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1.
Clin Imaging ; 111: 110174, 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38781615

RESUMEN

PURPOSE: To evaluate the yield of MR-directed ultrasound for MRI detected breast findings. METHODS: This retrospective study included 857 consecutive patients who had a breast MRI between January 2017-December 2020 and received a BI-RADS 4 assessment. Only exams recommended for MR-directed ultrasound were included in the study, yielding 765 patients. Findings were characterized by presence or absence of a sonographic correlate. Utilizing the electronic medical record, for those with a sonographic correlate, the size, location, and morphology were noted. Imaging guided (Ultrasound and MRI) pathology results as well as excisional pathology results were recorded. A multivariable logistical regression analysis was used to investigate the clinical utility of MR-directed ultrasound. RESULTS: There were 1262 MRI-detected BI-RADS category 4 findings in 765 patients. Of the 1262 findings, MR-directed ultrasound was performed on 852 (68 %). Of these, 291/852 (34 %) had an ultrasound correlate, including 143/291 (49 %) benign lesions, 81/291 (28 %) malignant lesions, 16/291 (5 %) with high-risk pathology and 51/291 (18 %) unknown due to lost to follow-up. Of those findings with ultrasound correlates, 173/291 (59 %) represented masses, 69/291 (24 %) were regions of non-mass enhancement, 22/291 (7.6 %) were foci and 27/291 (9.3 %) fell into the category of other which included lymph node, cysts, and scar tissue. Masses were significantly more likely to be identified on MR-directed ultrasound (p < 0.0001) compared to foci. CONCLUSION: The yield of MR-directed ultrasound is significantly higher for masses, than foci and non-mass enhancement, which should be taken into consideration when recommending an MR-directed ultrasound.

2.
Int J Mol Sci ; 25(8)2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38673996

RESUMEN

Gene function verification is a crucial step in studying the molecular mechanisms regulating various plant life activities. However, a stable and efficient homologous genetic transgenic system for herbaceous peonies has not been established. In this study, using virus-induced gene silencing technology (VIGS), a highly efficient homologous transient verification system with distinctive advantages was proposed, which not only achieves true "intact-plant" infiltration but also minimizes the operation. One-year-old roots of the representative species, Paeonia lactiflora Pall., were used as the materials; prechilling (4 °C) treatment for 3-5 weeks was applied as a critical precondition for P. lactiflora to acquire a certain chilling accumulation. A dormancy-related gene named HOMEOBOX PROTEIN 31 (PlHB31), believed to negatively regulate bud endodormancy release (BER), was chosen as the target gene in this study. GFP fluorescence was detected in directly infiltrated and newly developed roots and buds; the transgenic plantlets exhibited remarkably earlier budbreak, and PlHB31 was significantly downregulated in silenced plantlets. This study established a homologous transient silencing system featuring intact-plant infiltration and minimized manipulation for gene function research, and also offers technical support and serves as a theoretical basis for gene function discovery in numerous other geophytes.


Asunto(s)
Regulación de la Expresión Génica de las Plantas , Silenciador del Gen , Raíces de Plantas , Plantas Modificadas Genéticamente , Plantas Modificadas Genéticamente/genética , Raíces de Plantas/genética , Raíces de Plantas/crecimiento & desarrollo , Paeonia/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/metabolismo
3.
Front Immunol ; 15: 1336862, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38545111

RESUMEN

Background and purpose: Neutrophil-to-lymphocyte ratio (NLR) and monocyte-to-lymphocyte ratio (MLR) have been identified as potential prognostic markers in various conditions, including cancer, cardiovascular disease, and stroke. This study aims to investigate the dynamic changes of NLR and MLR following cerebral contusion and their associations with six-month outcomes. Methods: Retrospective data were collected from January 2016 to April 2020, including patients diagnosed with cerebral contusion and discharged from two teaching-oriented tertiary hospitals in Southern China. Patient demographics, clinical manifestations, laboratory test results (neutrophil, monocyte, and lymphocyte counts) obtained at admission, 24 hours, and one week after cerebral contusion, as well as outcomes, were analyzed. An unfavorable outcome was defined as a Glasgow Outcome Score (GOS) of 0-3 at six months. Logistic regression analysis was performed to identify independent predictors of prognosis, while receiver characteristic curve analysis was used to determine the optimal cutoff values for NLR and MLR. Results: A total of 552 patients (mean age 47.40, SD 17.09) were included, with 73.19% being male. Higher NLR at one-week post-cerebral contusion (adjusted OR = 4.19, 95%CI, 1.16 - 15.16, P = 0.029) and higher MLR at admission and at 24 h (5.80, 1.40 - 24.02, P = 0.015; 9.06, 1.45 - 56.54, P = 0.018, respectively) were significantly associated with a 6-month unfavorable prognosis after adjustment for other risk factors by multiple logistic regression. The NLR at admission and 24 hours, as well as the MLR at one week, were not significant predictors for a 6-month unfavorable prognosis. Based on receiver operating characteristic curve analysis, the optimal thresholds of NLR at 1 week and MLR at admission after cerebral contusion that best discriminated a unfavorable outcome at 6-month were 6.39 (81.60% sensitivity and 70.73% specificity) and 0.76 (55.47% sensitivity and 78.26% specificity), respectively. Conclusion: NLR measured one week after cerebral contusion and MLR measured at admission may serve as predictive markers for a 6-month unfavorable prognosis. These ratios hold potential as parameters for risk stratification in patients with cerebral contusion, complementing established biomarkers in diagnosis and treatment. However, further prospective studies with larger cohorts are needed to validate these findings.


Asunto(s)
Contusión Encefálica , Neutrófilos , Humanos , Masculino , Persona de Mediana Edad , Femenino , Monocitos , Estudios Retrospectivos , Estudios Prospectivos , Linfocitos , Pronóstico
4.
Materials (Basel) ; 17(4)2024 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-38399111

RESUMEN

The spatter generated by the interaction between laser and powder during Powder Bed Fusion-Laser Melting (PBF-LM) can significantly affect the quality of printed parts. A high-speed camera is used to observe the dynamic process of spatter's behavior under different layer thickness and laser powers during the printing process, and to analyze the printed samples' surface roughness, microstructure, and mechanical properties. In terms of spatter image processing, employing an optical flow approach to track and quantify the number of spatters efficiently eliminates statistical redundancy and improves statistical correctness. It is found that under the same laser power, the number of spatters produced by the laser scan direction with the gas flow (LSD-W) is more than that by the laser scan direction against the gas flow (LSD-A), and the number of spatters produced increases with the increase of laser power. Analyzing the mechanical properties and surface roughness of the printed samples under different process parameters quantitatively reveals that differences in the spatter amount generated under different process parameters in the PBF-LM process is not the determining factor affecting the difference in tensile strength of printed parts. During LSD-W, the number of spatters generated at laser power of 170 W and layer thickness of 0.03 mm is 87, and the tensile strength of the printed sample is 618 MPa. During LSD-W, the number of spatters generated at laser power of 320 W and layer thickness of 0.05 mm is 211, and the tensile strength of the printed sample is 680 MPa. Instead, spatter generation has a more direct impact on the surface roughness of printed parts. The layer thickness is 0.03 mm, the laser power is 170 W, and (Ra = 2.372 µm) is the surface roughness of the sample. The layer thickness is 0.05 mm, the laser power is 320 W, and (Ra = 8.163 µm) is the surface roughness of the sample.

6.
Int J Surg ; 110(2): 909-920, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38181195

RESUMEN

OBJECTIVE: The aim of this paper is to investigate the risk factors associated with intraoperative brain bulge (IOBB), especially the computed tomography (CT) value of the diseased lateral transverse sinus, and to develop a reliable predictive model to alert neurosurgeons to the possibility of IOBB. METHODS: A retrospective analysis was performed on 937 patients undergoing traumatic decompressive craniectomy. A total of 644 patients from Fuzong Clinical Medical College of Fujian Medical University were included in the development cohort, and 293 patients from the First Affiliated Hospital of Shantou University Medical College were included in the external validation cohort. Univariate and multifactorial logistic regression analyses identified independent risk factors associated with IOBB. The logistic regression models consisted of independent risk factors, and receiver operating characteristic curves, calibration, and decision curve analyses were used to assess the performance of the models. Various machine learning models were used to compare with the logistic regression model and analyze the importance of the factors, which were eventually jointly developed into a dynamic nomogram for predicting IOBB and published online in the form of a simple calculator. RESULTS: IOBB occurred in 93/644 (14.4%) patients in the developmental cohort and 47/293 (16.0%) in the validation cohort. Univariate and multifactorial regression analyses showed that age, subdural hematoma, contralateral fracture, brain contusion, and CT value of the diseased lateral transverse sinus were associated with IOBB. A logistic regression model (full model) consisting of the above risk factors had excellent predictive power in both the development cohort [area under the curve (AUC)=0.930] and the validation cohort (AUC=0.913). Among the four machine learning models, the AdaBoost model showed the best predictive value (AUC=0.998). Factors in the AdaBoost model were ranked by importance and combined with the full model to create a dynamic nomogram for clinical application, which was published online as a practical and easy-to-use calculator. CONCLUSIONS: The CT value of the diseased lateral transverse is an independent risk factor and a reliable predictor of IOBB. The online dynamic nomogram formed by combining logistic regression analysis models and machine learning models can more accurately predict the possibility of IOBBs in patients undergoing traumatic decompressive craniectomy.


Asunto(s)
Lesiones Traumáticas del Encéfalo , Craniectomía Descompresiva , Humanos , Estudios Retrospectivos , Craniectomía Descompresiva/efectos adversos , Craniectomía Descompresiva/métodos , Nomogramas , Lesiones Traumáticas del Encéfalo/diagnóstico por imagen , Lesiones Traumáticas del Encéfalo/cirugía , Encéfalo
7.
Sci Total Environ ; 912: 168743, 2024 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-38007124

RESUMEN

Though recombinant strains are increasingly recognized for their potential in heavy metal remediation, few studies have evaluated their safety. Moreover, biosafety assessments of fecal-oral pathway exposure at country as well as global level have seldom analyzed the health risks of exposure to microorganisms from a microscopic perspective. The present study aimed to predict the long-term toxic effects of recombinant strains by conducting a subacute toxicity test on the chromium-removal recombinant strain 3458 and analyzing the gut microbiome. The available disinfection methods were also evaluated. The results showed that strain 3458 induced liver damage and affected renal function and lipid metabolism at 1.0 × 1011 CFU/mL, which may be induced by its carrier strain, pET-28a. Strain 3458 poses the risk of increasing the number of pathogenic bacteria under prolonged exposure. When 500 mg L-1 chlorine-containing disinfectant or 250 mg L-1 chlorine dioxide disinfectant was added for 30 min, the sterilization rate exceeded 99.9 %. These findings suggest that existing wastewater disinfection methods can effectively sterilize strain 3458, ensuring its application value. The present study can serve a reference for the biosafety evaluation of the recombinant strain through exposure to the digestive tract and its feasibility for application in environmental pollution remediation.


Asunto(s)
Contención de Riesgos Biológicos , Desinfectantes , Ratones , Animales , Biodegradación Ambiental , Cromo/análisis , Desinfectantes/toxicidad , Medición de Riesgo
8.
Infection ; 52(2): 545-555, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38123753

RESUMEN

BACKGROUND: Existing panels for lower respiratory tract infections (LRTIs) are slow and lack quantification of important pathogens and antimicrobial resistance, which are not solely responsible for their complex etiology and antibiotic resistance. BioFire FilmArray Pneumonia (PN) panels may provide rapid information on their etiology. METHODS: The bronchoalveolar lavage fluid of 187 patients with LRTIs was simultaneously analyzed using a PN panel and cultivation, and the impact of the PN panel on clinical practice was assessed. The primary endpoint was to compare the consistency between the PN panel and conventional microbiology in terms of etiology and drug resistance, as well as to explore the clinical significance of the PN panel. The secondary endpoint was pathogen detection using the PN panel in patients with community-acquired pneumonia (CAP) or hospital-acquired pneumonia (HAP). RESULTS: Fifty-seven patients with HAP and 130 with CAP were included. The most common pathogens of HAP were Acinetobacter baumannii and Klebsiella pneumoniae, with the most prevalent antimicrobial resistance (AMR) genes being CTX-M and KPC. For CAP, the most common pathogens were Haemophilus influenzae and Staphylococcus aureus, with the most frequent AMR genes being CTX-M and VIM. Compared with routine bacterial culture, the PN panel demonstrated an 85% combined positive percent agreement (PPA) and 92% negative percent agreement (NPA) for the qualitative identification of 13 bacterial targets. PN detection of bacteria with higher levels of semi-quantitative bacteria was associated with more positive bacterial cultures. Positive concordance between phenotypic resistance and the presence of corresponding AMR determinants was 85%, with 90% positive agreement between CTX-M-type extended-spectrum beta-lactamase gene type and phenotype and 100% agreement for mecA/C and MREJ. The clinical benefit of the PN panel increased by 25.97% compared with traditional cultural tests. CONCLUSION: The bacterial pathogens and AMR identified by the PN panel were in good agreement with conventional cultivation, and the clinical benefit of the PN panel increased by 25.97% compared with traditional detection. Therefore, the PN panel is recommended for patients with CAP or HAP who require prompt pathogen diagnosis and resistance identification.


Asunto(s)
Antiinfecciosos , Infecciones Comunitarias Adquiridas , Neumonía , Infecciones del Sistema Respiratorio , Humanos , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Farmacorresistencia Bacteriana/genética , Neumonía/microbiología , Bacterias/genética , Infecciones del Sistema Respiratorio/diagnóstico , Infecciones Comunitarias Adquiridas/diagnóstico , Infecciones Comunitarias Adquiridas/microbiología
9.
J Psychosom Obstet Gynaecol ; 44(1): 2278015, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-38056467

RESUMEN

OBJECTIVE: This study aimed to evaluate the effectiveness of double ABCX-based psychotherapy for psychological distress during in vitro fertilization-embryo transfer (IVF-ET) among a female group (FG), couple group (CoG) and control group (CG). METHODS: A total of 201 women undergoing their first IVF-ET cycle were randomized into three groups. The 6-session intervention was delivered at each visit to the IVF clinic. The primary outcomes were depression and anxiety, and the secondary outcomes included sleep quality, serum cortisol (nmol/L) levels and the clinical pregnancy rate, which were assessed before and after the intervention. RESULTS: The group-by-time effects were significant for depression, anxiety, sleep quality and serum cortisol levels, with larger effect sizes in the FG than in the CoG. There was no significant difference in the pregnancy rate among the three groups. CONCLUSION: Psychotherapy effectively mitigated psychological distress, suggesting greater effectiveness for couples undergoing IVF couples than for women only. It is structured and easy to use during the IVF treatment cycle. TRIAL REGISTRATION NUMBER: https://register.clinicaltrials.gov (NCT03931187, retrospectively registered on April 23, 2019).


Double ABCX-based psychotherapy, which was developed in this study, effectively mitigated depression, anxiety, sleep disturbance and increased cortisol levels, suggesting greater effectiveness for couples undergoing IVF-ET than women only.Double ABCX-based psychotherapy is structured and easy to use during the IVF-ET treatment cycle, thereby presenting a promising and feasible approach to improve care for couples or women with assisted reproductive technique-related stress.


Asunto(s)
Fertilización In Vitro , Distrés Psicológico , Embarazo , Femenino , Humanos , Fertilización In Vitro/psicología , Hidrocortisona , Transferencia de Embrión , Psicoterapia
10.
ACS Nano ; 17(23): 24104-24114, 2023 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-37972379

RESUMEN

The deposition/stripping behavior of lithium metal is intriguing, and the associated formation of inactive lithium at various temperatures remains elusive, which hinders the practical application of lithium metal batteries. Here, utilizing the variable-temperature operando solid-state nuclear magnetic resonance (SS NMR) technique, we reveal the temperature effects on the lithium microstructure evolution in a carbonate-based electrolyte system. In addition, the mass spectrometry titration (MST) method is used to quantify the evolution of inactive lithium components, including dead lithium, solid electrolyte interface (SEI), and lithium hydride (LiH). Combined SS NMR and MST results show that the morphology of lithium metal is reasonably correlated to the amount of inactive Li formed. At low/ambient temperature, the lithium microstructure has a similar evolution pattern, and its poor morphology leads to a large amount of dead lithium, which dominates capacity loss; however, at high temperature large and dense lithium deposits form with less dead Li detected, and the intensified electrolyte consumption in SEI formation is the major cause for capacity loss. Our phase-field simulation results reveal that the compact lithium deposition formed at higher temperature is due to the more uniformly distributed electric field and Li+ concentration. Lastly, two strategies in forming a dense Li deposit are proposed and tested that show performance-enhancing results.

11.
Eur J Med Res ; 28(1): 432, 2023 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-37828549

RESUMEN

BACKGROUND: This study aimed to validate the efficacy the multiplication of neutrophils and monocytes (MNM) and a novel dynamic nomogram for predicting in-hospital death in patients with aneurysmal subarachnoid hemorrhage (aSAH). METHODS: Retrospective study was done on 986 patients with endovascular coiling for aSAH. Independent risk factors associated with in-hospital death were identified using both univariate and multivariate logistic regression analysis. In the development cohort, a dynamic nomogram of in-hospital deaths was introduced and made available online as a straightforward calculator. To predict the in-hospital death from the external validation cohort by nomogram, calibration analysis, decision curve analysis, and receiver operating characteristic analysis were carried out. RESULTS: 72/687 patients (10.5%) in the development cohort and 31/299 patients (10.4%) in the validation cohort died. MNM was linked to in-hospital death in univariate and multivariate regression studies. In the development cohort, a unique nomogram demonstrated a high prediction ability for in-hospital death. According to the calibration curves, the nomogram has a reliable degree of consistency and calibration. With threshold probabilities between 10% and 90%, the nomogram's net benefit was superior to the basic model. The MNM and nomogram also exhibited good predictive values for in-hospital death in the validation cohort. CONCLUSIONS: MNM is a novel predictor of in-hospital mortality in patients with aSAH. For aSAH patients, a dynamic nomogram is a useful technique for predicting in-hospital death.


Asunto(s)
Nomogramas , Hemorragia Subaracnoidea , Humanos , Mortalidad Hospitalaria , Estudios Retrospectivos , Hospitales
12.
Polymers (Basel) ; 15(17)2023 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-37688183

RESUMEN

Ultrasonic welding technology represents an advanced method for joining thermoplastic composites. However, there exists a scarcity of systematic investigations into welding parameters and their influence on the morphological characteristics and quality of the welded regions. Furthermore, a comprehensive experimental understanding of the welded joint failure mechanisms remains deficient. A robust model for simulating the failure behavior of welded joints under loading has yet to be formulated. In this study, ultrasonic welded specimens were fabricated using distinct welding control methods and varied parameter combinations. Diverse experimental methodologies are employed to assess the morphological features of the welded areas, ascertain specimen strength, and observe welding interface failure modes. Based on a cohesive model, a finite element model is developed to predict the strength of the ultrasonic welded joints and elucidate the failure mechanisms. The results showed that, under identical welding parameters, the specimens welded with a high amplitude and low welding force exhibit superior welding quality. The specimens produced under displacement control exhibit minimal dispersion in strength. The proposed finite element model effectively prognosticates both welded joint strength and failure modes.

13.
Theranostics ; 13(12): 4288-4302, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37554285

RESUMEN

Rationale: As a key endogenous negative regulator of ferroptosis, glutathione peroxidase 4 (GPX4) can regulate its antioxidant function through multiple post-translational modification pathways. However, the effects of the phosphorylation/dephosphorylation status of GPX4 on the regulation of inducible ferroptosis in hepatocellular carcinoma (HCC) remain unclear. Methods: To investigate the effects and molecular mechanism of GPX4 phosphorylation/dephosphorylation modification on ferroptosis in HCC cells. Sorafenib (Sora) was used to establish the ferroptosis model in HCC cells in vitro. Using the site-directed mutagenesis method, we generated the mimic GPX4 phosphorylation or dephosphorylation HCC cell lines at specific serine sites of GPX4. The effects of GPX4 phosphorylation/dephosphorylation modification on ferroptosis in HCC cells were examined. The interrelationships among GPX4, p53, and protein phosphatase 2A-B55ß subunit (PP2A-B55ß) were also explored. To explore the synergistic anti-tumor effects of PP2A activation on Sora-administered HCC, we established PP2A-B55ß overexpression xenograft tumors in a nude mice model in vivo. Results: In the Sora-induced ferroptosis model of HCC in vitro, decreased levels of cytoplasmic and mitochondrial GPX4, mitochondrial dysfunction, and enhanced p53 retrograde signaling occurred under Sora treatment. Further, we found that mitochondrial p53 retrograded remarkably into the nucleus and aggravated Sora-induced ferroptosis. The phosphorylation status of GPX4 at the serine 2 site (GPX4Ser2) revealed that mitochondrial p-GPX4Ser2 dephosphorylation was positively associated with ferroptosis, and the mechanism might be related to mitochondrial p53 retrograding into the nucleus. In HCC cells overexpressing PP2A-B55ß, it was found that PP2A-B55ß directly interacted with mitochondrial GPX4 and promoted Sora-induced ferroptosis in HCC. Further, PP2A-B55ß reduced the interaction between mitochondrial GPX4 and p53, leading to mitochondrial p53 retrograding into the nucleus. Moreover, it was confirmed that PP2A-B55ß enhanced the ferroptosis-mediated tumor growth inhibition and mitochondrial p53 retrograde signaling in the Sora-treated HCC xenograft tumors. Conclusion: Our data uncovered that the PP2A-B55ß/p-GPX4Ser2/p53 axis was a novel regulatory pathway of Sora-induced ferroptosis. Mitochondrial p-GPX4Ser2 dephosphorylation triggered ferroptosis via inducing mitochondrial p53 retrograding into the nucleus, and PP2A-B55ß was an upstream signal modulator responsible for mitochondrial p-GPX4Ser2 dephosphorylation. Our findings might serve as a potential theranostic strategy to enhance the efficacy of Sora in HCC treatment through the targeted intervention of p-GPX4 dephosphorylation via PP2A-B55ß activation.


Asunto(s)
Carcinoma Hepatocelular , Ferroptosis , Neoplasias Hepáticas , Fosfolípido Hidroperóxido Glutatión Peroxidasa , Proteína Fosfatasa 2 , Sorafenib , Animales , Humanos , Ratones , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Núcleo Celular , Regulación hacia Abajo , Resistencia a Antineoplásicos , Xenoinjertos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Ratones Endogámicos BALB C , Ratones Desnudos , Mitocondrias/patología , Trasplante de Neoplasias , Fosfolípido Hidroperóxido Glutatión Peroxidasa/química , Fosfolípido Hidroperóxido Glutatión Peroxidasa/genética , Fosfolípido Hidroperóxido Glutatión Peroxidasa/metabolismo , Fosforilación , Transducción de Señal/efectos de los fármacos , Sorafenib/uso terapéutico , Proteína Fosfatasa 2/metabolismo
14.
Eur J Med Chem ; 257: 115510, 2023 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-37269672

RESUMEN

Non-alcoholic fatty liver disease (NAFLD) is emerging as the largest burden of chronic liver disease worldwide. Nonalcoholic steatohepatitis (NASH) is a progressive form of NAFLD that can progress to cirrhosis and hepatocellular carcinoma. Unfortunately, current treatment options for NASH are very limited. Among the multiple pathways of NASH, peroxisome proliferators-activated receptors (PPARS) are recognized as an important and effective target. GFT 505 is a dual excitement agent for the treatment of PPAR-α/δ for the treatment of NASH. However, its activity and toxicity need to be further improved. Therefore, here we would like to report the design, synthesis and biological evaluation of 11 GFT 505 derivatives. The initial cytotoxicity through proliferation activity of HepG2 cells and in vitro anti-NASH activity evaluation demonstrated that under the same concentration, the compound 3d possess significantly lower cytotoxicity and better anti-NASH activity than that of GFT 505. Moreover, Molecular docking also shows that 3d and PPAR-α/δ can form a stable hydrogen bond and have the lowest binding energy. Therefore this novel molecule 3d was selected to go further in vivo investigation. Methionine-choline deficiency (MCD) induced C57BL/6J NASH model mice was used for the in vivo biological experiments and the compound 3d demostrated lower liver toxicity than that of GFT 505 in the body at the same dose, and it did more effectively improve hyperlipidemia, liver fat degeneration and liver inflammation as well as significantly enhance the content of the GSH which is inportant for the liver protection. This study suggested that the compound 3d is a very promising lead compound for the treatment of NASH.


Asunto(s)
Enfermedad del Hígado Graso no Alcohólico , PPAR delta , Ratones , Animales , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Simulación del Acoplamiento Molecular , Ratones Endogámicos C57BL , Hígado/metabolismo , PPAR alfa
15.
JAMA Dermatol ; 159(7): 791-793, 2023 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-37163259

RESUMEN

This case report describes a 28-year-old woman with Netherton syndrome who had large erythematous migratory patches with serpiginous double-edged scales on her face, neck, trunk, and extremities.


Asunto(s)
Síndrome de Netherton , Humanos , Síndrome de Netherton/diagnóstico , Síndrome de Netherton/tratamiento farmacológico , Pirimidinas , Sulfonamidas
16.
Materials (Basel) ; 16(9)2023 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-37176325

RESUMEN

For exploring an effective heat treatment schedule to enhance the strength-plasticity balance of the ferrite-austenite 12CrNi2 alloy steel additively manufactured by directed energy deposition (DED), 12CrNi2 was heat-treated with deliberately designed direct quenching (DQ) and cyclic quenching (CQ), respectively, and the differently quenched steels were then tempered at a temperature from 200 °C to 500 °C. It was found that the CQ, in contrast to the DQ, led the 12CrNi2 to have significantly increased tensile strength without losing its plasticity, based on the introduction of fine-grained lath martensite and the {112}<111>-type nanotwins. The nanotwins were completely degenerated after the 200 °C tempering. This led the CQ-treated steel to decrease in not only its tensile strength, but also its plasticity. In addition, an interesting phenomenon observed was that the DQ-induced laths and rod-like precipitates, and the tempering-induced laths and rod-like precipitates were all prone to be generated along the {112} planes of the martensitic crystal (α-Fe), which were exactly fitted with the {112}-type crystalline orientation of the long or short nanotwins in the CQ-induced martensite. The quenching-tempering-induced generation of the {112}-orientated laths and rod-like precipitates was explicated in connection with the {112}<111>-type long or short nanotwins in the CQ-induced lath martensite.

17.
R Soc Open Sci ; 10(4): 221057, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37035293

RESUMEN

Gene expression has inherent stochasticity resulting from transcription's burst manners. Single-cell snapshot data can be exploited to rigorously infer transcriptional burst kinetics, using mathematical models as blueprints. The classical telegraph model (CTM) has been widely used to explain transcriptional bursting with Markovian assumptions. However, growing evidence suggests that the gene-state dwell times are generally non-exponential, as gene-state switching is a multi-step process in organisms. Therefore, interpretable non-Markovian mathematical models and efficient statistical inference methods are urgently required in investigating transcriptional burst kinetics. We develop an interpretable and tractable model, the generalized telegraph model (GTM), to characterize transcriptional bursting that allows arbitrary dwell-time distributions, rather than exponential distributions, to be incorporated into the ON and OFF switching process. Based on the GTM, we propose an inference method for transcriptional bursting kinetics using an approximate Bayesian computation framework. This method demonstrates an efficient and scalable estimation of burst frequency and burst size on synthetic data. Further, the application of inference to genome-wide data from mouse embryonic fibroblasts reveals that GTM would estimate lower burst frequency and higher burst size than those estimated by CTM. In conclusion, the GTM and the corresponding inference method are effective tools to infer dynamic transcriptional bursting from static single-cell snapshot data.

18.
Angew Chem Int Ed Engl ; 62(17): e202300334, 2023 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-36859620

RESUMEN

We herein describe the chiral diboron-templated asymmetric homocoupling of aryl alkyl ketimines, providing for the first time a series of chiral vicinal tetrasubstituted diamines with excellent ee values and good to high yields. The powerful and efficient diboron-participated [3,3]-sigmatropic rearrangement is successfully demonstrated by the homocoupling of a variety of ketimines thanks to the rational design and engineering of chiral diborons. Systematic DFT studies suggest that two chiral diborons adopt different conformational assembling strategies to couple the diboron template with ketimine substrates in their tight concerted transition states to ensure the excellent enantioselectivities. The synthetic value of chiral vicinal tetrasubstituted diamines is demonstrated by the asymmetric α-bromination of aliphatic aldehydes by employing a chiral vicinal tetrasubstituted diamine-based organocatalyst.

19.
Artículo en Inglés | MEDLINE | ID: mdl-36767688

RESUMEN

On the basis of the data of 855 farmer households in the 2020 China Land Economic Survey, this paper uses an extended regression model to empirically study the impact of agricultural socialized services on the reduction in chemical fertilizer and the moderating effect of farm size in the above impact path. The results show that adoption of agricultural socialized services by farmers can significantly promote reduction in chemical fertilizer. The moderating effect test shows that the farm size is instrumental in strengthening the effect of promoting agricultural socialized services on the reduction in chemical fertilizer. The effect of technology-intensive services on fertilizer reduction was more pronounced than that of labor-intensive services. Agricultural socialized services have a greater effect on the reduction in chemical fertilizer for farmers with a higher degree of part-time employment, but farm size can significantly enhance the fertilizer reduction effect generated by the adoption of agricultural socialized services by farmers with a lower degree of part-time employment. Therefore, we recommend further developing agricultural socialized services, strengthening the supply of agricultural green production services, and playing the role of agricultural socialized services in chemical fertilizer reduction. We also posit that encouraging large-scale farmers to adopt agricultural socialized services would further promote fertilizer reduction.


Asunto(s)
Agricultura , Fertilizantes , Humanos , Granjas , Fertilizantes/análisis , Agricultura/métodos , Agricultores , Tecnología , China
20.
PLoS One ; 18(2): e0280983, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36730171

RESUMEN

In this paper, the cam connecting rod system of the high-speed group vertical machine flipping shaping mechanism is the research object. In order to solve the key problem that the flipping shaping mechanism cannot accurately complete the action when the vibration of the mechanism is large. In this paper, the finite element method is used to construct the dynamic model of the connecting rod subsystem of the flipped shaping mechanism. And The dynamic model of cam roller subsystem is established by centralized parameter method. Based on the MATLAB Genetic Algorithm toolbox and using Newmark's method, the dynamic equations of the flipped plastic mechanism system are solved. The optimal parameters of the connecting rod of the mechanism, the cam profile curve and the swing power and swing torque of the mechanism at different speeds are analyzed. The results show that the speed and convex contour line are important factors affecting the performance of the mechanism. And the pendulum force (swing torque) is the main cause of the vibration of the mechanism on the frame. Therefore, the mechanism pendulum dynamic and the swing moment are selected as the objective functions of the optimization model. By selecting the node parameters of the sixth order spline motion law and the cross-section parameters of the connecting rod as the design variables. The cam linkage system is optimally designed to obtain the optimal value. Finally, the optimal design of the flipped shaping mechanism was analyzed and compared with the original mechanism.


Asunto(s)
Fenómenos Mecánicos , Vibración , Movimiento (Física) , Algoritmos
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