1.03 [95% CI, 1.03-1.04]) and some circulating lipids (low-density lipoprotein cholesterol: OR, 1.06 [95% CI, 1.01-1.12]; apoA1: OR, 0.95 [95% CI, 0.92-0.98]; apoB: OR, 1.05 [95% CI, 1.01-1.09]; eicosapentaenoic acid: OR, 2.36 [95% CI, 1.41-3.96]) have causal relationships with the risk of IS onset. We identified 73 genes that are linked to blood pressure and circulating lipids in the context of IS, and 16 are differentially expressed associated genes. FURIN, MAN2A2, HDDC3, ALDH2, and TOMM40 were identified as feature genes for constructing the nomogram that provides a quantitative prediction of the risk of IS onset. CONCLUSIONS: This study indicates that there are causal links between blood pressure, certain circulating lipids, and the development of IS. The potential mechanisms underlying these causal relationships involve the regulation of lipid metabolism, blood pressure, DNA repair and methylation, cell apoptosis and autophagy, immune inflammation, and neuronal protection, among others.

9.
J Agric Food Chem ; 72(18): 10477-10486, 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38657166

RESUMEN

Cytotoxic enzymes often exist as zymogens containing prodomains to keep them in an inactive state. Protein-glutaminase (PG), which can enhance various functional characteristics of food proteins, is an enzyme containing pro-PG and mature-PG (mPG). However, poor activity and stability limit its application while tedious purification and activation steps limit its high-throughput engineering. Here, based on structural analysis, we replaced the linker sequence between pro-PG and mPG with the HRV3C protease recognition sequence and then coexpressed it with HRV3C protease in Escherichia coli to develop an efficient one-step purification and activation method for PG. We then used this method to obtain several mutants designed by a combination of computer-aided approach and beneficial point mutations. The specific activity (131.6 U/mg) of the best variant D1 was 4.14-fold that of the wild type, and t1/2 and T5010 increased by 13 min and 7 °C, respectively. D1 could effectively improve the solubility and emulsification of wheat proteins, more than twice the effect of the wild type. We also discussed the mechanism underlying the improved properties of D1. In summary, we not only provide a universal one-step purification and activation method to facilitate zymogen engineering but also obtain an excellent PG mutant.


Asunto(s)
Escherichia coli , Glutaminasa , Ingeniería de Proteínas , Escherichia coli/genética , Glutaminasa/química , Glutaminasa/genética , Glutaminasa/metabolismo , Estabilidad de Enzimas , Cinética , Triticum/química , Solubilidad , Proteínas de Plantas/química , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
10.
Adv Colloid Interface Sci ; 327: 103145, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38615561

RESUMEN

Friction and lubrication are ubiquitous in all kinds of movements and play a vital role in the smooth operation of production machinery. Water is indispensable both in the lubrication systems of natural organisms and in hydration lubrication systems. There exists a high degree of similarity between these systems, which has driven the development of hydration lubrication from biomimetic to artificial manufacturing. In particular, significant advancements have been made in the understanding of the mechanisms of hydration lubrication over the past 30 years. This enhanced understanding has further stimulated the exploration of biomimetic inspiration from natural hydration lubrication systems, to develop novel artificial hydration lubrication systems that are cost-effective, easily transportable, and possess excellent capability. This review summarizes the recent experimental and theoretical advances in the understanding of hydration-lubrication processes. The entire paper is divided into three parts. Firstly, surface interactions relevant to hydration lubrication are discussed, encompassing topics such as hydrogen bonding, hydration layer, electric double layer force, hydration force, and Stribeck curve. The second part begins with an introduction to articular cartilage in biomaterial lubrication, discussing its compositional structure and lubrication mechanisms. Subsequently, three major categories of bio-inspired artificial manufacturing lubricating material systems are presented, including hydrogels, polymer brushes (e.g., neutral, positive, negative and zwitterionic brushes), hydration lubricant additives (e.g., nano-particles, polymers, ionic liquids), and their related lubrication mechanism is also described. Finally, the challenges and perspectives for hydration lubrication research and materials development are presented.

12.
ACS Appl Mater Interfaces ; 16(12): 14965-14973, 2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38489479

RESUMEN

Electrochemical reduction of CO2 to highly valuable products is a promising way to reduce CO2 emissions. The shape and facets of metal nanocatalysts are the key parameters in determining the catalytic performance. However, the exposed crystal facets of ZnO with different morphologies and which facets achieve a high performance for CO2 reduction are still controversial. Here, we systematically investigate the effect of the facet-dependent reactivity of reduction of CO2 to CO on ZnO (nanowire, nanosheet, and flower-like). The ZnO nanosheet with exposed (110) facet exhibited prominent catalytic performance with a Faradaic efficiency of CO up to 84% and a current density of -10 mA cm-2 at -1.2 V versus RHE, far outperforming the ZnO nanowire (101) and ZnO nanoflower (103). Based on detailed characterizations and kinetic analysis, the ZnO nanosheet (110) with porous architecture increased the exposure of active sites. Further studies revealed that the high CO selectivity originated from the enhancement of CO2 adsorption and activation on the ZnO (110) facet, which promoted the conversion of CO2 toward CO. This study provides a new way to tailor the activity and selectivity of metal catalysts by engineering exposed specific facets.

13.
Saf Health Work ; 15(1): 42-52, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38496282

RESUMEN

Background: The lack of headforms that accurately reflect the head characteristics of Koreans and the demographic composition of the Korean population can lead to inadequate FFR testing and reduced effectiveness of FFRs. Method: Direct measurements of 5,110 individuals and 3D measurements of 2,044 individuals, aged between 9 and 69 years, were sampled from the data pool of Size Korea surveys based on the age and gender ratios of the Korean resident demographics. Seven head dimensions were selected based on the ISO 16976-2, availability of Size Korea measurements, and their relevance to the fit performance of FFRs. A principal component analysis (PCA) was performed using the direct measurements to extract the main factors explaining the head characteristics and then the main factors were standardized and remapped to 3D measurements, creating five size categories representing Korean head shapes. Lastly, representative 3D headforms were constructed by averaging five head shapes for each size category. Results: The study identified two main factors explaining Korean head characteristics by the PCA procedure specified in ISO 16976-2 and developed five representative headforms reflecting the anthropometric features of Korean heads: medium, small, large, short & wide, and long & narrow. Conclusion: This study developed representative headforms tailored to the Korean population for conducting total inward leakage (TIL) tests on filtering facepiece respirators (FFRs). The representative headforms can be used for TIL testing by employing robotic headforms to enhance the performance of FFRs for the Korean target population.

14.
Int J Biol Macromol ; 265(Pt 2): 130928, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38513901

RESUMEN

In this study, black highland barley semi-dried noodles (BHBSNs) were adjusted to acidic pH (5.0, 4.5, 4.0) with an acidity regulator (monosodium fumarate) for obtaining low glycemic index (GI) BHBSNs, and the changes in the in vitro starch digestion, free phenolic content, and α-amylase activity in BHBSNs were investigated. The estimated glycemic index (eGI) of BHBSNs decreased from 59.23 to 52.59, 53.89 and 53.61, respectively, as the pH was adjusted from 6.0 to 5.0, 4.5, 4.0. As the pH of BHBSNs decreased, the equilibrium hydrolysis (C∞) decreased, and kinetic coefficient (k) decreased and then increased. Compared to the control, the pH of the digestive fluid decreased during digestion with decreasing pH, and the α-amylase inhibition of BHBSNs with pH 5.0, 4.5, and 4.0 increased by 56.54 %, 75.18 %, and 107.98 %, respectively. In addition, as the pH of BHBSNs decreased, the free phenolic content and the content of released phenolics during digestion increased. Pearson correlations analysis showed that the increase in α-amylase inhibition and phenolic release during digestion induced by acidic pH was negatively correlated with the eGI and C∞ of BHBSNs. This study indicated that acidic pH condition could modulate starch digestion for preparing low GI BHBSNs.


Asunto(s)
Hordeum , Almidón , Almidón/química , alfa-Amilasas , Fenoles/farmacología , Digestión , Concentración de Iones de Hidrógeno
15.
J Mater Chem B ; 12(15): 3676-3685, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38530749

RESUMEN

An innate immune system intricately leverages unique mechanisms to inhibit colonization of external invasive Bacteria, for example human defensin-6, through responsive encapsulation of bacteria. Infection and accompanying antibiotic resistance stemming from Gram-negative bacteria aggregation represent an emerging public health crisis, which calls for research into novel anti-bacterial therapeutics. Herein, inspired by naturally found host-defense peptides, we design a defensin-like peptide ligand, bacteria extracellular trap (BET) peptide, with modular design composed of targeting, assembly, and hydrophobic motifs with an aggregation-induced emission feature. The ligand specifically recognizes Gram-negative bacteria via targeting cell wall conserved lipopolysaccharides (LPS) and transforms from nanoparticles to nanofibrous networks in situ to trap bacteria and induce aggregation. Importantly, treatment of the BET peptide was found to have an antibacterial effect on the Pseudomonas aeruginosa strain, which is comparable to neomycin. Animal studies further demonstrate its ability to trigger aggregation of bacteria in vivo. This biomimetic self-assembling BET peptide provides a novel approach to fight against pathogenic Gram-negative bacteria.


Asunto(s)
Trampas Extracelulares , Animales , Humanos , Ligandos , Bacterias Gramnegativas , Péptidos Catiónicos Antimicrobianos/farmacología , Defensinas/farmacología
16.
J Affect Disord ; 354: 491-499, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38508458

RESUMEN

BACKGROUND: Social anxiety is a common symptom that occurs after exposure to childhood trauma (CT), and pain tolerance is a protective factor against social anxiety in generic populations with CT. However, few studies have investigated whether and how this association varies across different CT subgroups. Thus, this study aimed to investigate (1) the effects of pain tolerance on social anxiety symptoms among youth with different subgroups of CT; (2) the nonlinear relationship between pain tolerance and social anxiety symptoms among different CT categories. METHODS: In this study, 15,682 college or university students with experiences of CT were identified in a large sample and divided into five CT subgroups. Linear and quadratic regression models were conducted to explore the association between pain tolerance and social anxiety symptoms among youth with different CT subgroups. RESULTS: The results of model revealed a linear relationship between pain tolerance and social anxiety symptoms among youth with most CT subgroups. Notably, an inverted U-shaped curve was found between pain tolerance and social anxiety symptoms in youth with emotional abuse. Social anxiety symptoms increased gradually with pain tolerance scores between 0 and 16, and then sharply decreased when scores reached above 16. LIMITATIONS: Limited by self-report measurements, the results of this study focused only on perceived pain tolerance and ignored behavioral pain tolerance. CONCLUSION: These findings highlight the importance of assessing pain tolerance thresholds in youth with emotional abuse and improving pain tolerance to prevent social anxiety symptoms in youth with different subgroups of CT.


Asunto(s)
Experiencias Adversas de la Infancia , Ansiedad , Humanos , Adolescente , Ansiedad/psicología , Autoinforme , Umbral del Dolor , Factores Protectores
17.
Sheng Wu Gong Cheng Xue Bao ; 40(3): 834-846, 2024 Mar 25.
Artículo en Chino | MEDLINE | ID: mdl-38545981

RESUMEN

The signal peptide is a key factor that affects the efficiency of protein secretion in Pichia pastoris. Currently, the most used signal peptide is the α-mating factor (MFα) pre-pro leader from Saccharomyces cerevisiae. This exogenous signal peptide has been successfully utilized to express and secret many heterologous proteins. However, MFα is not suitable for the secretory expression of all heterologous proteins. Many typical signal peptides are present in the secretory proteins of P. pastoris, which provides more options besides MFα. Therefore, it is necessary to analyze and identify more efficient endogenous signal peptides that can guide the secretion of heterologous proteins in P. pastoris. In this study, we employed bioinformatics tools such as SignalP, TMHMM, Phobius, WoLF PSORT, and NetGPI to predict endogenous signal peptides from the entire proteome of P. pastoris GS115 (ATCC 20864). Moreover, we analyzed the distribution, length, amino acid composition, and conservation of these signal peptides. Additionally, we screened 69 secreted proteins and their signal peptides, and through secretome validation, we identified 10 endogenous signal peptides that have potential to be used for exogenous protein expression. The endogenous signal peptides obtained in this study may serve as new valuable tools for the expression and secretion of heterologous proteins in P. pastoris.


Asunto(s)
Señales de Clasificación de Proteína , Proteoma , Saccharomycetales , Señales de Clasificación de Proteína/genética , Secuencia de Aminoácidos , Proteoma/genética , Pichia/genética , Pichia/metabolismo , Saccharomyces cerevisiae , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo
18.
Abdom Radiol (NY) ; 2024 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-38461433

RESUMEN

PURPOSE: To develop a contrast-enhanced ultrasound (CEUS) clinic-radiomics nomogram for individualized assessment of Ki-67 expression in hepatocellular carcinoma (HCC). METHODS: A retrospective cohort comprising 310 HCC individuals who underwent preoperative CEUS (using SonoVue) at three different centers was partitioned into a training set, a validation set, and an external test set. Radiomics signatures indicating the phenotypes of the Ki-67 were extracted from multiphase CEUS images. The radiomics score (Rad-score) was calculated accordingly after feature selection and the radiomics model was constructed. A clinic-radiomics nomogram was established utilizing multiphase CEUS Rad-score and clinical risk factors. A clinical model only incorporated clinical factors was also developed for comparison. Regarding clinical utility, calibration, and discrimination, the predictive efficiency of the clinic-radiomics nomogram was evaluated. RESULTS: Seven radiomics signatures from multiphase CEUS images were selected to calculate the Rad-score. The clinic-radiomics nomogram, comprising the Rad-score and clinical risk factors, indicated a good calibration and demonstrated a better discriminatory capacity compared to the clinical model (AUCs: 0.870 vs 0.797, 0.872 vs 0.755, 0.856 vs 0.749 in the training, validation, and external test set, respectively) and the radiomics model (AUCs: 0.870 vs 0.752, 0.872 vs 0.733, 0.856 vs 0.729 in the training, validation, and external test set, respectively). Furthermore, both the clinical impact curve and the decision curve analysis displayed good clinical application of the nomogram. CONCLUSION: The clinic-radiomics nomogram constructed from multiphase CEUS images and clinical risk parameters can distinguish Ki-67 expression in HCC patients and offer useful insights to guide subsequent personalized treatment.

19.
Acad Radiol ; 2024 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-38453602

RESUMEN

RATIONALE AND OBJECTIVES: We aimed to compare superb microvascular imaging (SMI)-based radiomics methods, and contrast-enhanced ultrasound (CEUS)-based radiomics methods to the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) for classifying thyroid nodules (TNs) and reducing unnecessary fine-needle aspiration biopsy (FNAB) rate. MATERIALS AND METHODS: This retrospective study enrolled a dataset of 472 pathologically confirmed TNs. Radiomics characteristics were extracted from B-mode ultrasound (BMUS), SMI, and CEUS images, respectively. After eliminating redundant features, four radiomics scores (Rad-scores) were constructed. Using multivariable logistic regression analysis, four radiomics prediction models incorporating Rad-score and corresponding US features were constructed and validated in terms of discrimination, calibration, decision curve analysis, and unnecessary FNAB rate. RESULTS: The diagnostic performance of the BMUS + SMI radiomics method was better than ACR TI-RADS (area under the curve [AUC]: 0.875 vs. 0.689 for the training cohort, 0.879 vs. 0.728 for the validation cohort) (P < 0.05), and comparable with BMUS + CEUS radiomics method (AUC: 0.875 vs. 0.878 for the training cohort, 0.879 vs. 0.865 for the validation cohort) (P > 0.05). Decision curve analysis showed that the BMUS+SMI radiomics method could achieve higher net benefits than the BMUS radiomics method and ACR TI-RADS when the threshold probability was between 0.13 and 0.88 in the entire cohort. When applying the BMUS+SMI radiomics method, the unnecessary FNAB rate reduced from 43.4% to 13.9% in the training cohort and from 45.6% to 18.0% in the validation cohorts in comparison to ACR TI-RADS. CONCLUSION: The dual-modal SMI-based radiomics method is convenient and economical and can be an alternative to the dual-modal CEUS-based radiomics method in helping radiologists select the optimal clinical strategy for TN management.

20.
Small ; : e2310870, 2024 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-38453669

RESUMEN

Developing tunable underwater adhesives that possess tough adhesion in service and easy detachment when required remains challenging. Herein, a strategy is proposed to design a near infrared (NIR) photothermal-responsive underwater adhesive by incorporating MXene (Ti3 C2 Tx )-based nanoparticles within isocyanate-modified polydimethylsiloxane (PDMS) polymer chains. The developed adhesive exhibits long-term and tough adhesion with an underwater adhesion strength reaching 5.478 MPa. Such strong adhesion is mainly attributed to the covalent bonds and hydrogen bonds at the adhesive-substrate interface. By making use of the photothermal-response of MXene-based nanoparticles and the thermal response of PDMS-based chains, the adhesive possesses photothermal-responsive performance, exhibiting sharply diminished adhesion under NIR irradiation. Such NIR-triggered tunable adhesion allows for easy and active detachment of the adhesive when needed. Moreover, the underwater adhesive exhibits photothermal antibacterial property, making it highly desirable for underwater applications. This work enhances the understanding of photothermal-responsive underwater adhesion, enabling the design of tunable underwater adhesives for biomedical and engineering applications.

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