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1.
Int J Mol Sci ; 25(13)2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-39000499

RESUMEN

General anesthetics may accelerate the neuropathological changes related to Alzheimer's disease (AD), of which amyloid beta (Aß)-induced toxicity is one of the main causes. However, the interaction of general anesthetics with different Aß-isoforms remains unclear. In this study, we investigated the effects of sevoflurane (0.4 and 1.2 maximal alveolar concentration (MAC)) on four Aß species-induced changes on dendritic spine density (DSD) in hippocampal brain slices of Thy1-eGFP mice and multiple epidermal growth factor-like domains 10 (MEGF10)-related astrocyte-mediated synaptic engulfment in hippocampal brain slices of C57BL/6 mice. We found that both sevoflurane and Aß downregulated CA1-dendritic spines. Moreover, compared with either sevoflurane or Aß alone, pre-treatment with Aß isoforms followed by sevoflurane application in general further enhanced spine loss. This enhancement was related to MEGF10-related astrocyte-dependent synaptic engulfment, only in AßpE3 + 1.2 MAC sevoflurane and 3NTyrAß + 1.2 MAC sevoflurane condition. In addition, removal of sevoflurane alleviated spine loss in Aß + sevoflurane. In summary, these results suggest that both synapses and astrocytes are sensitive targets for sevoflurane; in the presence of 3NTyrAß, 1.2 MAC sevoflurane alleviated astrocyte-mediated synaptic engulfment and exerted a lasting effect on dendritic spine remodeling.


Asunto(s)
Péptidos beta-Amiloides , Astrocitos , Región CA1 Hipocampal , Espinas Dendríticas , Ratones Endogámicos C57BL , Sevoflurano , Sinapsis , Sevoflurano/farmacología , Animales , Espinas Dendríticas/metabolismo , Espinas Dendríticas/efectos de los fármacos , Péptidos beta-Amiloides/metabolismo , Astrocitos/metabolismo , Astrocitos/efectos de los fármacos , Sinapsis/efectos de los fármacos , Sinapsis/metabolismo , Ratones , Región CA1 Hipocampal/metabolismo , Región CA1 Hipocampal/efectos de los fármacos , Región CA1 Hipocampal/citología , Masculino , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Anestésicos por Inhalación/farmacología
2.
Environ Sci Technol ; 58(28): 12430-12440, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-38968084

RESUMEN

Soil organic carbon (SOC) is pivotal for both agricultural activities and climate change mitigation, and biochar stands as a promising tool for bolstering SOC and curtailing soil carbon dioxide (CO2) emissions. However, the involvement of biochar in SOC dynamics and the underlying interactions among biochar, soil microbes, iron minerals, and fresh organic matter (FOM, such as plant debris) remain largely unknown, especially in agricultural soils after long-term biochar amendment. We therefore introduced FOM to soils with and without a decade-long history of biochar amendment, performed soil microcosm incubations, and evaluated carbon and iron dynamics as well as microbial properties. Biochar amendment resulted in 2-fold SOC accrual over a decade and attenuated FOM-induced CO2 emissions by approximately 11% during a 56-day incubation through diverse pathways. Notably, biochar facilitated microbially driven iron reduction and subsequent Fenton-like reactions, potentially having enhanced microbial extracellular electron transfer and the carbon use efficiency in the long run. Throughout iron cycling processes, physical protection by minerals could contribute to both microbial carbon accumulation and plant debris preservation, alongside direct adsorption and occlusion of SOC by biochar particles. Furthermore, soil slurry experiments, with sterilization and ferrous iron stimulation controls, confirmed the role of microbes in hydroxyl radical generation and biotic carbon sequestration in biochar-amended soils. Overall, our study sheds light on the intricate biotic and abiotic mechanisms governing carbon dynamics in long-term biochar-amended upland soils.


Asunto(s)
Carbono , Hierro , Microbiología del Suelo , Suelo , Suelo/química , Hierro/química , Hierro/metabolismo , Carbón Orgánico/química , Dióxido de Carbono/metabolismo
3.
Chronobiol Int ; : 1-10, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38953516

RESUMEN

Shift work is a recognized work pattern for nurses worldwide. The disruption of shift workers' biological clocks usually leads to sleep disorders and affects their awareness at work. Eveningness and occupational stress might be effective in causing burnout syndrome. Therefore, this study aimed to evaluate the chronotype, job burnout and perceived stress among Chinese tertiary hospital nurses, and understand the predictors of circadian rhythm in this group. Between July and September 2020, 23 hospitals were randomly selected from 113 tertiary hospitals in Hunan Province. Twenty-five percent of the nurses working in each hospital were targeted for selection. 28.1% and 17.6% of nurses reported eveningness type and morningness type, respectively. The scores for emotional exhaustion, depersonalization, and perceived stress of eveningness nurses were higher than those of morningness counterparts. Eveningness nurses also reported a lower sense of personal accomplishment. Risk factors of eveningness included being under 30 years old, never exercising, having the stressors of late-night shifts and career development, higher levels of emotional exhaustion, sleep latency, sleep duration, and hypnotic use. Shifts may be unavoidable for nurses, nevertheless, understanding the predictors and related factors of chronotype for nurses is necessary for nursing educators and managers to develop a reasonable shift system and appropriate measures to assist nurses in adjusting their work.

4.
Emerg Microbes Infect ; 13(1): 2373307, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38953857

RESUMEN

SARS-CoV-2 has been evolving into a large number of variants, including the highly pathogenic Delta variant, and the currently prevalent Omicron subvariants with extensive evasion capability, which raises an urgent need to develop new broad-spectrum neutralizing antibodies. Herein, we engineer two IgG-(scFv)2 form bispecific antibodies with overlapping epitopes (bsAb1) or non-overlapping epitopes (bsAb2). Both bsAbs are significantly superior to the parental monoclonal antibodies in terms of their antigen-binding and virus-neutralizing activities against all tested circulating SARS-CoV-2 variants including currently dominant JN.1. The bsAb1 can efficiently neutralize all variants insensitive to parental monoclonal antibodies or the cocktail with IC50 lower than 20 ng/mL, even slightly better than bsAb2. Furthermore, the cryo-EM structures of bsAb1 in complex with the Omicron spike protein revealed that bsAb1 with overlapping epitopes effectively locked the S protein, which accounts for its conserved neutralization against Omicron variants. The bispecific antibody strategy engineered from overlapping epitopes provides a novel solution for dealing with viral immune evasion.


Asunto(s)
Anticuerpos Biespecíficos , Anticuerpos Neutralizantes , Anticuerpos Antivirales , COVID-19 , Epítopos , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Anticuerpos Biespecíficos/inmunología , Anticuerpos Biespecíficos/química , Anticuerpos Biespecíficos/farmacología , SARS-CoV-2/inmunología , Anticuerpos Neutralizantes/inmunología , Humanos , Anticuerpos Antivirales/inmunología , Epítopos/inmunología , Glicoproteína de la Espiga del Coronavirus/inmunología , Glicoproteína de la Espiga del Coronavirus/química , COVID-19/inmunología , COVID-19/virología , COVID-19/prevención & control , Pruebas de Neutralización
5.
Vaccines (Basel) ; 12(6)2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38932395

RESUMEN

Therapeutic HPV vaccines that induce potent HPV-specific cellular immunity and eliminate pre-existing infections remain elusive. Among various candidates under development, those based on DNA constructs are considered promising because of their safety profile, stability, and efficacy. However, the use of electroporation (EP) as a main delivery method for such vaccines is notorious for adverse effects like pain and potentially irreversible muscle damage. Moreover, the requirement for specialized equipment adds to the complexity and cost of clinical applications. As an alternative to EP, lipid nanoparticles (LNPs) that are already commercially available for delivering mRNA and siRNA vaccines are likely to be feasible. Here, we have compared three intramuscular delivery systems in a preclinical setting. In terms of HPV-specific cellular immune responses, mice receiving therapeutic HPV DNA vaccines encapsulated with LNP demonstrated superior outcomes when compared to EP administration, while the naked plasmid vaccine showed negligible responses, as expected. In addition, SM-102 LNP M exhibited the most promising results in delivering candidate DNA vaccines. Thus, LNP proves to be a feasible delivery method in vivo, offering improved immunogenicity over traditional approaches.

6.
Sensors (Basel) ; 24(12)2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38931789

RESUMEN

Joint source-channel coding (JSCC) based on deep learning has shown significant advancements in image transmission tasks. However, previous channel-adaptive JSCC methods often rely on the signal-to-noise ratio (SNR) of the current channel for encoding, which overlooks the neural network's self-adaptive capability across varying SNRs. This paper investigates the self-adaptive capability of deep learning-based JSCC models to dynamically changing channels and introduces a novel method named Channel-Blind JSCC (CBJSCC). CBJSCC leverages the intrinsic learning capability of neural networks to self-adapt to dynamic channels and diverse SNRs without relying on external SNR information. This approach is advantageous, as it is not affected by channel estimation errors and can be applied to one-to-many wireless communication scenarios. To enhance the performance of JSCC tasks, the CBJSCC model employs a specially designed encoder-decoder. Experimental results show that CBJSCC outperforms existing channel-adaptive JSCC methods that depend on SNR estimation and feedback, both in additive white Gaussian noise environments and under slow Rayleigh fading channel conditions. Through a comprehensive analysis of the model's performance, we further validate the robustness and adaptability of this strategy across different application scenarios, with the experimental results providing strong evidence to support this claim.

7.
Adv Mater ; : e2310245, 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38839065

RESUMEN

Non-aqueous electrolytes, generally consisting of metal salts and solvating media, are indispensable elements for building rechargeable batteries. As the major sources of ionic charges, the intrinsic characters of salt anions are of particular importance in determining the fundamental properties of bulk electrolyte, as well as the features of the resulting electrode-electrolyte interphases/interfaces. To cope with the increasing demand for better rechargeable batteries requested by emerging application domains, the structural design and modifications of salt anions are highly desired. Here, salt anions for lithium and other monovalent (e.g., sodium and potassium) and multivalent (e.g., magnesium, calcium, zinc, and aluminum) rechargeable batteries are outlined. Fundamental considerations on the design of salt anions are provided, particularly involving specific requirements imposed by different cell chemistries. Historical evolution and possible synthetic methodologies for metal salts with representative salt anions are reviewed. Recent advances in tailoring the anionic structures for rechargeable batteries are scrutinized, and due attention is paid to the paradigm shift from liquid to solid electrolytes, from intercalation to conversion/alloying-type electrodes, from lithium to other kinds of rechargeable batteries. The remaining challenges and key research directions in the development of robust salt anions are also discussed. This article is protected by copyright. All rights reserved.

8.
Glob Ment Health (Camb) ; 11: e54, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38721485

RESUMEN

Background: Chinese nurses working with immense stress may have issues with burnout during COVID-19 regular prevention and control. There were a few studies investigating status of burnout and associated factors among Chinese nurses. However, the relationships remained unclear. Objectives: To investigate status and associated factors of nurses' burnout during COVID-19 regular prevention and control. Methods: 784 nurses completed questionnaires including demographics, Generalized Anxiety Disorder-7, Patient Health Questionnaire-9, Insomnia Severity Index, Impact of Event Scale-revised, Perceived Social Support Scale, Connor-Davidson Resilience Scale, General Self-efficacy Scale and Maslach Burnout Inventory. Results: 310 (39.5%), 393 (50.1%) and 576 (73.5%) of respondents were at high risk of emotional exhaustion (EE), depersonalization (DP) and reduced personal accomplishment (PA). The risk of EE, DP and reduced PA were moderate, high and high. Nurses with intermediate and senior professional rank and title and worked >40 h every week had lower scores in EE. Those worked in low-risk department reported lower scores in PA. Anxiety, post-traumatic stress disorder (PTSD), self-efficacy and social support were influencing factors of EE and DP, while social support and resilience were associated factors of PA. Conclusion: Chinese nurses' burnout during COVID-19 regular prevention and control was serious. Professional rank and title, working unit, weekly working hours, anxiety, PTSD, self-efficacy, social support and resilience were associated factors of burnout.

9.
Food Res Int ; 186: 114331, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38729716

RESUMEN

Peach fruit is prone to chilling injury (CI) during low-temperature storage, resulting in quality deterioration and economic losses. Our previous studies have found that exogenous trehalose treatment can alleviate the CI symptoms of peach by increasing sucrose accumulation. The purpose of this study was to explore the potential molecular mechanism of trehalose treatment in alleviating CI in postharvest peach fruit. Transcriptome analysis showed that trehalose induced gene expression in pathways of plant MAPK signaling, calcium signaling, and reactive oxygen species (ROS) signaling. Furthermore, molecular docking analysis indicated that PpCDPK24 may activate the ROS signaling pathway by phosphorylating PpRBOHE. Besides, PpWRKY40 mediates the activation of PpMAPKKK2-induced ROS signaling pathway by interacting with the PpRBOHE promoter. Accordingly, trehalose treatment significantly enhanced the activities of antioxidant-related enzymes such as superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), and gluathione reductase (GR), as well as the transcription levels AsA-GSH cycle related gene, which led to the reduction of H2O2 and malondialdehyde (MDA) content in peach during cold storage. In summary, our results suggest that the potential molecular mechanism of trehalose treatment is to enhance antioxidant capacity by activating CDPK-mediated Ca2 + -ROS signaling pathway and WRKY-mediated MAPK-WRKY-ROS signaling pathway, thereby reducing the CI in peach fruit.


Asunto(s)
Antioxidantes , Frío , Frutas , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Prunus persica , Especies Reactivas de Oxígeno , Transducción de Señal , Trehalosa , Trehalosa/farmacología , Trehalosa/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Antioxidantes/farmacología , Antioxidantes/metabolismo , Transducción de Señal/efectos de los fármacos , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Simulación del Acoplamiento Molecular , Malondialdehído/metabolismo
10.
Aging (Albany NY) ; 16(10): 8944-8964, 2024 05 22.
Artículo en Inglés | MEDLINE | ID: mdl-38787377

RESUMEN

SLAMF8, the eighth member of the Signaling Lymphocytic Activation Molecule Family (SLAMF), functions in the regulation of the development and activity of diverse immune cells as a costimulatory receptor within the SLAMF family. Studies had revealed that SLAMF8 is expressed higher in several autoimmune inflammation diseases and tumors. Nevertheless, the connection between SLAMF8 and pan-cancer remains undisclosed. The research investigated the correlation between SLAMF8 and various factors including the immune microenvironment, microsatellite instability, immune novel antigen, gene mutation, immune regulatory factors, immune blockade TMB, and immune or molecular subtypes of SLAMF8 in verse cancer types. Immunohistochemistry was ultimately employed to validate the presence of the SLAMF8 gene in various tumor types including hepatocellular carcinoma, prostate adenocarcinoma, and kidney renal clear cell carcinoma. Furthermore, the relationship between SLAMF8 expression and the therapeutic efficacy of the PD1 blockade agent, Sintilimab, treatment in gastric cancer was validated. The result of differential analysis suggested that SLAMF8 was over-expressed in pan-cancer compared with paracancerous tissues. The analysis of survival indicated a connection between SLAMF8 and the overall prognosis in different types of cancers, where higher levels of SLAMF8 were found to be significantly linked to unfavorable outcomes in patients but favorable outcome of immunotherapy in gastric cancer. Significant correlations were observed between SLAMF8 levels and pan-cancer tumorigenesis, tumor metabolism, and immunity. As a result, SLAMF8 may become an important prognostic biomarker in the majority of tumors and a hopeful gene target for immunotherapy against gastric cancer.


Asunto(s)
Inmunoterapia , Familia de Moléculas Señalizadoras de la Activación Linfocitaria , Neoplasias Gástricas , Microambiente Tumoral , Humanos , Familia de Moléculas Señalizadoras de la Activación Linfocitaria/genética , Familia de Moléculas Señalizadoras de la Activación Linfocitaria/metabolismo , Neoplasias Gástricas/inmunología , Neoplasias Gástricas/genética , Neoplasias Gástricas/terapia , Inmunoterapia/métodos , Pronóstico , Microambiente Tumoral/inmunología , Masculino , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/genética , Femenino , Regulación Neoplásica de la Expresión Génica
11.
Food Chem ; 452: 139580, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-38744129

RESUMEN

The absence of high-affinity antibodies has hindered the development of satisfactory immunoassays for dichlorvos (DDVP) and trichlorfon (TCP), two highly toxic organophosphorus pesticides. Herein, the de novo synthesis of a novel anti-DDVP hapten was introduced. Subsequently, a specific anti-DDVP monoclonal antibody (Mab) was produced with satisfying affinity to DDVP (IC50: 12.4 ng mL-1). This Mab was highly specific to DDVP, and TCP could readily convert into DDVP under mild alkaline conditions. Leveraging this insight, an indirect competitive ELISA was successfully developed for simultaneous detection of DDVP and TCP. The limit of detection in rice, cabbage and apple for DDVP /TCP was found to be 12.1/14.6 µg kg-1, 7.3/8.8 µg kg-1 and 6.9/8.3 µg kg-1, respectively. This study not only provides an effective strategy for producing a high-quality anti-DDVP Mab but also affords a reliable and cost-effective tool suitable for high-throughput detection of DDVP and TCP in food samples.


Asunto(s)
Anticuerpos Monoclonales , Diclorvos , Ensayo de Inmunoadsorción Enzimática , Contaminación de Alimentos , Haptenos , Oryza , Triclorfón , Haptenos/química , Haptenos/inmunología , Anticuerpos Monoclonales/inmunología , Anticuerpos Monoclonales/química , Animales , Contaminación de Alimentos/análisis , Ensayo de Inmunoadsorción Enzimática/métodos , Diclorvos/análisis , Oryza/química , Oryza/inmunología , Triclorfón/análisis , Triclorfón/inmunología , Ratones , Ratones Endogámicos BALB C , Malus/química , Brassica/química , Brassica/inmunología , Inmunoensayo/métodos
12.
Biomacromolecules ; 25(5): 3190-3199, 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38693753

RESUMEN

Intracellular bacteria in dormant states can escape the immune response and tolerate high-dose antibiotic treatment, leading to severe infections. To overcome this challenge, cascade-targeted nanoplatforms that can target macrophages and intracellular bacteria, exhibiting synergetic antibiotic/reactive oxygen species (ROS)/nitric oxide (NO)/immunotherapy, were developed. These nanoplatforms were fabricated by encapsulating trehalose (Tr) and vancomycin (Van) into phosphatidylserine (PS)-coated poly[(4-allylcarbamoylphenylboric acid)-ran-(arginine-methacrylamide)-ran-(N,N'-bisacryloylcystamine)] nanoparticles (PABS), denoted as PTVP. PS on PTVP simulates a signal of "eat me" to macrophages to promote cell uptake (the first-step targeting). After the uptake, the nanoplatform in the acidic phagolysosomes could release Tr, and the exposed phenylboronic acid on the nanoplatform could target bacteria (the second-step targeting). Nanoplatforms can release Van in response to infected intracellular overexpressed glutathione (GSH) and weak acid microenvironment. l-arginine (Arg) on the nanoplatforms could be catalyzed by upregulated inducible nitric oxide synthase (iNOS) in the infected macrophages to generate nitric oxide (NO). N,N'-Bisacryloylcystamine (BAC) on nanoplatforms could deplete GSH, allow the generation of ROS in macrophages, and then upregulate proinflammatory activity, leading to the reinforced antibacterial capacity. This nanoplatform possesses macrophage and bacteria-targeting antibiotic delivery, intracellular ROS, and NO generation, and pro-inflammatory activities (immunotherapy) provides a new strategy for eradicating intracellular bacterial infections.


Asunto(s)
Antibacterianos , Nanopartículas , Óxido Nítrico , Especies Reactivas de Oxígeno , Especies Reactivas de Oxígeno/metabolismo , Óxido Nítrico/metabolismo , Antibacterianos/farmacología , Antibacterianos/química , Ratones , Animales , Células RAW 264.7 , Nanopartículas/química , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Macrófagos/inmunología , Inmunoterapia/métodos , Vancomicina/farmacología , Vancomicina/química , Vancomicina/administración & dosificación , Infecciones Bacterianas/tratamiento farmacológico , Trehalosa/química , Trehalosa/farmacología
13.
Commun Med (Lond) ; 4(1): 84, 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38724730

RESUMEN

BACKGROUND: Artificial Intelligence(AI)-based solutions for Gleason grading hold promise for pathologists, while image quality inconsistency, continuous data integration needs, and limited generalizability hinder their adoption and scalability. METHODS: We present a comprehensive digital pathology workflow for AI-assisted Gleason grading. It incorporates A!MagQC (image quality control), A!HistoClouds (cloud-based annotation), Pathologist-AI Interaction (PAI) for continuous model improvement, Trained on Akoya-scanned images only, the model utilizes color augmentation and image appearance migration to address scanner variations. We evaluate it on Whole Slide Images (WSI) from another five scanners and conduct validations with pathologists to assess AI efficacy and PAI. RESULTS: Our model achieves an average F1 score of 0.80 on annotations and 0.71 Quadratic Weighted Kappa on WSIs for Akoya-scanned images. Applying our generalization solution increases the average F1 score for Gleason pattern detection from 0.73 to 0.88 on images from other scanners. The model accelerates Gleason scoring time by 43% while maintaining accuracy. Additionally, PAI improve annotation efficiency by 2.5 times and led to further improvements in model performance. CONCLUSIONS: This pipeline represents a notable advancement in AI-assisted Gleason grading for improved consistency, accuracy, and efficiency. Unlike previous methods limited by scanner specificity, our model achieves outstanding performance across diverse scanners. This improvement paves the way for its seamless integration into clinical workflows.


Gleason grading is a well-accepted diagnostic standard to assess the severity of prostate cancer in patients' tissue samples, based on how abnormal the cells in their prostate tumor look under a microscope. This process can be complex and time-consuming. We explore how artificial intelligence (AI) can help pathologists perform Gleason grading more efficiently and consistently. We build an AI-based system which automatically checks image quality, standardizes the appearance of images from different equipment, learns from pathologists' feedback, and constantly improves model performance. Testing shows that our approach achieves consistent results across different equipment and improves efficiency of the grading process. With further testing and implementation in the clinic, our approach could potentially improve prostate cancer diagnosis and management.

14.
Front Pharmacol ; 15: 1336232, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38708081

RESUMEN

Background: Chrysin (5,7-dihydroxyflavone) is a natural flavonoid that has been reported as a potential treatment for non-alcoholic fatty liver disease (NAFLD). However, extensive phase II metabolism and poor aqueous solubility led to a decrease in the chrysin concentration in the blood after oral administration, limiting its pharmacological development in vivo. Methods: In the present study, we synthesized a novel chrysin derivative prodrug (C-1) to address this issue. We introduced a hydrophilic prodrug group at the 7-position hydroxyl group, which is prone to phase II metabolism, to improve water solubility and mask the metabolic site. Further, we evaluated the ameliorative effects of C-1 on NAFLD in vitro and in vivo by NAFLD model cells and db/db mice. Results: In vitro studies indicated that C-1 has the ability to ameliorate lipid accumulation, cellular damage, and oxidative stress in NAFLD model cells. In vivo experiments showed that oral administration of C-1 at a high dose (69.3 mg/kg) effectively ameliorated hyperlipidemia and liver injury and reduced body weight and liver weight in db/db mice, in addition to alleviating insulin resistance. Proteomic analysis showed that C-1 altered the protein expression profile in the liver and particularly improved the expression of proteins associated with catabolism and metabolism. Furthermore, in our preliminary pharmacokinetic study, C-1 showed favorable pharmacokinetic properties and significantly improved the oral bioavailability of chrysin. Conclusion: Our data demonstrated that C-1 may be a promising agent for NAFLD therapy.

15.
Artículo en Inglés | MEDLINE | ID: mdl-38650462

RESUMEN

BACKGROUND: Cesarean hysterectomy is a dominant and effective approach during delivery in patients with placenta accreta spectrum (PAS). However, as hysterectomy results in a loss of fertility, conservative management is an alternative approach. However, management selection may be affected by a country's overall economic level. Thus the preferred treatment for PAS generates controversy in middle-income countries. OBJECTIVES: We aimed to compare conservative management and cesarean hysterectomy for managing PAS in middle-income countries. SEARCH STRATEGY: China National Knowledge Infrastructure, Wanfang Med Online Databases, Cochrane Library, Ovid MEDLINE, PubMed, Web of Science, EMBASE, clinicaltrials.gov, and Scopus were searched from inception through to October 1, 2022. SELECTION CRITERIA: We included studies that evaluated at least one complication comparing conservative management and hysterectomy. All cases were diagnosed with PAS prenatally and intraoperatively. DATA COLLECTION AND ANALYSIS: The primary outcomes were blood loss, adjacent organ damage, and the incidence of hysterectomy. Descriptive analyses were conducted for studies that did not meet the meta-analysis criteria. A fixed-effects model was used for studies without heterogeneity and a random-effects model was used for studies with statistical heterogeneity. MAIN RESULTS: In all, 11 observational studies were included, with 975 and 625 patients who underwent conservative management and cesarean hysterectomy, respectively. Conservative management was significantly associated with decreased blood loss and lower risks of adjacent organ injury and hysterectomy. Conservative management significantly reduced blood transfusions, hospitalization duration, operative time, intensive care unit admission rates, and infections. There were no significant differences in the risks of coagulopathy, thromboembolism, or reoperation. CONCLUSION: Given short-term complications and future fertility preferences for patients, conservative management appears to effectively manage PAS in middle-income countries. Owing to low levels of evidence, high heterogeneity and insufficient long-term follow-up data, further detailed studies are warranted.

16.
J Gastrointest Oncol ; 15(1): 425-434, 2024 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-38482241

RESUMEN

Background: Patients experiencing severe postoperative pain often show lower adherence to prescribed treatments, highlighting the clinical need for effective pain prediction and management strategies. This study aims to address this gap by identifying key risk factors associated with post-transarterial chemoembolization (TACE) pain and developing a predictive scoring system. Methods: We retrospectively analyzed data from liver cancer patients who underwent their first TACE procedure at our institution between January 2019 and December 2020. Pain levels were assessed using an 11-point numerical rating scale (NRS-11). Patients were randomly assigned to training and validation cohorts. In the training cohort, logistic regression was used to evaluate the correlation between various parameters and post-TACE pain, leading to the development of a risk prediction model. This model's performance was subsequently assessed in the validation cohort. Results: The study included 255 patients. Univariate analysis in the training cohort identified tumor number, size, microsphere volume, and operation time as factors associated with postoperative pain. These factors were included in a multivariate model, which demonstrated areas under the receiver operating characteristic (ROC) curve (AUCs) of 0.71 in the training cohort and 0.74 in the validation cohort for predicting moderate to severe pain. A nomogram was also developed for clinical application, categorizing patients with scores above 72.90 as high risk for moderate to severe pain. Conclusions: Our research successfully developed and validated a novel scoring system capable of predicting moderate to severe pain following initial TACE treatment. However, the study's predictive accuracy, as reflected by AUC values, suggests that further refinement and validation in larger, diverse cohorts are necessary to enhance its clinical utility. This work underscores the importance of predictive tools in improving postoperative pain management and patient outcomes.

17.
Mol Hortic ; 4(1): 10, 2024 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-38500223

RESUMEN

Artemisinin is primarily synthesized and stored in the subepidermal space of the glandular trichomes of Artemisia annua. The augmentation of trichome density has been demonstrated to enhance artemisinin yield. However, existing literature lacks insights into the correlation between the stratum corneum and trichomes. This study aims to unravel the involvement of TrichomeLess Regulator 3 (TLR3), which encodes the transcription factor, in artemisinin biosynthesis and its potential association with the stratum corneum. TLR3 was identified as a candidate gene through transcriptome analysis. The role of TLR3 in trichome development and morphology was investigated using yeast two-hybrid, pull-down analysis, and RNA electrophoresis mobility assay. Our research revealed that TLR3 negatively regulates trichome development. It modulates the morphology of Arabidopsis thaliana trichomes by inhibiting branching and inducing the formation of abnormal trichomes in Artemisia annua. Overexpression of the TLR3 gene disrupts the arrangement of the stratum corneum and reduces artemisinin content. Simultaneously, TLR3 possesses the capacity to regulate stratum corneum development and trichome follicle morphology by interacting with TRICHOME AND ARTEMISININ REGULATOR 1, and CycTL. Consequently, our findings underscore the pivotal role of TLR3 in the development of glandular trichomes and stratum corneum biosynthesis, thereby influencing the morphology of Artemisia annua trichomes.

18.
Magn Reson Imaging ; 109: 27-33, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38438094

RESUMEN

OBJECTIVE: The evaluate the feasibility of a novel deep learning-reconstructed ultra-fast respiratory-triggered T2WI sequence (DL-RT-T2WI) In liver imaging, compared with respiratory-triggered Arms-T2WI (Arms-RT-T2WI) and respiratory-triggered FSE-T2WI (FSE-RT-T2WI) sequences. METHODS: 71 patients with liver lesions underwent 3-T MRI and were prospectively enrolled. Two readers independently analyzed images acquired with DL-RT-T2WI, Arms-RT-T2WI, and FSE-RT-T2WI. The qualitative evaluation indicators, including overall image quality (OIQ), sharpness, noise, artifacts, lesion detectability (LC), lesion characterization (LD), cardiacmotion-related signal loss (CSL), and diagnostic confidence (DC), were evaluated in two readers, and further statistically compared using paired Wilcoxon rank-sum test among three sequences. RESULTS: 176 lesions were detected in DL-RT-T2W and Arms-RT-T2WI, and 175 were detected in FSE-RT-T2WI. The acquisition time of DL-RT-T2WI was improved by 4.8-7.9 folds compared to the other two sequences. The OIQ was scored highest for DL-RT-T2WI (R1, 4.61 ± 0.52 and R2, 4.62 ± 0.49), was significantly superior to Arms-RT-T2WI (R1, 4.30 ± 0.66 and R2, 4.34 ± 0.69) and FSE-RT-T2WI (R1, 3.65 ± 1.08 and R2, 3.75 ± 1.01). Artifacts and sharpness scored highest for DL-RT-T2WI, followed by Arms-RT-T2WI, and were lowest for FSE-RT-T2WI in both two readers. Noise and CSL for DL-RT-T2WI scored similar to Arms-RT-T2WI (P > 0.05) and were significantly superior to FSE-RT-T2WI (P < 0.001). Both LD and LC for DL-RT-T2WI were significantly superior to Arms-RT-T2WI and FSE-RT-T2WI in two readers (P < 0.001). DC for DL-RT-T2WI scored best, significantly superior to Arms-RT-T2WI (P < 0.010) and FSE-RT-T2WI (P < 0.001). CONCLUSIONS: The novel ultra-fast DL-RT-T2WI is feasible for liver imaging and lesion characterization and diagnosis, not only offers a significant improvement in acquisition time but also outperforms Arms-RT-T2WI and FSE-RT-T2WI concerning image quality and DC.


Asunto(s)
Aprendizaje Profundo , Neoplasias Hepáticas , Humanos , Estudios de Factibilidad , Imagen por Resonancia Magnética/métodos , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/patología , Artefactos
20.
Fish Shellfish Immunol ; 148: 109505, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38521144

RESUMEN

The E11 cell line, derived from striped snakehead fish (Channa striata), possesses a distinctive feature: it is persistently infected with a C-type retrovirus. Notably, it exhibits high permissiveness to piscine nodavirus and the emerging tilapia lake virus (TiLV). Despite its popularity in TiLV research, the absence of genome assembly for the E11 cell line and Channa striata has constrained research on host-virus interactions. This study aimed to fill this gap by sequencing, assembling, and annotating the E11 cell line genome. Our efforts yielded a 600.5 Mb genome including 24 chromosomes with a BUSCO score of 98.8%. In addition, the complete proviral DNA sequence of snakehead retrovirus (SnRV) was identified in the E11 cell genome. Comparative genomic analysis between the E11 cell line and another snakehead species Channa argus revealed the loss of many immune-related gene families in the E11 cell genome, indicating a compromised immune response. We also conducted transcriptome analysis of mock- and TiLV-infected E11 cells, unveiling new perspectives on virus-virus and host-virus interactions. The TiLV infection suppressed the high expression of SnRV in E11 cells, and activated some other endogenous retroviruses. The protein-coding gene comparison revealed a pronounced up-regulation of genes involved in immune response, alongside a down-regulation of genes associated with specific metabolic processes. In summary, the genome assembly and annotation of the E11 cell line provide valuable resources to understand the SnRV and facilitate further studies on nodavirus and TiLV. The RNA-seq profiles shed light on the cellular mechanisms employed by fish cells in response to viral challenges, potentially guiding the development of therapeutic strategies against TiLV in aquaculture. This study also provides the first insights into the viral transcriptome profiles of endogenous SnRV and evading TiLV, enhancing our understanding of host-virus interactions in fish.


Asunto(s)
Enfermedades de los Peces , Tilapia , Virus , Animales , Retroviridae , Cromosomas , Perfilación de la Expresión Génica/veterinaria
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